Mirko D'Onofrio, Paola Capelli, Paolo Pederzoli - Imaging and Pathology of Pancreatic Neoplasms - A Pictorial Atlas-Springer (2022)

Mirko D’Onofrio
Paola Capelli
Paolo Pederzoli
Editors
Imaging and Pathology

of Pancreatic Neoplasms
A Pictorial Atlas
Second Edition
123
Imaging and Pathology of Pancreatic Neoplasms
Mirko D'Onofrio • Paola Capelli
Paolo Pederzoli
Editors
Imaging and Pathology of

Pancreatic Neoplasms
A Pictorial Atlas
Second Edition
Editors
Mirko D'Onofrio Paola Capelli
Department of Radiology, University Department of Pathology, GB Rossi
of Verona, GB Rossi University Hospital University Hospital
Azienda Ospedaliera Universitaria Integrata Azienda Ospedaliera Universitaria Integrata
Verona Verona
Verona, Italy Verona, Italy
Paolo Pederzoli
Department of Surgery
Pederzoli Hospital
Peschiera del Garda (VR), Italy
ISBN 978-3-031-09830-7 ISBN 978-3-031-09831-4 (eBook)

https://doi.org/10.1007/978-3-031-09831-4
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Professor Carlo Procacci had the idea of an Atlas on the imaging and
pathology of pancreatic neoplasms around the year 2000. Carlo Procacci
was born in Corato, Puglia, Italy, in 1950 and died in Verona, Veneto, Italy,
in 2004. His idea was recovered in 2012 by Paola Capelli, and this book is
the result.
Thanks Professor, the teachings last forever.
Mirko D’Onofrio
“Friend, you will forever be in our thoughts as your thoughts will always be
part of us.”
Alec J. Megibow
Ipotesi
Ipotesi di vivere
di essere di divenire
speriamo andiamo
nell’ipotesi di noi stessi
niuna cosa è tesi solo la morte nella sua verità
Rubiamo ogni ora alla speranza
e risorgiamo
nell’ipotesi del nuovo
Anche il seme nella terra
è un’ipotesi
dell’erba e del fiore
Anche il bimbo nella mamma
è un’ipotesi
dell’uomo che sarà
Anche tutti noi che corriamo
gli altri siamo ipotesi
immagini solo negli occhi nei capelli
solo parvenze o mistificazioni
saremo certezze solo in ciò che daremo
È l’amore che fa il fiore
È il sorriso che fa il bambino
È l’attenzione alla apertura del cuore
che fa per noi la sapienza migliore
proiezione sicura per l’eternità
Maria Antonietta Cocco
(Tra ombra e luce, 2021)
Foreword to the Second Edition
When a book reaches its second edition, it can only be an exceptional book!
This is even more evident when it comes to a text on medical sciences; the widespread dis-
semination of information via the Web makes the pages of a medical book to leaf through and
study more and more (theoretically!) “useless”!
In the first edition foreword, I wrote “… I believe that Mirko D’Onofrio, one of the younger
and favorite of Carlo’s apprentices, has brilliantly compiled his teachings in this volume,
reflecting how Prof. Procacci was able to share his knowledge with others.”
The success of the book clearly demonstrates that I was perfectly right.
Mirko had promised himself in wanting to make this text a tribute to his master, but it is not
just a question of celebrating the memory of Prof. Procacci; this result is also the best way to
celebrate the “Verona Pancreas Institute” method and approach to the patient: relationship with
other disciplines and mutual interaction between different disciplines!
I am convinced that this is the real secret of this text: by reading it, you let yourself be trans-
ported from mere descriptive radiology to a modern clinical–radiological approach.
Thanks Mirko, and thanks to all your collaborating colleagues once again. Of course, I am
ready for more and more “forewords” in the next future!
Verona, Italy Claudio Bassi
vii
Acknowledgments
The volume editors wish to express their most sincere thanks to the following colleagues, for
their invaluable contribution and the precious exchange of constructive clinical and scientific
experiences: Alec J. Megibow, Cristina Hajdu, Christoph Dietrich, Enrico Martone, Giancarlo
Mansueto, Giovanni Carbognin, Carlo Biasiutti, Rossella Graziani, Alessandro Guarise,
Elisabetta Buscarini, Paolo Arcidiacono, Arnaldo Fuini, Marco Ferdeghini, Franco Bonetti,
Erminia Manfrin, Alice Parisi, Massimo Pregarz, Luigi Romano, Giuseppe Zamboni.
The volume editors are furthermore grateful to the following collaborators, for their effec-
tive technical support: Alma Olivieri, Renato Padovani, Flavio Rigo, Manola Crestani, Nicola
Sperandio, Stefano Minutelli.
ix
Contents
Ductal Adenocarcinoma�� 1

Mirko D’Onofrio, Riccardo De Robertis, Alessandro Beleù, Paolo Tinazzi Martini,
Emilio Barbi, Luca Geraci, Luisa Tomaiuolo, Giovanni Morana, and Paola Capelli
Ductal Adenocarcinoma: Downstaging�� 99
Riccardo De Robertis, Paola Capelli, Chiara Longo, and Mirko D’Onofrio
Neuroendocrine Neoplasms�� 141
Riccardo De Robertis, Mirko D’Onofrio, Paolo Tinazzi Martini, Stefano Gobbo,
Maria Gaia Mastrosimini, Lavinia Stefanizzi, Alessandro Beleù, Luca Geraci,
Aldo Scarpa, and Paola Capelli
Mimickers of Pancreatic Tumor �� 233
Mirko D’Onofrio, Antonio Giugliano, Gregorio Aluffi, Roberto Calbi,
Angela Calabrese, and Riccardo De Robertis

Intraductal Papillary Mucinous Neoplasm (IPMN) �� 251
Giovanni Morana, Mirko D’Onofrio, Paolo Tinazzi Martini,
Riccardo De Robertis, Alessandro Beleù, Claudio Luchini, Eda Bardhi,
Nicolò Cardobi, and Paola Capelli
Serous Neoplasms�� 327
Paola Capelli, Paolo Tinazzi Martini, Giovanni Morana, Riccardo de Robertis,
Claudio Luchini, Stefano Gobbo, and Mirko D’Onofrio
Mucinous Neoplasms �� 361
Mirko D’Onofrio, Paola Capelli, Claudio Luchini, Paolo Tinazzi Martini,
Emilio Barbi, and Riccardo De Robertis

Pseudocysts and Other Cystic Lesions�� 393
Valentina Ciaravino, Roberto Calbi, Antonio Giugliano, Luca Geraci,
Luisa Tomaiuolo, Chiara Longo, Riccardo De Robertis, and Mirko D’Onofrio
Secondary Tumors and Lymphoma �� 415
Paolo Tinazzi Martini, Eda Bardhi, Antonia Maria Olivieri, Marco Todesco,
Daniele Autelitano, Luisa Tomaiuolo, Luca Geraci, and Paola Capelli

Uncommon Presentations of Pancreatic Neoplasms, Rare Neoplasms,
and Peripancreatic Masses�� 435
Riccardo De Robertis, Antonia Olivieri, Angela Calabrese, Luca Geraci,
Nicolò Cardobi, Paolo Tinazzi Martini, Roberto Calbi, Paola Capelli,
and Mirko D’Onofrio
xi
xii Contents

Pancreatic Surgery and Post-Operative Complications �� 451
Riccardo De Robertis, Luca Geraci, Nicolò Cardobi, Luisa Tomaiuolo,
Antonia Maria Olivieri, Francesco Verrengia, Francesco Cicalò, Filippo Moro,
Roberto Calbi, and Mirko D’Onofrio

Imaging Methods for Pancreatic Neoplasms�� 463
Alessandro Beleù, Fabrizio Urraro, Roberto Calbi, Chiara Longo,
Annalisa Cominziolli, Riccardo De Robertis, Nicolò Cardobi,

Advanced Imaging of Pancreatic Neoplasms�� 481
Nicolò Cardobi, Riccardo De Robertis, and Mirko D’Onofrio

Elastography and New Ultrasound Techniques�� 495
Christoph F. Dietrich, Adrian Saftiou, Michael Hocke, and Liliana Chiorean

Percutaneous Interventional Procedures in Pancreatic Cancer�� 517
Mirko D’Onofrio, Antonia Maria Olivieri, Francesco Verrengia,
Filippo Moro, Luca Geraci, Luisa Tomaiuolo, Chiara Longo,
Francesco Cicalò, Cesare Cacciatore, Alice Parisi, Erminia Manfrin,
and Riccardo De Robertis

New Diagnostic and Interventional Endoscopic Techniques�� 535
Michael Hocke
Ductal Adenocarcinoma
Mirko D’Onofrio, Riccardo De Robertis,

Alessandro Beleù, Paolo Tinazzi Martini, Emilio Barbi,
Luca Geraci, Luisa Tomaiuolo, Giovanni Morana,
and Paola Capelli
Introduction artery, as well as for circumferential extension to the superior

mesenteric vein and superior mesenteric-portal vein conflu-
Ductal adenocarcinoma is the most common primary malig- ence [6].
nancy of the pancreas, accounting for about 80% of malig-
nant pancreatic tumors [1–3].
The incidence ranges from 1 to 10 on 100,000 people in Pathology
developed countries; 80% of patients with ductal adenocarci-
noma are between 60 and 80 years of age. It is a highly Ductal adenocarcinoma is a malignant epithelial neoplasm
aggressive tumor with an overall 5-year survival rate less with glandular (ductal) differentiation, without a predomi-
than 5% [1]. nant component of any other types of carcinoma [7].
Cigarette smoking is the main risk factor for this disease; Sixty to seventy percent of ductal adenocarcinomas are
other risk factors are not well established but include chronic located in the pancreatic head, 30% in the body and tail, and
pancreatitis and diabetes. Alcohol does not seem to be a risk 5% involve the whole organ. Multifocal disease has been
factor, unless an excessive consumption may cause chronic reported as well as synchronous or metachronous
pancreatitis. Pancreatic cancer is associated with a number carcinomas.
of well-defined molecular hallmarks. The most frequent Carcinomas of the pancreatic head tend to cause symp-
genetic aberrations comprise KRAS mutations, mostly toms such as painless jaundice, acute pancreatitis, and epi-
affecting codon 12, which are observed in 60–75% of pan- gastric pain that radiates to the back.
creatic cancers [4]. Carcinomas of the body-tail of the pancreas often present
Prognosis and treatment depend on whether the tumor is with unexplained weight loss, back pain, or distant
resectable or non-resectable, which mostly depends on the metastases.
time of diagnosis [5]. A pancreatic tumor is defined non- Sudden onset of diabetes mellitus may be the first sign of
resectable, not only for the presence of metastases and/or pancreatic cancer.
involvement of adjacent organs but also for the infiltration of Carcinomas of the pancreatic head are usually diagnosed
celiac trunk, common hepatic artery, and superior mesenteric earlier and are more often resectable than carcinomas that
involve the body-tail.
Surgically resected carcinomas of the pancreatic head are
M. D’Onofrio (*) · R. De Robertis · L. Geraci · L. Tomaiuolo generally significantly smaller than the tumors of the body
Department of Radiology, G.B. Rossi University Hospital,
and tail (2–3 cm versus 5–7 cm, respectively).
Verona, Italy
e-mail: mirko.donofrio@univr.it
A. Beleù · G. Morana
Department of Radiology, S. Maria di Ca’ Foncello Hospital, Macroscopy
Treviso, Italy
P. T. Martini · E. Barbi On the cut surface, the tumor usually appears as a solid firm
Department of Radiology, Casa di Cura Dott. Pederzoli, Verona, mass with infiltrative, indefinable margins, whitish color,
Italy and hard consistency.
P. Capelli The tumor is often surrounded by a phlogistic fibrous
Department of Pathology, G.B. Rossi University Hospital, Verona, “cuff,” derived from a focal peritumoral pancreatitis, making
Italy
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 1

M. D’Onofrio et al. (eds.), Imaging and Pathology of Pancreatic Neoplasms, https://doi.org/10.1007/978-3-031-09831-4_1
2 M. D’Onofrio et al.
it sometimes hard to identify the actual dimensions of the In most of the cases, cysts are adjacent or upstream
tumor, both at imaging and macroscopically. located in respect to the mass. These cysts are secondary to
Extensive areas of hemorrhage and necrosis with cystic duct obstruction, may grow to huge dimensions, and could
cavitation are uncommon, but microscopic foci are not so be colonized by neoplastic epithelium. These cases must not
uncommon. be mistaken for infiltrating IPMNs.
Carcinomas of the pancreatic head, with the exception of Finally, ductal adenocarcinomas with huge dilated ductal
those arising in the uncinate process, almost always infiltrate structures may macroscopically present as microcystic
both the common bile duct and Wirsung duct, leading to a lesions [14].
variable degree of stenosis and upstream dilation (radiologi-
cal “double-duct sign”). This causes jaundice and upstream
obstructive pancreatitis, which could lead to chronic pancre- Microscopy
atitis, characterized by the presence of fibrotic or fibro-
adipous components, associated with a variable degree of Ductal adenocarcinoma is composed by neoplastic tubules
acinar cells atrophy, with duct dilatation and retention cysts or glands embedded in abundant desmoplastic stroma, with
formation. low vascularization.
The involvement of duodenum and/or Vater’s ampulla, Neoplastic glands can have different degrees of differen-
frequently found in the carcinomas of the pancreatic head, tiation, ranging from duct-like and medium-sized glandular
causes retraction of the intestinal wall, and eventually muco- structures in well-differentiated cases to a mixture of densely
sal ulceration. packed, small irregular glands, solid sheets, and nests, as
Invasion and thrombosis of large peripancreatic vessels, well as individual cells, in the poorly differentiated ones.
such as the splenic vein, are frequently observed in body-tail The intense non-neoplastic stromal reaction accounts for
carcinomas. the scirrhous and firm macroscopic aspect and is responsible
The pathological evaluation of the retroperitoneal resec- for the low vascular density, which leads to the radiological
tion margin provides the most important information about detection as a hypovascular mass [15].
local recurrence and patient survival. This margin is defined The development of a marked peritumoral fibro-
as the peripancreatic adipose tissue behind the head of the inflammatory reaction due to obstructive chronic pancreatitis
pancreas, which is located ventral and lateral, in respect to can exacerbate the pathological findings, and, as a result, the
the superior mesenteric artery [8–11]. neoplastic epithelial cells in most pancreatic cancers com-
When the tumor involves the celiac trunk or the superior prise only a small portion of the cells in the tumor.
mesenteric artery, it is considered unresectable; so, this Most ductal adenocarcinomas infiltrate a variety of preex-
involvement is rarely present in surgical pathology speci- isting structures: pancreatic ducts, nerves, vessels, duodenal
mens. A focal and partial, noncircumferential, adhesion of wall, and vasculonervous structures. For these reasons, carci-
the posterior pancreatic surface to the mesenteric vein may nomas extend beyond the main pancreatic mass, leading to a
justify the surgical resection of a fragment of the vessel wall. radiological and macroscopic underestimation of the actual
Just the histological examination will then prove if this adhe- tumoral dimensions.
sion is caused by neoplastic infiltration or by a fibro- At diagnosis, a vast majority of adenocarcinomas has
inflammatory response to the tumor. spread beyond the pancreas (pT3), even in resectable cases.
Carcinomas of the head of the pancreas frequently metas- Perineural and vascular invasions are invariably present in
tasize in peripancreatic lymph nodes; almost all ductal ade- most cases.
nocarcinomas resected along with a sufficient amount of A variant of adenocarcinoma, named large duct adenocar-
lymph nodes are pN1 [12, 13]. cinoma, is composed by irregular and dilated glands
In advanced cases, especially in carcinomas that involve [16–18].
the body-tail, the tumor infiltrates the mesocolon, the trans-
verse colon with the encasement of the celiac trunk and
splenic vessels, the stomach, the spleen, the left adrenal Imaging
gland, and the peritoneum, leading to peritoneal carcinoma-
tosis and ascites. The common vascular spread via the portal Imaging techniques have the following roles: identify and
vein explains the relatively high incidence of liver characterize pancreatic adenocarcinoma, assess its resect-
metastases. ability, and stage the disease.
Most pancreatic adenocarcinomas are solid, but some can Ultrasound (US) is often the noninvasive imaging method
be cystic due to extensive necrosis, particularly in larger for the first evaluation of the pancreas [19]. Since adenocar-
ones. In such cases, a large degenerative cyst is usually found cinoma is the most common primary malignancy of the pan-
in the center of the neoplasm [13]. creas, each pancreatic solid mass detected at US has a high
Ductal Adenocarcinoma 3
probability of being an adenocarcinoma, even if not every located, often giving an erroneous cystic appearance to the
solid pancreatic mass detected at US is obviously an adeno- lesion.
carcinoma [20]. The tumor is characterized by infiltrative margins and
Contrast-enhanced ultrasound (CEUS) can characterize early diffusion in the adjacent parenchyma and structures,
pancreatic ductal adenocarcinoma [21, 22]. In particular, justifying the usual lack of clear-cut margins at US [19, 24,
every pancreatic solid hypoechoic mass detected at US, 28]. As a result, sometimes, the lesion can be difficult to
hypoenhancing in all phases at CEUS, has to be considered a identify or delineate. Harmonic US and compound tech-
ductal adenocarcinoma, until otherwise proven. niques may improve the correct identification of the margins
Multi-detector computed tomography (MDCT) remains of the tumor [29].
the imaging gold standard for ductal adenocarcinoma identi- At Doppler study, no vessels are usually observed within
fication, characterization, and staging [1]. ductal adenocarcinomas [30, 31].
Magnetic resonance imaging (MRI) may provide better The main pancreatic duct is often infiltrated and upstream-
tumor conspicuity than MDCT [23], paying in a lower spa- dilated. Particularly, tumors located in the pancreatic head
tial resolution, especially for resectability assessment. also determine the dilation of the common bile duct, with the
so-called double-duct sign [32, 33]. Thus, identification of
duct dilation with abrupt cutoff must be considered a second-
Ultrasound ary sign, highly suspicious for pancreatic cancer, even if the
tumor itself cannot be visualized [34]. As a consequence,
The detection of a pancreatic ductal adenocarcinoma at patients with unexplained dilation of the pancreatic duct with
transabdominal US is related, both to the exploration of the abrupt cutoff should be directly referred to second-line imag-
pancreatic lodge and to the conspicuity of the lesion, in terms ing methods, especially CT.
of size and echogenicity. A good conspicuity of the lesion is Sonoelastography is a real-time technique, capable of
almost always expected at US [24]. The high-contrast resolu- evaluating the stiffness of tissues, thus providing additional
tion makes in fact the US examination able to detect even information to improve the differential diagnosis among
very small pancreatic adenocarcinomas. It has been argued pancreatic lesions [35–37]. The most recent sonoelasto-
that the acoustic impedance of ductal adenocarcinoma is graphic applications could be theoretically used to detect
very low, with a significant difference between the lesion and even the pancreatic tumors not visible at conventional US:
the adjacent pancreatic parenchyma [19]. Moreover, this basically, as a result of the marked desmoplasia, which is
visual difference between the lesion and the adjacent paren- very often present in pancreatic adenocarcinoma, this tumor
chyma is sometimes greater than that observed at CT, regard- appears stiff at elastographic evaluation [24, 38, 39]. The
ing beam attenuation in both pre- and post-contrastographic quantitative sonoelastography methods such as ARFI
phases: in these cases, a simple US can cover the role of (Acoustic Radiation Force Impulse) make the results more
problem-solving, immediately after a doubtful CT examina- objective and reproducible. The wave speed values measured
tion, as the lesion can usually be immediately detected at US, inside a pancreatic ductal adenocarcinoma are higher (usu-
owing to its hypoechoic appearance and better conspicuity ally >3 m/s) than that measured in the adjacent parenchyma,
[19, 25]. considering the fact that the mean value in the healthy pan-
The reported sensitivity and specificity of US in the detec- creas is about 1.4 m/s [24, 40].
tion of pancreatic adenocarcinoma vary in the medical litera- The introduction of contrast agents has significantly
ture, owing to the obvious impact of operator experience on strengthened US diagnostic capability, increasing the accu-
these results. Moreover, the inferior penetration of the US racy of the first-line examination in the characterization of
beam in obese patients and, particularly, the interposition of pancreatic tumors, especially for pancreatic adenocarcinoma
intestinal gas can be, more the last and less the first, impor- [21, 22, 41–44].
tant limitations. The mean sensitivity ranges from 72 to 98%, Dynamic observation of the contrast-enhanced phases
lower than that reported for CT, where specificity exceeds (early arterial, arterial, pancreatic, portal/venous, and late
90% [1, 25–27]. phases) begins immediately after the injection of second-
At US, pancreatic adenocarcinoma almost always pres- generation microbubble-based contrast medium. Contrast-
ents as a solid and markedly hypoechoic mass in compari- enhanced ultrasound (CEUS) is the only imaging method
son to the adjacent pancreatic parenchyma, because of its capable of providing this real-time evaluation of enhance-
very low acoustic impedance [19]. In highly aggressive ment, throughout all the dynamic phases [24], by maintain-
forms, necrosis is common, resulting from the difference ing the same scanning frame rate of the preliminary
between the tumor growth rate and the formation of new conventional B-mode examination [42]. As a consequence,
microvessels from neoangiogenesis [24]. The necrotic/liq- the study of tumoral macro- and microvasculature can pro-
uid, anechoic, portion of the tumor is usually centrally vide excellent results at CEUS [45].
Ductal adenocarcinoma shows poor enhancement in all creatitis [50]. Ductal adenocarcinoma, typically without cal-
phases. This hypovascular, hypoenhancing pattern is present cifications, is detectable in the pre-contrast phase only when
in about 90% of cases [43, 46, 47]. The hypoenhancing its dimensions modify pancreatic shape and contours,
aspect depends on the marked desmoplasia and on the mean because of its isodensity, relatively to the adjacent paren-
vascular density (MVD), which is low and usually inferior to chyma. A central necrotic degeneration usually provides an
the normal pancreatic parenchyma, together with the pres- inhomogeneous hypodensity to the lesion [24]. The main
ence of necrosis or mucin [41, 48, 49]. The MVD of pancre- pancreatic duct is usually markedly upstream dilated, and the
atic adenocarcinoma is also influenced by different degrees double-duct sign can be observed in tumors located in the
of differentiation. It has been shown that the enhancement head of the gland, even in the pre-contrast phase.
pattern at CEUS correlates with MVD, tumor differentiation, Contrast-enhanced CT appearance mainly depends on
aggressiveness, and prognosis [41]. To obtain a more objec- contrast medium volume, iodine concentration, and injec-
tive evaluation of CEUS perfusion, a quantification analysis tion flow rate. It is important to tailor the amount of con-
can also be obtained directly on the US scanner. The result- trast medium to the patient’s weight, using 1.5 ml/kg of a
ing color maps actually seem very similar to those obtained high iodine concentration contrast medium, for example,
at perfusion CT. 370 mgI/ml; the maximum amount of iodine should not
CEUS can increase the differential diagnosis between exceed 35–45 g, independently from the concentration
pancreatic lesions and should be recommended in patients [24]. The contrast medium is injected intravenously, fol-
with a proper visualization of the gland at US. So, a solid lowed by 50 ml of saline solution, at a flow rate of 3–5 ml/s.
hypovascular pancreatic mass at CEUS has to be considered To increase parenchymal enhancement, either a higher
a ductal adenocarcinoma, until proven otherwise. For the injection rate or a higher iodine concentration may be
above-explained reasons, the first recommendation in the applied, considering that only the latter does not depend on
2011 European Guidelines for Pancreatic Application of the intravenous access caliber [50]. Keeping constant the
CEUS is in fact: focal pancreatic lesions identified with US injection rate and the volume, the use of a contrast media
can be studied with CEUS to improve the characterization of with higher concentration of iodine significantly improves
ductal adenocarcinoma [22]. the arterial and portal venous phases’ enhancement and
pancreatic carcinoma conspicuity [51].
The administration of contrast medium involves the use
Computed Tomography of bolus tracking technique to exactly determine the timing
of scan delay for a precise individual study. Pancreatic phase
Multi-detector computed tomography, allowing pancreatic starts about 35–40 s after contrast administration or, using
imaging with a very high spatial and temporal resolution bolus tracking technique, 15–20 s after the aortic threshold
within a short breath-hold, is still considered the gold stan- enhancement [50], corresponding to a late arterial phase.
dard for the evaluation of focal solid pancreatic lesions. During this phase, there is maximal conspicuity of the mark-
The accuracy in the diagnosis of pancreatic solid tumors edly hypovascular tumor; this phase is furthermore useful to
is very high, owing to the isotropic or near-isotropic resolu- evaluate the peripancreatic arteries for the detection of vas-
tion (data set with a similar spatial resolution in each dimen- cular invasion [52, 53]. During the venous/portal phase, there
sion), thinner slice collimation (<1 mm), and multiphasic is a pancreatic washout, and the contrast agent begins to dif-
imaging [50]. fuse into the interstitium of the lesion, with the tumor becom-
The typical CT aspect of ductal adenocarcinoma is that of ing less conspicuous. Furthermore, during this phase, it is
a hypo−/isodense solid mass on unenhanced scan, hypodense possible to evaluate the peripancreatic veins for the detection
during dynamic study [20]. of vascular invasion. This phase is moreover ideal for the
After a minimum fast of 6 h, 500–700 ml of negative oral detection of liver metastases [54]. The late phase has no sig-
contrast medium (water) should be administered about nificant advantages for the detection of both pancreatic ade-
10 min before CT examination [50]. nocarcinoma and liver metastasis [55]; despite this, the
A triphasic CT examination is usually performed for the persistence of a pancreatic focal enhancement during this
evaluation of pancreatic adenocarcinoma, including a non- phase is suggestive of contrast medium pooling within a
enhanced phase, a late arterial or pancreatic phase (15 s highly fibrotic process, as an adenocarcinoma.
delay from the aortic enhancement threshold, using bolus The overall sensitivity of CT in the detection of pancreatic
tracking technique), and a portal venous phase (35 s delay). adenocarcinomas has improved over the recent years with the
Pre-contrast CT examination is performed from the top of advent of multi-detector CT scanners, ranging between 75 and
the diaphragm to the lower poles of the kidneys; this phase is 100%, with a specificity of 70–100% [56–62].
important to assess the presence of bile duct stones, blood Different post-processing reconstructions can be used to
clots, or pancreatic calcifications, as a sign of chronic pan- maximize the diagnostic yield of the CT scan and to improve
the visualization of the peripancreatic vasculature and the conventional contrast-enhanced CT [65]. Moreover, this
biliary tree. The reconstructions most frequently used are functional imaging may add useful information on tumor
maximum intensity projections, which easily and efficiently aggressiveness, affecting treatment strategy and patient man-
display vascular structures; volume-rendered imaging, which agement: it has been reported that considering both peak
is more complex but able to display both vessels and soft tis- enhanced index (PEI) and blood volume (BV) perfusional
sue elements, useful for the evaluation of early local infiltra- parameters with the related cutoff values (17.8 HU and
tion; minimum intensity projections, able to demonstrate low 14.8 ml/100 g, respectively), it is possible to characterize
attenuation structures; and multiplanar and curved recon- high-grade adenocarcinomas with 60% sensitivity, 100%
structions, the latter created along the pancreatic duct to specificity, a positive predictive value of 100%, a negative
show the entire Wirsung duct in one or two 2D images. Such predictive value of 60%, and 75% accuracy [75].
additional 2D and 3D reformatted images provide useful
information about the tumor extent, vascular involvement,
and ductal abnormalities, which could be difficult to evaluate Magnetic Resonance Imaging
only on axial images [50].
Regarding tumor detection, as reported earlier, the con- Pancreatic adenocarcinomas are usually investigated by
spicuity of pancreatic adenocarcinomas is sometimes greater means of contrast-enhanced MDCT; however, not infre-
at US examination than at CT [19, 25]. This could be proved quently, these lesions are studied with double examinations,
by measuring and comparing the difference in echogenicity both MDCT and MRI, as a result of an incorrect
in respect to Hounsfield Units (HU) of the same lesion and management.
by analyzing some results already reported in the literature The MRI study of pancreatic adenocarcinoma is based on
on the use of ultrasound, both percutaneously and endoscop- T1- and T2-weighted sequences, dynamic post-contrast
ically [25, 61–63]. Pancreatic lesions are detectable at CT if images, and magnetic resonance cholangiopancreatography
a difference with the circumstant parenchyma of 10–15 HU (MRCP) sequences [76].
exists [59, 64]. Pancreatic adenocarcinoma is usually inhomogeneously
Multi-detector computed tomography is still considered hypointense on T1-weighted images, because of its high
the most reliable technique for determining the nonresect- fibrotic component, due to marked desmoplasia [77, 78]; on
ability of a tumor, with reported sensitivity and specificity T2-weighted images, pancreatic adenocarcinoma has a vari-
values ranging, respectively, between 79–94% and 82–89% able signal intensity, especially if necrotic degeneration
[58, 65–67]. occurs [5], but it is mainly slightly hypointense in respect to
Finally, CT obviously covers the fundamental role of the surrounding pancreatic parenchyma. Thus, T1-weighted
staging. In particular, it is well known that imaging tech- images with fat saturation remain the most important pre-
niques, particularly CT, are highly sensitive for the evalua- contrast sequence for the detection of pancreatic adenocarci-
tion of the T and M stages. T1 and T2 tumors are distinguished noma at MRI.
on the basis of size (<2 cm or >2 cm, respectively); T3 dis- As for CT, the highest conspicuity of pancreatic adeno-
ease is defined as an extension into the peripancreatic soft carcinoma is obtained during the pancreatic phase, per-
tissues, without the invasion of the stomach, colon, celiac formed 35–45 s after the administration of gadolinium
axis, or SMA, whose invasion characterizes a T4 tumor. chelates contrast medium, when the lesion appears hypoin-
Conversely, it has been reported that CT is not accurate in the tense in respect to the background pancreatic parenchyma.
assessment of the N stage [68, 69]. The highly desmoplastic forms usually show a delayed
Perfusion CT is a relatively new imaging technique able peripheral rim enhancement [5, 20]. MRCP images are use-
to provide qualitative and quantitative information on tissue ful to evaluate the pancreatic ductal system and the biliary
perfusion, which have been demonstrated to be correlated ducts; the most common finding is the presence of the
with histological markers of angiogenesis. The excellent lin- double-duct sign for pancreatic head adenocarcinoma and of
ear relationship between tissue attenuation and iodinated an abrupt narrowing with upstream dilation of the main pan-
contrast agent concentration allows an objective quantifica- creatic duct. The differential diagnosis between a benign and
tion of the perfusion parameters correlated with the hemody- a malignant stenosis of the main pancreatic duct without
namic changes caused by angiogenesis [70–72]. Perfusion direct visualization of a focal pancreatic mass can be
CT can be applied to the study of the pancreas, and with this achieved by performing a dynamic MRCP after the adminis-
imaging technique, many authors have reported that the per- tration of secretin. Benign stenosis dilates after the adminis-
fusion of pancreatic carcinoma is significantly lower, com- tration of secretin, with the so-called duct-penetrating sign,
pared to healthy pancreatic parenchyma [73, 74]; as a while malignant stenosis does not dilate after secretin.
consequence, it has been reported that perfusion CT may be Diffusion-weighted imaging (DWI) is a relatively new MRI
useful to better delineate pancreatic carcinomas not visible at technique. It seems that DWI is able to differentiate between
normal pancreatic parenchyma and solid tumors in 92% of artery, the splenomesenteric-portal confluence, and the celiac
cases [79], helping also in detecting metastases. trunk. Lesions in the uncinate process tend to infiltrate the
superior mesenteric vein and/or artery. Lesions located in the
body/tail tend to infiltrate the splenic vessels.
Clinical Presentation In more than 95% of cases, regardless of the site, pan-
creatic ductal adenocarcinoma is diagnosed at an
Symptomatic advanced stage, with locally advanced or metastatic dis-
ease [41, 80, 81].
Obstructive jaundice occurs with pancreatic head cancers
that determine infiltration of the common bile duct. This may
be accompanied by other symptoms related to cholestasis, Atypical
such as pruritus, and by other symptoms such as abdominal
discomfort and weight loss. Less commonly, pancreatic adenocarcinoma presents with-
Other clinical presentations of the tumor can be epigastric out a true focal mass, but with a diffuse vessel thickening,
pain and backache, especially for pancreatic body-located which indicates the extension beyond the pancreatic pseudo-
tumors due to the infiltration of peripancreatic vessels and capsule into the perivascular lymphatics [82].
nervous plexus, but also newly onset diabetes, and acute pan- Pancreatic adenocarcinoma can also grow enlarging the
creatitis caused by the infiltration of the pancreatic duct. pancreatic gland without clear signs of infiltration, thus
Nausea and vomiting, resulting from gastroduodenal mimicking inflammatory process, repeating a mild
obstruction, may also be symptoms of this disease. pancreatitis-like morphology.
Asymptomatic Variants
Rarely, ductal adenocarcinoma of the pancreas is inciden- Pathology

tally discovered. The presence of an incidental focal solid
hypoechoic hypovascular lesion of the pancreas at US and More than 90% of pancreatic cancers is given by ductal ade-
CEUS should be considered a ductal adenocarcinoma, even nocarcinomas with conventional tubular morphology, but
in asymptomatic patients. other rare variants and mixed forms exist.
Regarding tumors located in the pancreatic body-tail, they Most variants have macroscopic and radiological aspects
produce symptoms only in an advanced stage and may be similar to ductal adenocarcinoma and cannot be easily dis-
asymptomatic for a long time; when these tumors become tinguished at imaging, but they have distinct clinical and
symptomatic, symptoms are generally related to the diffu- prognostic features.
sion of the disease. Variants include adenosquamous carcinoma, colloid car-
cinoma (mucinous noncystic carcinoma), medullary carci-
noma, and undifferentiated/anaplastic carcinoma. Colloid
Behavior and medullary carcinomas are associated with a better prog-
nosis, while adenosquamous and undifferentiated variants
Typical have a worse prognosis.
Pancreatic cancer typically presents as a focal mass, which denosquamous Carcinoma (ASC)
A
tends to infiltrate the surrounding structures and the main Malignant epithelial neoplasm with glandular (ductal) and
pancreatic duct, which is upstream dilated. squamous differentiation. The squamous component repre-
The tumor can involve arterial vessels, such as superior sents at least 30% of the neoplasms. They account for 0.9–
mesenteric, splenic, celiac, hepatic, and left renal arteries, in 4.4% of all pancreatic malignancies. Clinical presentation,
descending order of frequency, while venous involvement radiological and gross appearance may completely mimic a
can affect superior mesenteric, splenic, portal, and left renal conventional adenocarcinoma. At the time of symptoms
veins. onset, the majority of patients arrives to clinical evaluation
Typically, lesions located in the pancreatic head tend to with an advanced stage of the disease and generally die early
involve the duodenum, the superior mesenteric vein and/or due to local or systemic dissemination. For those patients
suffering from locally advanced or metastatic ASC, median The necrotic/fluid part of the tumor is mainly located cen-
overall survival rate is exceptionally dismal, even worse than trally [96]. As mentioned before, this necrosis results from
that of ductal adenocarcinoma, amounting to 4.5 months the difference between tumor growth rate and formation of
[83–86]. new microvessels from neoangiogenesis [24].
In these cases, what appears at imaging to be a cyst (a
olloid Carcinoma (Mucinous Noncystic
C macrocyst) is a solid, necrotic non-viable tissue surrounded
Carcinoma) by a cuff of viable carcinoma.
Malignant epithelial neoplasm, characterized by the pres-
ence of mucin-producing neoplastic epithelial cells “float-
ing” in large pools (>80%) of extracellular mucin, without Isodense Mass
stromal attachment. They are rare, accounting for 1–3% of
all pancreatic exocrine malignancies. Their gross appearance Ductal adenocarcinoma can be well vascularized and almost
is that of a soft gelatinous mass, large and better demarcated isovascular to the upstream pancreas, in which reduction of
than the typical ductal carcinoma. The mucin is usually the vascularization is induced by obstructive chronic
dense and thick. Typical colloid carcinoma must be differen- pancreatitis.
tiated from colloid carcinoma associated with intestinal-type It has been reported that up to 11% of pancreatic adeno-
IPMN [87]. carcinomas at CT show no difference in attenuation, com-
pared to the surrounding pancreatic tissue, the so-called
Undifferentiated Carcinoma (Anaplastic isoattenuating pancreatic adenocarcinomas [97–99]. Yoon
Carcinoma) et al. [98] reported that 27% of small (≤20 mm) pancreatic
Malignant epithelial neoplasm without glandular differentia- adenocarcinomas are isoattenuating at CT, and hence not
tion or other features indicating a definitive direction of dif- directly visible without the use of some secondary signs,
ferentiation. Anaplastic carcinoma is a rare high-grade such as upstream dilation of main pancreatic duct, the
pancreatic neoplasm. Macroscopically, it appears as a volu- double-duct sign, an abrupt cutoff of the main pancreatic
minous mass with a variegated aspect on cut section, due to duct. Moreover, small well-differentiated pancreatic adeno-
degenerative changes such as necrosis and hemorrhage. carcinomas, which are associated with a better survival rate
Microscopically, malignant cells are undifferentiated, with- after resection, are isoattenuating in more than 50% of cases
out gland and tubule formation. This neoplasm is composed [98–100].
by pleomorphic large cells, giant cells (anaplastic giant cell Ultrasound, both with transabdominal and––even bet-
carcinoma), or spindle cells (sarcomatoid carcinoma). ter––with endoscopic approach, can be resolutive by directly
Osteoclastic giant cell carcinoma is an uncommon, well- visualizing the lesion, using the differences in the acoustic
circumscribed, large tumor, characterized by abundant non- impedance; CEUS can characterize and better visualize these
neoplastic osteoclastic-type giant cells associated with a lesions as hypovascular masses, due to the differences
sarcomatoid carcinoma. The prognosis of anaplastic carci- between imaging techniques in terms of contrast resolution
noma is worse than that of conventional ductal adenocarci- (suppression of the basal background tissue signals, viewing
noma [88–92]. only the contrast material) and blood pool contrast agent
(microbubbles).
Medullary Carcinoma
Malignant epithelial neoplasm characterized by poorly differ-
entiated cells with a syncytial growth pattern, pushing tumor Pitfalls and Errors
borders without a significant desmoplastic reaction. A rich
T-cell infiltration is present in some cases. From a genetic A ductal adenocarcinoma infiltrating the pancreatic duct
standpoint, it has been estimated that approximately one- may result in mild acute focal pancreatitis epiphenomenon.
fourth of all medullary carcinomas displays microsatellite This epiphenomenon must not be misinterpreted, which
instability, which therefore represents a typical genetic fea- might lead to the wrong final diagnosis of simple focal
ture, rarely observed in conventional pancreatic cancer [93]. pancreatitis.
Pancreatic cancer can also cause ductal obstruction, lead-
ing to either cystic dilation of the upstream ducts or forma-
Cystic Aspect at Imaging tion of small “retention” cysts, usually at the periphery of the
neoplasm [95, 96].
Necrotic/degenerative changes with cavities formation have Pancreatic pseudocysts may also be observed in associa-
been described in 1–8% of pancreatic adenocarcinomas, tion with pancreatic ductal adenocarcinoma, probably as a
typically in poorly differentiated and large lesions [94, 95]. result of episodes of acute pancreatitis [101].
These epiphenomena must not be misinterpreted, which within the lesion often characterizes hypervascular
in fact might lead to the wrong final diagnosis of a cystic masses, while no vessels are usually observed within
lesion. hypovascular tumors, such as pancreatic ductal adenocar-
cinoma. This is even more clear after the administration of
ultrasound contrast medium, as well as at dynamic CT
Imaging-Pathologic Correlation and/or MRI.
Another important differential diagnosis is between
As previously mentioned, the main characteristic of pancre- ductal adenocarcinoma and mass-forming pancreatitis.
atic ductal adenocarcinoma is its marked desmoplasia, with CEUS can improve this differential diagnosis: while duc-
a large amount of fibrosis. This is associated with a low mean tal adenocarcinoma remains hypovascular during all
vessel density, which is reflected, during dynamic imaging dynamic phases, the inflammatory mass shows a paren-
studies (CEUS, MDCT, MRI), in a markedly hypovascular chymal enhancement, as previously reported [102]. The
appearance. presence of a parenchymal enhancement, somewhat simi-
Furthermore, using CT or MRI, in which contrast lar to that of the adjacent pancreas during the dynamic
media can diffuse into the interstitium, it is possible to see study, is therefore a CEUS finding consistent with an
a delayed enhancement within the pancreatic adenocarci- inflammatory origin. The intensity of this parenchymal
noma, due to the diffusion of the contrast media into the enhancement is related to the length of the underlying
tumor fibrosis. inflammatory process [103]: the more chronic and long-
Moreover, the fibrosis determines the typical appearance standing the inflammatory process is, the less intense is
of pancreatic adenocarcinoma at sonoelastography, giving the enhancement. It is likely that this is related to the
very high stiffness values in the lesion [24]. entity of the associated fibrosis. In contrast, in acute mass-
forming pancreatitis, the enhancement is usually more
intense and prolonged [103].
Differential Diagnosis Mimics of pancreatic adenocarcinoma include mass-
forming inflammatory conditions (autoimmune pancreatitis,
Any solid pancreatic mass must be differentiated from ductal groove pancreatitis), other pancreatic tumors (hypovascular
adenocarcinoma. neuroendocrine tumors, solid pseudopapillary tumor, acinar
The second most frequent pancreatic solid mass is the cell carcinoma), hypovascular metastases, and other rare
neuroendocrine tumor, characterized by a hypervascular pancreatic masses, such as lymphoma, which will be dis-
appearance. At Doppler study, the detection of vessels cussed in a related chapter.
Image Gallery
a
b c
Fig. 1 Ductal adenocarcinoma. (a) Surgical specimen (pancreaticodu- neoplastic tissue is composed by few glandular structures in abundant
odenectomy): pancreatic ductal adenocarcinoma (asterisk) presenting fibrous desmoplastic stroma. Immunohistochemical staining with
as a white hard mass with irregular margins. Both the Wirsung duct (W) CD34 (brown traces in c) reveals scant blood vessels within the lesion
and the common bile duct (C) are dilated. (b, c) Histopathology: the (Courtesy of Piccin Editore, Milan, Italy)
a b
Fig. 2 Ductal adenocarcinoma. (a) Conventional US study: typical US within the lesion according to the very low vascular density of the neo-
presentation of pancreatic ductal adenocarcinoma as a hypoechoic solid plastic tissue. (c) CEUS: the lesion typically shows a markedly hypo-
mass (arrow). (b) Color Doppler analysis: no Doppler signal is visible vascular pattern (arrow)
b
a
Fig. 3 Ductal adenocarcinoma. (a) Conventional US study: hypoechoic fibrotic mass with irregular margins infiltrating the Wirsung duct (W)
round-shaped lesion (asterisk) with blurred margins located in the pan- and the common bile duct (C). (d, e) Histopathology: the neoplastic
creatic head, with a slight dilation of the Wirsung duct. (b) CEUS: the tissue is typically composed by few glandular structures in abundant
lesion typically shows a markedly hypovascular pattern (asterisk). (c) fibrous desmoplastic stroma. Immunohistochemical staining with
Surgical specimen (pancreaticoduodenectomy): pancreatic ductal ade- CD34 (brown traces in e) reveals scant blood vessels within the lesion
nocarcinoma of the pancreatic head presenting as a white stiff highly
d e
Fig. 3 (continued)
a b
c d
Fig. 4 Ductal adenocarcinoma. (a–e) Complete US study: round- (3.86 m/s in c) is confirmed in respect to the pancreatic body paren-
shaped hypoechoic mass (box in a) located in the pancreatic head, chyma (1.40 m/s in d). At CEUS (e), the lesion typically shows a mark-
resulting stiff, (red) due to the rich desmoplastic stroma in the elasto- edly hypovascular pattern (arrow in e)
gram (b). At the quantitative ARFI elastography, high-velocity value
Fig. 4 (continued)
a b
Fig. 5 Ductal adenocarcinoma. (a) EUS study: small tumor (T) lesion and the superior mesenteric vein (smv) and portal vein (pv) wall;
obstructing both the common bile duct (c) and the Wirsung duct (w). (b) c, common bile duct. (d) EUS study: staging of a pancreatic tumor (T)
EUS study: staging of a pancreatic tumor (T) shows a clear interface shows the loss of interface (arrows) between the lesion and the portal
(arrow) with the superior mesenteric artery (sma). (c) EUS study: stag- vein (pv), which is surrounded by the tumor; the Wirsung (w) is
ing of a pancreatic tumor (T) shows the contact (arrow) between the obstructed by the tumor
Fig. 6 Ductal adenocarcinoma. (a–c) EUS study: elastography (a), sound in low MI mode (c). Stiff structure (blue) in elastography; only a
contrast-enhanced endoscopic ultrasound in high MI Doppler mode few arterial vessels are visible using pulse-waved Doppler mode and
with microvessel analysis (b), and contrast-enhanced endoscopic ultra- markedly low contrast-enhancing effect in low MI mode
Fig. 6 (continued)
a b
Fig. 7 Ductal adenocarcinoma. (a) IOUS: pancreatic head mass (aster- vein. The wall of the vein appears irregular with deformation of the ves-
isk) not involving the main vessels. (b) IOUS: pancreatic head sel. (c) IOUS: pancreatic head mass (asterisk) involving the superior
hypoechoic mass (asterisk) not separated from the superior mesenteric mesenteric vein (V) and artery (A)
vein with a small neoplastic portion (arrow) within the lumen of the
a b
c d
e f
Fig. 8 Ductal adenocarcinoma. (a–d) dynamic CT: the study demon- mal. (e) Surgical specimen (pancreaticoduodenectomy): the presence of
strates a round-shaped lesion, hypovascular hypodense (arrow) in the a round-shaped ductal adenocarcinoma (asterisk) of the pancreatic head
pancreatic (a) and venous (b) phases with blurred margins located in is confirmed. (f–i) Superimposed drawings on CT images (f–h) and
the pancreatic head. Coronal (c) and sagittal (d) planes show the abrupt specimen (i) better clarify the relationships among the lesion (brown
cutoff of the Wirsung duct, which appears slightly upstream-dilated, circle), the Wirsung duct (yellow line), and the common bile duct (green
and of the common bile duct. The superior mesenteric vessels are nor- line)
g h
Fig. 8 (continued)
a b
c d
Fig. 9 Ductal adenocarcinoma imaging correlation. (a–c) CT study: e) on T2-weighted images, with diffusion restriction, appearing hyper-
typical appearance of a small pancreatic ductal adenocarcinoma, pre- intense on high b value DW images (f). At dynamic study, the lesion
senting as slightly hypodense (arrow in a) lesion in the baseline (a) appears hypovascular (arrow in g and h) in comparison to the adjacent
acquisition with blurred margins in the pancreatic head, typically hypo- pancreatic parenchyma in the pancreatic (g) and venous (h) dynamic
vascular (arrow in b) in comparison to the adjacent pancreatic paren- phases. (i, j) MRCP: the neoplasm causes an abrupt cutoff of the
chyma in the pancreatic (b) and venous (c) dynamic phases. (d–h) MRI Wirsung duct (arrow in i), upstream-dilated, not regressing after secre-
study: the lesion typically appears hypointense (arrow in d) on tin stimulation (j)
T1-weighted fat-saturated images and slightly hyperintense (arrow in
e f
g h
i j
Fig. 9 (continued)
a b
Fig. 10 Ductal adenocarcinoma. (a–e) MRI study: small oval-shaped shows the abrupt cutoff (arrow in c) and the upstream dilation of the
nodule of the pancreatic body appearing hypointense (arrow in a) on Wirsung duct. At dynamic study, the lesion appears typically hypovas-
T1-weighted images and slightly hypointense (arrow in b) on cular (arrow in d) in comparison to the adjacent pancreatic parenchyma
T2-weighted images. The upstream portion of the Wirsung duct (W in in the pancreatic (d) and venous (e) dynamic phases
b) is dilated with atrophic pancreatic parenchyma. MRCP study better
a b
c d
Fig. 11 Ductal adenocarcinoma. (a–d) MRI study: small irregular- (arrow in b) fat-saturated images. At dynamic study, the lesion appears
shaped lesion of the pancreatic head appearing hypointense on typically hypovascular (arrow in d) in comparison to the adjacent pan-
T1-weighted (arrow in a) and slightly hypointense on T2-weighted creatic parenchyma in the pancreatic (c) and venous (d) dynamic phases
a b
c d
e f
Fig. 12 Ductal adenocarcinoma. (a–f) MRI study: small round-shaped MRCP shows a markedly dilated biliary tree, with an abrupt cutoff of
lesion with blurred margins of the pancreatic head, appearing hypoin- the common bile duct (C in d) in the head of the pancreas and a dilated
tense (arrow in a) on T1-weighted fat-saturated images and slightly Wirsung duct (W in d). At dynamic study (e, f), the lesion appears
hyperintense (arrow in b) on T2-weighted fat-saturated images, and almost isovascular in comparison to the adjacent pancreatic
with diffusion coefficient restriction with high b value on DWI (c). parenchyma
a b
c d
Fig. 13 Ductal adenocarcinoma with double-duct sign. (a–d) MRI hypovascular (arrow in c) in comparison to the adjacent pancreatic
study: pancreatic head-neck round-shaped mass with blurred margins, parenchyma in the post-contrastographic pancreatic phase. MRCP (d)
typically appearing hypointense (arrow in a) on T1-weighted fat- shows a significant dilation of the biliary tree and Wirsung duct (double-
saturated images and slightly hyperintense (arrow in b) on T2-weighted duct sign)
fat-saturated images. At dynamic study, the lesion appears markedly
Fig. 14 Ductal adenocarcinoma with double-duct sign.

Surgical specimen (pancreaticoduodenectomy): typical
macroscopic appearance of pancreatic ductal
adenocarcinoma, presenting as a hard, whitish lesion
(asterisk) with irregular faint margins. Tumoral margins
present infiltrative growth pattern, with the involvement
of Wirsung duct (W) and common bile duct (C), both
upstream-dilated (double-duct sign)
Fig. 15 Ductal adenocarcinoma with main pancreatic duct dilation. (a) Wirsung duct (W). (b) Surgical specimen (distal pancreatectomy) of
CEUS: the study shows a hypoechoic hypovascular round-shaped different case: hard, whitish round-shaped ductal adenocarcinoma
lesion (arrow) of the pancreatic body, causing upstream dilation of the (arrow) in the pancreatic body with a slightly dilated Wirsung duct (W)
a b
c d
Fig. 16 Ductal adenocarcinoma with main pancreatic duct dilation. (a, hypovascular hypodense nodule (arrow in d). Multiplanar reconstruc-
b) US study: small round-shaped lesion, hypoechoic (arrow in a) at tion (e) with MinIP algorithm clearly demonstrates the small hypovas-
conventional ultrasound and hypovascular (arrow in b) at CEUS in the cular nodule (arrow in e) in the pancreatic neck, causing upstream
pancreatic neck, with marked upstream dilation of the Wirsung duct (W dilation of the Wirsung duct
in a). (c–e) dynamic CT: dilated Wirsung duct (W in c), stopped in
a b
Fig. 17 Ductal adenocarcinoma with main pancreatic duct dilation. (a) duct (W). (b) Surgical specimen (distal pancreatectomy): small ductal
Ultrasound study: small round-shaped hypoechoic nodule (calipers) in adenocarcinoma of pancreatic body (asterisk) with markedly dilated
the pancreatic body causing marked upstream dilation of the Wirsung Wirsung duct (W)
Fig. 18 Ductal adenocarcinoma with main pancreatic duct involve- Wirsung duct (W). (b) Surgical specimen of different case: small ductal
ment. (a) Surgical specimen (distal pancreatectomy): pancreatic ductal adenocarcinoma (asterisk) with stenosis (arrow) of the Wirsung duct
adenocarcinoma (asterisk), causing marked upstream dilation of the (W), not upstream-dilated
a b
Fig. 19 Double-duct sign. (a, b) dynamic CT: the study shows dilation in b) and the Wirsung duct (W in b). (c) Surgical specimen (pancreati-
of the biliary tree and of the Wirsung duct (W in a). Multiplanar recon- coduodenectomy) of different case: ductal adenocarcinoma (asterisk),
struction with MinIP algorithm shows a hypodense mass (asterisk in b) causing dilation of both the common bile duct (C) and the Wirsung duct
in the pancreatic head, causing dilation of both the common bile duct (C (W)
a b
c d
e f
Fig. 20 Double-duct sign in pancreatic head necrotic adenocarcinoma. shows peripheral diffusion restriction with mild central T2-shine through
(a-h) MRI study: round-shaped pancreatic head mass with regular mar- effect (necrotic component) (e). At dynamic study (f–h), the lesion appears
gins, appearing slightly hypointense (arrow in a) on T1-weighted fat-sat- markedly hypovascular (arrow in f) with avascular portions in the pancre-
urated images and slightly hyperintense (arrow in b and c) on T2-weighted atic (f), venous (g), and late (h) phases. (i, j) Surgical specimen (pancreati-
axial (b) and coronal (c) images. MRCP (d) shows a dilated common bile coduodenectomy) of different case: ductal adenocarcinoma with
duct (C in d) and Wirsung duct (W in d) (double-duct sign). The mass intralesional cystic necrotic portion (asterisk in i and j)
g h
i j
Fig. 20 (continued)
a b
c d
e f
Fig. 21 CT virtual pancreaticoduodenectomy and pathological corre- (red). Pancreaticoduodenectomy (d), with the vascular bed highlighted
lation. (a, b) CT-pathological correlation: volume-rendering (a) of the (red) on the surgical specimen. (e, f) CT-pathological correlation:
right pancreas after virtual resection with pancreatic neck margin high- volume-rendering (e) of the right pancreas after virtual resection with
lighted (green). Pancreaticoduodenectomy (b), with the pancreatic mar- pancreatic posterior retroperitoneal margin highlighted (black).
gin highlighted (green) on the surgical specimen. (c, d) CT-pathological Pancreaticoduodenectomy (f), with the pancreatic posterior retroperito-
correlation: volume-rendering (c) of the right pancreas after virtual neal margin highlighted (black) on the surgical specimen. Probe in the
resection with the vascular bed, where the superior mesenteric vein/ common bile duct
portal vein and the superior mesenteric artery originally lie, highlighted
a d
Fig. 22 Resectable ductal adenocarcinoma. (a–c) Ultrasound study: con- hypovascular (arrow). (d) Surgical specimen (pancreaticoduodenec-
ventional examination (a) shows a hypoechoic round-shaped lesion tomy): small adenocarcinoma (arrow), confined in the pancreatic head
(arrow) in the pancreatic head with regular aspect of the superior mesen- periampullary region. Common bile duct (C)
teric vessels (arrows in b). At CEUS (c), the lesion is typically markedly
a d
b e
Fig. 23 Ductal adenocarcinoma with small venous infiltration. (a–c) tration (arrow in c) of the superior mesenteric vein wall. (d, e) Surgical
Ultrasound study: conventional examination shows hypoechoic ill- specimen (pancreaticoduodenectomy): on the posterior surface of the
defined mass (arrow in a) in the pancreatic head with main duct (W) surgical specimen, a small irregularity of the vascular bed (circle) is
upstream dilation. The mass involves the uncinate process infiltrating documented and better visible on the detail image (e). Probes in the
the posterior wall of the superior mesenteric vein (V in b). At longitudi- Wirsung duct and in the common bile duct are visible
nal scan (c) with Doppler clarification is clearly visible the small infil-
a b
Fig. 24 Ductal adenocarcinoma and vessels infiltration. (a) Surgical bed (green). (b) Surgical specimen: ductal adenocarcinoma (asterisk),
specimen (pancreaticoduodenectomy): on the posterior surface of the involving the main pancreatic duct (W) and the common bile duct (C)
specimen, partial vascular resection (circle) is visible along the vascular with superior mesenteric vein resection (circle)
Fig. 25 Ductal adenocarcinoma and inflammatory

vessel involvement. Histopathology: fibro-
inflammatory (asterisk) adhesion to the resected
portion of superior mesenteric vein (V)
a b
c d
e f
Fig. 26 Borderline resectable ductal adenocarcinoma. (a) Conventional (d) phases in contact with the superior mesenteric artery (A in c) and
ultrasound: hypoechoic solid mass (asterisk) of the uncinate process of vein (V in d). (e, f) MRI study: solid mass of the uncinate process of the
the pancreas with small infiltration of the superior mesenteric vein (V) pancreas, slightly hypointense on T1- (arrow in e) and T2- (arrow in f)
and in contact with the superior mesenteric artery (A). (b–d) CT study: weighted images, with small infiltration of the superior mesenteric vein
solid mass of the uncinate process of the pancreas, isodense (arrow in (V in e), and in contact with the superior mesenteric artery (A in e)
b) in the baseline study, and hypodense in the pancreatic (c) and venous
a b
c d
Fig. 27 Borderline resectable pancreatic head ductal adenocarcinoma. mesenteric artery (arrowhead). (d) Pathologic specimen from Whipple’s
(a) The main pancreatic duct and common bile duct (**) are distended. resections shows a whitish tumor mass within the head of the pancreas.
The intrahepatic bile ducts and gallbladder are dilated. (b) The mass in The probe is in the dilated common bile duct. A dilated main pancreatic
the head of the pancreas shows low attenuation on the pancreatic phase. duct is visualized. The tumor was 4.5 cm, moderately differentiated
The mass contacts the gastroduodenal artery (arrow). The superior with microscopic extension into the peripancreatic soft tissue.
mesenteric vein is smoothly compressed. The superior mesenteric Lymphovascular and perineural invasions were present. This finding
artery appears free of tumor contact. (c) Image slightly more inferior could be suspected by the unclear margins along the inferior portion of
reveals vague increased density in the fat in the vicinity of the superior the superior mesenteric artery (b, c)
a b
c d
Fig. 28 Borderline resectable ductal adenocarcinoma. (a–d) CT study: and late (d) phases in contact with the superior mesenteric vein (V in c);
solid mass of the uncinate process of the pancreas, isodense (arrow in hyperdensity of the fat next to the superior mesenteric artery (A in c)
a) in the baseline study and hypodense in the pancreatic (b), venous (c), can be seen
Fig. 29 Ductal adenocarcinoma with infiltration of superior mesen- mesenteric artery (A in d). (e) Surgical specimen (pancreaticoduode-
teric vein. (a, b) Ultrasound study: hypoechoic solid mass (asterisk in nectomy): ductal adenocarcinoma (asterisk) involving the Wirsung duct
a) in the uncinate process of the pancreas with main pancreatic duct (W (W). The common bile duct (C) is normal. The pancreatic surface of the
in a) dilation. The mass results typically markedly hypovascular (aster- vascular bed is involved (arrow). (f–j) Superimposed drawings better
isk in b) at CEUS. (c, d) CT study: dilation of the Wirsung duct (W in clarify the lesion (brown circle), the Wirsung duct (yellow line), and the
c) caused by a hypodense mass (asterisk in d) in the uncinate process of common bile duct (green line) in the imaging and surgical specimen.
the pancreas. Common bile duct (C in c) is normal. The mass infiltrates (k–l) Histopathology: the tumor (T in k) involves the superior mesen-
the superior mesenteric vein (V in d) and is very close to the superior teric vein (V in k and l) resected
c d
e f
Fig. 29 (continued)
h i
j k
Fig. 29 (continued)
a b
Fig. 30 Ductal adenocarcinoma with infiltration of the splenic artery. (S in a). (c) Surgical specimen (distal pancreatectomy): ductal adeno-
(a, b) CT study: solid mass hypodense (arrow in a) in the pancreatic (a) carcinoma (asterisk) with dilation of the Wirsung duct (W) infiltrating
and venous (b) dynamic phases in the body of the pancreas with main the splenic artery (S)
pancreatic duct (W in b) dilation. The mass infiltrates the splenic artery
a b
c d
Fig. 31 Ductal adenocarcinoma with infiltration of the superior mes- superior mesenteric artery (A in b and d) with long extension along this
enteric artery. (a–d) CT study: solid mass in the uncinate process of the vessel (asterisk in d), better visible on multiplanar-reconstructed coro-
pancreas, isodense on baseline (arrow in a) and hypodense in the pan- nal image (d)
creatic (b) and venous (c) dynamic phases. The mass infiltrates the
Fig. 32 Ductal adenocarcinoma a

with arterial infiltration. (a, b) CT
study: hypodense neoplastic tissue,
infiltrating the hepatic artery (arrow
in a) originating from the superior
mesenteric artery, is growing from a
hypodense mass (asterisk in b) of
the uncinate process of the pancreas.
The mass infiltrates also the
superior mesenteric artery (A in b)
b
a b
c d
Fig. 33 Ductal adenocarcinoma with retroperitoneal spread and ves- portal vein (P in b), superior mesenteric artery (A in c), and the splenic
sels infiltration. (a–d) CT study: hypodense neoplastic tissue involving vein (V in d). The main pancreatic duct (W in b) is dilated
diffusely the retroperitoneum, infiltrating the celiac trunk (C in a), the
Fig. 34 Ductal adenocarcinoma with

retroperitoneal spread and vessels infiltration. (a, b) a
CT study: neoplastic tissue hypodense in the
pancreatic (a) and venous (b) dynamic phases
involving diffusely the retroperitoneum infiltrating
the celiac trunk (C in a) and the diaphragmatic
pillar (asterisk in b)
b
Fig. 35 Ductal adenocarcinoma with superior mesenteric vessels infil- (d) and fat-saturated (arrow in e). The mass shows diffusion restriction
tration. (a, b) Ultrasound study: hypoechoic mass (asterisk in a) of the on DWI (f) with high b value. In the pancreatic dynamic phase, the
uncinate process of the pancreas, resulting markedly hypovascular at mass is hypovascular (arrow in g) with progressive contrast medium
CEUS. The mass infiltrates the superior mesenteric vein (V in a and b) retention in the following phases (h and i). In the coronal acquisition,
and artery (A in a and b). (c–j) MRI study: uncinate process pancreatic the involvement of the duodenum and the Treitz ligament is visible
mass, hypointense on T1-weighted fat-saturated image (arrow in c) and (arrow in i). On MRCP (j), the Wirsung duct (W) is dilated
slightly hyperintense on T2-weighted images, both non-fat saturated
c d
e f
g h
i j
Fig. 35 (continued)
a b
Fig. 36 Ductal adenocarcinoma with metastatic spread. (a, b) CT study: hypodense uncinate process mass (asterisk in a). Liver metastases
(arrows in a and b) are visible
a b
Fig. 37 Ductal adenocarcinoma. (a, b) Ultrasound study: hypoechoic contrast medium retention, due to accumulation in the fibrotic tissue,
mass (arrow in a) of the pancreatic head with no intralesional color clearly visible in the late phase (e), appearing inhomogeneously hyper-
Doppler signal, resulting markedly hypovascular (arrow in b) at CEUS. dense (arrow in e). (f) Surgical specimen (pancreaticoduodenectomy)
(c–e) CT study: the pancreatic head mass is hypodense (arrow in c) in of different case: highly fibrotic ductal adenocarcinoma (asterisk) with
the pancreatic (c) and venous (d) dynamic phases, with progressive dilation of the Wirsung duct (W) and the common bile duct (C)
c f
Fig. 37 (continued)
a b
c d
Fig. 38 Ductal adenocarcinoma. (a–d) MRI study: pancreatic mass Ventral border retraction (arrow in b) is visible at the pancreatic body.
with elongated morphology, diffusely involving the body-tail region, At dynamic MRI, the mass is hypovascular (arrow in c) in the pancre-
appearing hypointense (arrow in a) on T1-weighted fat-saturated atic (c) phase, with progressive contrast medium retention starting from
images and isointense on T2-weighted (b) non-fat saturated images. the venous (d) phase
a b
c d
e f
Fig. 39 Ductal adenocarcinoma. (a–g) MRI study: large pancreatic images, and showing diffusion restriction with high b value on DWI
head round-shaped mass with blurred margins, appearing hypointense (d). At dynamic MRI, the lesion is hypointense (arrow in e) with a
(arrow in a) on T1-weighted fat-saturated images, hyperintense (arrow hyperintense rim in both pancreatic (e) and venous (f) phases, with evi-
in b) on T2-weighted, both fat-saturated (b) and non fat-saturated (c) dent progressive contrast medium retention in the late (g) phase
Fig. 39 (continued)
a b
Fig. 40 Ductal adenocarcinoma. (a–f) MRI study: small irregular nod- of small branch ducts ectasia (arrow in c). At dynamic MRI, the lesion
ule of the pancreatic body, appearing isointense on T1-weighted, both is hypovascular, clearly hypointense (arrow in d) in both pancreatic (d)
not fat-saturated (a) and fat-saturated (b) images, and on T2-weighted and venous (e) phases, and isointense due to the progressive contrast
(c) image. The Wirsung duct (W in c) is markedly dilated with evidence medium retention on late (f) phase
c d
e f
Fig. 40 (continued)
a b
e f
Fig. 41 Necrotic ductal adenocarcinoma. (a–c) CT study: pancreatic T1-weighted fat-saturated images and inhomogeneously hypointense
body-tail oval-shaped lesion, appearing isodense (arrow in a) in the on T2-weighted fat-saturated (e) images. At dynamic MRI study, the
baseline CT examination. At dynamic CT study, the lesion, involving lesion (arrow in f) is characterized by a peripheral rim enhancement
the splenic artery, is characterized by markedly hypodense (arrow in b and a central avascular necrotic area in both pancreatic (f) and venous
and c) aspect in the pancreatic (b) and venous (c) phases. (d–h) MRI (g) phases. Progressive accumulation of contrast medium in the fibrotic
study: the pancreatic lesion appears hypointense (arrow in d) on thick annular portion of the lesion is visible on the late (h) phase
g h
Fig. 41 (continued)
a b
Fig. 42 Necrotic ductal adenocarcinoma. (a–c) CT study: large round- (b) phases. Perfusion CT (c) color map clearly shows an avascular pan-
shaped pancreatic head mass with irregular margins, markedly creatic head tumor
hypodense (arrow in a and b) in the dynamic pancreatic (a) and venous
a b
c d
Fig. 43 Ductal adenocarcinoma with small necrotic portion. (a) (arrow in d) necrotic area, which is better visible at MRCP (e) as a cyst-
Conventional US study: large inhomogeneously hypoechoic (calipers) like (arrow in e) component. At dynamic MRI, the tumor is hypointense
pancreatic body mass. (b, c) CT study: the lesion appears isodense with (arrow in f) in the pancreatic (f) and venous (g) phases, with hyperin-
an eccentric ipodense necrotic area in comparison to the adjacent pan- tensity (arrow in h) due to contrast medium retention in the late (h)
creatic parenchyma (arrow in b and c) in the baseline (b) examination phase. The eccentric necrotic area remains avascular. (i) Surgical speci-
and in the venous (c) phase. The eccentric necrotic area remains avas- men (distal pancreatectomy): ductal adenocarcinoma, highly fibrotic
cular. (d–h) MRI study: the pancreatic tumor is almost isointense on (asterisk) at the transverse cut section, with an eccentric cyst-like (C)
T2-weighted (d) fat-saturated images, with a markedly hyperintense component
e f
Fig. 43 (continued)
a d
Fig. 44 Necrotic ductal adenocarcinoma with intralesional cyst-like resulting avascular in the mass that shows typical hypovascularity on
cavity. (a–c) MRI study: pancreatic body mass, hypointense on dynamic phase (c). (d) Surgical specimen (pancreaticoduodenectomy)
T1-weighted image (asterisk in a) and with intralesional hyperintense of different case: ductal adenocarcinoma with necrotic intralesional
cystic cavity (arrow in b) on T2-weighted fat-saturated image (b), cyst-like cavity (arrow)
a b
c d
Fig. 45 Ductal adenocarcinoma with microcystic appearance. (a) vascular in the dynamic phase (d). On MRCP, a microcystic lesion
Ultrasound study: pancreatic body mass (asterisk), hypoechoic on con- (arrow in e) is visible in the pancreatic body. (f, g) Surgical specimen
ventional ultrasound. (b–e) MRI study: pancreatic body mass, hypoin- (distal pancreatectomy) and histopathology: ductal adenocarcinoma
tense on T1-weighted image (arrow in b) and with multiple microcysts with microcystic (f) appearance (large duct adenocarcinoma) better vis-
within the lesion (arrow in c) on T2-weighted image, resulting hypo- ible on histopathology (g)
e f
Fig. 45 (continued)
a b
Fig. 46 Mucin-producing ductal adenocarcinoma. (a, b) CT study: (arrow in b). The Wirsung duct (W in b) is upstream-dilated. (c)
pancreatic body mass, hypodense (arrow in a) in the pancreatic (a) and Surgical specimen, particular: ductal adenocarcinoma with intratu-
venous (b) dynamic phases, with markedly hypodense small areas moral small mucus pools (arrow)
a b
c
d
e f
Fig. 47 Ductal adenocarcinoma with cystic cavity. (a) Ultrasound (d) dynamic phases. (e) MRI study: pancreatic head inhomogeneous
study: complex solid and cystic mass (calipers) in the pancreatic head. cystic mass hyperintense (asterisk in e) on T2-weighted images. (f)
(b–d) CT study: pancreatic head inhomogeneous cystic mass (asterisk Surgical specimen (pancreaticoduodenectomy): ductal adenocarcinoma
in b) with thick wall and internal septa in the pancreatic (c) and venous with large central mucus pool (asterisk in f)
a b
c d
Fig. 48 Huge cystic degeneration of ductal adenocarcinoma. (a–c) CT Surgical specimen (distal pancreatectomy): complex mass invading the
study: pancreatic body, inhomogeneous cystic mass (asterisk in a), with stomach (S in d) and with cystic component (arrow in d), with the final
extremely close and attached solid mass, typically hypodense in the diagnosis of ductal adenocarcinoma (arrow in e) with cystic changes
pancreatic (arrow in b) and venous (arrow in c) dynamic phases. (d–f) (asterisk in e) containing dense and sticky mucus (f)
e f
Fig. 48 (continued)
a b
Fig. 49 Isodense ductal adenocarcinoma. (a) CT study: pancreatic changes, as secondary sign, can be visible. (b) Ultrasound study: a
body ductal adenocarcinoma, isodense (arrow) in the pancreatic simple conventional ultrasound evaluation clearly shows hypoechoic
dynamic phase. Upstream initial obstructive chronic pancreatitis lesion (arrow) in the body of the pancreas
Fig. 50 Isodense ductal

adenocarcinoma. (a, b) Ultrasound a
study: pancreatic head, medial
region, hypoechoic lesion (arrow in
a), resulting hypovascular at CEUS
(arrow in b), with final biopsy-
proven diagnosis of ductal
adenocarcinoma. (c) CT study: the
lesion is perfectly isodense, not
visible in the dynamic phase
Fig. 50 (continued)
a b
c d
Fig. 51 Isodense ductal adenocarcinoma. (a) MRCP image reveals creatic head (arrowhead). This could not be seen without subtraction.
double-duct sign. (b) MDCT pancreatic phase image shows both CBD (d) The CBD (white arrow) and MPD (black arrowhead) are both
and MPD dilatation. A vague lucency is seen at the transition zone dilated. The 1.8 cm tumor (T) is a small whitish mass in the pancreatic
(arrowhead). (c) Subtraction view from pancreatic phase gadolinium- head. It is a well-differentiated adenocarcinoma, invading the duodenal
enhanced GRE image reveals a well-circumscribed lucency in the pan- wall and peripancreatic soft tissue
a b
Fig. 52 Incidental ductal adenocarcinoma. (a, b) Ultrasound study: small (c) Surgical specimen (pancreaticoduodenectomy): small (about 1 cm)
round hypoechoic nodule (arrow in a) is visible in the uncinate process of ductal adenocarcinoma (arrow) of the uncinate process of the pancreas.
the pancreas. The nodule is markedly hypovascular (arrow in b) at CEUS. Probes in the Wirsung duct (W) and in the common bile duct (C)
a b
c d
Fig. 53 Ductal adenocarcinoma with double-duct sign. (a–d) MRI slightly hypointense on T1-weighted (arrow in b) and isointense on
study: MRCP (a) shows dilation of the main pancreatic duct (W in a) T2-weighted (c) images is visible resulting hypovascularized in the
and common bile duct (C in a), in which lumen an endoprosthesis dynamic phase (arrow in d). The biliary endoprosthesis is visible within
(arrow in a) is placed. In the pancreatic head, a very small lesion the lesion
a b
Fig. 54 Ductal adenocarcinoma with double-duct sign. (a) Surgical and common bile duct (C). (b) Surgical specimen (pancreaticoduodenec-
specimen (pancreaticoduodenectomy): ductal adenocarcinoma (asterisk) tomy): ductal adenocarcinoma (asterisk) in the periampullary region with
in the periampullary region with dilation of the main pancreatic duct (W) dilation of the main pancreatic duct (probe) and common bile duct (C)
a b
c d
Fig. 55 Pancreatitis epiphenomenon of ductal adenocarcinoma. (a) CT hypoechoic lesion (arrow in b) of the pancreatic body is visible on con-
study: pancreatic body ductal adenocarcinoma (asterisk) causing dila- ventional ultrasound, resulting markedly hypovascular (arrow in c) at
tion of the main pancreatic duct (W) and related slight edema of the left CEUS. The main pancreatic duct is upstream-dilated (W in b and c). (d)
portion of the pancreatic gland, resulting hypodense in respect to the Surgical specimen (distal pancreatectomy): ductal adenocarcinoma
right portion of the pancreas on coronal multiplanar reconstructed (asterisk) with upstream dilation of the main pancreatic duct (W)
image in the dynamic pancreatic phase. (b, c) Ultrasound study:
a b
c d
Fig. 56 Ductal adenocarcinoma involving the groove region. (a–d) CT the late phase (c). The gastroduodenal artery (G in a and d) is infil-
study: neoplastic tissue from the pancreas is invading the groove, result- trated. The coronal reconstruction (d) shows that hypodense lesion
ing hypodense (arrow in a and b) in the dynamic pancreatic (a) and (asterisk in d) reaches the cranial surface of the pancreatic head. A bili-
venous (b) phases with progressive contrast medium accumulation in ary stent (arrow in d) is present
a b
c d
Fig. 57 Ductal adenocarcinoma involving the groove region. (a–f) MRCP (d), dilation of both the main pancreatic duct (W in c) and the
MRI study: pancreatic head mass with groove invasion, resulting common bile duct (C in c) is clearly shown. The lesion results typically
hypointense (arrow in a) on T1-weighted image and iso−/hyper-intense hypovascular (arrow in e) on the dynamic pancreatic phase. Contrast
on T2-weighted image (b). On coronal T2-weighted image (c) and on medium retention in the lesion starts in the venous phase (f)
Fig. 57 (continued)
f
b c
Fig. 58 Ductal adenocarcinoma involving the groove region. (a) infiltrated. (b, c) Surgical specimen (pancreaticoduodenectomy) and
Surgical specimen (pancreaticoduodenectomy): pancreatic ductal ade- macrosection: pancreatic ductal adenocarcinoma (asterisk in b and T in
nocarcinoma (asterisk) involving the groove with dilation of the com- c) involving groove with dilation of the common bile duct (C in b and
mon bile duct (C); main pancreatic duct (W) is well visible and not c)
a b
Fig. 59 Ductal adenocarcinoma of the cranial portion of the pancreatic common bile duct (C in b). (c) Surgical specimen (pancreaticoduode-
head. (a, b) CT study: hypodense hypovascular lesion (arrow in a and nectomy): ductal adenocarcinoma (asterisk) of the cranial portion of
b) is visible in the pancreatic head along its cranial margin dilating the the pancreatic head infiltrating the common bile duct (C)
a b
Fig. 60 Ductal adenocarcinoma of the cranial portion of the pancreatic coduodenectomy): ductal adenocarcinoma (asterisk) in the cranial
head. (a) Surgical specimen (pancreaticoduodenectomy): ductal adeno- region of the pancreatic head growing along the common bile duct (C)
carcinoma (asterisk) of the cranial margin of the pancreatic head upstream dilated
involving the common bile duct (C). (b) Surgical specimen (pancreati-
a b
c d
Fig. 61 Small ductal adenocarcinoma in pancreas divisum. (a–d) MRI mon bile duct (C in b) dilation is detectable. On T1-weighted image,
study: MRCP (a) shows dilated biliary system and common bile duct (C small hypointense lesion (arrow in c) is visible in the pancreatic head.
in a), and pancreas divisum with the main pancreatic duct (P in a) not The lesion is well vascularized (arrow in d) in the dynamic pancreatic
dilated. On coronal T2-weighted image, no clear lesion causing com- phase
a b
Fig. 62 Cystic epiphenomenon of ductal adenocarcinoma. (a) CT cystic ectasia (arrow). (b, c) MRI study: the tumor appears almost
study: large neoplastic lesion with blurred margins located in the pan- isodense on both T1-weighted (b) and T2-weighted (c) fat-saturated
creatic body diffusely involving the celiac trunk. The lesion appears images. Wirsung duct dilation (W in c) and secondary duct cystic ecta-
hypodense in the pancreatic phase at dynamic CT and causes upstream sia (arrow in c) in the pancreatic body are visible
a b
c d
e f
Fig. 63 Ductal adenocarcinoma with perilesional secondary duct cys- image (c) and MRCP (d), double-duct sign is present, and also perile-
tic ectasia. (a–f) MRI study: round-shaped lesion in the pancreatic sional secondary duct cystic ectasia (arrows in d) are visible. The lesion
head, hypointense (arrow in a) on T1-weighted image, showing diffu- shows hypovascular pattern (arrow in e) in the dynamic pancreatic (e)
sion restriction on DWI (b) with high value of b. On coronal T2-weighted and venous (f) phases
b c
Fig. 64 Ductal adenocarcinoma with perilesional secondary duct cys- of different case: ductal adenocarcinoma (asterisk in b) with the main
tic ectasia. (a) MRCP: slight dilation of the common bile duct (C) with pancreatic duct (W in b) dilation and perilesional secondary duct cystic
stenosis in the pancreatic head, surrounded by perilesional secondary ectasia (arrows in b and asterisks in c)
duct cystic ectasia (arrow). (b, c) Surgical specimen and histopathology
a b
Fig. 65 Ductal adenocarcinoma with cystic epiphenomenon. (a, b) CT b). Dilation of the main pancreatic duct (W in a) is also visible in the
study: two cystic lesions (arrows in a), next to the pancreatic body, pancreatic body. The superior mesenteric vein is stenotic infiltrated
related to cystic epiphenomenon of a solid mass, hypodense in the from the mass, with multiple secondary collateral vein networks
dynamic phases, visible more caudally in the pancreatic head (arrow in
a b
Fig. 66 Cystic epiphenomenon of ductal adenocarcinoma. (a–c) CT the splenic artery (S in b). The coronal view (c), more panoramically,
study: large cystic lesion (asterisk in a and b) caused by pancreatic shows the cystic lesion (asterisk in c) and the mass (arrow in c)
body mass, hypodense in the dynamic phases (arrow in b), infiltrating
Fig. 66 (continued)
a b
Fig. 67 Pancreatitis-like morphology of ductal adenocarcinoma. (a) pancreatic body is present a mass with elongated morphology,
Ultrasound study: the pancreatic body is uniformly swollen and hypodense in both pancreatic (arrow in b) and venous (arrow in c)
hypoechoic (arrow) at conventional ultrasound. (b, c) CT study: in the dynamic phases, simulating an inflammatory process
a b
c d
Fig. 68 Necrotic ductal adenocarcinoma with pancreatitis-like mor- in d) on T1-weighted image and hyperintense on T2-weighted (arrow
phology. (a–c) CT study: in the pancreatic body, a mass with elongated in e) image, is present. A small secondary ductal ectasia is also visible
morphology, slightly hypodense in both baseline (arrow in a), pancre- in the tail. At dynamic MRI, the mass is markedly hypovascular in the
atic (arrow in b), and venous (arrow in c) dynamic phases, simulating pancreatic phase (arrow in f), with necrotic avascular portions together
an inflammatory process, is present. (d–h) MRI study: in the pancreatic with areas of progressive retention of contrast medium, due to fibrosis
body, a mass with elongated morphology, slightly hypointense (arrow in the venous (g) and late (h) phases
e f
g h
Fig. 68 (continued)
a b
Fig. 69 Pancreatitis-like morphology of ductal adenocarcinoma. (a–c) bubbles contrast medium injection, the mass is typically markedly
Ultrasound study: an oval-shaped solid mass, slightly hypoechoic hypovascular (arrow in c). (d) Surgical specimen (pancreaticoduode-
(arrow in a) on conventional ultrasound, is visible in the pancreatic nectomy) of different case: ductal adenocarcinoma with oval-shaped
body with no dilation of the Wirsung duct. At ARFI elastography (b) morphology and intense desmoplastic reaction. The probe indicates the
with quantification, the mass is extremely stiff (3.4 m/s). After micro- Wirsung duct that remains visible within the tumor
a b
c d
Fig. 70 Pancreatitis-like morphology of ductal adenocarcinoma. (a–d) main pancreatic duct is visible. At dynamic MRI, the mass is markedly
MRI study: a small mass with elongated morphology, hypointense (arrow hypovascular in the pancreatic phase (arrow in c) with progressive reten-
in a) on T1-weighted image and slightly hyperintense (arrow in b) on tion of the contrast medium, starting in the venous (d) phase, especially
T2-weighted image, is present in the pancreatic body. No dilation of the in the peripheral more viable fibrotic tissue (arrow in d)
a
b
c d
Fig. 71 Mucinous noncystic carcinoma (colloid carcinoma). (a) CT specimen (pancreaticoduodenectomy): gelatinous mass, better demar-
study: markedly hypodense mass (arrow in a) in the pancreatic head cated than ductal adenocarcinoma. (d) Histopathology: cluster of cells
during dynamic phase. (b) CEUS study: thick vascularized septa floating in abundant extracellular mucin
(arrow) are clearly visible within the pancreatic head mass. (c) Surgical
a b
c d
Fig. 72 Anaplastic carcinoma. (a, b) Ultrasound study: an oval-shaped shaped mass, hyperintense (arrow) on T2-weighted image. (d, e)
mass markedly hypoechoic (arrow in a) on conventional ultrasound is Histopathology of different case: well-demarcated tumor mass with
visible in the pancreatic body. After microbubbles contrast medium evident central hemorrhagic necrosis (asterisk in d). The neoplastic
injection, the mass shows thick wall vascularization (arrow in b) with cells (e) show extreme anaplasia and grow in poorly cohesive sheets
evident central necrotic area. (c) MRI study: pancreatic body oval- supported by scanty desmoplastic stroma
a b
c d
Fig. 73 Ductal adenocarcinoma with gross calcification. (a–c) CT venous (c) dynamic phases. (d) Surgical specimen (pancreaticoduode-
study: gross calcification (arrow in a) in the pancreatic head. A biliary nectomy): ductal adenocarcinoma (asterisk) and ductal gross calcifica-
endoprosthesis (E in a) is present. Around the calcification, slightly tion (arrow)
hypodense halo (arrow in b and c) is visible in the pancreatic (b) and
a b
c d
Fig. 74 Postpancreatitis scar with pseudocystic epiphenomenon. (a–e) level of the abrupt cutoff of the main pancreatic duct, a slightly hypoin-
MRI study: MRCP (a) and coronal T2-weighted (b) image show a cys- tense (arrow in c) small portion is visible, resulting slightly hypovascu-
tic lesion (asterisk in b) and a dilated main pancreatic duct (W in a) with lar in the pancreatic (arrow in d) and venous (arrow in e) dynamic
abrupt cutoff of the duct (arrow in a). On T1-weighted (c) image, at the phases
Fig. 75 Autoimmune pancreatitis. (a)

Ultrasound study: diffuse form of a
autoimmune pancreatitis appearing as
diffuse enlargement with typical “sausage”
shape of the pancreatic gland, slightly
hypoechoic on conventional ultrasound. (b)
CEUS study: focal form of autoimmune
pancreatitis involving the pancreatic head,
resulting isovascular (asterisk) in respect to
the rest of the pancreatic parenchyma
b
c d
Fig. 76 Focal autoimmune pancreatitis. (a, b) Ultrasound study: pan- d) CT study: pancreatic head lesion, isodense in the pancreatic (arrow
creatic head mass, slightly hypoechoic (calipers in a) at conventional in c) and venous (d) dynamic phases. Presence of biliary endoprosthesis
ultrasound, but isovascular (arrow in b) at CEUS. Presence of biliary (E in d), but no dilation of the main pancreatic duct
endoprosthesis (E in b), but no dilation of the main pancreatic duct. (c,
a b
c d
e f
Fig. 77 Focal autoimmune pancreatitis. (a–d) MRI study: pancreatic study shows resolution of the mass with normalization of signal inten-
body mass, slightly hypointense (arrow in a) on T1-weighted image, sity of the pancreatic body on T1-weighted (arrow in e) image and in
showing inhomogeneous hypovascularity (arrow in b) in the pancreatic the pancreatic (f) and venous (g) dynamic phases. At control MRCP
dynamic phase, but isointensity (arrow in c) in the venous phase. At (h), ductal stenosis is no more visualized, and the Wirsung duct appears
MRCP (d), the Wirsung duct is stenotic for a long tract (asterisk in d) regular in caliber along the whole gland
without any upstream dilation. (e–h) MRI control study: the control
g h
Fig. 77 (continued)
14. Paik KY, Choi SH, Heo JS, et al. Solid tumors of the pancreas
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Ductal Adenocarcinoma: Downstaging
Riccardo De Robertis, Paola Capelli, Chiara Longo,

Introduction be performed before biliary stenting, while restaging should

be performed within 4 weeks from the presumed surgery [6].
Pancreatic ductal adenocarcinoma (PDAC) is usually diag- Multidetector computed tomography (MDCT) is the pre-
nosed at an advanced stage of disease with involvement of ferred imaging modality for the diagnosis and staging of
major peripancreatic vessels, extra-pancreatic invasion, or pancreatic cancer [7]. While magnetic resonance imaging
metastases. For this reason, fewer than 20% of patients are (MRI) has not yet demonstrated a clear advantage over CT
suitable for surgical resection [1]. The advent of effective for local staging [8], contrast-enhanced MRI can be of value
neoadjuvant chemotherapy has allowed an increase in the for the characterization of CT-indeterminate liver lesions,
number of unresectable PDACs undergoing surgery, with when suspected pancreatic tumors are not visible on CT or in
encouraging results in long-term survival rates. Neoadjuvant cases of allergy to iodinated contrast media; moreover, MRI
chemoradiotherapy has three important advantages: it seems to be more accurate than CT in the identification of
improves local tumor control that increases the likelihood of small (<1 cm) liver metastases [9]. The role of PET/CT in
achieving negative-margin resection; it can identify patients PDAC staging remains unclear [6]. Most commonly, MDCT
with a rapidly progressive disease, who can be spared the is performed by acquiring thin-section (<3 mm, preferably
morbidity associated with potentially useless surgery; and it 0.5–1 mm) images obtained at least during the post-contrast
may warrant access to chemotherapy in the event that an pancreatic and portal/venous phases. The conspicuity of
adjuvant treatment could not be administered in the post- PDAC, usually hypoenhancing, and the rest of the organ is
surgical phase [2]. Among unresectable PDAC patients, 70% highest during the pancreatic phase; this phase also allows
already present stage IV at diagnosis and then can only ben- good visualization of major arterial and venous structures,
efit from palliation [3]; around 30% of unresectable PDAC thereby assessing vascular invasion [6]. The delayed post-
patients, including locally advanced and borderline resect- contrast phase could be useful in the detection of isodense
able cancers, can be downstaged by neoadjuvant chemora- and small PDACs [10]. The use of multiplanar reconstruc-
diotherapy and may achieve negative-margin resection (R0) tion and 3D rendering is highly recommended as they allow
[4, 5]. Resectability of PDAC is a multidisciplinary concept, precise visualization of the relationship of the primary tumor
and imaging has a central role for the proper description of to the surrounding structures as well as detection of sub-
the extent of tumor, which has great importance for optimal centimetric metastatic lesions [6]. Recently, a multidisci-
therapeutic decision-making and for ongoing management plinary expert consensus group defined a standardized
of patients. High-quality imaging of the pancreas should be language to report imaging findings. The template recom-
performed at presentation and following neoadjuvant treat- mended by the panel included morphologic, arterial, venous,
ments to provide adequate staging and assessment of resect- and extra-pancreatic evaluations [11]. The morphologic eval-
ability status. When possible, pre-treatment imaging should uation included the documentation of tumor appearance,
size, and location, as well as the presence of narrowing or
abrupt cut-off of the pancreatic duct or biliary tree. The arte-
R. De Robertis · C. Longo · M. D’Onofrio (*)
Department of Radiology, G.B. Rossi University Hospital, rial evaluation should include the assessment of the celiac
Verona, Italy axis, the superior mesenteric artery, and the common hepatic
e-mail: mirko.donofrio@univr.it artery, including the extent of tumor-vessel contact, the pres-
P. Capelli ence of perivascular hazy attenuation or stranding, and focal
Department of Pathology, G.B. Rossi University Hospital, vessel narrowing or contour irregularity. Venous evaluation
Verona, Italy

100 R. De Robertis et al.
should include the assessment of the portal vein and the tion that can potentially be mitigated by neoadjuvant
superior mesenteric vein; the presence of venous thrombus therapy. Approaching to locally advanced stage, there is a
should also be reported. The extra-pancreatic evaluation high risk of positive resection margins and, therefore, a
should include documentation of liver lesions, peritoneal or poorer prognosis [15].
omental nodules, ascites, suspicious lymph nodes, and other
extra-pancreatic disease deposits [6]. In the literature, the
performance of multidetector CT for detecting vascular inva- Neoadjuvant Therapy
sion had a specificity value from 82% to 100% and sensitiv-
ity from 70% to 96% [12–14]. The neoadjuvant approach is appropriate for locally advanced
tumors in order to allow conversion to resectability and, for
borderline resectable tumors, in order to increase the chances
Resectability of a margin-negative resection. The neoadjuvant approach
usually includes chemotherapy and chemo-sensibilization
From a surgical perspective, the first step in the management concomitant to long-course conventionally fractionated
of PDAC is to determine the resectability. For this reason, radiotherapy (RTCT) and stereotactic body radiotherapy
several classifications have been created. At present, the (SBRT) [16]. Patients with borderline resectable disease
most widely accepted staging classification is the National should be considered for neoadjuvant therapy, followed by
Comprehensive Cancer Network (NCCN) classification [6]: restaging and resection in patients without disease progres-
sion precluding surgery [6]. Several meta-analyses suggested
1. Tumors considered resectable should demonstrate: that approximately one-third of initially unresectable disease
(a) No distant metastases. (including both borderline resectable and unresectable)
(b) Clear fat planes around the celiac axis, hepatic artery, tumors achieved margin-negative resection following neoad-
and superior mesenteric artery (no arterial tumor juvant therapy [17–20]. Controversial results have been
contact). reported regarding the effectiveness of neoadjuvant therapy
(c) No radiological evidence of superior mesenteric vein in terms of median survival: while some authors reported a
and portal vein infiltration, distortion, tumor throm- non-significant difference between patients who underwent
bus, or encasement (no venous tumor contact or neoadjuvant therapy and those who underwent upfront sur-
≤180° contact without vein contour irregularity). gery [21, 22], other studies proved that patients who under-
2. Tumors considered borderline resectable include: went surgery after neoadjuvant therapy had a substantially
(a) No distant metastases. increased overall survival (ranging from 26 and 37.7 months)
(b) For pancreatic head/uncinate process: solid tumor [23, 24]. Despite these encouraging results, some patients
contact with the common hepatic artery without receiving neoadjuvant chemotherapy recurred within
extension to the celiac axis or hepatic artery bifurca- 12 months of their operation [23]. Several studies have also
tion; solid tumor contact with the superior mesenteric considered the use of neoadjuvant chemoradiation in patients
artery ≤180°. with resectable disease [25–30]: a retrospective review sug-
(c) For pancreatic body/tail: solid tumor contact with gested that the use of preoperative chemoradiation therapy in
celiac artery ≤180°. patients with resectable disease is advantageous because
(d) Venous involvement of the superior mesenteric vein approximately 25% of patients who are restaged after ther-
or portal vein demonstrating contact >180°, or contact apy are found to have progressive disease and are therefore
≤180° with deformity or vein thrombosis but allowing spared the morbidity of a surgical procedure that would not
safe and complete resection and reconstruction. benefit them [31]; a recent study analyzed the possible effect
(e) Contact with the inferior vena cava. of chemoradiotherapy on the subsequent surgical field and
3. Tumors considered locally advanced include: found that there were no statistically significant differences
(a) For pancreatic head/uncinate process: tumor contact with regard to surgical time, blood transfusions, overall and
>180° with the superior mesenteric artery or celiac axis. abdominal complications, pancreatic fistula, and mortality
(b) For pancreatic body/tail: contact of >180° with the [21]. Other potential advantages of the neoadjuvant approach
superior mesenteric artery or celiac artery; aortic in patients with resectable disease have also been described,
involvement. including sterilization of the field before resection poten-
(c) Unreconstructible involvement of the superior mes- tially reducing spread during surgery, increased rates of
enteric vein or portal vein. margin-negative resections, decreased incidence of pancre-
atic fistulas, prevention of delays or reductions of adjuvant
Proceeding from resectable to borderline resectable dis- therapy after surgery, and improved delivery of chemother-
ease, there is an increasing risk of a margin-positive resec- apy and radio-sensitizing oxygenation [26, 32, 33]. Regarding
Ductal Adenocarcinoma: Downstaging 101
radiation therapy, recent studies have underlined that SBRT tomy after neoadjuvant therapy achieved R0 resection status
after systemic therapy can increase survival in locally [40]. In another study by Ferrone et al., 40 patients with
advanced pancreatic cancer compared to either chemother- locally advanced or borderline cancer received neoadjuvant
apy alone or conventionally fractionated radiation therapy chemotherapy and 87 did not; despite imaging after neoadju-
[34]. In fact, SBRT, following induction chemotherapy, may vant chemotherapy still classifying 19 patients as locally
improve the chance of resection. To date, the optimal sched- advanced and 9 as borderline, ultimately 92% had a R0
ule has not been determined yet, but the administration of a resection, where pathologic analysis demonstrated no active
higher biologically effective dose is essential to achieve cancer, but significant fibrosis resulting from the therapy
durable tumor control and impact on survival [35]; in par- [41]. Thus, they stated that current radiologic imaging can-
ticular, the administration of ablative doses can sterilize the not distinguish between fibrosis and viable cancer. Morgan
tumor boundaries involving peripancreatic vessels and, et al. and Cassinotto et al. also found that CT after neoadju-
together with mass shrinkage, potentially allow surgery [36]. vant therapy overestimated tumor size and the degree of vas-
Moreover, some studies identified that stereotactic body cular involvement, reducing the accuracy of predicting R0
radiotherapy with the novel techniques of simultaneous inte- resection status [42, 43]. Besides, Truty et al. assessed that
grated boost (SIB) and simultaneous integrated protection radiologic downstaging is uncommon (<25%) with rare
(SIP) allows maximization of the radiotherapy therapeutic tumor recession from encased vascular structures; despite
window by delivering ablative doses on the tumor burden minimal downstaging, the majority of patients in this series
area while reducing the dose to critical organs at risk [37]. had R0 resections [44]. These authors added that in the
absence of radiologic changes, CA 19.9 decrease can serve
as effective response surrogates but is likely inadequate as
adiological Evaluation After Neoadjuvant
R sole indicator. Further comparative studies were conducted
Chemoradiotherapy between groups of patients who received chemoradiation
therapy and others who did not receive neoadjuvant therapy.
Radiological assessment of residual disease after neoadju- In one of these studies, Kim et al. described that the overall
vant chemoradiotherapy represents one of the major radio- accuracy of resectability on pancreatic head adenocarcinoma
logical challenges in pancreatic cancer management [2]. was slightly higher in patients with neoadjuvant treatment
Radiologic evaluation should be performed both prior to and (83% vs 81%), but the overall accuracy of tumor staging was
at the conclusion of neoadjuvant therapy. On one hand, a low significantly lower with neoadjuvant therapy (58% vs 95%),
false-positive rate is crucial to ensure that patients without overestimating all those cases that did not match the patho-
vascular invasion are not deprived of potentially curative sur- logic examination [45]; the positive predictive value of mul-
gery [2], while on the other hand, the radiologist should tidetector CT for resectable cancer after neoadjuvant therapy
accurately evaluate the worsening of disease that would pre- was higher than in patients without therapy (91% vs 75%);
clude resection, such as the development of metastases or however, the negative predictive value was lower between
worsening of vascular involvement. As the accuracy of the two groups (0% vs 100%). This means that multidetector
MDCT in excluding distant metastatic disease depreciates CT predictive value in the resectability of pancreatic head
over time, patients should undergo a repeat MDCT within adenocarcinoma in patients after neoadjuvant chemoradia-
25 days of any planned definitive operative intervention for tion therapy is comparable to patients without preoperative
pancreatic cancer to avoid unexpectedly metastatic disease at therapy, even though tumor restaging is less accurate.
surgery [38]. There is growing awareness that imaging char- With all this considered, previous researches tried to
acteristics may not be a reliable indicator of resectability in identify imaging predictors for negative-margin resection.
borderline resectable and locally advanced patients who In literature, it is reported that a 25 mm cut-off of the tumor
have received neoadjuvant therapy [6]. The first one to notice extension as a marker revealed to be 64% sensitive, 78%
this fact was White et al. in 2001, describing how CT tends specific, and 69% accurate in predicting an R+ resection;
to overestimate the extension of a locally advanced PDAC the 25 mm cut-off was also 67% sensitive, 90% specific, and
subjected to neoadjuvant CRT [39]; they hypothesized that 77% accurate in assessing real tumor dimension after the
the overestimation is due to multiple factors, especially the anatomopathological specimen examination [46]. They
presence of peripancreatic edema and fibrosis induced by the depicted also that each 5 mm increase in tumor dimension
neoadjuvant treatment. Since then, numerous studies in the reported an OR of 1.79 for R+ resection, with an OR of 6.56
literature have apported their contribution to this thesis. In a when bigger than 25 mm. On the contrary, the presence of
study by Katz et al., among a cohort of 122 borderline resect- the perivascular cuff at imaging evaluation reported a non-
able patients treated with various neoadjuvant strategies, significant accuracy in determining tumor persistence and
only 1 patient had disease downstaging to resectable status retroperitoneal margin infiltration in the pathological speci-
by imaging criteria, but 81 of 85 who underwent pancreatec- men. Tumor density homogeneity in venous and delayed
phases reported an accuracy of 50% and 63%, respectively, ative liver on CT and 7 had indeterminate hepatic lesions on
in evaluating tumor persistence, whereas tumor enhance- CT [51]. Motosugi et al. compared the sensitivity in the
ment in both phases was not an accurate parameter. However, detection of liver metastases between gadoxetic acid-
the presence of enhancement in the venous and delayed enhanced MRI and CT: MRI reported a significantly higher
phases was found to be an accurate measure of the presence sensitivity (85% vs 69%) due to higher lesion-to-liver con-
of fibrosis, with respective accuracy of 95% and 89% [46]. trast on hepatocyte phase. A prospective study by Holzapfel
Michelakos et al. found that tumor size was the only patho- et al. showed that MRI including diffusion-weighted imag-
logic factor independently predictive of a poor ing (DWI) had significantly higher sensitivity (86.7%) and
OS. Conversely, The time elapsed from diagnosis to resec- specificity (97.5%) for the detection of hepatic metastases
tion longer than 8 months was associated with poor disease- compared to MDCT (53.3% and 77.8%, respectively) [52].
free survival. On the opposite, traditional pathological Similarly, another study reported that 23.2% of patients
factors such as lymph node positivity and vascular and peri- with negative liver on CT showed occult liver metastases on
neural invasion did not emerge as independent predictors of MRI [53]. These results would suggest that by adding MRI
disease-free survival [23]. In parallel, current research is with DWI to multidetector CT, the therapeutic strategy can
ongoing to utilize other imaging modalities that may more be changed or more confidently decided upon through a bet-
readily differentiate desmoplastic reaction or tumor fibrosis ter evaluation of the liver. Jeon et al. showed that all “too-
from true neoplastic tissue. For example, recent studies uti- small-to-characterize” liver lesions which benefitted from
lizing quantitative dynamic contrast-enhanced MR imaging the addition of MRI with DWI were 1 cm or smaller [54].
to measure fibrotic and vascular density have shown prom- On the contrary, the diagnostic performance of MRI for
ise in reliably differentiating tumor from non-tumoral tissue evaluating vascular invasion is still controversial.
[47, 48]. Another encouraging example is the computed tex- Multidetector CT remains the preferred imaging modality,
ture analysis, a new tool that evaluates every pixel’s value, but recent advances in MR technology have made the diag-
variations, and distribution [49, 50]. As our understanding nostic performance of the two imaging modalities compa-
of these advanced applications and functional imaging rable for vascular infiltration (mean sensitivity, 80% vs.
improve, MRI and other modalities may eventually be 65%; mean specificity, 98% vs. 97%, respectively) [13, 55].
incorporated into what is now a strictly CT-based set of bor-
derline pancreatic cancer imaging classification criteria. For
the time being, however, CT remains the mainstay of imag- Conclusions
ing [15]. There is no uniform consensus on whether MRI
should be added to CT in patients with a resectable At present, literature has indeed concluded that surgical
PDAC. MRI has higher sensitivity compared to CT in exploration with intent for primary resection should be con-
detecting small PDACs or minimal changes of the pancre- sidered in all operable candidates without evidence of dis-
atic ductal system that may suggest the presence of a small ease progression or metastasis after neoadjuvant therapy [23,
PDAC, as well as a higher sensitivity for identification of 44, 56].
hepatic metastases [38]. Kim et al. analyzed 216 patients In particular, some authors suggest that surgery must be
with both preoperative CT and MRI and demonstrated that considered for tumors that after neoadjuvant chemoradio-
additional MRI modified surgical resectability and treat- therapy are smaller than 25 mm, with reduction of vascular
ment in a significant proportion of patients: 14.4% who had contact, independently from the persistence of the perivascu-
a potentially resectable disease on CT were changed to have lar cuff or inhomogeneous enhancement [46].
unresectable disease by MRI owing to the detection of liver With all this considering, it is still very difficult to assess
metastases, major vascular invasion, enlarged para-aortic universal management, and it is recommended by the guide-
lymph node, and peritoneal seeding; moreover, of the 16 lines that resectability and surgical therapy should be made
patients with liver metastases diagnosed by MRI, 9 had neg- on an individualized basis in a multidisciplinary setting [6].
Image Gallery
a b
Fig. 1 Ductal adenocarcinoma downsizing. (a) CT: huge mass in the pancreatic body-tail hypovascular so inhomogeneous hypodense in the
pancreatic phase. (b) CT: downsizing of the tumor with an important volume reduction of pancreatic mass
a b
c d
Fig. 2 Ductal adenocarcinoma downsizing. (a, b) CT: pancreatic head mass hypodense (a) in the pancreatic phase involving the superior mesen-
teric vein (b). (c, d) CT: downsizing with small volume reduction of the tumor (c) less involving the superior mesenteric vein (d)
a b
Fig. 3 Ductal adenocarcinoma downsizing. (a) CT: huge mass in the tant volume reduction of pancreatic mass. At pathology, no neoplastic
pancreatic body-tail hypovascular, and inhomogeneous hypodense in cells were visible and R0 margins were reported
the pancreatic phase. (b) CT: downsizing of the tumor with an impor-
a b
Fig. 4 Ductal adenocarcinoma downsizing. (a) MRI: mass hypovascu- tumor with volume reduction of pancreatic mass no longer directly
lar in the pancreatic phase at the uncinate process of the pancreas involving the superior mesenteric artery
involving the superior mesenteric artery. (b) MRI: downsizing of the
a b
c d
e f
Fig. 5 Comparison of different responses after chemotherapy in ductal appears minimally smaller still involving the vein which appears less
adenocarcinoma. (a, b) CT head pancreatic tumor: small mass at the deformed. At pathology, no neoplastic cells were visible and R0 mar-
pancreatic head involving the superior mesenteric vessels (a). After gins were reported. (e, f) CT head pancreatic tumor: mass at the pancre-
treatment (b), the mass appears minimally smaller. At pathology, neo- atic head involving the superior mesenteric vessels (e). After treatment
plastic cells were still present, and R1 margins were reported. (c, d) CT (f), the mass appears smaller with less involvement of the superior mes-
head pancreatic tumor: mass at the pancreatic head involving the supe- enteric vessels. At pathology, no neoplastic cells were visible, and R0
rior mesenteric vein at the confluence (c). After treatment (d), the mass margins were reported
a b
c d
Fig. 6 Ductal adenocarcinoma downsizing. (a, b) CT head pancreatic mass is drastically reduced in volume resulting slightly hypodense in
tumor: mass at the pancreatic head appearing hypodense in the pancre- dynamic phases (f) with no contact with the superior mesenteric ves-
atic (a) and venous (b) phases and minimally in contact with superior sels. (g, h) Surgical specimen: pancreaticoduodenectomy (g) with small
mesenteric vessels. (c, d) At CT, after treatment, the mass is drastically pancreatic head showing irregular surfaces with fat tissue attached.
reduced in volume resulting slightly hypodense in the pancreatic (c) Small tumor is hardly visible at sections evaluation (asterisk in h). The
and venous (d) phases. With less contact with the superior mesenteric common bile duct (arrow in h) is markedly dilated with thick wall post
vessels. (e, f) At MRI, diffusion restriction is visible; at DWI (e), the biliary stent
e f
g h
Fig. 6 (continued)
a b
c d
Fig. 7 Ductal adenocarcinoma downstaging with downsizing. (a, b) atic duct dilation. (c, d) At CT after treatment, the mass is drastically
CT body-tail pancreatic tumor: pancreatic mass hypodense in the pan- reduced in volume resulting isodense in the pancreatic (c) and venous
creatic (a) and isodense in the venous (b) phases causing main pancre- (d) phases
a b
c d
e f
Fig. 8 Ductal adenocarcinoma downstaging with downsizing. (a–c) (d–f) At MRI after treatment, the mass is reduced in volume hypoin-
MRI: pancreatic mass in the pancreatic isthmus hypointense on T1 (a) tense on T1 (d) with less restriction on DWI (e) and hypovascular at
with restriction on DWI (b) and hypovascular at dynamic phases (c). dynamic phases (f)
a b
c d
Fig. 9 Ductal adenocarcinoma local staging. (a–c) CT: small pancre- hilum. (d) Surgical specimen of different case: small tumor of the cra-
atic mass of the upper portion of the pancreatic head (a) involving the nial portion of the pancreatic head running (arrows) to the liver hilum.
celiac trunk (b) and running along the hepatic artery (c) to the liver Major papilla (P)
a b
c d
e f
Fig. 10 Ductal adenocarcinoma downstaging. (a, b) CT: mass at the hypodense in the pancreatic (c) and isodense in the venous (d) phases
pancreatic body involving the celiac trunk (a, b) appearing hypodense with persistent regular perivascular thickening giving cuffing of the
in the pancreatic (a) and isodense in venous (c) and late (d) phases celiac trunk. At pathology, good response to therapy was found with
causing upstream dilation of the main pancreatic duct. (e, f) At CT after perivascular not neoplastic fibrosis
treatment, the mass is drastically reduced in volume resulting slightly
a b
c d
Fig. 11 Ductal adenocarcinoma downstaging with downsizing. (a–c) an evident diffusion restriction is visible on DWI showing a huge mass.
CT body-tail pancreatic tumor: pancreatic mass isodense in the pancre- (d) At CT after treatment, the mass is drastically reduced in volume
atic (a) and venous (b) phases infiltrating the splenic vessels. At MRI, with residual limited contact with splenic vessels
a b
c d
e f
Fig. 12 Ductal adenocarcinoma downstaging with downsizing. (a–c) stent. (g–k) At MRI after treatment, the small residual mass appears to
CT head pancreatic tumor: pancreatic mass slightly hypodense in the be slightly hypointense on T1FS (g) and isointense on T2 (h) causing
pancreatic (a) and isodense in the venous (b) and late (c) phases with stenosis of the main pancreatic duct upstream dilated at MRCP (i). No
limited spread in peripancreatic fat with superior mesenteric contact. evident diffusion restriction is visible on DWI (j). In dynamic phase, the
(d–f) At CT after treatment, the mass studied in the pancreatic (d), small residual lesion is hypovascular (k). Presence of biliary stent
venous (e), and late (f) phases is drastically reduced. Presence of biliary
g h
i j
Fig. 12 (continued)
a b
c d
e f
C
C
W
Fig. 13 Ductal adenocarcinoma downstaging. (a, b) CT head pancre- therapy was found with highly fibrotic lesion in the pancreatic head and
atic tumor: pancreatic mass hypodense in the pancreatic (a) and venous perivascular not neoplastic fibrosis. (e, f) Surgical specimen of different
(b) phases involving the superior mesenteric artery and the superior case: pancreaticoduodenectomy with margins highlighted (e). Superior
mesenteric vein that is clearly deformed. (c, d) At CT after treatment, mesenteric vein bed (red) is documented. Probes in Wirsung (W) and
the mass studied in the pancreatic (c) and venous (d) is reduced in vol- common bile ducts (C). At section evaluation (f), highly fibrotic lesion
ume with remaining contact with the superior mesenteric artery. Less (asterisk) infiltrating peripancreatic fat tissue (highlighted in black in e)
deformation of the superior vein is clearly appreciable in the venous (d) along the inferior margin of the pancreatic head (arrow in f) causing
phase. Presence of biliary stent. At pathology, good response to the stenosis of the common bile duct (C) upstream markedly dilated
a b
c d
e f
Fig. 14 Ductal adenocarcinoma. (a) CT head pancreatic tumor: pancreatic (b) and venous (c) is hypodense and reduced in volume. Presence of
atic mass hypodense in the pancreatic phase in advanced stage involving biliary stent and duodenal prothesis. (e, f) Surgical specimen: pancreati-
the superior mesenteric vein and extensively the duodenum and the gas- coduodenectomy (e) with duodenal metallic prothesis causing multiple
tric antrum. (b, c) At CT after treatment, the mass studied in the pancre- inflammatory pseudopolyps of the duodenal mucosa (f)
a b
c d
Fig. 15 Ductal adenocarcinoma downstaging with downsizing. (a, b) sional foci are present. (e) Surgical specimen (distal spleno-
CT: pancreatic body mass hypodense in the pancreatic (a) and venous pancreatectomy): lesion with sharp margins in the body of the pancreas
(b) phases infiltrating the splenic vessels. (c, d) At CT after treatment, with multiple necrotic intralesional foci (arrows) and obstructive
the mass studied in the pancreatic (c) and venous (d) is clearly reduced chronic pancreatitis upstream
in volume showing sharp margins. Multiple small hypodense intrale-
a b
c d
Fig. 16 Ductal adenocarcinoma downstaging with downsizing. (a, b) (c) is slightly reduced in volume with modification of the superior mes-
CT head pancreatic tumor: pancreatic mass hypodense in the pancreatic enteric vessels relationship being better visible the perivascular fat.
(a) and venous phases abutting the superior mesenteric vessels. (c, d) At Presence of biliary stent and duodenal prothesis
CT after treatment, the mass studied in the pancreatic (b) and venous
a b
c d
Fig. 17 Ductal adenocarcinoma downstaging with downsizing. (a) CT margin (black). Probe in common bile duct. At sections evaluation (d),
head pancreatic tumor: pancreatic mass hypodense in the pancreatic small highly fibrotic lesion in the pancreatic head causing stenosis of
phase. (b) At CT after treatment, the mass is reduced in volume. the common bile duct upstream markedly dilated. In the cranio-caudal
Presence of biliary stent and duodenal prothesis. (c–e) Surgical speci- transversal sections (e) the lesion extends from peripapillary region to
men of different case: pancreaticoduodenectomy (c) with margins high- the dorsal surface of the pancreatic head (arrows in e) causing stenosis
lighted: superior mesenteric vein bed (green) and retroperitoneal of the common bile duct upstream markedly dilated
a b
c d
e f
Fig. 18 Ductal adenocarcinoma downsizing. (a, b) CT: pancreatic pancreas due to the presence of abundant fat attached to the anterior-
mass in the uncinate process of the pancreas hypodense in the pancre- inferior surface. Specimen with margins highlighted (h): pancreatic
atic (a) and venous (b) phases with infiltration of the superior mesen- margin with main pancreatic duct dilated (asterisk in g); superior mes-
teric vein receiving the teardrop deformation. (c–f) At CT after enteric vein bed (red); retroperitoneal margin (black); fat thickening
treatment, the mass is reduced in volume (c) with normal appearance of (yellow; arrow in g) around attached to the anterior-inferior surface of
the superior mesenteric vein (d). In the more caudal scans, thick nodu- the pancreatic head anterior surface (blue). At section evaluation, in the
lar appearance of the fat along the ventral surface of the pancreatic head cranio-caudal transversal sections, (i) the tumor was present in all pan-
(e) and along the wall of the vein (f) is visible. (g–i) Surgical specimen: creatic head sections and extending in the peripancreatic fat attached as
pancreaticoduodenectomy (g) with irregular aspect of the head of the neoplastic diffusion
g h
Fig. 18 (continued)
a b
Fig. 19 Ductal adenocarcinoma downstaging. (a, b) CT after treatment: pancreatic head mass hypodense in the pancreatic (a) and venous (b)
phases with sharp margins and rounded morphology. Presence of biliary stent
a b
c d
Fig. 20 Ductal adenocarcinoma downstaging with downsizing. (a, b) of the splenic-mesenteric confluence. (c, d) At CT after treatment, the
CT: mass at the isthmus of the pancreas hypodense in the pancreatic and mass is reduced in volume. Normal mesenteric vessels. Presence of
venous phases with small retention cyst and involving the ventral wall biliary stent
a b
c d
Fig. 21 Ductal adenocarcinoma downstaging with downsizing. (a–c) superior mesenteric artery. At pathology, R1 superior mesenteric ves-
At CT after treatment, small mass (reduced in volume) is visible at sels vascular margins. (d, e) Pathology evaluation of different case: sec-
uncinate process resulting hypodense in the pancreatic (a) phase and tion analysis (d) with blue-tricromica di masson (e) with tumor with
isodense in the venous (b) phase. Minimal residual contact with the fibrotic changes infiltrating the resected vessel showing neoplastic cells
mesenteric vein is visible (b) confirmed at coronal (c) view and with the within the vascular wall
a b
c d
Fig. 22 Ductal adenocarcinoma downstaging with downsizing. (a, b) reduced in volume still but less in contract with the splenic-mesenteric-
CT: pancreatic head mass hypodense in the pancreatic and venous portal venous confluence. The neoplastic tissue is more persistent
phases infiltrating the splenic-mesenteric-portal venous confluence. around the biliary stent following the common bile duct wall. At pathol-
Presence of biliary stent. (c, d) At CT after treatment, the mass is ogy, R1 margins with neoplastic cells toward the hepatic hilum
a b
c d
e f
Fig. 23 Ductal adenocarcinoma downstaging with downsizing. (a–c) pancreas with a narrow strip of gastric wall (arrows) resected with the
At CT after treatment, pancreatic body tail mass studied in the pancre- mass (d). Highlighted (red) the tumoral surface infiltrating the gastric
atic (a) and venous (b) phases hypodense infiltrating the splenic vessels wall (e). At section evaluation (f), the mass is necrotic in the centre
but with well visible wall of the venous confluence at the pancreatic (asterisk in f) infiltrating the splenic artery (S) and the peripancreatic fat
neck. At coronal multiplanar reconstruction (c) involvement of the gas- and arriving to the highlighted (black) margin (f). Occluded encased
tric wall is visible. (d–f) Surgical specimen (distal spleno- splenic vein (arrow in f)
pancreatectomy): lesion with irregular margins in the body tail of the
a b
c d
Fig. 24 Ductal adenocarcinoma downstaging with downsizing. (a, b) mesenteric-portal venous confluence recovers quite normal caliber but
CT: pancreatic head mass, involving the isthmus of the pancreas, is still surrounded by the mass. (e, f) Surgical specimen (total pancre-
hypodense in the pancreatic (a) and venous (b) phases infiltrating the atectomy and splenectomy) of different case: the pancreatic head lesion
mesenteric-portal venous confluence reduced in caliber and deformed. infiltrates mesenteric-portal venous confluence (e) resected in bloc
The gastroduodenal artery is encased. Presence of biliary stent. (c, d) At (probe). Specimen with margins highlighted (f): superior mesenteric
CT after treatment, the pancreatic mass is drastically reduced in volume vein bed (red); retroperitoneal margin (black); mesenteric-portal venous
slightly hypodense in the pancreatic (c) and venous (d) phases. The confluence resected in bloc (probe)
e f
Fig. 24 (continued)
a b
c d
Fig. 25 Ductal adenocarcinoma downstaging. (a, b) At CT after treat- peritoneal margin (black); biliary duct (probe). At section evaluation
ment, pancreatic mass in the medial portion of the pancreatic head with cranio-caudal transversal sections (d) small highly fibrotic well-
isodense in the pancreatic (a) and venous (b) phases infiltrating the defined lesion (asterisk in d and e) is visible in the medial portion of the
superior mesenteric vein that is tear drop deformed. Presence of biliary pancreatic head causing stenosis of the common bile duct upstream
stent. (c–e) Surgical specimen (pancreaticoduodenectomy): specimen dilated involving the superior mesenteric vein bed (red in e)
with margins highlighted (c): superior mesenteric vein bed (red); retro-
a b
c d
C
W
*
W
Fig. 26 Ductal adenocarcinoma downstaging. (a, b) At CT after treat- tomy) of different case: rounded solid well-defined highly fibrotic mass
ment, pancreatic mass of the isthmus markedly hypodense with rounded (asterisk in c) involving the splenic artery (arrow in d) and causing dila-
morphology in the arterial (a) and venous (b) phases after treatment tion of the main pancreatic duct (W in c and d). Common bile duct (C
with metallic intralesional fiducials infiltrating the celiac trunk and the in c)
splenic vein confluence. (c, d) Surgical specimen (total pancreatec-
a b
c d
e f
Fig. 27 Ductal adenocarcinoma downstaging. (a–d) At CT after treat- Presence of intralesional fiducials. (f–i) Surgical specimen (total pan-
ment, pancreatic mass of the isthmus markedly hypodense with rounded createctomy posterior surface): the pancreatic head lesion infiltrates
morphology in the pancreatic (a) and venous (b) phases after treatment venous mesenteric-portal confluence (f) resected en bloc (probe).
with metallic intralesional fiducials infiltrating the splenic-mesenteric Specimen with margins highlighted (f): superior mesenteric vein bed
vein confluence. On coronal multiplanar reconstruction (c) biliary tree (red); retroperitoneal margin (black). At section evaluation (g), volumi-
and common bile duct are dilated. Presence of intralesional fiducials. nous mass (asterisk in g) extended from the head to the isthmus of the
On coronal multiplanar reconstruction more dorsally (d) the infiltration pancreas. Section analysis (h) with Masson’s trichrome stain (i) with
of splenic-mesenteric-portal vein confluence is visible with extension vessel involved by fibrosis but not infiltrated
confirmed in the oblique reconstruction (e). Common bile duct dilated.
h i
Fig. 27 (continued)
a b
c d
e f
Fig. 28 Ductal adenocarcinoma downstaging with downsizing. (a, b) the body of the pancreas slightly hypointense on T1FS (c), with diffu-
At CT after treatment, small mass in the body of the pancreas hypodense sion restriction in DWI at high b value (d), hypovascular in the pancre-
in the pancreatic (c) and venous (d) phases with rounded morphology atic (e) and venous (f) phases with rounded morphology and
and well-defined margins. (a, b) At MRI after treatment, small mass in well-defined margins
a b
c d
Fig. 29 Ductal adenocarcinoma downstaging with downsizing. (a, b) (d) phases. (e, f) Surgical specimen (pancreaticoduodenectomy): pan-
CT: pancreatic head mass, involving the duodenum and the gastroduo- creatic head with normal dimension and appearance (e). Margins high-
denal artery slightly hypodense in the pancreatic (a) and venous (b) lighted: superior mesenteric vein bed (green) smooth and regular;
phases. (c, d) At CT after treatment, the pancreatic mass is drastically retroperitoneal margin (black) isolated from the specimen. Minimal
reduced in volume slightly hypodense in the pancreatic (c) and venous residual tumor in the “groove” paraduodenal space
a b
Fig. 30 Ductal adenocarcinoma downstaging with downsizing. (a, b) CT after treatment: tumor mass at the pancreatic isthmus involving the
superior mesenteric vein. (c) Surgical specimen (distal pancreatectomy posterior surface): pancreatic lesion infiltrating the mesenteric vein
a b
Fig. 31 Ductal adenocarcinoma downstaging. (a–c) At CT after treat- On sagittal multiplanar reconstruction (c) the patency and regular
ment, pancreatic mass of the uncinate process hypodense in the pancre- lumen of the superior mesenteric artery and hepatic artery are con-
atic (a) and venous (b) phases involving the superior mesenteric artery firmed. At pathology good response to the therapy was found with peri-
with periarterial cuffing along the hepatic artery originating from the vascular not neoplastic fibrosis
superior mesenteric artery. The vessels lumen and profile are normal.
a b
Fig. 32 Ductal adenocarcinoma downstaging with downsizing. (a, b) of the main Pancreatic duct with atrophy of the pancreatic gland paren-
At CT after treatment very small mass pancreatic body lesion slightly chyma. At pathology very good response to the therapy was found with
hypodense in the pancreatic (a) and venous (b) phases causing dilation tumor regression
a b
c d
Fig. 33 Ductal adenocarcinoma downstaging with downsizing. (a, b) deformed. (c, d) At CT after treatment, the pancreatic mass is drasti-
CT: pancreatic mass at the isthmus slightly hypodense in the pancreatic cally reduced in volume appearing isodense in the pancreatic (c) and
(a) and venous (b) phases involving the superior mesenteric vein venous (d) phases with normal superior mesenteric vein
a b
c d
e f
Cy
Fig. 34 Ductal adenocarcinoma downstaging with downsizing. (a–d) resected vessels (surgical staples) in bloc (circle in (e). At section evalu-
At CT after treatment, pancreatic mass at the isthmus appears hypodense ation, solid tumor (asterisk in f) and resected involved vessels (arrow in
in the pancreatic (a, b) and venous (c, d) phases involving the celiac f). Presence of voluminous retention cyst (Cy in f). The tumor (asterisk
trunk with arterial vessels narrowed and distorted and the splenic-mes- in f) shows ill-defined margins being difficult to delimitate in the body-
enteric venous confluence. A peritumoral retention cyst is present. (e–g) tail of the pancreas with neoplastic involvement (g)
Surgical specimen (distal pancreatectomy): pancreatic tumor with
Fig. 34 (continued)
g
a b
Fig. 35 Ductal adenocarcinoma downstaging with downsizing. (a) phy of inferior pancreatic duodenal is well visible, and, through the
Surgical specimen (Appleby procedure: distal pancreatectomy with pancreatic arcades, hypertrophic gastroduodenal artery with inverted
celiac trunk resection): pancreatic tumor with resected celiac trunk flow maintains the proper hepatic artery flow
(probes) en bloc. (b) At CT volume vascular reconstruction, hypertro-
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Neuroendocrine Neoplasms
Riccardo De Robertis, Mirko D’Onofrio,

Paolo Tinazzi Martini, Stefano Gobbo,
Maria Gaia Mastrosimini, Lavinia Stefanizzi,
Alessandro Beleù, Luca Geraci, Aldo Scarpa,
and Paola Capelli
Introduction complex (TSC), glucagon cell hyperplasia and neoplasia [4,

5], and familial insulinomatosis [6]. Germline mutations in
Pancreatic neuroendocrine neoplasms (PanNENs) are epi- DNA repair genes (MUTYH, CHEK2, and BRCA2) have
thelial tumors with neuroendocrine differentiation. The rela- been described in patients with apparently sporadic NETs
tive prevalence of NENs among the pancreatic tumors is [7]. Sporadic NETs are solitary lesions, whereas hereditary
2–5%. NENs show no difference in gender distribution and forms are usually multifocal [8]. Insulinomas and gastrino-
can be encountered at any age, with the highest incidence in mas are the most common functioning NETs; the syndromic
a range of 30–60 years of age. NENs include both well- symptoms associated allow to detect them early and thus at a
differentiated neuroendocrine tumors (NETs) and poorly dif- small size [2, 9]. Insulinomas are the most common func-
ferentiated neuroendocrine carcinomas (NECs) regardless of tioning NETs (4–20%), usually benign (85–99%) and soli-
clinical stage. NETs are divided into functioning (syndromic) tary; however, multiple insulinomas are shown in about 10%
or non-functioning (non-syndromic) based on the clinical of patients, most often in the setting of MEN-1 syndrome.
syndromes caused by abnormal secretion of hormones by the Hyperinsulinemic hypoglycemia leads to the typical clinical
tumor [1, 2]. Associated or not with endocrine syndromes, presentation with symptoms related to hypoglycemia, low
they are, as a rule, less aggressive than ductal adenocarci- plasma glucose levels at the time of the symptoms, and relief
noma; despite this, in some cases, metastases can be present of symptoms when the glucose is raised to normal, also
at the time of diagnosis [3]. Non-functioning NETs outnum- known as “Whipple’s triad.” Gastrinomas represent about
ber functioning NETs and account for >60% of all NENs. 4–8% of all pancreatic NETs, and they are generally large,
NETs are usually sporadic, but 10–20% are associated with multiple, and malignant. The uncontrolled gastric secretion
genetically determined hereditary syndromes such as multi- causes the Zollinger-Ellison syndrome (duodenal ulcers and/
ple endocrine neoplasia type 1 (MEN-1), von Hippel-Lindau or gastroesophageal reflux disease) [10]. Other functioning
(VHL), neurofibromatosis type 1 (NF1), tuberous sclerosis NETs (VIPoma, glucagonoma, somatostatinoma, ACTH-
producing neuroendocrine tumor, Serotonin-producing neu-
roendocrine tumor) are rare and indeed altogether account
The current chapter is based on the original chapter written by Paola
for about 20% of functioning pancreatic NETs [11–13].
Capelli, Mirko D’Onofrio, Stefano Crosara, Paolo Tinazzi Martini,
Riccardo De Robertis, Matteo Fassan, Stefano Gobbo, Aldo Scarpa, Non-functioning neuroendocrine tumors (NFNETs) account
and Roberto Pozzi Mucelli in the previous edition of the book. for up to 70–80% of all pancreatic NTEs, and their clinical
R. De Robertis (*) · M. D’Onofrio · L. Geraci

Verona, Italy
e-mail: riccardo.derobertislombardi@univr.it
P. Tinazzi Martini · A. Scarpa · P. Capelli
M. G. Mastrosimini · L. Stefanizzi
Department of Radiology, Pederzoli Hospital, Verona, Italy
Department of Pathology, G.B. Rossi University Hospital,
S. Gobbo Verona, Italy
A. Beleù
Department of Pathology, University of Ferrara, Ferrara, Italy Department of Radiology, Ca Foncello Hospital, Treviso, Italy
prevalence is increased over the past 40 years because of entiated NECs; both express neuroendocrine markers, but
improved imaging [14]. Pancreatic NFNETs are discovered they are not a closely related neoplasm. Pancreatic NETs are
incidentally or become clinically noticeable because of their graded as G1, G2, or G3 based on the proliferative activity,
large size (mass effect), involvement of adjacent organs, or as assessed by Ki-67 proliferation index and mitotic rate.
metastases [11]. Indeed, the tumor dimension ranges from 1 Pancreatic NECs are considered high grade by definition,
to 20 cm in diameter and shows a higher malignancy rate, up and they include two subtypes, small-cell NEC (SCNEC)
to 90%, although NFETs are less aggressive than ductal ade- and large-cell NEC (LCNEC), which are morphologically
nocarcinoma [1]. NECs are divided into small cell NEC and different from NETs (Table 1).
large cell NEC; they are rare and account 2–3% of all pan- The staging of pancreatic NENs follow the eighth edition
creatic NENs. The clinical presentation is like that of the (2017) of the Union for International Cancer Control
ductal adenocarcinoma (back pain, nonspecific abdominal (UICC) TNM classification and the American Joint
symptoms, jaundice). The vast majority (>90%) of patients Committee on Cancer (AJCC) cancer staging manual, which
present with metastasis at the time of diagnosis [14]. rely on macroscopic assessment of site, tumor size, and
Syndromes associated with pancreatic NETs such as MEN1 metastases [18, 19].
or VHL do not seem to be involved in NECs. NECs are char-
acterized by specific genetic alteration different from NETs
and ductal adenocarcinoma, such as mutations of TP53 and Macroscopy
inactivation of the RB1/p16 pathway determined by either
mutation in RB1 or loss of expression of p16 [15]. The pancreatic NETs’ macroscopic aspect is usually homo-
The diagnosis of pancreatic NENs is usually based on geneous, the color tends to be brown to reddish, and the con-
clinical and biochemical workup. Imaging is needed to local- sistency varies from soft to higher than the surrounding
ize the tumor and to provide local and distant staging. pancreatic parenchyma, but not hard. The amount of the
stroma and vascularization causes the color and consistency
of the tumor, which may vary from one tumor to another and
Pathology within different regions of the same tumor. In most cases, the
tumor is rich in small vessels and poor in fibrotic stroma. In
NENs can be located anywhere within the pancreas. rare cases, these masses present hemorrhagic foci or appear
Typically, the tumor’s diameter ranges from 1 to 5 cm, but considerably hemorrhagic, with a purple to bluish color and
larger masses are not uncommon. Usually, NENs are a soli- soft consistency. Necrosis is uncommon, but large masses
tary, solid, circumscribed mass with lobulated or pushing can have some yellowish areas with a soft infarct-like consis-
borders. They are sharply demarcated from the adjacent pan- tency [8, 16, 20]. The NECs’ gross appearance is a large
creatic parenchyma, and they are surrounded by a fibrotic mass, solid and compact, flashier, and more demarcated than
pseudocapsule, at least in part, but are rarely encapsulated. ductal adenocarcinoma. The color varies from whitish-gray
Overall, these characteristics indicate an expansive pattern of or tan-red to yellowish, and hemorrhage is common.
growth that differs from the infiltrative pattern of a ductal
adenocarcinoma. NENs occur in the head of the pancreas
and have a pushing periphery which usually compresses and Microscopy
deviates the main pancreatic and/or the biliary duct, rather
than infiltrates them. Large-size NENs extending outside the NETs are well-differentiated tumors, whose histological
pancreas usually displace, rather than invade, the adjacent appearance is sufficient to suggest an endocrine origin.
structures, likewise, retroperitoneal major blood vessels. Immunohistochemistry is needed primarily to confirm the
Large NENs can exhibit gross invasion into peripancreatic neuroendocrine nature of the neoplasm and thus to differen-
tissues, perivisceral adipose tissue (also as satellite nodule), tiate NETs from other tumor types. It is also useful for deter-
or adjacent organs (stomach, duodenum, colon, and spleen). mining the type of hormones produced by the neoplastic
Vascular invasion may be grossly evident, particularly into cells.
the splenic vein resulting in thrombosis and splenic infarcts. NETs typically have an organoid architecture likewise
The presence of multiple lesions should lead to the suspicion solid nests, macro-microtrabecular/gyriform pattern with
of pancreatic involvement within a MEN1 syndrome [8, 16]. cords, festoons, and ribbons; sometimes, a glandular-like or
In the 2019 WHO classification of digestive system tumor, acinar pattern can be observed. Though one pattern is gener-
NENs have been classified according to the International ally prevalent, more than one can be seen in different regions
Agency for Research on Cancer (IARC) and World Health of the same tumor, particularly in large-sized tumors. A
Organization (WHO) expert consensus proposal [17]. NENs richly vascular network characterizes most of NETs, and it
are divided into well-differentiated NETs and poorly differ- corresponds to the hypervascular radiological appearance.
Neuroendocrine Neoplasms 143
Table 1 Neuroendocrine neoplasms classification

Differentiation Grade Mitotic rate (mitoses/2 mm2) Ki-67 index (%)
NET, G1 Well differentiated Low <2 <3
NET, G2 Intermediate 2–20 3–20
NET G3 High >20 >20
SCNEC Poorly differentiated High >20 >20
LCNEC >20 >20
The stroma that surrounded the vessels varies from numer- the demonstration of their hypervascularity. Necrotic/cystic
ous capillary-sized vessels to broad areas of dense, hyalin- degeneration may arise, especially in larger lesions [21–23].
ized collagen; rarely, it shows prevalent wide sclero-hyaline As previously reported, solid pancreatic tumors should be
bands with scattered calcified foci. When sclerosis is wide- investigated with contrast-enhanced CT; despite this, not
spread, the cells may appear to float in this fibrous tissue. infrequently are studied with double examinations, both CT
Calcifications, either large deposits or psammoma bodies, and MRI, as a result of an incorrect management with the
are rare. Perineural and vascular invasions are most easily exception of cases with inconclusive previous results.
recognized in peritumoral nerves and vessels within or adja- PET-CT is a well-established imaging method to visualize
cent to the pseudocapsule [8, 16]. pancreatic neuroendocrine tumors [24], and it is helpful
NETs cells have similar cytologic features, regardless of especially in detecting occult intrapancreatic lesions and
the growth pattern. The cells are usually small to medium in small, unsuspected, distant metastases [25–27].
size. The cytoplasm is moderately abundant, eosinophilic to
amphophilic, and finely granular. The nuclei are usually cen-
trally located, round or oval, and uniform in size and show Ultrasound
finely stippled chromatin with inconspicuous or absent
nucleoli. The distinctive “endocrine” chromatin feature is The reported detection rate for small NETs of transabdomi-
referred to as “salt and pepper.” These morphologic features nal US is low (about 60%), while absolutely better results in
are generally uniform throughout the tumor. The nuclei may tumor detection are reported for EUS [11]. Insulinoma, the
be peripherally located, resulting in a plasmacytoid appear- most common NET, usually appears as a small homoge-
ance of the cells. The mitotic rate is generally undetectable. neously hypoechoic nodule, well-defined, encapsulated, and
Necrosis is rare and can be evident only histologically, hyper-enhancing at contrast-enhanced ultrasound (CEUS)
appearing as punctate foci in the center of the neoplastic [2, 11, 22, 28]. Sometimes, very small calcifications can be
nests. At times, foci of necrosis may be large and confluent present, especially in larger lesions [2, 11]. At the time of
(“infarct-like”), especially in large masses [8, 16]. clinical presentation, about 50% of insulinomas are smaller
NECs are poorly differentiated and high-grade malignant than 1.5 cm [12, 13]. When malignant, however, they are
epithelial neoplasm with neuroendocrine differentiation. generally greater than 3 cm, and about a third of these have
NECs have a less nested architectural pattern toward a metastases at the time of diagnosis [29]. The preoperative
growth in sheet. Large-cell PanNECs are a more common US detection of small insulinomas can sometimes be diffi-
subtype and are composed by round to polygonal large cells cult, but still possible: the US detection rate of insulinomas
with coarse chromatin and prominent nuclei. Small-cell has steadily increased in recent years, thanks to the increase
NECs are characterized by cells with scant cytoplasm, round in spatial and contrast resolution provided by technologic
or elongated nuclei, and finely granular chromatin. As in the developments in the field of US [12]. Gastrinoma usually
pulmonary counterpart, nuclear molding may be also pres- presents as a homogeneous hypoechoic mass, located within
ent. Both subtypes show necrotic areas, often with a comedo- the so-called gastrinoma’s triangle (junction of cystic duct
like appearance [15, 17]. and common bile duct, second and third duodenal portions,
pancreatic head and neck) [29]. Usually of moderate size, in
60% of cases, liver metastases are detected at the time of
Imaging diagnosis [13]. Other functioning neuroendocrine tumors are
rare and quite always larger than insulinomas and gastrino-
Neuroendocrine tumors usually present as a solid hypervas- mas at presentation.
cular mass, without main pancreatic duct infiltration. A well- Non-functioning neuroendocrine tumors present as
organized relationship exists between neoplastic cells and large, well-marginated hypoechoic masses, usually easy to
vessels traveling into tumoral stroma and explains their typi- detect, thanks to their large size, which also justifies their
cal hypervascular appearance [21]; for this reason, the char- tendency to contain necrosis and hemorrhage, giving them
acterization of these tumors at imaging mainly depends on a typical inhomogeneous appearance at imaging [2, 23, 30].
Very small intralesional calcifications, central necrotic/ functioning tumors, which can also be inhomogeneous
hemorrhagic/cystic degeneration, better identified at ultra- owing to the presence of central hypodense necrotic areas or
sound harmonic imaging, can be present within NETs [2, hyperdense hemorrhagic portions [33–36]. Neuroendocrine
30]. At Doppler study, small vessels characterized by arte- tumors rarely cause infiltration of the main pancreatic duct
rial flow are very often detected, owing to a well-organized that, however, can also be compressed and therefore deviated
relationship between tumoral cells and neovessels traveling and upstream dilated by larger lesions. During the pancreatic
into the neoplastic stroma; however, Doppler “silence” phase, neuroendocrine tumors are.
does not exclude the diagnosis of neuroendocrine tumor typically hypervascular, therefore appearing homoge-
because of the small size of the tumoral vascular network neously hyperdense, generally well depictable in respect to
or owing to the size and location of the lesion [22, 31]. the adjacent parenchyma. During the portal/venous phase,
Neuroendocrine tumors typically appear hypervascular at they tend to remain hyperdense or become isodense.
CEUS, showing a rapid and intense enhancement in the Regarding tumoral perfusion, it has been reported a positive
early contrast-enhanced phases [22, 31]. As previously correlation between the results of perfusion CT, reflecting
reported, a well-organized relationship between neoplastic angiogenesis, and the prognosis [37]. Rarely, neuroendocrine
cells and neovessels traveling into the tumor stroma exists tumors are characterized by cystic degeneration, showing a
and explains the hypervascular pattern [21]. For this reason, central avascular portion, surrounded by a thick enhancing
the characterization of NETs relies on the demonstration of wall [34, 35]. Non-functioning neuroendocrine tumors may
their hypervascularity [21–23]. Non-functioning neuroendo- also present as hypovascular masses at CT, lacking the typical
crine tumors also show a rapid intense enhancement in the arterial enhancement, making their correct characterization
early dynamic phase at CEUS, with the exclusion of eventual more difficult. Their expansive growth, the well-demarcated
necrotic intralesional areas, and microbubble entrapment dur- margins, and their relative larger dimensions may help in the
ing the late phase [22, 32]. Moreover, at CEUS, different differential diagnosis with ductal adenocarcinoma [33–36].
hypervascular enhancement patterns can be observed in rela- In studying neuroendocrine neoplasms, 68GA-DOTANOC
tion to the size of the tumor and of the intralesional vessels PET/CT shows high sensitivity for the detection of well-dif-
[32]. For example, in small-to-moderate-size tumors, only a ferentiated neuroendocrine tumors. 68GA-DOTANOC PET/
capillary blush enhancement can be present during the early CT, by showing the high somatostatin receptor density of a
phase, mirroring the most characteristic angiographic feature pancreatic lesion suspected to be of neuroendocrine origin,
of these tumors [21]. Considering that the characterization of can confirm with high probability the diagnosis.
both functioning and non-functioning NETs at imaging is
mainly linked to the detection of their hypervascularity, imag-
ing methods with a high sensitivity in the detection of tumor Magnetic Resonance Imaging
macrocirculation and microcirculation are required [23, 32].
Last but not the least, non-functioning neuroendocrine tumors Neuroendocrine tumors usually present as well-defined
can also be hypovascular [22]: this is directly linked to the rounded lesions, homogeneously hypointense on
amount of intralesional stroma, which is dense, hyalinized, T1-weighted images and slightly hyperintense on
and thus obviously hypovascularized. However, it is neces- T2-weighted images, and are better visualized with fat-
sary to stress that in some pancreatic neuroendocrine tumors suppression techniques [33, 34, 38]. Some studies have dem-
appearing hypodense at dynamic CT, a clear enhancement is onstrated that diffusion-weighted imaging (DWI) may be
visible at CEUS [22]. The high capability of CEUS in demon- useful in detecting and characterizing neuroendocrine tumors
strating pancreatic tumor vascularity is the result of the high of the pancreas [39]. After intravenous administration of
resolution of the state-of-the-art US imaging, combined with gadolinium chelates, all features of neuroendocrine tumors
the size and the blood-pool distribution of the microbubbles resemble those of contrast-enhanced CT, typically appearing
[9]. Summarizing, there are consistent evidences that CEUS hypervascularized during the arterial phase and isointense or
can be a useful tool to improve the characterization of the slightly hyperintense during the portal/venous one [33–36].
pancreatic neuroendocrine tumors [21]. As reported for CT, NFETs rarely cause infiltration of the
main pancreatic duct, which, however, can be compressed
and therefore upstream dilated by larger lesions. Infrequently,
Computed Tomography NETs are characterized by cystic degeneration, appearing
hyperintense on T2- and hypointense on T1-weighted
Neuroendocrine tumors typically present as homogeneously images, without enhancement, surrounded by a thick enhanc-
isodense or slightly hypodense, well-defined masses during ing wall. In non-functioning hypovascular neuroendocrine
precontrast phase [11, 33–36]. Very small intralesional calci- tumors, the typical arterial enhancement is lacking, making
fications may be detected, especially in the largest non- their correct characterization more difficult, but as reported
for CT, expansive growth, well-demarcated margins, and syndrome is characterized by watery diarrhea, hypokalemia,
relative larger dimensions may help in the differential diag- and achlorhydria (WDHA). Somatostatinoma secretes soma-
nosis with ductal adenocarcinoma [38]. tostatin, resulting in diarrhea, cholelithiasis, indigestion, and
hypochlorhydria [35]. In pancreatic “carcinoid” tumor, also
known as serotoninoma or serotonin-producing tumor, the
Clinical Presentation serotonin produced by the tumor can stimulate focal fibrosis,
which leads to Wirsung’s duct obstruction and acute pancre-
Incidental non-syndromic neuroendocrine tumors are being atitis episodes [44].
incidentally discovered with increasing frequency. Non-syndromic tumors produce symptoms related to
Neuroendocrine tumors generally present as symptomatic mass effect, such as nonspecific abdominal pain when large
lesions, producing symptoms related to inappropriate hor- (>5 cm); moreover, jaundice associated with the “double-
mone production. duct sign” can be the presentation of large enough neuroen-
docrine neoplasm. Non-functioning neuroendocrine tumors,
more frequently than the functioning ones, can be malignant
Asymptomatic with the infiltration of retroperitoneal structures causing pain
at the time of presentation [35].
Small non-syndromic neuroendocrine tumors are being inci-
dentally discovered with increasing frequency in asymptom-
atic patients, due to the advances in imaging techniques and Behavior
increasing number of imaging abdominal scans [40].
Typical
Syndromic neuroendocrine tumors early present clinical evi-
Symptomatic dence of hormone production, and they are of relatively
small size (<3 cm) and non-metastatic at diagnosis [35].
Syndromic NETs usually manifest when they have a rela- Despite this, there is some difference in behavior among dif-
tively small size, compared with non-syndromic neuroendo- ferent histotypes: insulinomas usually have a benign course
crine tumors, owing to the symptoms produced by the (85–99%); gastrinomas, instead, tend to be malignant. Small
associated hormone production [28]. Most syndromic neuro- non-syndromic neuroendocrine tumors are being
endocrine tumors actually produce multiple hormones, but incidentally.
the predominant hormone usually determines the clinical discovered with increasing frequency in asymptomatic
syndrome [41]. Insulinoma presents with the classic patients, due to the advances in imaging techniques [40].
“Whipple’s triad,” which includes fasting serum glucose lev- Non-syndromic tumors are however generally larger than
els less than 50 mg/dL, symptoms of hypoglycemia, and syndromic neuroendocrine tumors and more often at an
relief of symptoms after glucose administration [35]. Patients advanced stage at diagnosis.
may also report palpitations, sweating, and headache, related
to catecholamine release [42]. Gastrinoma presents with Atypical
Zollinger-Ellison syndrome. Most patients have epigastric Less commonly syndromic neuroendocrine tumors have
pain related to recurrent or intractable peptic ulcer disease or larger size at diagnosis.
with ulcers in unusual locations [35]. Patients may also have Malignant non-functioning neuroendocrine tumors prog-
diarrhea due to excessive delivery of acid to the small bowel ress with local diffuse infiltration and diffuse metastatic
[43]. Patients with glucagonoma present the typical “4D syn- spread, mimicking the typical behavior of ductal
drome” (dermatosis, diarrhea, depression, and deep vein adenocarcinoma.
thrombosis), characterized by a migratory rash called necro- More often, the neoplastic involvement of ducts and,
lytic migratory erythema, usually affecting the genitals; especially, vessels can be characterized by a colonization of
patients may also have stomatitis, anemia, and weight loss. their lumen.
Sometimes, diabetes mellitus results from the elevated levels Functioning neuroendocrine tumors other than insulino-
of glucagon. Vipoma secretes a variety of hormones, includ- mas and gastrinomas are rare; so, their behavior can be atypi-
ing vasoactive intestinal peptide (VIP) [41]. This hormone cal as a rule. Glucagonomas, for example, are reported to be
binds to receptors on the epithelial cells in the intestine, stim- over 5 cm in size in 70% of patients, and most of these
ulating production of cyclic adenosine monophosphate, patients have metastases at the time of diagnosis.
resulting in fluid and electrolyte secretion into the lumen, Vipomas, also, are usually over 3 cm in size, and almost
causing a characteristic watery diarrhea. This peptide also one-half of the patients have liver metastases at the time of
inhibits gastrin production, resulting in achlorhydria. The diagnosis [41].
Despite syndromic neuroendocrine tumors being mainly Involvement of the Main Pancreatic Duct
non-metastatic at the time of diagnosis, it has been reported
that one-half of the patients with somatostatinoma present NET does not usually involve the main pancreatic duct.
with metastatic disease, typically involving the liver or The duct usually is compressed and deviated or dilated
lymph nodes [35]. upstream to the tumor site. However, NET may rarely
grow within the duct itself or, more rarely, infiltrate the
duct and cause stricture. A few cases of NET with intra-
Variants ductal growth have been described as case reports. They
are non-functioning tumors that grow within the main pan-
Macroscopy creatic duct and may completely obstruct the lumen. The
intraductal growth may be connected to an extraductal
Fibrotic lesion. The origin of NET with this unique growth remains
When extensive fibrosis is present, the tumor can have a controversial. In most of these cases, symptoms of pancre-
whitish color, ill-defined margins, and a firm consistency, atitis have been reported, due to the obstruction of the
which can resemble a ductal adenocarcinoma. main pancreatic duct [47–52].
NET may present as lesion growing around the main pan-
Cystic creatic duct, and extension into its wall causes abrupt-type
They represent 5–10% of pancreatic neuroendocrine neo- stricture with upstream dilatation and a normal-caliber duct
plasms and are usually non-functioning tumors [45]. downstream the stricture. There are cases of minute NETs
The initial hypothesis maintains that cystic NETs are sec- characterized by a fibroblastic proliferation surrounding and
ondary to solid-tumor necrosis or hemorrhage and subse- infiltrating the duct, producing stenosis [49–52].
quent cystic degeneration. However, conflicting reports show
that cystic NETs are distinctive, more likely associated with
MEN-1, and present with well-differentiated and less aggres- Black and Yellow
sive behavior compared with solid pNETs. Notably, the
degree of the cystic component may predict biological Sometimes, NET may rarely present as a “pigmented black
behavior and prognosis [46]. The etiology, clinicopathologi- NET” due to the presence of cells with abundant, intracyto-
cal features, and prognosis of cystic pNETs are controver- plasmic, brown-black pigment consistent with lipofuscin.
sial, and it is uncertain whether they represent a distinct This tumor may mimic metastatic melanoma [53, 54].
subgroup of NETs or just the cystic degeneration of their
solid counterparts.
They are either a unilocular cyst or multilocular micro- Lipid Rich
cystic pattern, non-communicating cysts with the pancreatic
ducts. The cyst is usually single, a thin-walled locule located NETs may show diffusely yellow color because of the pres-
centrally to eccentrically within the tumor and surrounded ence of prominent lipid droplets in neoplastic cells. This
by a rim of neoplastic parenchyma. The cyst lining was tumor can mimic adrenal cortical neoplasia [55, 56].
smooth without excrescences and is filled with a clear, some-
times hemorrhagic fluid instead of necrotic debris. Small
buds of yellowish-brownish tissue, recalling typical endo- Microscopy
crine tissue, are visible at close inspection.
Microcystic tumors are characterized by a distinct archi- Unusual cytological features can be occasionally seen in oth-
tecture: multiple fluid-filled cavities, separated by delicate erwise conventional NETs. When these features become
septa formed by tumor cells. The preoperatively diagnoses of prevalent, the tumor is described as a morphological variant.
cystic NETs are more difficult than solid NETs, unless they Oncocytic, lipid-rich, clear cell, and rhabdoid variants, as
display suggestive radiologic features, such as enhancement well as tumors with marked nuclear pleomorphism and intra-
due to hypervascularity of the tumor rim or images of cyst cellular or extracellular inclusions, have been reported. The
into cyst. In many instances, these tumors can be mistaken clinical outcome of these tumors does not significantly differ
for other types of cystic neoplasia. To confirm a radiologic from that of conventional NETs. The main reason for recog-
diagnosis of cystic NETs, octreoscan scintigraphy is likely to nizing these tumors lies in avoiding misdiagnosis with other
be of particular value. pancreatic or more aggressive extrapancreatic neoplasms. In
fact, the unusual morphologic appearance may obscure the Pitfalls and Errors
endocrine nature of the neoplasm. Immunohistochemistry
can readily establish the endocrine nature of the tumor cells Hypervascular pseudolesions are the most important cause
and then the correct diagnosis, if the possibility of a NET is of false-positive results for pancreatic neuroendocrine neo-
considered. plasms at imaging; arterial kinking or small peripancreatic
aneurysms are important sources of false-positives. A multi-
planar imaging approach, better obtained with CT, may rep-
Fibrotic resent the solution in the majority of these cases. Second,
rarely encountered intrapancreatic accessory spleen may
Pancreatic neuroendocrine tumors with extensive fibrosis mimic a neuroendocrine neoplasm, but the site, quite exclu-
may mimic ductal adenocarcinoma at imaging, appearing sively located in the tail, and the radiologic similarity with
hypovascular. In this neuroendocrine tumor variant, the the spleen during pre- and postcontrast-enhanced phases at
involvement of the main pancreatic duct is absolutely more US, CT, and especially MRI can lead to the correct diagno-
frequent, and, if the lesion is located in the head of the gland, sis. Finally, extrapancreatic and peripancreatic hypervascu-
at the time of diagnosis, a double-duct sign could be present lar tumors such as gastrointestinal stromal tumor (GIST) or
due to the concomitant involvement of the common bile paragangliomas may mimic NETs.
duct. Imaging presentation of this neuroendocrine tumor
variant, especially if small in dimension, can be therefore
very similar to the expected picture of a ductal adenocarci- Imaging-Pathologic Correlation
noma, rendering the definitive cytological confirmation man-
datory in every case. As previously mentioned, the main characteristics of pancre-
atic neuroendocrine neoplasms are the size, expected to be
small if hyperfunctioning and larger if not, because of late
Cystic onset of symptoms, and a well-defined, encapsulated aspect
at imaging. Another important feature of neuroendocrine
Pancreatic neuroendocrine tumors may present cystic neoplasms is their rich vascular network, both composed of
changes. Neuroendocrine tumors with cystic changes are macrovessels and microvessels, generally resulting in a high
more frequently non-syndromic, both benign and malig- mean microvascular density (MVD), giving as a result the
nant, or of uncertain behavior. In contrast to the cystic typical hypervascularization at CEUS, CE-CT, and CE-MRI,
changes that develop in other solid tumors, cyst formation which is a fundamental aspect for diagnosis. Moreover, this
in these neoplasms does not appear to be due to necrosis. high number of vascular spaces gives the lesion a typical
Rather, the cysts are lined by a ragged cuff of well-pre- hyperintense aspect on T2-weighted images. Other typical
served neoplastic neuroendocrine cells, visible as a thick aspects of neuroendocrine tumors are a very high cellularity,
viable tumoral tissue rim and filled with a clear fluid thus providing a hypoechoic appearance at ultrasound exam-
instead of necrotic debris. The cyst is usually unilocular ination and, more importantly, a hyperintense appearance on
and central. Some cystic pancreatic neuroendocrine neo- high b value diffusion-weighted images (DWI), due to the
plasms achieve significant size, up to 25 cm [57]. In some evident restriction of water molecules’ diffusion.
cases, however, this feature is rather microcystic, with The differential diagnosis includes all other “solid cellu-
multiple small cysts, giving inhomogeneous appearance to lar” pancreatic neoplasms. The unusual morphological vari-
the lesion. At imaging, cystic neuroendocrine tumors usu- ants of NETs are prone to misdiagnosis with more aggressive
ally are 3 cm or larger in size and show calcifications and neoplasms of pancreatic or extrapancreatic origin. NETs
complex features, such as irregular thick wall, septa, and with rich fibrotic stroma, or which present as cystic lesions,
nodules. A well-encapsulated rounded lesion characterized should be distinguished from other pancreatic neoplastic
by a wide central cystic area can be demonstrated at US, lesions (i.e., ductal adenocarcinoma and cystic tumors).
CT, and MRI. After the administration of contrast agent, a These solid-cellular neoplasms include all solid masses with
typical rapid enhancement of the solid, usually thick, com- a hypercellular low-power microscopic appearance: acinar
ponents is easily documented around the central un- cell carcinomas, pancreatoblastomas, and solid-
enhancing portion [1, 45, 46, 58–60]. On the contrary, pseudopapillary tumors. These tumor types frequently pres-
cystic NETs with thin walls and septa cannot be defini- ent with symptoms related to the local effects of the enlarging
tively differentiated from mucinous cystadenoma at masses with a pushing growth and a relatively circumscribed
imaging. periphery. However, each of these neoplasms has diagnostic
relevant clinical, histological, and immunohistochemical cell carcinoma, which is a hypervascular neoplasm [64]. In
features. Other pancreatic neoplasms that may be confused these cases, clinical history of a prior primary malignancy
with NETs include solid serous adenoma and clear-cell can help the distinction [62]. Other hypervascular histotypes
“sugar” tumor. The latter is a member of a family of lesions, of pancreatic tumor may mimic NETs, such as acinar cell
characterized by the presence of a perivascular epithelioid neoplasm and well-vascularized ductal adenocarcinoma or
cell, which also includes lymphangioleiomyomatosis and anaplastic tumor. Neuroendocrine cystic tumors usually
angiomyolipoma (AML) [61]. present a unilocular central cyst, with solid complex compo-
When the patient has no neuroendocrine syndrome and a nents, such as irregular thick wall, septa, and nodules; this
pancreatic lesion is detected, differential diagnosis becomes aspect can also be found in some other cystic pancreatic
important. The main radiologic differential diagnosis for tumors (e.g., mucinous cystic neoplasms, IPMNs) and in
neuroendocrine tumors includes adenocarcinoma, microcys- other solid pancreatic neoplasms with cystic component or
tic adenoma, and pancreatic metastases [62]. cystic degeneration,
The hypervascularity of neuroendocrine tumors is funda- such as solid pseudopapillary tumor, adenocarcinoma,
mental to differentiate them from adenocarcinoma, which is and metastases [1, 45, 46, 58–60]. On the contrary, as previ-
the most common solid pancreatic neoplasm, and is mainly ously stated, in case of cystic presentation with thin wall and
hypovascular. This feature can be estimated at Doppler ultra- septa, no possible definitive differential diagnosis in respect
sound imaging, as previously reported, but dynamic exami- to mucinous cystadenoma can be made at imaging [65–69].
nations (CEUS and CT or MRI) are always required for
confirmation [31].
In the differential diagnosis, extremely microcystic serous Image Gallery
cystadenomas may have a pseudosolid aspect both at US and
CT [29, 32] and be hypervascular, owing to the homoge- See Figs. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,
neous hyperenhancement of the extremely compacted inter- 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,
nal septa [63]. 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,
Hypervascular pancreatic metastases may mimic features 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,
of neuroendocrine tumors. In fact, it has been reported that 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, and 76.
the most frequent metastasis to the pancreas is from renal
a b
c d
Fig. 1 Insulinoma. (a) Angiography: small hypervascular nodule (c, d) Histopathology: high cellularity at hematoxylin and eosin stain-
(arrow) in the body of the pancreas, characterized by the typical capil- ing, and faint positivity at immunohistochemical staining with anti-
lary blush. (b) Surgical specimen (enucleation): small nodule of 1 cm. insulin antibody
a b
Fig. 2 Insulinoma. (a) Surgical specimen (enucleation): small round surrounding the lesion (asterisk in c). Positivity at immunohistochemi-
capsulated nodule. (b–d) Histopathology: hematoxylin and eosin stain- cal staining (d) with anti-insulin antibody
ing demonstrates high cellularity and the presence of a thick capsule
a b
Fig. 3 Insulinoma. (a) Conventional ultrasound: a small hypoechoic sels within the nodule. (c) CEUS: nodule marked enhancement, result-
round nodule (calipers) with sharp margins within the pancreatic body. ing hyperechoic (arrow) in the arterial phase
(b) Color Doppler ultrasound: positive examination with arterial ves-
a c
b
d
Fig. 4 Insulinoma. (a) Conventional ultrasound: small hypoechoic sels within the nodule. (c) CEUS: nodule marked enhancement, result-
round nodule (calipers) with sharp margins in the pancreatic body. (b) ing hyperechoic (arrow) in the arterial phase. (d) Surgical specimen
Color Doppler ultrasound: slightly positive examination with few ves- (enucleation): small nodule of 1 cm
a b
c d
Fig. 5 Small neuroendocrine neoplasms. (a) High-frequency conven- ferent case: mainly negative examination, with no significant vessels
tional ultrasound: small hypoechoic round nodule in the pancreatic showed within a hypoechoic nodule (nT in c) with sharp margins. (d) At
head with upstream dilation of the main pancreatic duct. (b) Color contrast-enhanced endoscopic ultrasonography, the nodule shows high
Doppler ultrasound: negative examination with no vessels within the vascularity becoming hyperechoic (arrow in d) in the arterial phase
nodule. (c) High-frequency endoscopic color Doppler ultrasound of dif-
a b
Fig. 6 Insulinoma. (a) Conventional ultrasound: a small hypoechoic round nodule (calipers) with sharp margins in the pancreatic neck. (b, c)
CEUS and CT study: the nodule is markedly hypervascular at CEUS (arrow in b) and markedly hypervascular (arrow in c) at CT
a b
Fig. 7 Insulinoma. (a) CT study: a small hypervascular round nodule in the pancreatic head. (b) CT multiplanar reconstructions: the view on the
coronal plane with maximum intensity projection (MIP) algorithm makes the lesion (circle) better detectable
a b
c d
Fig. 8 Insulinoma: typical MRI features. (a, b) Typical MRI aspect: on T2-weighted axial images. (c, d) Typical MRI aspect of a different
small insulinoma of the pancreatic head, appearing hypointense (arrow case: small insulinoma of the pancreatic neck, hypointense (arrow in c)
in a) in respect to the surrounding pancreatic parenchyma on on T1-weighted fat-saturated axial images and with diffusion restric-
T1-weighted fat-saturated axial images and hyperintense (arrow in b) tion, resulting hyperintense (arrow in d) on DWI with high b values
a b
c d
e f
Fig. 9 Insulinoma: typical MRI features. (a–d) Typical MRI aspect: tion (b–d) on DWI (b = 50; b = 400; b = 800). (e, f) Dynamic MRI:
small insulinoma of the pancreatic head, hyperintense (arrow in a) on study demonstrates hypervascularization of the nodule (arrow in e and
T2-weighted fat-saturated axial images with typical diffusion restric- f)
a b
c d
e f
Fig. 10 Insulinoma: typical MRI features. (a, b) Typical MRI aspect: lesion presents diffusion restriction on progressive increasing b values
small insulinoma of the pancreatic tail, slightly hypointense on (b = 50; b = 400; b = 800). (f) Dynamic MRI: study shows hypervascu-
T1-weighted fat-saturated axial images (a) and hyperintense (arrow in larity of the nodule (arrow in f) in respect to the surrounding pancreatic
b) on T2-weighted fat-saturated axial images (b). (c–e) DWI study: the parenchyma
a b
c d
Fig. 11 Small neuroendocrine neoplasm: atypical MRI features and in c) in respect to the surrounding pancreatic parenchyma. The lesion
relationship with the main pancreatic duct. (a, b) Atypical MRI aspect: appears to be strictly close to the main pancreatic duct (arrow in d)
round-shaped insulinoma of the pancreatic head, slightly hypointense making enucleation impossible. (e) Surgical specimen (pancreaticodu-
(arrow in a) on T1-weighted fat-saturated axial images (a) and isoin- odenectomy): small round nodule (arrow) strictly close to the main pan-
tense on T2-weighted fat-saturated axial images (b). (c, d) Dynamic creatic duct (W). Common bile duct (C) is visible
MRI: study demonstrates typical hypervascularity of the nodule (arrow
a b
c d
e f
Fig. 12 Groove small neuroendocrine neoplasm. (a, b) Dynamic CT: a (arrow in f) on T1-weighted fat-saturated axial images. The lesion pres-
small round-shaped slightly hypervascular nodule is better visible on ents diffusion restriction (g–i) on DWI (b = 50; b = 400; b = 800). (j, k)
the multiplanar reconstruction coronal plane (arrow in b), exactly in the Dynamic MRI demonstrates the hypervascularity of the nodule (arrow
paraduodenal space. (c–k) Complete MRI study: the nodule is mark- in j) in respect to the surrounding pancreatic parenchyma. (l) Surgical
edly hyperintense (arrow in c) on T2-weighted fat-saturated axial specimen (pancreaticoduodenectomy): the presence of a small capsu-
images and slightly hyperintense on T2-weighted axial (d) and coronal lated nodule (arrow) is visible in close relationship with the duodenal
(e) images without fat saturation. Slight hypointensity of the lesion wall within the groove
g h
i j
k l
Fig. 12 (continued)
a b
c d
Fig. 13 Insulinoma with small calcifications. (a, b) Conventional spots, are visible. (c, d) Macrosection and hystopathology of the surgi-
ultrasound: examination shows a small hypoechoic lesion bulging from cal specimen: typical lesion with high cellularity and with small
the ventral surface of the pancreatic body. In the zoomed image (b), calcifications
small calcifications within the lesion, appearing as small hyperechoic
a b
c d
e f
Fig. 14 Isovascularized small neuroendocrine neoplasm. (a, b) hyperintense (arrow in d) on T2-weighted fat-saturated and not satu-
Conventional ultrasound: examination (a, axial and b, sagittal planes) rated sagittal images (e). The nodule typically presents diffusion coef-
shows a hypoechoic round-shaped nodule (calipers in b) with sharp ficient restriction (f, g) on DWI (b = 400; b = 800). At dynamic MRI
margins in the pancreatic neck. (c–h) MRI examination: the lesion (h), the lesion is hardly recognizable, being isovascularized in respect
appears hypointense on T1-weighted fat-saturated axial images (c) and to the surrounding pancreatic parenchyma
g h
Fig. 14 (continued)
a b
c d
Fig. 15 Hypovascularized insulinoma. (a–c) MRI study: round-shaped cally appears isointense in respect to the surrounding pancreatic
nodule of the pancreatic head, slightly hypointense (arrow in a) on parenchyma. (d) Surgical specimen (pancreaticoduodenectomy): small
T1-weighted axial images and almost isointense on T2-weighted fat- capsulated insulinoma (arrow) of the pancreatic head
saturated axial images (b). At dynamic MRI study (c), the lesion atypi-
a b
c d
Fig. 16 VIPoma. (a–c) CT dynamic study: large round-shaped capsu- onstrated. (d) Surgical specimen (pancreaticoduodenectomy): large
lated mass (M in b) with sharp margins in the pancreatic head. well circumscribed pancreatic mass with final diagnosis of VIPoma.
Surrounding anatomical structures are displaced rather than infiltrated The probe in the common bile duct (C) ends in the papilla major. The
by the lesion. A slightly inhomogeneous hypervascularization of the probe in the Wirsung duct (W) ends in the papilla minor
mass with a progressively increasing conspicuity of the capsule is dem-
a a
Fig. 18 Nonfunctioning neuroendocrine neoplasm. (a) Surgical speci-

men (intermediate pancreatectomy): typical macroscopic aspect of a
small nonfunctioning neuroendocrine neoplasm, presenting as a small
well-demarcated nodule with regular margins. (b) Surgical specimen
Fig. 17 ACTHoma. (a) Dynamic CT: the study shows a large round- (distal pancreatectomy): typical macroscopic aspect of a large nonfunc-
shaped lesion with irregular margins in the pancreatic body, resulting tioning neuroendocrine neoplasm, presenting as a large well-demarcated
hypovascular (asterisk) in respect to surrounding pancreatic paren- mass with regular margins
chyma in the postcontrastographic arterial phase. Also, metastatic liver
lesions are detectable. (b) Surgical specimen (distal pancreatectomy):
large firm pancreatic mass with final diagnosis of ACTH-producing
neuroendocrine tumor
a b
c d
Fig. 19 Nonfunctioning small neuroendocrine neoplasm. (a, b) round-shaped lesion in the pancreatic head. (d, e) Histopathology:
Conventional and color Doppler US examinations: small hypoechoic small round-shaped lesion (d) with diagnosis of neuroendocrine neo-
round-shaped nodule (asterisk in a) with sharp margins in the pancre- plasm (e), showing high cellularity at hematoxylin and eosin staining
atic head. Intense positivity at color Doppler (b) analysis is visible. (c) and high intralesional vascular network, demonstrated by CD34 immu-
Surgical specimen (pancreaticoduodenectomy): small well-defined nohistochemical staining (brown traces in e)
Fig. 20 Nonfunctioning neuroendocrine tumor. (a, b) Conventional only few vessels within the lesion. (c) Dynamic CT: the lesion typically
and color Doppler US examinations: round-shaped hypoechoic lesion appears inhomogeneously hyperenhancing (arrow) in respect to sur-
(arrow in a) with sharp margins in the pancreatic neck involving the rounding pancreatic parenchyma
spleno-portal venous confluence. Color Doppler analysis (b) shows
a b
c d
e f
Fig. 21 Nonfunctioning neuroendocrine tumor. (a, b) US and CEUS neously hyperenhancing in respect to the surrounding pancreatic paren-
examinations: large hypoechoic mass (asterisk in a) with small calcifi- chyma in the dynamic phases (d–e). (f) Dynamic MRI: inhomogeneous
cations in the pancreatic head, causing upstream dilation of the Wirsung hypervascularity of the lesion. (g) Surgical specimen (distal pancreatec-
duct. This lesion is inhomogeneously hypervascularized at CEUS (b). tomy) of different case: large well clear-cut margins firm mass with
(c–e) CT examination: the pancreatic mass appears hypodense with final diagnosis of neuroendocrine tumor
small calcifications in the precontrastographic phase (c) and inhomoge-
Fig. 21 (continued)
a b
c d
Fig. 22 Nonfunctioning neuroendocrine tumor. (a, b) Dynamic CT: hancing (arrow in a) in the postcontrastographic phases. (c, d) Perfusion
oval-shaped lesion with slightly irregular margins in the pancreatic CT: color-map analysis demonstrates high blood volume and peak
head, endorsed on the ventral surface of inferior vena cava, hyperen- enhancement values of the lesion
a b
c d
e f
Fig. 23 Nonfunctioning neuroendocrine tumor. (a) Conventional US lesion also shows diffusion restriction (b = 50; b = 400; b = 800) and
examination: hypoechoic round-shaped capsulated lesion (calipers) hypointensity (arrow in h) on ADC map. (i, j) Dynamic MRI: the lesion
with sharp margins bulging from the surface of the pancreatic body. is hypervascular (arrow in i) in respect to the surrounding pancreatic
(b–d) MRI examination: the lesion presents hypointensity (arrow in b) parenchyma, with increasing conspicuity of the capsule on the venous
in respect to the surrounding pancreatic parenchyma on T1-weighted phase (j). (k, l) Surgical specimen (distal pancreatectomy): the lesion is
fat-saturated images and hyperintensity on T2-weighted images, both clearly visible (arrow in k), bulging from the anterior surface of the
without (c) and with fat-saturation (arrow in d). (e–h) DWI study: the pancreatic body and appearing well demarcated on the cut section (l)
g h
i j
k l
Fig. 23 (continued)
a a
b b
Fig. 24 Nonfunctioning neuroendocrine neoplasm at DWI. (a, b) MRI

examination: pancreatic neck isointense lesion both on T1-weighted
fat-saturated and T2-weighted images. The lesion is clearly visible,
showing typical diffusion restriction, appearing hyperintense (arrow in
c) on DWI
Fig. 25 Nonfunctioning neuroendocrine tumor with atypical shape.
(a) Conventional US examination: hypoechoic elongated lesion (cali-
pers) with sharp margins on the ventral surface of the pancreatic neck.
(b, c) Dynamic CT: the lesion typically appears hypervascular (arrow in
b)
Fig. 26 Multiple small neuroendocrine neoplasms. (a) Conventional ing pancreatic parenchyma. No other lesions are clearly visible. (c)
US examination: small hypoechoic nodule with sharp margins (arrow) Surgical specimen (distal pancreatectomy): the lesion (arrow) is con-
on the ventral surface of the pancreatic body is visible. (b) Dynamic firmed at the pancreatic body, but other smaller lesions (circles), not
CT: the small lesion is hypervascular (arrow) in respect to the surround- recognizable at preoperative imaging, can be seen
a b
c d
e f
Fig. 27 Giant nonfunctioning neuroendocrine tumor. (a, b) hypervascular and with intravascular growth colonizing the splenic vein
Conventional US examination: huge hypoechoic mass from the neck to (asterisk in d). (e, f) Surgical specimen (distal pancreatectomy): huge
the tail of the pancreas with intense positivity at color Doppler analysis mass (e) with voluminous neoplastic thrombus (asterisk in f) into the
(b). (c, d) Dynamic CT: the huge lesion appears inhomogeneously splenic vein
a b
c d
e f
Fig. 28 Nonfunctioning neuroendocrine tumor with irregular margins. images (b). (c–e) Dynamic MRI: this irregular mass appears inhomoge-
(a, b) MRI study: large irregular-shaped lesion (asterisk in a) of the neously hypervascular (c) with a progressive enhancement homogeniza-
body–tail of the pancreas, with protruding finger-like portion, growing tion in the venous (d) and late (e) phases. (f) Surgical specimen (distal
in the mesenteric fat tissue and in the retroperitoneal space, hypointense pancreatectomy) of different case, showing large nonfunctioning irregu-
in respect to the surrounding pancreatic parenchyma on T1-weighted lar-shaped tumor of the pancreas with protruding finger-like neoplastic
fat-saturated axial images (a) and isointense on T2-weighted axial tissue, resulting from the nodal involvement (asterisks) of the tumor
Fig. 29 Nonfunctioning well-differentiated neuroendocrine tumor. (a, At CEUS (b), the lesion appears hypervascularized in respect to the
b) US examination: hypoechoic round-shaped capsulated lesion (arrow surrounding pancreatic parenchyma. (c) Dynamic CT: the lesion is
in a) of the pancreatic body, with upstream dilation of the Wirsung duct. homogeneously hypervascularized (arrow)
a b
c d
Fig. 30 Nonfunctioning poorly differentiated neuroendocrine tumor. in the arterial (b) and venous (c) phases. (d) Surgical specimen (distal
(a–c) CT study: large inhomogeneous mass of the body–tail of the pan- pancreatectomy): markedly inhomogeneous tumor with necrotic areas
creas characterized by markedly inhomogeneous contrast enhancement
a b
c d
e f
Fig. 31 Neuroendocrine tumor. (a–c) Dynamic CT: large mass (arrow study: multiple hyperintense areas on T2-weighted images are visible in
in a) of the body–tail of the pancreas, showing markedly inhomoge- the mass, resulting inhomogeneous hypervascular in the postcontrasto-
neous enhancement in the arterial (a), venous (b), and late (c) phases, graphic arterial (e) and venous (f) phases
due to the presence of multiple intratumoral necrotic areas. (d–f) MRI
a b
d
c
Fig. 32 Locally invasive neuroendocrine tumor. (a–d) Dynamic CT: superior mesenteric artery (A in b). The main pancreatic duct is
precontrast-enhanced phase shows a large hypodense mass with irregu- upstream dilated (W in c). The mass infiltrates the superior mesenteric
lar margins and calcification in the pancreatic head (asterisk in a), vein (V in d)
resulting hypervascular in the dynamic phase with infiltration of the
a b
Fig. 33 Locally invasive neuroendocrine tumor and metastatic neuro- isk) with regular margins of the body of the pancreas, appearing hyper-
endocrine tumor. (a) Dynamic CT: large mass (asterisk) with irregular vascular and infiltrating the splenic artery. The pancreatic tail
margins, originating from the pancreatic head and body, appearing parenchyma is atrophic with dilation of the Wirsung duct. Hypervascular
inhomogeneously hypervascular and infiltrating the celiac trunk and its liver metastases (arrow) are present
branches. (b) Dynamic CT: relatively small round-shaped lesion (aster-
a b
c d
Fig. 34 Small metastatic neuroendocrine tumor. (a) Dynamic CT: tense (arrow in b) on T1-weighted fat-saturated axial images and inho-
small round-shaped lesion (arrow) of the uncinate process of the pan- mogeneously hyperintense (arrow in c), with a hypointense peripheral
creatic, appearing inhomogeneously but well vascularized. A large rim, on T2-weighted axial images. At dynamic MRI study, the lesion is
hypovascular metastatic lesion (asterisk) is recognizable in the right almost isovascular in respect to the surrounding pancreatic parenchyma
liver lobe. (b–e) MRI study: the pancreatic tumor is slightly hypoin- on postcontrastographic arterial (d) and venous (e) phases
a b
Fig. 35 High-cellularity vs. low-cellularity nonfunctioning neuroendocrine tumors. (a) Hematoxylin and eosin staining: typically highly cellu-
lated neuroendocrine tumor. (b) Hematoxylin and eosin staining: atypical neuroendocrine neoplasm with low cellularity and rich fibrous stroma
a b
f
e
Fig. 36 Nonfunctioning fibrous neuroendocrine tumor. (a) MRI study, lesion is inhomogeneously hypovascular in respect to the
Conventional US examination: hypoechoic lesion (calipers) with regu- surrounding pancreatic parenchyma in the postcontrastographic pan-
lar margins in the pancreatic tail. (b–e) MRI examination: the lesion creatic phase (arrow in d), but with progressive intense contrast medium
appears hypointense both on T1-weighted fat-saturated axial images accumulation in the late phase (arrow in e). (f) Surgical specimen (dis-
(arrow in b) and T2-weighted axial images (arrow in c). At dynamic tal pancreatectomy) of the fibrous neuroendocrine tumor
a b
e f
Fig. 37 Nonfunctioning fibrous neuroendocrine tumor with double- arterial (arrow in g) phase, with progressive slight accumulation of con-
duct sign. (a–i) MRI examination: MRCP (a) shows dilation of both the trast medium in the venous phase (h) and late (i) phase. (j) Surgical
common bile duct and Wirsung duct caused by a pancreatic head lesion specimen (pancreaticoduodenectomy) of different case: fibrous neuro-
isointense on T1-weighted fat-saturated axial images (b) and almost endocrine tumor (asterisk) of the pancreatic head with dilated Wirsung
isointense on T2-weighted axial images (c), showing diffusion coeffi- duct (W) and common bile duct (C); the aspect of the lesion is similar
cient restriction (d–f) on DWI (b = 50; b = 400; b = 800). At dynamic to a ductal adenocarcinoma
MRI study, the lesion appears hypovascular in the postcontrastographic
g h
Fig. 37 (continued)
a b
c d
Fig. 38 Nonfunctioning fibrous neuroendocrine tumor with double- a pancreatic head lesion, slightly isointense on T1-weighted fat-
duct sign, simulating pancreatic ductal adenocarcinoma. (a–d) MRI saturated axial images (arrow in b) and on T2-weighted (arrow in c)
examination: MRCP (a) shows double-duct sign with dilation of both axial images. At dynamic MRI study, the lesion appears hypovascular
the Wirsung duct (W in a) and the common bile duct (C in a), caused by (arrow in d)
a b
Fig. 39 Pancreatic “carcinoid”. (a, b) MRI examination: MRCP (a) study shows the Wirsung duct dilation caused by a small rounded pancreatic
lesion, hypointense (arrow in b) on T2-weighted coronal images
a b
c d
f
e
Fig. 40 Wirsungocele caused by small nonfunctioning fibrous neuro- in the pancreatic neck. At dynamic MRI study (e–g), the lesion in the
endocrine tumor. (a–g) MRI examination: pronounced Wirsungocele neck of the pancreas appears isovascular in respect to the surrounding
(W in a) caused by small ill-defined lesion in the pancreatic neck, pancreatic parenchyma in the postcontrastographic arterial (e) and
slightly hypointense in respect to the surrounding pancreatic paren- venous (f) phases, but slightly hypointense (arrow in g) in the late phase
chyma on T2-weighted fat-saturated axial images (arrow in a), (g), surrounded by a thin hyperintense rim. (h, i) Intraoperative US: the
T2-weighted coronal images (arrow in b), and T1-weighted fat- intraoperative study clearly shows the small hypoechoic nodule (cali-
saturated axial images (arrow in c). At MRCP (d), the huge dilation of pers in h and i) in the pancreatic neck with upstream huge dilation of
the Wirsung duct ends in a very short interruption (arrow in d) located the main pancreatic duct (W in i)
g h
Fig. 40 (continued)
Fig. 41 Wirsungocele caused

by small nonfunctioning
a
fibrous neuroendocrine tumor.
(a–c) Surgical specimen
(distal pancreatectomy):
Wirsungocele of the body–tail
of the pancreas: the body and
tail of the gland is entirely
occupied by a huge dilation of
the main pancreatic duct. The
cut shows the smooth internal
wall of the Wirsung duct that
is markedly dilated along the
whole gland, ending in a very
small (about 1 cm) lesion
(arrow in c), causing duct (W
in c) cut-off
b
c
a b
Fig. 42 Pancreatic neuroendocrine tumor. (a) Dynamic CT: markedly axial images (b) and dynamic images (c). (d, e) Surgical specimen
dilated Wirsung duct (W) in the pancreatic body and tail with abrupt (pancreaticoduodenectomy): the presence of a small round-shaped nod-
cut-off, but without certain lesion detection. (b, c) MRI study: markedly ule in the pancreatic head is visible (arrow in d and e), causing dilation
dilated Wirsung duct (W in b and c) in the pancreatic body and tail with of the main pancreatic duct (W in e)
abrupt cut-off, but without a certain lesion detection on T2-weighted
a b
Fig. 43 Small cystic neuroendocrine tumor. (a, b) MRI examination: acterization is possible at imaging. (c) Surgical specimen (distal pan-
small cystic lesion with thin walls of the pancreatic body, hyperintense createctomy): small cystic lesion with thin walls and thin septa. The
(arrow in a) on T2-weighted (a) axial images. At dynamic MRI (b) Wirsung duct (W) is normal
study, the lesion presents thin walls and thin septa. No definitive char-
a b
Fig. 44 Small cystic neuroendocrine neoplasm. (a–f) MRI examina- dynamic MRI (e and f), the cyst walls appear slightly hypervascular
tion: small round-shaped cystic lesion with thick walls in the pancreatic (arrow in e), and a thin septum is visible (arrow in f). (g) CEUS: the
head (arrow in a), causing dilation of the main pancreatic duct (W in c). contrast-enhanced ultrasound study confirms the presence of thin sep-
The pancreatic cystic lesion appears hyperintense with declivitous cor- tum (arrow) in the context of the cystic pancreatic lesion. (h) IOUS:
pusculated content on T2-weighted axial (a) and hypointense on intraoperative ultrasound confirms the presence of cystic lesion with
T1-weighted axial (b) images. MRCP (d) study better shows together thin septum in the pancreatic head, causing dilation of the main pancre-
the cystic lesion in the pancreatic head and the upstream dilation of the atic duct (W)
Wirsung duct. The common bile duct presents regular diameter. At
g h
Fig. 44 (continued)
a b
Fig. 45 Cystic neuroendocrine neoplasm. (a) Surgical specimen men: small cystic pancreatic neuroendocrine neoplasm with visible
(intermediate pancreatectomy): small cystic pancreatic neuroendocrine wall and thin inner septa. (c) Macrosection: small cystic pancreatic neu-
neoplasm with visible wall and thin peripheral septa. (b) Surgical speci- roendocrine neoplasm with visible wall and thin inner septa
a b
c
d
Fig. 46 Cystic pancreatic neuroendocrine tumor. (a–c) MRI study: signal center (arrow in c). (d) Pathologic specimen: a 2.5-cm thick-
T2-weighted image reveals hyperintense mass in the pancreatic body walled lesion with a cystic center, classified as a well-differentiated
(arrow in a). In phase noncontrast, T1-weighted image reveals the neuroendocrine tumor. The main pancreatic duct is draped over the
lesion (asterisk in b) appearing hypointense. Gadolinium-enhanced mass. Adjacent pancreas is grossly normal, yet there is histologic evi-
GRE image in the portal phase reveals a thick enhancing wall with low dence of chronic pancreatitis
a b
Fig. 47 Cystic pancreatic neuroendocrine tumor. (a, b) Ultrasound lesion (arrow in b). (c) Dynamic CT: in the pancreatic phase, the cystic
examination: conventional image (a) shows large cystic mass (asterisk pancreatic lesion shows hypervascular thick wall (arrow in c) and sep-
in a) with thick wall of the pancreatic head. Contrast-enhanced ultra- tum. (d) Surgical specimen (distal pancreatectomy): cystic pancreatic
sound (b) demonstrates the hypervascularization of the thick wall neuroendocrine tumor with thick wall
a b
e f
Fig. 48 Microcystic neuroendocrine tumor. (a–f) MRI examination: tense (arrow in d) on T1-weighted fat-saturated axial images. At
large cystic mass with microcystic appearance on T2-weighted fat- dynamic MRI study (e–f), the cystic mass presents walls and septa
saturated (arrow in a) and not fat-saturated coronal (arrow in b) images hypervascularity (arrow in e) and hyperintense peripheral capsule
in the pancreatic tail. MRCP study (c) clearly shows the lesion again (arrow in f). (g) CEUS study: contrast-enhanced ultrasound confirms
with microcystic appearance in the pancreatic tail. The lesion is hypoin- the hypervascular walls and septa of the cystic pancreatic mass
Fig. 48 (continued)
Fig. 49 Nonfunctioning huge cystic neuroendocrine tumor. irregular thick wall; at enhancement quantification, perfusional map of
Conventional US study shows an inhomogeneously hypoechoic pancre- the highest vascularized tumoral portions can be obtained
atic head huge mass. CEUS demonstrates the high vascularity of the
a b
Fig. 50 Nonfunctioning cystic neuroendocrine tumor. (a) Conventional body–tail mass (arrow), with extremely thick wall, slightly hypervascu-
US: hypoechoic round-shaped pancreatic body–tail mass (calipers) lar in respect to the adjacent pancreatic parenchyma in the postcon-
with a large central cystic area. (b) Dynamic CT: cystic pancreatic trastographic arterial phase
a b
Fig. 51 Nonfunctioning cystic neuroendocrine tumor. (a–e) CT study: pancreatic parenchyma and slightly hyperdense in the late phase (arrow
on baseline image (a), large isodense mass (arrow in a) with eccentric in d). Multiplanar reconstruction (e) on the coronal plane with maxi-
cystic area and small calcification is bulging from the dorsal surface of mum intensity projection (MIP) algorithm better demonstrates the
the pancreatic body. At dynamic phase (b–d), the lesion is inhomoge- lesion (arrow in e). (f) Surgical specimen (distal pancreatectomy): neu-
neously hypovascular (arrow in b and c) in respect to the surrounding roendocrine tumor (T) with evident eccentric cystic area (C)
Fig. 51 (continued)
a b
d
c
Fig. 52 Microcystic neuroendocrine tumor. (a–c) MRI examination: cuar in respect to the surrounding pancreatic parenchyma, with avascu-
large lesion in the pancreatic neck and body, appearing slightly hyper- lar microcystic small areas visible in both the postcontrastographic
intense (arrow in a) on T2-weighted axial images, with multiple small arterial (b) and venous (c) phases. (d) Surgical specimen, particular:
hyperintense microcystic areas. At dynamic MRI, the lesion is hypovas- microcystic appearance of nonfunctioning neuroendocrine tumor
a b
c
d
Fig. 53 Multiple pancreatic solid and cystic neuroendocrine neo- tous corpusculated content on T2-weighted axial images (asterisk in c).
plasms. (a, b) CT study: baseline image (a) shows enlarged pancreas On dynamic MRI study (d, e) in the largest cystic lesion in the tail, very
(arrows in a) with multiple hypodense cystic lesions, appearing avascu- thin septa are visible. (f) Surgical specimen (total pancreatectomy) mul-
lar at dynamic study (arrow in b), and multiple calcifications together tiple solid (not detected on preoperative imaging) and cystic neuroen-
with dilated Wirsung duct (W in b). (c–e) MRI study: multiple cystic docrine neoplasms are visible distributed in the entire pancreatic gland;
lesions are visible on T2-weighted fat-saturated axial images (c) and the only solid lesion (arrow) detected at MRI is confirmed in the pan-
one solid slightly hyperintense nodule (arrow in c) in the pancreatic tail. creatic tail
The largest cystic lesion in the tail appears hyperintense with declivi-
Fig. 54 Cystic epiphenomenon in small solid neuroendocrine tumor neoplasm (arrow) causing upstream, perilesional, marked dilation of
with intraductal growth. Surgical specimen (pancreaticoduodenec- the pancreatic ducts (circle)
tomy): small intraductal (main pancreatic duct) solid neuroendocrine
a b
c d
f
e
h
g
Fig. 55 Neuroendocrine tumor with coarse calcification. (a) Conventional T2-weighted fat-saturated axial images. The mass also presents typical
US: hypoechoic mass with sharp margins in the pancreatic body with a diffusion coefficient restriction (e–g) on DWI (b = 50; b = 400; b = 800)
coarse contextual calcification (arrow) with posterior acoustic shadowing. and related hypointensity (arrow in h) on ADC map. Dynamic MRI study
(b) CEUS demonstrates the high vascularity of the lesion (arrows). (c–i) (i) shows the hypervascularity of the lesion (arrow in i) in respect to the
MRI examination: the mass appears slightly hypointense (arrow in c) on surrounding pancreatic parenchyma. (j) Surgical specimen (distal pancre-
T1-weighted fat-saturated axial images and hyperintense (arrow in d) on atectomy): neuroendocrine tumor with coarse central calcification (arrow)
i j
Fig. 55 (continued)
a b
Fig. 56 Small neuroendocrine tumor in relationship with the main erative ultrasound evaluation of a small hypoechoic nodule (asterisk)
pancreatic duct. (a) MRI example: small nodule with sharp margins with sharp margins in the dorsal side of the pancreatic body, located
hyperintense (arrow) on T2-weighted axial image on the dorsal side of closely and posterior to the main pancreatic duct (W), thus not suitable
the pancreatic body, located closely and posterior to the main pancreatic for enucleation
duct (W), thus not suitable for enucleation. (b) IOUS example: intraop-
a b
e
f
Fig. 57 Capsulated neuroendocrine tumor. (a) Conventional US study: contrastographic arterial (g) and venous (h) phases, with progressive hyper-
hypoechoic round-shaped lesion (calipers) with sharp margins located in the intensity of the capsule better visible in the late (i) phase. The lesional
pancreatic head. (b–j) MRI study: the pancreatic head lesion is slightly capsule is also well demonstrated in dynamic MRI postcontrastographic
hypointense (arrow in b) on T1-weighted fat-saturated axial images and coronal late phase (arrowheads in j). Moreover, in the late hepatospecific
presents diffusion restriction (c–e) on DWI (b = 50; b = 400; b = 800). phase with contrast medium (Gd-BOPTA), the common bile duct is clearly
MRCP (f) demonstrates that, despite the close relationship, the common bile visible, not dilated (C in k), since it is displaced but not compressed by the
duct (C) and the main pancreatic duct (W) are not dilated. Dynamic MRI lesion. (l) Surgical specimen (pancreaticoduodenectomy) of different case:
study (g–i) shows the inhomogeneous hypovascularity (arrow in g and h) of capsulated neuroendocrine tumor (asterisk) of the pancreatic head, displac-
the lesion in respect to the surrounding pancreatic parenchyma in the post- ing the main pancreatic duct (W) and the common bile duct (C)
g h
Fig. 57 (continued)
a b
e
f
Fig. 58 Neuroendocrine tumor obstructing the main pancreatic duct. high b value. MRCP study (e) perfectly demonstrates an uniformly
(a) Conventional US: hypoechoic mass (arrow) bulging from the ven- dilated main pancreatic duct (W in e), upstream to the mass, causing the
tral surface of the pancreatic body. (b–f) MRI examination: the mass duct interruption (asterisk in e). Dynamic MRI study (f) shows the
appears slightly hypointense (arrow in b) on T1-weighted fat-saturated slightly inhomogeneous hypervascularity of the lesion (arrow in f) in
axial images and slightly hyperintense (arrow in c) on T2-weighted respect to the surrounding pancreatic parenchyma
axial images and typically presents diffusion restriction on DWI (d) for
a b
c
d
f
e
Fig. 59 Neuroendocrine tumor obstructing the main pancreatic duct duct with the visualization of the typical double-duct sign. MRCP study
and the common bile duct. (a–f) MRI study: large mass located in the (d) demonstrates the double-duct sign with dilation of both the main
pancreatic head, appearing almost isointense (asterisk in a) on pancreatic duct (W in d) and the common bile duct (C in d). Dynamic
T1-weighted fat-saturated axial images and slightly hyperintense MRI study (e–f) shows the hypervascularity of the lesion (asterisk in e)
(asterisk in b and c) on T2-weighted coronal images, and the in respect to the surrounding pancreatic parenchyma. The late phase on
T2-weighted fat-saturated axial images responsible for marked the coronal plane shows the washout of the lesion (asterisk in f) sur-
upstream dilation of both the main pancreatic duct and the common bile rounded by hyperintense capsule
a b
e f
Fig. 60 Hypovascular neuroendocrine tumor with double-duct sign. saturated axial images and slightly hyperintense (arrow in c) on
(a–f) MRI study: MRCP (a) demonstrates uniformly dilated main pan- T2-weighted axial images is visible. The small nodule presents diffu-
creatic duct (W in a) and common bile duct (C in a), with an abrupt sion restriction (arrow in d) on DWI for high b value. At dynamic MRI
cut-off in the pancreatic head region. Small round-shaped lesion with examination, the lesion is hypovascular (arrow in e and f) in respect to
sharp margins located in the pancreatic head, isointense (arrow in b) in the surrounding pancreatic parenchyma in both arterial (e) and venous
respect to the surrounding pancreatic parenchyma on T1-weighted fat- (f) phases
a b
Fig. 61 Giant neuroendocrine tumor. (a) Surgical specimen (distal pancreatectomy): huge mass of pancreatic body and tail. (b) Surgical specimen
after cut: huge mass of pancreatic body with multiple nodal (N) involvement. Splenic artery (arrow)
a b
d
c
e f
Fig. 62 Neuroendocrine tumor growing in the hepatoduodenal liga- MRI examination (g–k), the lesion is slightly hypervascular (asterisk in
ment with double-duct sign. (a–k) MRI examination: large mass with g) in respect to the surrounding pancreatic parenchyma, with a necrotic
sharp margins located in the pancreatic head appearing slightly hypoin- avascular area in the caudal section (arrow in h). In the venous (i) phase
tense (asterisk in a) on T1-weighted fat-saturated axial images and and late (j and k) phase on coronal (j) and axial (k) planes, the mass
hyperintense (asterisk in b and c) on T2-weighted axial images, both presents progressive washout with hyperintense capsule (arrows in k).
with and without fat suppression. On T2-weighted coronal images, the (l) At (68)Ga-PET/CT study, the mass presents high radiopharmaceuti-
mass (asterisk in d) is growing cranially along the hepatoduodenal liga- cal uptake. (m) Surgical specimen (pancreaticoduodenectomy): from
ment. The mass presents diffusion restriction (asterisk in e) on DWI for the pancreatic head (P) originates the huge neuroendocrine tumor with
high b value. MRCP study (f) demonstrates uniformly dilated main necrotic area (asterisk) and longitudinal growth involving the hepatic
pancreatic duct (W in f) and common bile duct (C in f). At dynamic hilum
g h
Fig. 62 (continued)
Fig. 62 (continued)
a b
Fig. 63 Neuroendocrine tumor growing in the main pancreatic duct. from the neoplasm and growing within the duct. (b, c) Surgical speci-
(a) Conventional US: round-shaped hypoechoic lesion (asterisk) men (distal pancreatectomy) and macrosection: the dilated main pan-
located in the pancreatic body. The duct of Wirsung is downstream creatic duct is filled by neoplastic tissue (arrows in b and c) from the
dilated and filled by a solid hypoechoic appendage (arrow) originating neuroendocrine tumor (T in b)
a b
Fig. 64 Neuroendocrine tumor growing in the main pancreatic duct. upstream-dilated Wirsung duct at the pancreatic body, filled by solid
(a–c) Dynamic CT: uncinate process slightly inhomogeneous hypervas- vascularized appendage (arrow in c), originating from the neoplasm
cular tumor (asterisk in a and b). More cranial scan demonstrates an growing within the duct
a b
c d
Fig. 65 Neuroendocrine tumor growing in the main pancreatic duct. study (c) demonstrates a slightly dilated Wirsung duct (W in c) in the
(a–c) MRI study: pancreatic head hypervascular mass (asterisk in a) pancreatic body upstream to the solid tumoral portion growing within
with solid portion (arrow in a) growing within the Wirsung duct. More the duct. (d) Surgical specimen (pancreaticoduodenectomy) of different
caudal section shows the growth of the neoplastic tissue also in the case: neuroendocrine neoplastic tissue (arrow) growing in the main
main pancreatic duct from the tumor to the papilla (arrow in b). MRCP pancreatic duct toward the major papilla (circle)
a b
Fig. 66 Neuroendocrine tumor growing in the main pancreatic duct. (a, b) Surgical specimen (pancreaticoduodenectomy): neuroendocrine tumor
growing into the main pancreatic duct (arrow in a) and colonizing (arrow in b) the major papilla (probe P in b). Common bile duct (probe C in b)
Fig. 67 Neuroendocrine tumor growing in the main pancreatic duct.

Surgical specimen: neuroendocrine tumor (T) growing into the main
pancreatic duct (curved line), reaching the major papilla (P)
a b
c d
Fig. 68 Neuroendocrine tumor growing in the splenic vein. (a) growing within the lumen (arrows) of the splenic vein. (c–e) Surgical
Conventional US: hypoechoic mass (asterisk) located in the pancreatic specimen (distal pancreatectomy): neuroendocrine tumor (asterisk in c)
body colonizating the lumen (arrows) of the splenic vein. (b) Dynamic with splenic vein neoplastic tissue colonization (asterisk in d and e)
MRI: pancreatic body mass (asterisk), inhomogeneously vascularized,
a b
c
d
Fig. 69 Neuroendocrine tumor growing in the portal vein. (a–d) CT neoplastic thrombus (arrow in b and c) invading the portal vein.
study: baseline examination (a) shows a large hypodense mass (arrows Multiplanar reconstruction on the coronal plane (d) better demonstrates
in a) with small contextual calcifications, diffusely involving the pan- the neoplastic growth within the portal vein lumen (asterisk in d) from
creatic gland. At dynamic CT study (b–d), the lesion appears hypervas- the tumor (T in d)
cular (b) with extensive involvement of the splenic vessels and
a b
f
e
Fig. 70 Neuroendocrine tumor growing in the portal vein. (a–f) MRI plastic appendage (arrow in d). Postcontrastographic coronal images
study: dynamic MRI shows a large hypovascular mass (arrow in a–c) of obtained in the venous phase (e), and coronal T2-weighted (f) images
the pancreatic body with irregular margins causing dilation of the main better show the growth of the neoplastic solid tissue within the portal
pancreatic duct (W in c), invading the portal vein lumen with solid neo- vein lumen (arrow in e and f)
Fig. 71 Neuroendocrine tumor in Von Hippel–Lindau syndrome.

Surgical specimen (total pancreatectomy) showing a round-shaped cap-
sulated neuroendocrine tumor (asterisk) in the pancreatic head. The
entire pancreatic gland is altered by the presence of diffuse serous neo-
plasm. Probe in the common bile duct
a b
Fig. 72 Pitfalls and errors: paraganglioma. (a–e) MRI examination: without (b) and with (c) fat suppression with septa and irregular thick
large cystic mass with thick walls, regular margins, and inhomogeneous wall. Dynamic MRI study (d–e) demonstrates hypoenhancing thick
fluid content (arrow in a–c), next to the region of the pancreatic body wall (arrow in d and e). (f, g) Surgical specimen (distal pancreatec-
appearing inhomogeneously hypointense on T1-weighted fat-satured tomy): cystic mass with final diagnosis of paraganglioma and thick wall
axial images (a) and hyperintense on T2-weighted axial images, both (arrows in g) at cut specimen
c d
f
e
Fig. 72 (continued)
a b
c d
Fig. 73 Pitfalls and errors: intrapancreatic accessory spleen. (a–c) CT during the dynamic phases (arrow in b and c). (d) CEUS study: the
examination: at baseline scan (a), isodense nodule (arrow in a) with lesion (calipers) presents the same enhancement of the spleen (S)
sharp margins in the pancreatic tail, presenting the density of the spleen
a b
d
c
Fig. 74 Pitfalls and errors: intrapancreatic accessory spleen. (a) (b–d) MRI study: the pancreatic tail nodule appears isointense to the
Dynamic CT: oval-shaped nodule (arrow) with sharp margins in the spleen on T2-weighted fat-saturated image (arrow in b), DWI for high
pancreatic tail, as hypervascular as the spleen, in the arterial phase. b value (arrow in c), and on dynamic study (arrow in d)
a b
Fig. 75 Pitfalls and errors: pancreatic neuroendocrine neoplasm vs. intrapancreatic accessory spleen. (a) Surgical specimen: pancreatic neuroen-
docrine neoplasm. (b) Surgical specimen: intrapancreatic accessory spleen. The Wirsung duct (W in a and b) is visible
a b
c d
Fig. 76 Pitfalls and errors: biopsy-proven pancreatic splenosis, years vascularized (arrow in b) and external to the pancreatic gland, com-
after splenectomy for traumatic splenic rupture. (a) Conventional ultra- pressing the contours (arrows in c). Multiple other splenic implants
sound: hypoechoic round-shaped nodule (asterisk) with sharp margins (arrows in d) are also visible
in the pancreatic head. (b–d) Dynamic CT: the nodule appears well
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Mimickers of Pancreatic Tumor
Mirko D’Onofrio, Antonio Giugliano, Gregorio Aluffi,

Roberto Calbi, Angela Calabrese,
Introduction images and are usually characterized by poor enhancement

on both contrast-enhanced CT and MRI [4]. CEUS has
Pancreatic ductal adenocarcinoma (PDAC) is the most fre- shown good results in differentiating ductal adenocarcinoma,
quent and known pancreatic malignant neoplasm; therefore, which remains hypoechoic in all contrast-enhanced phases,
any pancreatic lesion with similar imaging features is con- and inflammatory masses, which exhibit enhancement simi-
sidered suspicious for PDAC, but misdiagnosis especially of larly to the adjacent pancreatic parenchyma [5].
benign origin could be very important. Different studies Furthermore, both may show involvement of the main
reveal that 5–10% of pancreatic resections performed with pancreatic duct, peripheral fibrotic retraction, involvement
clinical and radiologic diagnosis of PDAC turn out to be of peripancreatic tissues, lymphadenopathies, and vessel
benign lesions on histologic evaluations [1–3]. However involvement [6].
benign pancreatic condition may mimic also other pancreatic Some useful imaging findings to differentiate chronic
tumors. This chapter is focused on a brief presentation of pancreatitis from PDAC are discussed below.
possible non-neoplastic mimickers of pancreatic tumors and Duct involvement: The evaluation of the main pancreatic
differential diagnosis. duct (MPD) and of the common bile duct (CBD) on mag-
netic resonance cholangiopancreatography (MRCP) images
is essential in distinguishing a pancreatic tumor from focal
Inflammatory Pancreatic Conditions inflammatory changes since both can cause upstream dilata-
tion of MPD and CBD. A mass causing an abrupt obstruction
Chronic Pancreatitis of MPD or CBD (or both, in lesions involving pancreatic
head; “double-duct sign”) with upstream duct dilation is
Chronic pancreatitis is characterized by recurrent episodes highly suggestive for PDAC [7, 8]. Visualization of smoothly
of pancreatitis, leading to parenchymal fibrosis and glandu- stenotic or normal MPD coursing through the mass without
lar atrophy but in 27–50% of cases can manifest as a focal interruption (“duct-penetrating sign”) or multiple and long
mass-forming inflammation. duct narrowings are significantly more frequent in inflamma-
Both focal chronic pancreatitis and PDAC appear tory changes of the pancreas [7–9].
hypoechoic at US, hypodense at CT, hypointense at Parenchymal atrophy: A severe upstream parenchymal
T1-weighted images, and iso- to hyperintense at T2-weighted atrophy with associated MPD dilatation (duct-to-parenchyma
ratio > 0.34) is a typical feature of PDAC, while a duct-to-
M. D’Onofrio (*) · G. Aluffi · R. De Robertis
parenchyma ratio <0.34 indicates more probably an inflam-
Department of Radiology, G.B. Rossi University Hospital, matory etiology [10, 11]. The dilatation of collateral ducts
Verona, Italy due to fibrosis is more frequent in focal pancreatitis [11].
e-mail: mirko.donofrio@univr.it Calcifications: Presence of calcifications within a focal
A. Giugliano mass is typical of pancreatitis. Otherwise, a pancreatic can-
Department of Radiology, Ospedale Evangelico Betania, cer arising on a chronic pancreatitis causes peripheral dis-
Naples, Italy
placement of the calcifications [12, 13].
R. Calbi Vessels: Rarely, inflammation can involve peripancreatic
Department of Radiology, Miulli Hospital, Bari, Italy
fat mimicking malignant vessel encasement [7]. Vessel
A. Calabrese deformity, such as teardrop sign of SMV, suggests neoplas-
Department of Radiology, Oncologic Hospital, Bari, Italy
tic involvement [14], even if multiple acute attacks of pan- features can be found in chronic settings of paraduodenal
creatitis in chronic inflammatory condition of the pancreatic pancreatitis [21–23].
gland may led to distortion and thrombosis of venous On the contrary, PDAC arising in the periampullary
vessels. region will usually cause early encasement of gastroduo-
Some studies affirm that SMA/SMV ratio > = 1 could be sug- denal artery and CBD with biliary dilatation and jaundice
gestive for cancer. The arterial dilation would be related to the [22].
release of vasoactive substances from neoplastic tissue [15].
Autoimmune Pancreatitis
Paraduodenal Pancreatitis
Autoimmune pancreatitis (AIP) is an inflammatory disease
Paraduodenal pancreatitis or Groove pancreatitis (GP) is a focal characterized by lymphocyte infiltration and associated
inflammatory disease that affects mainly middle-aged men with fibrosis.
a history of chronic alcoholism [16]. It involves either the groove AIP typically manifests with diffuse enlargement of the
between pancreatic head and duodenum (groove-predominant gland with loss of lobular contours described as “sausage-
type or “pure” form) or the groove plus the pancreatic head like” appearance, a capsule-like rim enhancement surround-
(pancreas-involving type or “segmental” form) [17]. ing the pancreas, minimal peripancreatic stranding unlike
Furthermore, a solid variant (in 32%) can be distinguished many other forms of pancreatitis, and absence of calcifica-
from a cystic variant (in 68%), in which cysts, from small to tion or vascular encasement [24].
large, are located mainly in the groove or in the duodenal In 28–41% of cases, AIP appears as a focal parenchymal
wall, with MRCP being useful in their detection [18]. enlargement, more often within the head/uncinate process,
Pure forms may be differentiated from PDAC by the char- difficult to differentiate from pancreatic adenocarcinoma
acteristic “sheet-like” crescentic mass appearance associated based only on morphologic appearance, attenuation values,
with duodenal wall thickening in which tiny cysts may be or T1- and T2-weighted images.
present. Sheet-like appearance is best appreciated on coronal Imaging findings useful to differentiate autoimmune pan-
multiplanar reformatted images and is characterized by creatitis from PDAC are discussed below.
delayed enhancement on multiphase imaging, as a result of Duct involvement: The “duct-penetrating sign” is fre-
an abundant fibrotic component, and by a mildly hypoin- quently found in focal AIP [25], with only mild main pancre-
tense signal on T1-weighted images. atic duct upstream dilatation (≤ 5 mm) [26].
The solid segmental type nonetheless is often misdiag- The presence of multiple strictures of MPD and CBD is a
nosed as PDAC since it shares the same echogenicity/attenu- typical feature of AIP [27], while a single abrupt stenosis is
ation/signal intensity and mass-forming characteristics with usually found in neoplastic disease. Absence of secondary
the enlargement of the pancreatic head that may obscure ducts dilatation and severe upstream MPD or CBD dilatation
groove involvement [4, 17, 19, 20]. suggests inflammatory etiology [28].
In chronic settings, both forms can lead to diffuse changes Enhancement: Lesions appear hypodense (hypointense) on
of traditional chronic pancreatitis such as parenchymal atro- pancreatic phase to the normal parenchyma. In 90% of the
phy, calcifications and narrowing, and dilatation or beading cases, AIP, however, shows progressive enhancement during
of the duct [21]. portal-venous and delayed phases resulting in iso-hyperdense
The imaging findings suggesting non-neoplastic diag- (iso-hyperintense), while PDAC usually persists hypodense
nosis are “duct-penetrating sign,” widening of medial (hypointense) [27, 29]. This pattern of enhancement is thought
duodenal wall, clear thickening of the duodenal wall, to be due to preserved acinar cells with mild interstitial fibro-
small cysts in the duodenal wall, displacement on the left sis, even if the amount of fibrosis in AIP can be extremely
of the common bile duct and gastroduodenal artery, hypo- different, so affecting the sign [30]. However, in 11% of cases,
vascular longitudinal strip mass in the “groove” along the PDAC appears iso-attenuating to pancreatic parenchyma in
duodenal wall, increased distance between ampulla and the post-contrast phases [31]; in these cases, differentiating the
duodenal lumen, displacement without encasement of two entities can be nearly impossible on the basis of imaging.
gastro-duodenal artery and CBD, lack of significant Moreover, on the late phase, ductal adenocarcinoma can be
upstream dilatation of MPD or CBD, and lack of signifi- slightly hyperdense due to accumulation of contrast in the
cant upstream parenchymal atrophy even if these two last dense compact fibrosis from desmoplastic reaction.
Mimickers of Pancreatic Tumor 235
Imaging sign of AIP: A periferic capsule-like rim, Its clinical relevance is mainly discussed in the setting of
hypodense on CT images, hypointense on both T1- and recurrent pancreatitis.
T2-weighted images with subtle delayed enhancement, is Very few cases of focal mass appearance of the pancreatic
observed in 12–40% of cases and is highly specific of AIP head associated with this condition and mistaken for malig-
[32]. This finding is believed to be suggestive of inflamma- nant lesions have been described in literature [38].
tory peripancreatic extension and is absent in PDAC in Partial or complete agenesis of dorsal pancreas: It is a
which, on the contrary, an enhanced rim may be recognized rare congenital variant in which only pancreatic head is pres-
in locally invasive tumors. ent. It can mimic a neoplasm of the head with consequent
AIP and PDAC show an overlap of absolute values at atrophy of the body and tail. Unlike PDAC, in these cases,
diffusion-weighted MRI; so, DWI sequence cannot distin- there is no upstream dilatation of MPD [39].
guish AIP from PDAC [33]. Pseudomass-lobulation: A pancreatic lobulation is a focal
Extra-pancreatic signs: Autoimmune pancreatitis can bulging of pancreatic edge greater than 1 centimeter.
occur simultaneously with other forms of autoimmune Lobulations are classified into three types: type I (anterior),
inflammation such as sclerosing cholangitis, RCU, tubulo- type II (posterior), and type III (horizontal) [40].
interstitial nephritis, and sclerosing sialadenitis [34]. They may mimic small tumors, but they can be distin-
guished from a cancer because they have the same imaging
features of the normal parenchyma at all radiologic evalua-
Inflammatory Pseudotumor tions [41].
Pseudomass-tuber omentale: It is a focal bulging of ante-
Inflammatory pseudotumor is a very rare focal mass-forming rior surface of pancreatic body to the left of superior mesen-
inflammatory disease that on histological evaluation shows teric vessels that may mimic a pancreatic cancer [36].
inflammatory cells and myofibroblastic spindle cells. Due to
its uncommonness, there are very few studies in literature
that describe its imaging features and the findings that sug- Fatty Replacement
gest a non-neoplastic etiology. At CT scan, it has variable
characteristics [35]. Usually fatty replacement (lipomatosis) of pancreas involves
the entire gland. Sometimes, however, it may have an irregu-
lar distribution with fatty replacement areas and focal-
natomic Pancreatic Variants (See First
A sparing areas.
Edition) Fatty replacement areas do not represent diagnostic prob-
lem, thanks to the unique features of fatty tissue.
Duct caliber changes: could be present as a variant at the On the contrary, focal-sparing areas may be misdiagnosed
level of the fusion of Santorini and Wirsung ducts. Unlike as pancreatic neoplasms.
neoplastic stenosis, this stricture does not cause upstream However, the absence of mass effect or deformity of pan-
dilatation of MPD [36]. creatic shape and the absence of duct or vessels displacement
Annular pancreas: This variant is a rare congenital anomaly are useful secondary findings that differ focal-sparing areas
in which pancreatic tissue encircles, completely or partially, the from pancreatic neoplasms [42].
second portion of the duodenum. In adults, it is most often
asymptomatic and discovered incidentally usually in the
Rare Non-neoplastic Pancreatic Diseases
incomplete partial form, whereas complete annular pancreas is
more often symptomatic in childhood with symptoms resulting
Sarcoidosis
from gastric outlet obstruction secondary to mass effect [37].
On CT, the duodenum lumen surrounded by pancreatic
Sarcoidosis rarely involves the pancreas. It may manifest with
parenchyma may mimic a solid pancreatic mass. In dubious
single or multiple masses that appear hypoechoic at US,
cases, MRCP is the preferred non-invasive modality to dem-
hypodense at CT, hypointense at T1-weighted MRI, hyperin-
onstrate the pancreatic duct encircling the duodenum.
tense at T2-weighted MRI, and hypo-enhancing, resembling
Pancreas divisum: It is the most frequent congenital vari-
to PDAC.
ant and consists in an aberrant fusion of the embryologic
dorsal and ventral pancreatic ducts.
Unlike PDAC, it causes a long and smooth narrowing of Peripancreatic Structures

CBD.
A history of sarcoidosis or extra-pancreatic findings, such Lymph Nodes
as lung hilar lymph node involvement, may suggest sarcoid-
osis. However, biopsy with histological evaluation is essential Porto-caval, peri-portal, peripancreatic, and celiac lymph
[43, 44]. node enlargement, due to lymphoma rather than any inflam-
matory disease, can simulate a pancreatic lesion [6, 49].
Castleman Disease
Vessels
In the rare cases of pancreatic involvement, it may present as
a mass hypoechoic at US, hypodense at CT, hypointense at Alterations of the splenic and portal-mesenteric vessels, such
T1-weighted MRI, hyperintense at T2-weighted MRI, and as aneurysms and thrombosis, can simulate a pancreatic
with intense ring-like enhancement [45]. Calcifications and mass [6, 49].
cystic changes may be present.
Organs
Tuberculosis
Malignant and benign lesions in the stomach and duodenum can
Pancreatic tuberculosis is a rare condition with variable simulate pancreatic masses. In these cases, diagnostic errors can
radiological features. It may manifest as a hypoechoic or be prevented by using neutral oral contrast material before CT
cystic mass at US evaluation [46], usually a hypodense and scan in order to expand the visceral lumen [49]. Masses of small
hypo-enhancing lesion with irregular borders at CT scan, loops, adrenals, or kidneys and peripancreatic fatty tissue altera-
hypointense at T1-weighted MRI, and mixed hypo−/hyper- tions, such as retractile, desmoid, carcinoid, or sclerosant mes-
intense at T2-weighted MRI [47]. enteritis, also can mimic a pancreatic neoplasm [6, 49].
Similarly to PDAC, tuberculosis shows peripancreatic Intrapancreatic or peripancreatic accessory spleen may simulate
and peri-portal lymph node enlargement and, sometimes, pancreatic tumor [50]. After splenectomy, splenic tissue can be
also vascular invasion. Unlike PDAC, it does not cause duct found near or more distally adjacent to other organs such as
dilations [47, 48]. pancreas and liver causing differential diagnosis problems.
Image Gallery
a b
c d
Fig. 1 Chronic pancreatitis. (a, b) MRI: dilation of the main pancreatic pancreatic neck in the site of the main pancreatic duct stenosis. (c, d)
duct at MRCP (a). Retention cyst is visible at the body-tail of the pan- CT: multiple calcifications along the pancreatic parenchyma that is
creas. Important stenosis of the main pancreatic duct at the head of the atrophic with dilation of the main pancreatic duct (c). At the neck of the
pancreas. In the dynamic phase (b) hypovascular tissue is visible at the pancreas, an intraductal calcification is clearly visible (d)
a b
c d
Fig. 2 Mass-forming chronic pancreatitis. (a–d) CT: pancreatic gland Inside the pancreatic head, the Santorini and the main pancreatic ducts
is atrophic at the pancreatic body-tail (a) with dilation of the main pan- are visible (b and c). At the level of pre-papillary tract of the main pan-
creatic duct that stops at a relatively enlarged pancreatic head (b and c). creatic duct, an endoluminal calcification is detected (d)
a b
c d
Fig. 3 Mass-forming chronic pancreatitis. (a–d) CT: pancreatic head enhancement is markedly inhomogeneous (c). The mesenteric vessels
enlargement appearing markedly inhomogeneous with multiple calcifi- are involved especially the superior mesenteric vein no longer visualiz-
cations (a). The main pancreatic duct upstream is dilated (b), and the able (d) with collateral venous vessels
a b
c d
Fig. 4 Paraduodenal pancreatitis. (a–d) MRI: in the head of the pan- within the duodenal wall that shows asymmetric thickening along the
creas, a long stenosis of the main pancreatic duct is clearly visible at groove (c). On dynamic phase, the head of the pancreas shows inhomo-
MRCP (a). On T2, the head is markedly enlarged with inhomogeneous geneous enhancement, and the duodenal wall along the groove is thick
intensity (b). At zoom T2, a small cystic lesion is clearly depictable and hypovascular (d)
a b
c d
Fig. 5 Paraduodenal pancreatitis. (a–d) MRI: initial dilation of the dynamic phase, the enhancement of the head of the pancreas is still
main pancreatic duct at MRCP (a). On T2 the head is slightly enlarged preserved, but marked thickening of the duodenal wall is visible appear-
with thick duodenal wall showing tiny intraparietal cystic lesion (b). On ing inhomogeneous hypovascular in all phases (c and d)
a b
Fig. 6 Paraduodenal pancreatitis. (a, b) CT: the pancreatic region is The superior mesenteric vessels are involved. On coronal, the duodenal
markedly enlarged (a) and inhomogeneous with fluid collections and lumen with air is stenosed and surrounded by cystic lesions (b)
peripancreatic fat thickening due to edema during acute pain attack.
Fig. 7 Autoimmune pancreatitis. CT: diffuse enlargement of the

pancreatic gland with smooth margins and important reduction of
glandular contour of the pancreas and no dilation of the main
pancreatic duct no more clearly visible, compressed. The pancreas
is surrounded by tiny hypodense halo corresponding to typical
pseudo-capsule
a b
Fig. 8 Autoimmune pancreatitis. (a–c) MRI: on T2 diffuse enlarge- the pancreatic gland (b). On dynamic phase, the enhancement of the
ment of the pancreatic gland with smooth margins and reduction of pancreatic gland is preserved with no defect (c). The pancreas is sur-
glandular contour with numerous long stenosis of the main pancreatic rounded by tiny hypointense halo hypovascular during the dynamic
duct (a). On DWI, minimal but inhomogeneous restriction foci along study
a b
Fig. 9 Multifocal autoimmune pancreatitis. (a–c) MRI: on DWI, mul- the body-tail (b) and at the head (c) of the pancreas. No dilations of the
tiple restriction foci along the pancreatic gland (a) resulting in hypoin- main pancreatic duct are visible
tense hypovascular during dynamic phases diffuse along the gland, at
a b
Fig. 10 Type 1 autoimmune pancreatitis. (a, b) MRI: on T2 diffuse enlargement of the pancreatic gland with smooth margins (a). On ADC map,
multiple restriction foci at the kidney (b) bilaterally, referring to tubulointerstitial nephritis
a b
c d
e f
Fig. 11 Autoimmune pancreatitis. (a, b) CT: diffuse enlargement of tion of glandular contour of the pancreas. On dynamic phase, inhomo-
the pancreatic body-tail with smooth margins and important reduction geneous enhancement is visible in the pancreatic (d) and venous (e)
of glandular contour of the pancreas and no dilation of the main pancre- phases. The pancreatic gland is surrounded by exuberant halo hypoin-
atic duct no more clearly visible, compressed. The pancreas is sur- tense hypovascular in the pancreatic (d) and venous (e) phases, involv-
rounded by exuberant hypodense halo, corresponding to pseudo-capsule, ing peripancreatic vessels, with progressive retention of contrast so
involving peripancreatic vessels. (c–f) MRI: on T1 diffuse enlargement resulting isointense in the late phase (f)
of the pancreatic body-tail with smooth margins and important reduc-
a b
Fig. 12 Pseudolesion of the pancreas. (a, b) CT: hypodense appearance in pre- (a) and post-contrast phases (b) of the pancreatic head due to
fat accumulation
a b
Fig. 13 Intrapancreatic accessory spleen. (a–c) CT: a small nodule with sharp margin and isodense to the spleen in pre- (a) and post-contrast
graphic phases (b and c) is visible in the pancreatic tail
Fig. 14 Peripancreatic accessory spleen. CT: a small nodule

with sharp margin and isodense to the spleen is visible along
the posterior surface of the pancreatic tail
a b
c d
Fig. 15 Peripancreatic splenosis. (a) US: hypoechoic nodule with sharp (b) and slightly hyperdense on the venous phase (c) is visible on the pan-
margin imprinting the anterior surface of the pancreatic head. (b–d) CT: creatic head imprinting the anterior profile of the gland. Status post sple-
a nodule with sharp margin and well vascularized in the pancreatic phase nectomy with other splenosis foci in the left upper abdominal quadrant
a b
c d
Fig. 16 Splenosis. (a–e) MRI: on T1, hypointense nodules (a) are vis- (c) showing “zebra pattern” and resulting isointense in venous phase
ible along the posterior profile of the right liver lobe. The nodules are (e). Status post splenectomy with other splenosis foci in the left upper
slightly hyperintense on T2 (b) showing restriction on DWI (c). On abdominal quadrant
dynamic phases, the nodules are well vascularized in the arterial phase
a b
Fig. 17 Splenosis. (a, b) CT: a small nodule with sharp margin and homogeneous in the pancreatic (a) and venous (b) phases is visible in the left
upper abdominal quadrant. Patient affected by pancreatic head ductal adenocarcinoma. Presence of biliary endoprosthesis
14. Hough TJ, Raptopoulos V, Siewert B, Matthews JB. Teardrop supe-

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PMid:19620443 2008;9(2):162–74.
Intraductal Papillary Mucinous
Neoplasm (IPMN)
Giovanni Morana, Mirko D’Onofrio, Paolo Tinazzi Martini,

Riccardo De Robertis, Alessandro Beleù, Claudio Luchini,
Eda Bardhi, Nicolò Cardobi, and Paola Capelli
Introduction cant differences in frequencies of malignancy in IPMNs

according to the morphological types, higher for MD type
Intraductal papillary mucinous neoplasms (IPMNs) are a (mean 61.6%) and lower for BD type (25.5%) [13].
group of exocrine mucin-producing tumors, diagnosed at a
mean age of 60 years, with male prevalence [1, 2].
Improvements in imaging techniques have led to an Pathology
increasing incidental detection of IPMNs: in several studies,
the prevalence of incidental cystic pancreatic lesions can be Intraductal neoplasms of the pancreas are cystic or mass-
up to 19.6%, with MRI being the most sensitive imaging forming epithelial tumors with ductal differentiation, which
technique [3, 4], with a significant proportion of IPMNs and typically grow primarily within the ductal system [14]. Two
mucinous cystic neoplasms (MCNs) [3–5]. main groups have been defined: intraductal papillary muci-
The demonstration of the involvement or the communica- nous neoplasms (IPMNs) and intraductal tubulopapillary
tion with the pancreatic ductal system is fundamental for the neoplasms (ITPNs).
appropriate diagnosis of IPMN [6]. Epithelial morphology and mucin expression patterns
Three types of IPMNs have been described [1, 7]: the define four main histologic subtypes of IPMN [15]: intesti-
main-duct type (MD-IPMN) [8], the branch-duct type nal, gastric, oncocytic, and pancreaticobiliary. Recent papers
(BD-IPMN) [2], and the mixed type [9], which meets the support the hypothesis of distinct pathways for carcinogen-
diagnostic criteria for both MD-IPMN and BD-IPMN. esis among the different IPMN subtypes [16, 17].
IPMN arises from the epithelium of the pancreatic ductal IPMNs are defined as an intraductal grossly visible (typi-
system and can display the full spectrum of histologic dys- cally >1 cm, a threshold useful to distinguish IPMNs from
plasia, including hyperplasia, adenoma, borderline tumor, PanINs) epithelial neoplasm made up of mucin-producing
and in situ or invasive carcinoma [10–12]. There are signifi- cells, arising in pancreatic ductal system [14].
The neoplastic cells usually have a papillary attitude, with
G. Morana (*) · A. Beleù a variable degree of mucin production, duct dilatation/cyst
Department of Radiology, S. Maria di Ca’ Foncello Hospital, formation, and cellular atypia. Noninvasive IPMNs are histo-
Treviso, Italy logically classified according to their degree of epithelial
e-mail: g.morana@ulss.tv.it atypia in three subtypes: (a) low-grade dysplasia IPMN, (b)
M. D’Onofrio · R. De Robertis · E. Bardhi intermediate-grade dysplasia IPMN, and (c) high-grade dys-
Department of Radiology, G.B. Rossi University Hospital, plasia IPMN; IPMNs with a component of infiltrating carci-
Verona, Italy
e-mail: mirko.donofrio@univr.it noma are defined as “IPMN with an associated invasive
carcinoma” [14].
P. T. Martini
Department of Radiology, Casa di Cura Dott. Pederzoli, IPMNs are generally characterized by abundant quanti-
Verona, Italy ties of mucin, which led to a secondary pancreatic ductal tree
C. Luchini · P. Capelli dilatation. In some cases, the mucin can be seen extruding
Department of Pathology, G.B. Rossi University Hospital, from the papilla of Vater, a virtually diagnostic finding of
Verona, Italy IPMN [18].
e-mail: paola.capelli@ospedaleuniverona.it The incidence in the general population is not well
N. Cardobi defined because most are asymptomatic and incidentally
Radiology, Ospedale Maggiore, Verona, Italy
252 G. Morana et al.
found during clinical evaluation for other pathological or pancreatic regions more often interested by these lesions are
non-pathological conditions [14]. Due to their slow growth, the head and the neck of the pancreas, and particularly the
the clinical manifestations mainly regard the advanced uncinate process, which often demonstrates a grape-like
stages of IPMNs. Typical symptoms are generally related to aspect and may protrude from the pancreatic parenchyma.
intermittent obstruction of the pancreatic duct by the thick However, BD-IPMNs can also involve the tail of the pan-
mucin produced by the neoplasm. Common presenting creas or can be multifocal. The most common macroscopic
symptoms therefore range from abdominal or back pain and finding is the presence of several small cysts, which are usu-
anorexia to weight loss and recurrent episodes of pancreati- ally stuffed with thick mucus. These cysts show either
tis. Jaundice is not a typical sign like for adenocarcinomas; grossly visible papillae or a smooth internal surface. By defi-
when it is present, it is due to the obstruction of bile flow by nition, in BD-IPMNs, Wirsung duct is not involved. The pan-
mucin plugs. Hematochemical analysis usually reveals ele- creatic parenchyma adjacent to BD-IPMN is frequently
vated serum amylase and lipase levels, but CA 19–9 is not normal; in fact, in this kind of lesions, contrary to MD-IPMN,
of value [14]. there are not so usually obstructive phenomena with conse-
IPMNs occur in men slightly more often than in women quent inflammatory and fibrotic modifications of the
(ratio 1.5:1) and are more common in the elderly. The mean parenchyma.
age at diagnosis is 63 years, but with a large range (25– When both the main and branch ducts are significantly
94 years); main risk factors are cigarette smoking and a fam- interested by the neoplasm, IPMNs are defined as “combined
ily history of pancreatic carcinoma [18]. or mixed.” In mixed IPMNs, the risk of malignant transfor-
Most IPMNs are circumscribed and located in the pancre- mation is very similar to that of MD-IPMN, and the clinical
atic head, but these tumors can diffusely involve the entire management is the same.
pancreas; gross and microscopic multifocality has been In all types of IPMNs, it is fundamental to look for an
reported in 20–30% of cases. invasive carcinomatous constituent. BD-IPMN has a lower
risk of carcinomatous transformation (24%) in comparison
with MD-IPMNs and mixed IPMNs (30–50%) [19]. If pres-
Macroscopy ent, invasive carcinoma produces irregular, heterogeneous
thickening of the cyst wall, fibrotic foci in endoluminal
Macroscopically, IPMNs are divided into (a) main-duct type papillary-nodular vegetations, or gelatinous stromal masses.
(MD-IPMNs), (b) branch-duct type (BD-IPMNs), and (c)
combined or mixed type.
In MD-IPMNs, Wirsung duct is typically dilated and Microscopy
filled with thick mucin. The dilation could be diffuse or seg-
mental. Intraluminal papillary vegetations and solid nodules IPMNs are characterized by a spectrum of changes, rang-
are often documented. The head of the pancreas is most often ing from flat epithelium, microscopic folds, to simple or
involved by this type of lesions, with progressive extension branching papillae, lined by cells that show distinct lines
along Wirsung duct to branch ducts. With a slow, indolent of differentiation. Defining the subtype of epithelial dif-
growth pattern, this process can extend involving the entire ferentiation is clinically relevant because the risk of
gland before symptom onset. When IPMNs involve the malignant transformation is associated with distinct histo-
major and/or minor papilla, the endoscopist can appreciate logic types. The classification is based on the cell lineage,
an everted papilla with a patulous orifice: the mucin often the morphology of papillae, and immunophenotype [15,
protrudes into the duodenum. These pathognomonic findings 20–25] and classifies IPMNs into (a) gastric type, (b)
are present in about 50% of cases but, unfortunately, are con- intestinal type, (c) pancreatobiliary type, and (d) onco-
sistently present only in advanced stages and are more com- cytic type.
mon in patients with in situ carcinoma or invasive carcinoma. The gastric type, characteristically found in BD-IPMNs,
In rare cases, projections of neoplastic papillae and thick is characterized by columnar cells resembling gastric foveo-
mucus grow out of the ampullary region onto duodenal sur- lar cells, showing either flat or short papillary projections.
face. The normal pancreatic parenchyma surrounding the Although most of the gastric-type lesions are low-grade
dilated duct, especially in advanced stages, is frequently lesions, they may merge with other more aggressive sub-
replaced by fibrous and edematous tissue, a clear sign of a types (most of the cases acquire biliary-type morphology
long-standing ductal obstructive history that can culminate and immunophenotype). The gastric foveolar cells express
in an obstructive pancreatitis. MUC5AC, the pyloric gland-like structure at the base of the
BD-IPMNs are characterized by the dilation of single or cysts shows MUC6-positivity, with no reactivity for MUC1,
multiple small peripheral ductal branches. These can form MUC2 (with the exception of the scattered goblet cells), or
clusters of cysts with a typical grape-like appearance. The CDX2 is present.
Intraductal Papillary Mucinous Neoplasm (IPMN) 253
Intestinal-type IPMN accounts for a significant portion of In mixed IPMNs, both branch ducts and the main pancre-
MD-IPMNs. They are characterized by villous papillae, sim- atic duct are involved with evidence of dilation of main pan-
ilar to those found in villous adenomas of the colon. The creatic duct with dilated branch ducts along its course [9,
lesions frequently exhibit moderate or severe dysplasia. The 28]. However, in case of BD-IPMN with dilation of main
epithelium expresses the intestinal markers MUC2 and pancreatic duct due to the overproduction of mucin by the
CDX2 and coexpresses the foveolar marker MUC5AC, but tumor and not to the involvement of main pancreatic duct,
does not express MUC1 and MUC6. Most of the invasive the differential diagnosis with mixed-type IPMN can be dif-
carcinomas arising from intestinal-type MD-IPMNs are col- ficult [9].
loid carcinomas. A clear differentiation between IPMNs with different
Pancreatobiliary-type IPMN is less common, typically pathologic expressions can be difficult, unless clear evi-
involves the main pancreatic duct and consists of complex, dence of malignancy is present [29, 30]. However, some
thin, papillary projections lined by highly atypical cells. imaging findings can be suggestive of aggressive behavior
Pancreatobiliary-type IPMNs are usually associated with of the IPMN (13). There are significant differences in fre-
high-grade dysplasia. The cells are MUC1 and MUC5AC quencies of malignancy in IPMNs according to the mor-
positive and MUC2, MUC6, and CDX2 negative. Invasive phological types, being higher for MD type (mean 61.6%)
carcinomas associated with this subtype have features of the and lower for BD type (25.5%) [13]. High-risk stigmata
common-type pancreatic adenocarcinomas. suggesting the high possibility that the lesion is malignant,
Oncocytic-type IPMNs arise most frequently in thus requiring surgical resection if patient fits for surgery,
MD-IPMNs and can extend into branch ducts. The striking are the following: main-duct diameter > 10 mm for
feature is the presence of oncocytic cells. They are character- MD-IPMN, presence of solid enhancing nodules within the
ized by dilated main pancreatic duct or cystic dilated branch cyst in BD-IPMN, or obstructive jaundice in the presence
ducts filled with mucin and containing solid areas and friable of a cystic lesion of the pancreatic head. Worrisome fea-
papillary projections. Most of the lesions show severe atypia/ tures suggesting the possibility that the lesion could evolve
carcinoma in situ modifications. Immunohistochemically, in malignant, thus requiring further workup by EUS to bet-
the cells show diffuse positivity for MUC6 and focal positiv- ter risk stratify the lesion and a strict follow-up, are as fol-
ity for MUC1, whereas they lack MUC5AC, MUC2, and lows: cyst >3 cm, thickened enhanced cyst walls, MPD size
CDX2 expression (usually restricted to the sparse goblet of 5–9 mm, non-enhancing mural nodules, and abrupt
cells). change in the MPD caliber with distal pancreatic atrophy
and lymphadenopathy. Other suggested features of malig-
nancy consist of the presence of coarse calcifications [31]
Imaging and a rapid increase of cysts size [32].
The management of IPMN is mainly based on the loca-
The location and type of an IPMN determine its imaging tion (MD- and mixed-type IPMN versus BD-IPMN), the size
appearance. IPMNs appear with a cystic dilation of the of the largest cyst in BD-IPMN, and the presence of the pre-
involved segment, either main duct or branch ducts. The pro- viously described “high-risk stigmata” or “worrisome fea-
duction of mucin is the main cause of the dilation of the tures.” Moreover, risk stratification for age and fit for surgery
ducts. must be considered.
In main-duct IPMNs, ductal dilation is common and International consensus guidelines [13] recommend
may be along the entire length of the duct or segmental, resection in the presence of high-risk stigmata, while in the
with or without intraductal hypointense masses [1]. In presence of “worrisome features,” the lesion should be eval-
advanced MD-IPMN, adjacent parenchymal atrophy is fre- uated by EUS to further risk stratify the lesion.
quently seen [26]. Patients with BD-IPMN, cysts >3 cm, and no other
BD-IPMNs can present as unilocular or multilocular “worrisome features” can be considered for EUS to verify
communicating cystic lesions, with grape-like clusters with a the absence of thickened walls or mural nodules, particu-
variable diameter from few millimeters to some centimeters, larly if the patient is elderly, whereas if the patient is young
uni- or multifocal. The cysts are separated by thin septa, and fit for surgery, surgery should be strongly considered.
which usually enhance after contrast media administration. BD-IPMN with cysts <3 cm and no other “worrisome fea-
In studying BD-IPMN, the demonstration of a communica- tures” should be considered for observation according to
tion with the main pancreatic duct is necessary in order to size stratification [13]. MD-IPMN with MPD dilation of
make the correct diagnosis [2, 27]. When BD-IPMN is very 5–9 mm is considered as a worrisome feature, with a rec-
close to the main pancreatic duct, evaluation of single slice at ommendation of further evaluation, but no immediate
3D MRCP can be useful for correct characterization. resection [13].
Ultrasound Accurate post-processing is needed in order to obtain

multiplanar curved reconstructions, which allow demon-
Conventional US of the pancreas is not able to definitively strating a communication between the cystic pancreatic
diagnose cystic pancreatic lesions. In case of IPMNs, US lesion and the main pancreatic duct, although with a slightly
fails in two important aims: the demonstration of the lower capacity than MRI, having a sensitivity of 83–87%
communication with the main pancreatic duct, essential for [41, 42] and an AUROC of 0.774–0.790 [45]. Moreover,
the final diagnosis, and the evaluation of the number of focal or diffuse dilation of MPD is easily recognized with
lesions (e.g., multifocal IPMNs) [33]. Therefore, US detec- MDCT, whereas the presence of solid enhancing nodules
tion of a cystic pancreatic lesion must always be followed by within the lesion is assessed with a variable degree of sensi-
MDCT or better MRI, if lesion is at least >1 cm [13]. tivity (0–100%), according to different authors [42, 46].
At US, IPMN usually appears as a complex indefinite MDCT is highly accurate in differentiating benign from
hypoechoic mass with dilation of the main pancreatic duct, if malignant cystic pancreatic lesions with an accuracy of
involved [34, 35]. To improve its accuracy, harmonic imag- 71–84.2% [42]. In case of IPMNs, MDCT has a sensitivity
ing must be used to confirm the fluid nature [36]. of 70% in the diagnosis of benignity vs malignancy accord-
The correct technique for the US evaluation of a cystic ing to some features (nodules, main pancreatic duct >10 mm,
pancreatic lesion requires the use of contrast agent injec- thick septa, and calcifications) [46].
tion as reported in the 2011 EFSUMB guidelines [37]. In
cases of IPMNs, CEUS has a sensitivity of 88.2% in identi-
fying enhancing solid nodules [38]. With CEUS, the Magnetic Resonance Imaging
enhancement of internal vegetations sometimes can be bet-
ter demonstrated than with other imaging modalities, An MRI scanner of at least 1.5 T must be used. Oral admin-
thanks to real-time evaluation and high spatial resolution istration a few minutes before the examination of a negative
that allows the detection of single microbubbles passing contrast is useful to reduce the signal from overlying stom-
through the septa and parietal nodules [39, 40]. However, ach and duodenum: 300 ml of pure pineapple or blueberry
CEUS, as US, is limited by meteorism, body habitus, and juice can be used, thanks to the manganese content of these
expertise of the operator. juices, which results in a reduced signal on T2-weighted
images; however, a proprietary silicone-coated superpara-
magnetic iron oxide particle suspension is commercially
Computed Tomography available, which provides a good signal suppression of fluid
content of the stomach and duodenum.
MDCT (at least four rows) is needed with an acquisition An adequate evaluation of the pancreatic parenchyma and
thickness of 2.5 mm and reconstruction of 1.25 mm with the pancreaticobiliary ductal system requires the following
0.65 mm of interval [41]. sequences [47]:
Patient fasts 3–4 h before examination; 10–15 min before
examination, the patient must drink about 500 ml of water in • T2-weighted axial and coronal 2D sequences, usually
order to obtain an adequate distension of the duodenum. turbo spin-echo (TSE) or a variant of TSE Half-Fourier
One hundred to one hundred fifty milliliters of iodinated Acquisition Single-Shot Turbo Spin-Echo, HASTE) in
contrast agent with a concentration of 350–370 mg/ml at a breath-hold.
flow rate of 3–4 ml/s are injected via a power injector, fol- • 2D (breath-hold) and 3D (respiratory-triggered) MRCP
lowed by 20 ml of saline solution at the same flow rate. Flow • T1-weighted axial 2D in-out of phase in breath-hold.
rate influences the degree of pancreatic parenchyma enhance- • T1-weighted axial 2D gradient-echo with fat-saturation in
ment in the pancreatic phase, while the amount of iodine breath-hold.
injected influences the degree of pancreatic parenchyma • T1-weighted axial 3D gradient-echo before and after
enhancement in the venous phase. gadolinium.
At first diagnosis, at least a triphasic technique must be • Optional: DWI acquisition with at least 3 b values (e.g.,
used: an unenhanced phase, a pancreatic phase (35–40 s 50–400-800).
after start of injection), and a venous phase (60–70 s after
start of injection) [41–43]. In the follow-up, a biphasic T2-weighted 2D TSE sequences show pancreatic abnor-
technique can be sufficient, with an unenhanced and a malities as hyperintense areas, whose intensity depends on
venous phase. Unenhanced phase is necessary in order to the content of the lesion: solid lesions are slightly hyperin-
evaluate the degree of enhancement of eventually present tense, whereas cystic lesions are markedly hyperintense.
nodules to differentiate a mucin plug from an enhancing Thus, with these sequences, cystic lesions as IPMNs can be
nodule [44]. easily detected.
MRI with MRCP has the highest capacity to assess the to evaluate the enhancement of lesions, which are hyperin-
presence of communication with main pancreatic duct, with tense in the unenhanced phase.
a sensitivity of 91.4–100%; in case of IPMN, MRI with DWI is emerging as a potential tool in order to evaluate
MRCP has a sensitivity, specificity, and accuracy of 70, 92, solid and cystic lesions of the pancreas [50]. Respiratory-
and 80%, respectively, in the diagnosis of benignity vs triggered acquisitions with multiple b values (0–800) are
malignancy according to some features (nodules, main pan- necessary to obtain good-quality images and information on
creatic duct >10 mm, thick septa, and calcifications) [42, 46, restricted movement of water protons within a lesion, pro-
48]. Moreover, unlike ERCP, the images provided by MRCP vided by ADC values. Controversies still exist about the
are not dependent upon pressure to fill all of the mucin-filled diagnostic value of this technique, as overlapping in ADC
side branches, allowing an accurate characterization of values is observed between both benign and malignant solid
IPMN type and extent. In the differential diagnosis between or cystic lesions. However, high b values are useful to detect
benign and malignant CPL, MRI with MRCP has an accu- small solid portions within cystic masses, which appear
racy of 73–81.6% [42, 49]. 2D MRCP is useful in patients hyperintense. Similarly, mucin plugs, pseudonodules, or
with irregular breathing cycles, as it is acquired in a single nonmalignant nodules within cystic lesions tend to have low
short breath-hold (approximately 5 s). It is allowed to repeat signal intensity on high b values, thus helping in the correct
every few seconds, so that dynamic information on duct dis- assessment of the risk of the lesion. However, small hemor-
tension as well as pancreatic fluid flow can be obtained after rhagic changes within IPMN have a restricted diffusion sig-
secretin injection. 3D MRCP allows a multiplanar recon- nal, which can simulate a solid nodule, but these areas also
struction with MIP algorithm, so that detailed information on appear markedly hyperintense on T1-weighted fat-sat
duct anatomy can be obtained. It requires a regular breathing images.
cycle of the patient for optimal image quality. 2D and 3D
MRCP can be acquired also after gadolinium-based contrast
agent (GBCA) administration, in order to utilize the super- PET
paramagnetic effect of GBCA in the distribution phase: in
such a way, pancreatic parenchyma is markedly hypointense According to several authors, 18FDG studies have a high
on MRCP images, whereas pancreatic ducts and cystic specificity in detecting malignancy in IPMN [51–54].
lesions are hyperintense, thus increasing the contrast to noise However, despite these reported added benefits, the role
ratio of cystic lesions. of PET-CT is not yet established in managing cystic
T1-weighted 2D GRE in-out of phase is useful in the eval- neoplasms.
uation of other organs of the upper abdomen such as the liver
(steatosis; fat content of hepatic lesions) and adrenals (fat
content of adrenal lesions, such as adenomas). EUS
T1-weighted 2D GRE with fat saturation is a sensitive
sequence in order to detect pancreatic abnormalities, EUS provides the highest spatial resolution imaging of the
although its specificity is quite low; pancreatic abnormalities pancreas with an extremely accurate evaluation of the mor-
are seen as hypointense areas, although no clear differences phologic features of cystic tumors. On EUS, any intraductal
can be observed between pancreatic tumors and inflamma- mass, mural nodule, or projection noted within the main duct
tory pancreatic lesions. or off a cyst wall should be sampled by FNA [55]. If no vis-
T1-weighted 3D GRE sequence allows dynamic imaging ible lesions are noted, the main or branch ducts can be punc-
of the pancreas after GBCA administration. The 3D acquisi- tured for cytology and tumor markers. Cytology can reveal
tion permits to obtain thin slices (<3 mm) with a good signal- thick mucin and fragments of papillary mucinous epithelium
to-noise ratio, thus permitting multiplanar reconstructions, in on FNA.
less than 20 s, allowing repeated acquisition after a bolus On the basis of the detection of worrisome features, the
injection of GBCA. 0.1 mmol/kg (0.2 ml/kg with a concen- accuracy of EUS for malignancy is 86% [56, 57]. EUS is
tration of 0.5 M) of GBCA must be used with a flow rate of more sensitive but less specific than MDCT in detecting
2 ml/s, followed by 20 ml of saline flush with the same flow solid components in IPMNs [58].
rate. In order to synchronize the arrival of bolus with imag- EUS-FNA can target areas inside the lesion that are not
ing acquisition, a test bolus or an online bolus detection tech- obtainable by other bioptic modalities. The combination of
nique (Smart Prep and CARE Bolus) is required. Thanks to cytology and fluid analysis is the best modality for diagnos-
the lack of ionizing radiations, multiple acquisitions can be ing malignant lesions [59, 60].
obtained without harming the patient. Usually, a precontrast, EUS-FNA is indicated when a previous diagnostic modal-
a pure arterial, a pancreatic phase, a venous phase, and a dis- ity has depicted IPMNs with worrisome features other than an
tribution phase are acquired. Subtraction technique is useful enhancing solid component, without a definite diagnosis [61].
Clinical Presentation Atypical
Asymptomatic Rarely, atypical appearances of complicated IPMNs have

been reported: intraductal hemorrhage, perforation, and fis-
Due to widespread availability of noninvasive imaging tech- tula formation [68].
niques of the abdomen (US, CT, and MRI), IPMNs nowa- At non-contrast CT, intraductal hemorrhage can be appre-
days are mostly incidentally detected when imaging is ciated as high attenuation areas, whereas at MRI, it can be
performed for unrelated indications [3]. Therefore, many detected as high signal intensity areas on T1-weighted
patients with IPMNs are asymptomatic, and the lesion is images with fat saturation. Although the mechanism of intra-
incidentally found. ductal hemorrhage is still unclear, it is believed that the
exposure of the neoplastic epithelium to high pressure pro-
duced by mucin results in denudating the epithelium, with
Symptomatic intraductal hemorrhage occurring due to injury to the small
vessels around the epithelium [68].
The impaired outflow of pancreatic juice induced by the The same mechanism of denudating epithelium caused by
hypersecretion of mucin [26] may cause pain and produces high mucin pressure is at the base of perforation and fistula
laboratory test abnormalities related to pancreatitis, as hyper- formation, mainly into the duodenum, stomach, and choled-
amylasemia [28]. Thus, IPMN can be discovered after an ochus. Direct invasion of IPMN into other organs and auto-
episode of acute pancreatitis. More severe symptoms, such digestion by enzyme-rich fluid seems also to play an
as jaundice, severe abdominal pain, weight loss, anorexia, important role in fistula formation [69, 70].
and diabetes, are more likely associated with a malignant During the follow-up of some patients with BD-IPMN, a
behavior. dimensional reduction of the lesion can be observed, due to
the widening of the communicating channel between the
lesion and the main pancreatic duct, previously blocked by
Behavior thick mucin; in such cases, the passage of mucin from the
lesion to the main pancreatic duct reduces the pressure inside
Typical the lesion, which shrinks.
In MD-IPMNs, total or segmental ductal dilation is observed,

with or without intraductal hypointense masses. BD-IPMNs Variants
present as unilocular or multilocular communicating cystic
lesion, uni- or multifocal, separated by thin septa. Different pathologic features do not necessarily reflect in
Communication with the MPD is usually appreciated. In different imaging. This is particularly true not only for the
mixed IPMNs, both branch ducts and the main pancreatic different subtypes of epithelial differentiation (gastric
duct are involved. As already stated, some imaging features type, intestinal type, pancreatobiliary type, and oncocytic
are related to an increased risk of malignant degeneration: type) but also for the distinction between IPMNs and intra-
main-duct diameter >5 mm for MD-IPMN, the presence of ductal tubulopapillary neoplasms (ITPNs). Despite this,
nodules within the cyst in BD-IPMN, cyst >3 cm, thickened some distinctive CT and MRI findings of ITPNs have been
enhancing cyst walls, abrupt change in the MPD caliber with reported, as the “two-tone duct sign” and the “cork-of-
distal pancreatic atrophy, lymphadenopathy, and coarse wine-bottle sign” [71], but these findings should be con-
calcifications. firmed in larger series.
In patients with IPMN, pancreatic ductal carcinoma may
develop independently and separately in the pancreatic duct
[62, 63]. Pathology
Increased risk for extra pancreatic malignancies,
mostly gastric and colorectal tumors, has been reported in The intraductal tubulopapillary neoplasm (ITPN) is the last
several studies [64–66]. However, a recent analysis of lit- defined and most recently discovered type of intraductal neo-
erature has criticized these results, as most studies were plasms of the pancreas and is identified as a relatively sepa-
retrospective and only one multicentric, while this asso- rate entity in the 2010 WHO classification of tumors of the
ciation was not reported by the largest and only prospec- digestive system [14].
tive study available, thus not allowing any definitive The most important characteristics that distinguish ITPNs
conclusion [67]. from IPMNs are represented by typical solid and firm growth
pattern with multiple well-circumscribed neoplastic nodules, ADC values between pancreatic juice, IPMN, serous cystad-
presence of evident necrosis with a comedo-like pattern, pre- enoma (SCA), and mucinous cystadenoma.
dominant tubular or tubulo-cribriform architecture, and lack Some authors have shown that MRCP is even superior to
of mucin accumulation. Papillary components are often ERCP in IPMN evaluation, since in the latter the thick mucin
absent or minimum in ITPNs, which tend to form nodules of can sometimes obstruct the communicating duct, thus pre-
back-to-back tubular glands, resulting in large cribriform venting adequate inflow of contrast medium into the dilated
structures within ectatic Wirsung duct. Solid areas with branches, whereas with MRCP, it is still possible to observe
scanty tubular pattern may also be seen. The cellular ele- a continuity of high signal intensity from the MPD to the
ments of this type of neoplasms are cuboidal and resemble cystic dilatation of BD, due to the high signal intensity of
the normal ductal cells. The neoplasms have typically high- mucin [76].
grade dysplasia with invasive carcinoma present in about the In advanced IPMNs with worrisome features, the prolifer-
65% of cases. ating tissue is characterized by enhancement after contrast
The immunophenotype of the cells presents MUC6 posi- media administration, thus overcoming the limit of ERCP,
tivity, a focal MUC1 positivity, and MUC2, MUC5AC, and where the growth of tumor is seen as a filling defect, such as
CDX2 negativity [72–74]. mucin [26]. The enhancement of the nodules can be appreci-
ated with all imaging techniques (CEUS, CT, and MRI),
after administration of contrast media. With power Doppler,
Pitfalls and Errors if lesion is clearly visible, a vascular signal can be appreci-
ated, especially at EUS.
The clinical presentation of IPMN with acute pancreatitis Moreover, at MRI, it is possible to demonstrate the prolif-
can masquerade the underlying lesion, which can be erating tissue within the IPMNs, thanks also to the restricted
misdiagnosed. diffusion of water molecule by using DWI sequences. Non-
Extensive pancreatic calcifications are generally thought enhancing nodules can be dense mucin plugs, which do not
to be a sign of chronic pancreatitis, but it may occur simulta- show restriction at DWI.
neously with IPMN leading to diagnostic difficulties [75].
Marked parenchymal atrophy can mislead to a diagnosis
of enhancing tick walls of IPMN, which are actually caused Differential Diagnosis
by a residual pancreatic parenchyma close to the lesion. DWI
can help in differential diagnosis, as in this case there is no Using a combination of clinical history, sex, age, imaging
sign of restricted diffusion. characteristics, cytology, cyst fluid chemical analyses of car-
Sometimes, the communication between BD-IPMN and cinoembryonic antigen (CEA), and amylase, pancreatic
the main pancreatic duct is not clearly visible, thus giving cysts can be characterized, and a reliable preoperative diag-
problems in differential diagnosis, which, in this case, is nosis can be made [13].
mostly based on other morphological findings. MD-IPMN must be differentiated from main-duct dila-
MRI is not able to identify calculi within the ducts; thus, tion seen in chronic pancreatitis [9]. It must be taken into
in some cases, calcifying chronic obstructive pancreatitis account that chronic pancreatitis may also be caused by
with enlargement of main pancreatic duct can be interpreted IPMNs, making the clinical and radiological differential
as an MD-IPMN. diagnosis even more difficult [28]. In a comparative study
between IPMNs and chronic pancreatitis, the reported spe-
cific imaging findings for IPMN were ductal dilation without
Imaging-Pathologic Correlation strictures, bulging ampulla, nodule in a duct, grape-like sec-
ondary ducts dilatation, and nodule presence within a cyst;
The flat epithelium-producing mucin is not recognizable on the other hand, the reported specific findings for chronic
with current imaging techniques; thus, in non-complicated pancreatitis were duct dilation with strictures, the presence
IPMNs, we usually observe only ductal dilation caused by of stones, and side-branch ectasia with non-cystic appear-
mucin overproduction. Mucin has usually the same pattern ance. Duct dilation without stricture and a grape-like cyst
of pancreatic juice with the different imaging techniques shape were independently associated with IPMNs, whereas
(hypoechoic at US, hypodense at CT, hyperintense on duct dilation with strictures was independently associated
T2-weighted images, and hypointense on T1-weighted with the chronic pancreatitis [77]. In chronic pancreatitis, in
images at MRI); thus, it is not possible to differentiate mucin the absence of parenchymal atrophy, parenchymal signal
from pancreatic juice. Although some authors suggested that intensity changes at MRI can be observed, such as a decrease
with DWI it is possible to differentiate the content of cystic of T1 signal and a delayed uptake of contrast material, indic-
lesions of the pancreas [75], there is a significant overlap in ative of fibrosis [78, 79].
Branch-duct and mixed IPMNs may be similar to MCNs cysts’ fluid, the carcinoembryonic antigen (CEA) levels are
and to macrocystic SCAs [80]. Differentiation can be elevated in many mucinous cystic tumors. In this setting,
obtained evaluating the communication with the pancreatic CEA levels in the cyst fluid provide the best predictor; the
ductal system, present only in IPMNs. However, in some most valuable cutoff value for SCN diagnosis is CEA < 5 ng/
cystic tumors closely located to the main pancreatic duct, a ml, whereas the best cutoff value to differentiate a mucinous
communication cannot be easily confirmed or excluded. lesion is CEA > 192 ng/ml [83, 84].
Mucinous cystic neoplasms are usually located at pancreatic Acinar cell cystadenoma (ACC), also known as acinar
body/tail [81] and, as SCAs, do not communicate with the cystic transformation of the pancreas, is an uncommon path-
pancreatic duct. ological entity that was first described in 2002 [85, 86]. ACC
Imaging findings suggesting a serous neoplasm are micro- is a benign cystic epithelial lesion lined with cells that are
cystic appearance, lobulated margins, and a central scar, but morphologically and immunohistochemically similar to aci-
only a microcystic appearance is significantly associated nar cells. The origin of ACC is still a subject of debate.
with the diagnosis of serous cystic neoplasm. A central scar Although it was initially considered to be a non-neoplastic
has a sensitivity, specificity, and PPV of 32, 100, and 100%, entity, some authors suggest that lack of ductal obstruction,
respectively. The combination of microcystic appearance chronic inflammation, and fibrosis in the adjacent pancreatic
and lobulated margins has a sensitivity, specificity, and PPV tissue eliminate the probability of this being a non-neoplastic
of 68, 100, and 100%, respectively [42]. lesion [85, 87].
In an analysis of 41 patients with histologically confirmed Most of the reported ACCs were misdiagnosed as cystic
macrocystic neoplasms of the pancreas (10 serous macrocys- tumor by the preoperative radiologic examination. Because it
tic cystadenomas, 13 mucinous cystadenomas, and 18 is a benign condition that is not aggressive, correct diagnosis
IPMNs), significant differences in lesion shape were found of ACC on imaging would certainly change patient manage-
between serous macrocystic cystadenoma and the other mac- ment and would prevent pancreatic resection in most of these
rocystic neoplasms [82]. Serous macrocystic cystadenoma patients. Imaging appearance of ACC is a well-delineated,
usually shows a multicystic or lobulated contour with or homogeneously hypovascular cystic mass with thin septa-
without septation (90% specificity), whereas mucinous cyst- tions [87]. In case of multilocular ACCs, numerous clustered
adenoma has a smooth contour with or without septation peripheral cysts, with tiny calcifications, not communicating
(92.2% specificity), while IPMNs have either a pleomorphic with the main pancreatic duct are observed [88].
or a clubbed finger-like cystic shape (77.8% specificity).
Serous macrocystic cystadenoma showed proximal MPD
dilatation from the lesion, whereas IPMN usually showed Pathologic Differential Diagnosis
distal or whole MPD dilatation. No significant difference
was apparent among the three diseases in terms of location Pathologic differential diagnosis mainly interest ITPNs ver-
and greatest dimension [81]. To differentiate IPMNs from sus IPMNs: the first usually have solid and firm growth pat-
other cystic pancreatic lesions, MDCT has a sensitivity, tern with multiple well-circumscribed nodules, evident
specificity, PPV, NPV, and an AUROC of 80, 86, 89, 76%, necrosis with a comedo-like pattern, predominant tubular or
and 0.850–0.875, whereas MR has a sensitivity, specificity, tubulo-cribriform architecture, and lack mucin accumula-
PPV, NPV, and AUROC of 96.8, 90.8, 92.3, 95.1%, and tion. Papillary components are often absent or minimum.
0.932–0.995, respectively [45]. Moreover, immunolabeling of MUC5AC is common in
Ultrasound-guided aspiration of the cystic fluid may be IPMNs but negative in the vast majority of ITPNs.
helpful; while the levels of amylase are increased in pseudo-
Image Gallery
a b
Fig. 1 IPMN branch-duct type: morphology. (a) Surgical specimen cystic lesion (arrow) involving the branch duct filled by thick tenacious
(pancreaticoduodenectomy, particular): uncinate process of the pan- mucoid material. Probe in the common bile duct (Courtesy of Piccin
creas with a small multicystic grape-like lesion (arrow) involving the Editore, Milan, Italy)
branch ducts. (b) Surgical specimen (pancreaticoduodenectomy): uni-
Fig. 2 IPMN branch-duct type: site. Whole

mount macrosection, surgical specimen
(pancreaticoduodenectomy): small unicystic
BD-IPMN (asterisk) involving the uncinate
process of the pancreas. Wirsung duct (W).
Common bile duct (C)
a b
Fig. 3 IPMN branch-duct type: content. (a) Surgical specimen (pan- unicystic lesion (arrow) with solid content in the form of papillary veg-
creaticoduodenectomy): unicystic lesion (arrow) with viscous translu- etations. Probe in the Wirsung duct
cent fluid content. (b) Surgical specimen (pancreaticoduodenectomy):
a b
Fig. 4 IPMN branch-duct type. (a) Ultrasound study: small unicystic lesion (arrow) in the uncinate process of the pancreas. (b) Ultrasound study:
multicystic lesion with thick septa (arrow) and lobulated contours
a b
Fig. 5 IPMN branch-duct type: multicystic appearance. (a) Ultrasound T2-weighted images (b) and lobulated contours (arrow in b). On MRCP
study: multicystic branch-duct IPMN (arrow). (b, c) MRI study: (c), the cystic lesion (arrow in c) is connected with the main pancreatic
branch-duct IPMN with typical cystic hyperintense appearance on duct (W in c)
a b
Fig. 6 IPMN branch-duct type. (a) CEUS study: pancreatic body-tail small multicystic grape-like lesion (arrow) with lobulated contours
small multicystic lesion with lobulated contours (arrow) and multiple bulging the pancreatic profile
vascularized septa. (b) Surgical specimen (distal pancreatectomy):
a b
c d
Fig. 7 IPMN mixed type. (a) CEUS study: pancreatic head multicystic (arrow in c) in the body of the pancreas with a dilated Wirsung duct in
lesion with lobulated contours (arrow) and multiple thin centrally ori- between. On MRCP (d) the two lesions (arrows in d) with dilated
entated vascularized septa. (b–d) MRI study: axial T2-weighted (b) Wirsung duct in between are perfectly shown. Initial dilation of the
images show pancreatic head complex multicystic lesion with lobulated common bile duct (C in d) is also appreciable. (e) Surgical specimen
contours (arrow in b) and multiple thin septa. Coronal T2-weighted (c) (total pancreatectomy): multifocal IPMN; multiple cystic lesions are
images show also a complex multicystic lesion with lobulated contours visible on the cut section (zoomed particular)
Fig. 7 (continued)
a b
Fig. 8 IPMN with invasive carcinoma. (a) Ultrasound study: pancre- (pancreaticoduodenectomy): mucoid material dissociates the uncinate
atic hypoechoic mass (arrowheads) in the uncinate process of the pan- process of the pancreas. Residual fibrous pancreatic parenchyma
creas with very thin hyperechoic strings (arrow). (b) Surgical specimen (arrow) is present. Wirsung duct (W)
a b
c d
Fig. 9 IPMN branch-duct type. (a) Ultrasound study: pancreatic images (b) and lobulated contours (arrow in b). On dynamic phases (c,
hypoechoic small nodule (calipers). (b–d) MRI study: branch-duct d), multiple very thin vascularized septa (arrow in c) are detectable
IPMN with typical multicystic hyperintense appearance on T2-weighted delimitating the small lesion cystic cavity
Fig. 10 IPMN branch-duct type. (a)

Ultrasound study: unique unicystic lesion a
(ROI) at ultrasound studied by means of
acoustic radiation force impulse
ultrasound. (b) MRCP study: the cystic
lesion (arrow) is confirmed, but other
cystic lesions are visible connected with
the main pancreatic duct in the pancreatic
tail and in the pancreatic body
b
Fig. 11 IPMN branch-duct type: content. (a) CEUS study: unicystic MRI study: the cystic lesion is confirmed with typical hyperintense
lesion with elongated morphology and vascularized hyperechoic intral- appearance on T2-weighted images and with clear vegetation defect
esional papillary vegetation (arrow) during the dynamic phases. (b) (arrow) in the lumen
Fig. 12 IPMN branch-duct type. EUS

study: small cystic lesion (ipmt-s) of
the pancreatic isthmus with a normal
sized Wirsung duct (W)
a b
Fig. 13 IPMN branch-duct type. (a, b) CT study: on dynamic phase (a), a small cystic hypodense lesion is visible (arrow in a). On minimum
intensity projection reconstructions (b), a connection (arrow in b) between the cystic lesion and the main pancreatic duct is clearly visible
a b
Fig. 14 IPMN branch-duct type. (a) CT study: minimum intensity pro- dynamic phase (c), a small cystic hypodense lesion is visible (arrow in
jection reconstructions showing a cystic lesion with lobulated contours c) in the uncinate process of the pancreas. On minimum intensity pro-
(arrow) connected with the main pancreatic duct. (b) CT study: mini- jection reconstructions (d), a connection (arrow in d) between the cys-
mum intensity projection reconstructions showing a small cystic lesion tic lesion and the main pancreatic duct is visible
(arrow) connected with the main pancreatic duct. (c, d) CT study: in the
a b
Fig. 15 IPMN branch-duct type. (a, b) MRI study: branch-duct IPMN image (b), the lesion is clearly in connection with the main pancreatic
with typical cystic hyperintense appearance on T2-weighted images (a) duct (W in b)
and lobulated contours (arrow in a). On T2-weighted more caudal axial
a b
Fig. 16 IPMN branch-duct type. (a, b) MRCP (a) and T2-weighted HASTE (b). A monofocal unilocular finger-like dilation of a branch duct is
visible in the neck of the pancreas
a b
d
c
e f
Fig. 17 IPMN branch-duct type. (a–f) MRI study: a monofocal multi- With GE T1-weighted fat-sat (e), the septa are slightly visible. With
locular dilation of a branch duct in the uncinate process is appreciated Gd-enhanced MRI (f), no pathological enhancement of solid nodules is
with MRCP (a). The main pancreatic duct downstream is slightly appreciable; slight enhancement of the septa. At surgical resection, no
dilated. With T2 HASTE (b), no evidence of solid nodules. Thin septa involvement of main pancreatic duct was observed, whose dilation was
are visible (white arrow in b). With DWI, at b 600 (c), no evidence of due to the overproduction of mucin by the lesion in the branch duct
solid nodules. With ADC map (d), the signal intensity is high (n = 2.9).
a b
c d
Fig. 18 IPMN branch-duct type: ubiquity. (a) MRI study: small small branch-duct IPMN in the isthmus of the pancreas. (d) MRI study:
branch-duct IPMN in the uncinate process of the pancreas. (b) MRI small branch-duct IPMN in the body of the pancreas
study: small branch-duct IPMN in the pancreatic head. (c) MRI study:
a b
Fig. 19 IPMN branch-duct type. (a, b) MRI study: large cystic lesion With sub-MIP reconstruction (b), the communication between the cys-
very close to the main pancreatic duct is appreciated in the body of the tic lesion and the main pancreatic duct is clearly visible
pancreas at MRCP (a). Dilation of cisterna chyli (* in a) is appreciable.
a b
c d
Fig. 20 IPMN branch-duct type. (a, b) Ultrasound study: lobulated contours (arrow in c, d). On DWI (e), the lesion is slightly hyperintense
cystic lesion (calipers in a) of the pancreatic head. At CEUS (b), the on high b-value evaluation (T2 shine-through artifact). On MRCP (f),
lesion shows thin wall and vascularized septa. (c–h) MRI study: branch- the cystic lesion (arrow in f) is connected with the main pancreatic duct
duct IPMN with typical cystic appearance hypointense on T1-weighted (W in f). On dynamic phases (g, h), very thin vascularized intralesional
images (c) and hyperintense on T2-weighted images (d) and lobulated septa are visible
e f
g h
Fig. 20 (continued)
a b
c d
Fig. 21 IPMN branch-duct type. (a, b) MRI study: axial T2-weighted coronal T2-weighted image (c) in which a multicystic grape-like lesion
image (a) in which a lobulated cystic lesion (arrow in a) is visible in the (arrow in c) is visible in the pancreatic head. At MRCP (d), a very thin
pancreatic tail. At MRCP (b), a connection (arrow in b) between the connection between the lesion and the main pancreatic duct is visible
lesion and the main pancreatic duct is demonstrated. (c, d) MRI study:
a b
Fig. 22 IPMN branch-duct type: multifocal aspect. (a) MRCP study: clearly detectable in the pancreatic head. (b) MRCP study: multifocal
large cystic lesion (long arrow) in the pancreatic tail in connection with branch-duct IPMN
the main pancreatic duct. Other small cystic lesion (small arrow) is
a b
Fig. 23 Multifocal branch-duct type IPMN. (a) MRCP study: multiple small hyperintense cystic lesions with a Wirsung duct regular in caliber.
(b) Surgical specimen (distal pancreatectomy): multifocal (arrows) branch-duct IPMN. Main pancreatic duct (W) is normal
Fig. 24 Multifocal branch-

duct type IPMN: intralesional
a b
deposits. (a–e) MRI study:
lobulated cystic lesion (arrow
in a) with thin septa is visible
in the pancreatic body
hyperintense on axial
T2-weighted images (a) and
with deposits and fluid-fluid
level on coronal T2-weighted
images (b) within the lesion
(arrow in b). On MRCP (c),
multiple cystic lesions are
easily detected. In the
dynamic phases (d, e), the
lesion shows intralesional
vascularized thin septa
c d
e
a b
c d
Fig. 25 Branch-duct type IPMN with pseudonodule. (a–c) MRI study: With T2-weighted HASTE (b), DWI b 800 (c), and Gd-enhanced MRI
a large multiloculate cystic lesion communicating with the main pan- (d), no nodules are recognized in the lesion. Due to previous Billroth II
creatic duct is visible in the uncinate process at MRCP (a). In the surgical procedure, an EUS was not feasible. (e) Macrosection: multi-
infero-lateral portion of the cyst, a defect is recognizable (arrow in a). loculated cystic lesion with no evidence of solid nodules
a b
c d
Fig. 26 Multifocal branch-duct type IPMN and pseudonodule. (a–d) b 600 (c), no diffusion restriction is appreciated within the lesion. With
MRI study: multifocal BD-IPMN with non-enhancing nodule. At Gd-enhanced MRI (d), no enhancement can be appreciated in the
MRCP (a), a multifocal BD-IPMN is recognizable. With T2-weighted nodule
HASTE (b), a solid nodule is visible in the largest lesion. With DWI at
a b
Fig. 27 IPMN branch-duct type: pseudo-solid ultrasound appearance. At CEUS (b), the pancreatic mass is completely avascular (arrow in b).
(a, b) Ultrasound study: at conventional ultrasound (a), hypoechoic (c) MRI study: branch-duct IPMN with typical cystic appearance
mass (arrow in a) is detected in the uncinate process of the pancreatic. hyperintense on T2-weighted images (arrow)
Fig. 27 (continued)
Fig. 28 IPMN branch-duct type: stable at follow-up. (a) MRCP study

(Mar 1999): multiple small branch-duct IPMNs. (b) MRCP study (Mar
2000): essentially unchanged multiple small branch-duct IPMNs
a b
d
c
Fig. 29 IPMN branch-duct type. (a) MRCP: small cystic dilation of a significant alterations of the pancreatic parenchyma at T2-weighted
branch duct. (b) MRCP 1 year later: unchanged. (c–e) MRI study HASTE (d) and DWI b 800 (e)
4 years later: on MRCP (c), the lesion is markedly decreased with no
a b
c d
Fig. 30 Multifocal branch-duct type IPMN: progression. (a–c) MRI enhancing tissue around the cystic cavity on dynamic images (f, g).
study: in the uncinate process of the pancreas, cystic lesion (arrow in a) (h–l) MRI study (after 3 months): on axial T2-weighted images (h, i),
hyperintense on axial T2-weighted images (a). Other multiple cystic the known cystic lesions in the uncinate process of the pancreas (arrow
lesions are easily detected in the head and in the body-tail of the gland in h) and in the pancreatic tail (arrow in i) show thicker wall. On DWI
hyperintense on axial T2-weighted images (b). MRCP (c) panorami- (j), in the lesion of the tail of the pancreas, small nodules (arrow in j)
cally shows the evident multifocal aspect of the disease. The main pan- with clear diffusion restriction at high b-value are detected. On dynamic
creatic duct (arrow in c) is regular in caliber. (d–g) MRI study (after phases (k), the lesion in the tail of the pancreas is enlarged, and the
6 months): on axial T2-weighted images (d, e), the known cystic lesions enhancement of cystic wall is clearly more irregular and thick. MRCP
at the uncinate process of the pancreas (arrow in d) and in the pancre- (l) shows dilated main pancreatic duct (arrow in l)
atic tail (arrow in e) show irregular thick wall with inhomogeneous
e f
g h
i j
Fig. 30 (continued)
k l
Fig. 30 (continued)
a b
Fig. 31 Branch-duct type IPMN with nodule. (a–c) MRI study: coro- cystic pancreatic body lesion with intralesional vascularized nodule
nal T2-weighted images (a) showing a pancreatic body cystic lesion (arrow). (e, f) Surgical specimen (distal pancreatectomy): cystic lesion
(arrow in a) with hypointense vegetation that is confirmed at MRCP (b) (arrow in e) bulging the inferior profile of the pancreatic body. At the
as an intracystic nodule (arrow in b). In the dynamic phase (c), focal cut section (f), the presence of intralesional solid nodule (N in f) is
enhancing thickening of the wall is detected (arrow in c). (d) CEUS: confirmed
e f
Fig. 31 (continued)
a b
c d
Fig. 32 IPMN branch-duct type: progression. (a–d) MRI study: on hypointense on T2-weighted HASTE (f), hyperintense on DWI b 800
MRCP (a), a unifocal multilocular 4 cm BD-IPMN is visible in the (g), and enhancing after Gd administration (h). The patient refused sur-
uncinate process. With T2 HASTE (b), DWI b 800 (c), and Gd-enhanced gery. (i–l) MRI study after 6 months: a large mass is appreciated on
MRI (d), no solid nodules are appreciated. (e–h) MRI study at 4-month T2-weighted HASTE (i), markedly hyperintense on DWI b 800 (j),
follow-up: a solid nodule appears visible as a defect at MRCP (e), hypoenhancing after Gd administration (k), with liver metastases (l)
e f
h
g
k l
Fig. 32 (continued)
a b
Fig. 33 IPMN main-duct type. (a) Surgical specimen (pancreaticodu- profile (arrow). Common bile duct (C) is dilated. (b) Macrosection of
odenectomy): the main pancreatic duct (W) is enlarged and filled by the Wirsung duct: the main pancreatic duct (W) is dilated and with mul-
multiple small papillary vegetations giving to the lesion an irregular tiple papillary projections along the wall
Fig. 34 IPMN main-duct type. (a–c) a

Surgical specimen (total pancreatectomy):
the main pancreatic duct is dilated, and
after a longitudinal cut (a), the internal
surface is smooth. Downstream (b) and
upstream (c) at transverse cut, the main
pancreatic duct is confirmed to be dilated
and with regular smooth internal surface.
Distally the main pancreatic duct is
extremely more dilated appearing as a
cystic lesion collapsed after cut
c
a b
Fig. 35 IPMN main-duct and branch-duct type: content. (a) Surgical small papillary projections are visible along the internal wall of the
specimen (distal pancreatectomy): the main pancreatic duct (W) is sur- dilated main pancreatic duct (W) and into the dilated branch ducts
rounded by multiple dilated branch ducts. (b) Macrosection: multiple
Fig. 36 IPMN main-duct and branch-duct type: content.

Macrosection: the main pancreatic duct (W) is dilated and filled
by multiple grossly visible papillary vegetations. Also the
branch ducts (arrow) are dilated and filled by multiple papillary
vegetations
b c
Fig. 37 IPMN main-duct type. (a) Ultrasound study: dilated (calipers) main pancreatic duct. (b, c) MRCP: main-duct IPMN with typical uniform
dilation of the main pancreatic duct (W in c) from the tail to the major papilla
a b
Fig. 38 IPMN main-duct type. (a) Ultrasound study: dilated main pancreatic duct (W) ending in an inhomogeneously hypoechoic mass (arrow)
only partially cystic. (b, c) CT study: dilated main pancreatic duct (W in b) ending in an inhomogeneously hypodense cystic mass (arrow in c)
a b
Fig. 39 IPMN main-duct type. (a–d) MRI study: segmental dilation of map (c), the ROI shows no restricted diffusion of water molecules in the
main pancreatic duct in the head of the pancreas is visible at MRCP (a). pancreatic lumen (n = 3.6). With Gd-enhanced MRI (d), no pathologi-
With T2 HASTE (b), no evidence of solid nodules. With DWI, at ADC cal enhancement of solid nodules is appreciable
Fig. 40 IPMN. EUS study: branch-duct

IPMN (BD-IPMN) in communication with the
Wirsung duct (W) slightly dilated
Fig. 41 IPMN. MRCP (left) and ERCP (right) studies: on MRCP, branch-duct IPMN (white arrow) is visible in communication with the Wirsung
duct (W) slightly dilated. On ERCP, only the dilated Wirsung duct (W) and the lesion communication (black arrow) are injected
Fig. 42 IPMN mixed type. MRCP:

multiple cystic dilation of branch ducts and
main pancreatic duct dilation in the
body-tail
a b
c d
Fig. 43 IPMN mixed type. (a–d) MRI study: at MRCP (a) significant nodules are highlighted. After Gd injection (d), slight enhancement of
segmental dilation of the main pancreatic duct is visible in the neck of the septa can be appreciated. No solid nodule enhancement. (e)
the pancreas. A BD-IPMN is recognizable in the body of the pancreas. Macrosection: the Wirsung duct (W) appears enlarged with small endo-
With T2 HASTE (b), thin septa can be appreciated in the main lesion luminal papillary proliferations
due to the involvement of branch duct. With DWI at b 800 (c), no solid
a c
Fig. 44 IPMN main-duct type: nodular/papillary vegetations. (a, b) (SMV). (e) Intraductal ultrasound: endoscopic ultrasound inside the
Ultrasound study: at conventional ultrasound (a), a dilated Wirsung Wirsung duct (W) shows some very small nodules (arrows) on the duct
duct (W in a) is visible with echoic vegetation (arrow in a) in the lumen. wall. (f, g) Surgical specimen (pancreaticoduodenectomy): in the
After contrast medium administration (b), the enhancement of the Wirsung duct (probe in f), a nodule (arrow in f, particular) is visible.
endoductal nodule becoming hyperechoic (arrow in b) is appreciable. After longitudinal cut of the Wirsung duct (W in g), the nodule (arrow
(c) Dynamic MRI: enhancement of small nodule (arrow) completely in g) is confirmed to originate from the ductal wall of the main pancre-
inside a focally dilated Wirsung duct. (d) EUS: small papillary vegeta- atic duct. Moreover, other small irregularities of the Wirsung wall are
tions (arrow) inside a cystic pancreatic lesion. Superior mesenteric vein present
d e
f g
Fig. 44 (continued)
a b
c d
Fig. 45 IPMN main-duct type: intraductal large nodular vegetation. T2-weighted HASTE (b), the nodule is isointense. With DWI b 600 (c),
(a) Dynamic CT: significant enlargement of the main pancreatic duct the nodule is markedly hyperintense. With Gd-enhanced MRI (d), a
with a solid enhancing nodule is appreciated. (b–d) MRI study: on significant enhancement of the nodule can be appreciated
a b
c d
e f
Fig. 46 IPMN mixed type: papillary vegetations. (a) Ultrasound ducts. On T2-weighted HASTE (d), the solid component is hypoin-
study: dilation of main pancreatic duct with solid component is visible. tense, with enhancement after gadolinium injection (e). (f) Surgical
(b) CT study: enhancement of the solid component (asterisk) is appre- specimen (distal pancreatectomy): the Wirsung duct is probed and sec-
ciated. (c– e) MRI study: with MRCP (c), diffuse enlargement of the tioned. The papillary growth (arrow) is visible
main pancreatic duct is recognized with the involvement of branch
a b
c d
Fig. 47 IPMN main-duct type: intraductal large nodular vegetations. ble. At DWI moving from low (c–d) to high (e) b-values, a clear
(a–h) MRI study: coronal T2-weighted image (a) showing a huge diffusion restriction is visible in the intraductal nodular vegetations
enlargement of the main pancreatic duct containing solid vegetations (arrows in e). Dynamic MRI (f–h) perfectly demonstrates the vascular-
(arrow in a). MRCP (b) confirms the diffuse dilation of the main pan- ization of the nodular vegetations (arrow in f) inside the dilated main
creatic duct (W in b) with endoductal defects (arrow in b) clearly visi- pancreatic duct
e f
g
h
Fig. 47 (continued)
a b
c d
e f
Fig. 48 IPMN mixed type: pseudonodular vegetation at imaging. (a– Histopathology: at macrosection (d), enlarged Wirsung duct and branch
c) MRI study: on T2-weighted HASTE (a), both branch duct and main ducts with a residual normal parenchyma (arrow in d) are visible. On
pancreatic duct appear enlarged in the tail of the pancreas. A solid com- magnification (e), normal residual pancreatic parenchyma. The enlarged
ponent is visible in the tail (arrow in a). With Gd-enhanced MRI (b), lumen of Wirsung duct is visible (W in e). On magnification (f), branch
the solid component shows enhancement (arrow in b). With DWI b 800 duct with mucinous epithelium showing low-grade dysplasia
(c), the solid component does not show increased signal intensity. (d–f)
a b
c d
e f
Fig. 49 IPMN main-duct type with ductal adenocarcinoma. (a, b) MD-IPMN is unchanged (c). In the uncinate process appeared a solid
Dynamic CT study: dilation of main pancreatic duct in the body-tail of mass, hypointense on T2-weighted HASTE (d), hyperintense on DWI b
the pancreas is appreciated. On more caudal plan (b), the uncinate pro- 600 (e) with restricted diffusion at ADC map (f), and hypovascularized
cess is normal. (c–g) MRI study performed 9 months later: the after Gd injection (g) and diagnosed at FNA as ductal adenocarcinoma
a b c
Fig. 50 IPMN: bulging papilla. (a, b) MRI study: on coronal duodenectomy) of different case: duodenal wall (c) with bulging major
T2-weighted image (a) and on MRCP (b) is visible a large cystic com- papilla (P). On cut section (d), the Wirsung duct is hugely dilated and
plex mass (arrow in a) connected with the main pancreatic duct bulging filled by mucoid material (asterisk in d)
in the major papilla (arrow in b). (c, d) Surgical specimen (pancreatico-
a b
Fig. 51 IPMN main-duct type: duodenal invasion. (a) MRCP: huge different case: from a dilated main pancreatic duct (W) through the
dilation of the main pancreatic duct (W). The region of the major papilla major papilla neoplastic tissue (arrow in b) is invading the lumen of the
is occupied by a clear large defect caused by the presence of neoplastic duodenum. The common bile duct (C) is consequently dilated
solid vegetation. (b) Surgical specimen (pancreaticoduodenectomy) of
a c
Fig. 52 IPMN main-duct type: symptomatic. (a–c) MRI study: axial T2-weighted images (a), MRCP (b), and dynamic pancreatic phase (c) show
a sectorial dilation of the main pancreatic duct (arrow in a)
a b
c d
Fig. 53 Mixed-type IPMN: perilesional logistic changes. (a, b) MRI steatonecrosis (asterisk in e). Longitudinal cut of Wirsung duct (W in f)
study: at MRCP (a) diffuse dilation of main pancreatic duct is appre- with papillary proliferations with moderate-grade dysplasia. Pancreatic
ciable in the body-tail of the pancreas with a diameter > 10 mm. With parenchyma shows fibrosis and slight atrophy of the acinar component
T2-weighted HASTE (b), no significant solid nodules are appreciable. (asterisk in f). Severe atrophic changes of the perilesional pancreas with
(c, d) CT study: on unenhanced scans (c, d), a coarse calcification can residual islet of Langerhans (arrow in f). On magnification (g) Wirsung
be appreciated in the wall of the lesion. No other calcification can be duct (W in g) with dilated branch duct (asterisk in g) with low-grade
appreciated. Fatty infiltration in the head of the pancreas. (e–h) dysplasia (arrow in h)
Histopathology: at macrosection (e), duodenal wall (D in e) and area of
e f
Fig. 53 (continued)
a b
c d
Fig. 54 IPMN main-duct type: symptomatic. (a) Dynamic CT: marked dence of solid nodules. With DWI, at ADC map (d), the ROI shows no
diffuse dilation of main pancreatic duct with significant atrophy of pan- restricted diffusion of water molecules (n = 4.0) in the pancreatic
creatic parenchyma is visible. (b–e) MRI study: with MRCP (b), the lumen. With Gd-enhanced MRI (e), no pathological enhancement of
dilation of main pancreatic duct is clearly visible for all extension, with solid nodules is appreciable
no evidence of pancreatic duct stenosis. With T2 HASTE (c), no evi-
a b
c d
Fig. 55 IPMN mixed type: symptomatic. (a–d) MRI study: on axial ducts throughout the entire pancreatic gland. The common bile duct (C
T2-weighted images (a–c) and on MRCP (d), diffuse dilation of the in d) is normal
main pancreatic duct (W in d) is visible together with some branch
Fig. 56 IPMN main-duct

type: symptomatic. MRCP:
diffuse dilation of the main
pancreatic duct (MPD)
reaching and bulging the
minor papilla (santorinicele).
The common bile duct (C) is
normal
a b
c d
Fig. 57 IPMN mixed type. (a) MRCP: cystic pancreatic mass (arrow) communication with a dilated main pancreatic duct (orange line). The
in communication with a dilated main pancreatic duct (W). The com- common bile duct (green line) is dilated. (d) Superimposed drawings
mon bile duct (C) is dilated. (b) Surgical specimen (pancreaticoduode- on surgical specimen: IPMN branch-duct type (circle) in communica-
nectomy): IPMN branch-duct type (arrow) in communication with a tion with a dilated main pancreatic duct (orange line). Common bile
dilated main pancreatic duct (W). Common bile duct (C) is normal. (c) duct (green line)
Superimposed drawings on MRCP: cystic pancreatic mass (circle) in
a b
d
c
e f
Fig. 58 IPMN mixed type: solid component with pathologic correla- solid components (arrows in e). At dynamic MRI (f, g), the cystic pan-
tion. (a–g) MRI study: on coronal T2-weighted image (a), a cystic mass creatic head mass shows vascularized irregular thick wall (arrow in f)
(arrow in a) is visible in the pancreatic head. On MRCP (b), the pancre- and thick intralesional vascularized septa (arrow in g). (h) Surgical
atic head cystic lesion is in communication with a minimally dilated specimen, transverse cut section of the cystic lesion: IPMN branch-duct
main pancreatic duct (W in b). At DWI moving from low (c, d) to high type with solid component along the wall (asterisk) and thick intrale-
(e) b-value, a clear diffusion restriction is visible in small intralesional sional septa (arrow)
g h
Fig. 58 (continued)
a b
Fig. 59 IPMN main-duct type: solid component with pathologic cor- vascularized thin irregular septa (arrow in e). (f–j) Surgical specimen
relation. (a, b) Ultrasound study: at conventional scan (a), the main (pancreaticoduodenectomy): IPMN with dilated main pancreatic duct
pancreatic duct (W in a) is enormously dilated stopping into an ill- (W in f). Probe in the common bile duct. Particular of the main pancre-
defined inhomogeneous mass of the pancreatic head. At CEUS (b), atic duct (g) that presents multiple intraductal papillary projections
inside, the mass solid enhancing papillary projections (arrow in b) are (arrow in g). The longitudinal cut (h) along the main pancreatic duct
clearly detected. (c–e) MRI study: on T2-weighted image (c), a large (W in h) highlights the multiple intraductal papillary projections (arrow
cystic mass (arrow in c) is visible in the pancreatic head. On MRCP (d), in h). Transverse cut (i) shows cystic lesion rich in papillary vegeta-
the cystic mass (arrow in d) is directly connected with a dilated main tions. Macrosection (j) of the cystic lesion filled by papillary vegeta-
pancreatic duct (W in d). At dynamic MRI (e), the cystic mass shows tions (Courtesy of Piccin Editore, Milan, Italy)
c d
e f
Fig. 59 (continued)
g h
i j
Fig. 59 (continued)
a b
c d
Fig. 60 IPMN main-duct type: solid component, degeneration, and images (d), inside the lesion, solid a component (arrow in d) is clearly
duodenal infiltration. (a) Ultrasound study: the main pancreatic duct visible. MRCP (e) shows that the mass (arrow in e) is connected with the
(calipers) is dilated stopping into an ill-defined inhomogeneous mass of main pancreatic duct (W in e) diffusely dilated. On dynamic phases (f),
the pancreatic head. (b–f) MRI study: on T1-weighted images (b), a inhomogeneous enhancement of the mass (arrow in f) is appreciable.
large, ill-defined especially in respect to the duodenum, inhomogeneous Involvement of the duodenum and superior mesenteric vein infiltration
hypointense mass (arrow in b) is confirmed in the pancreatic head. On is present. (g) Surgical specimen (pancreaticoduodenectomy) of differ-
T2-weighted images (c), the mass (arrow in c) shows predominant cys- ent case: IPMN with infiltrating mucinous component involving the pan-
tic component but with thick irregular wall. On coronal T2-weighted creatic head and the duodenum. Dilated Wirsung duct (W)
Fig. 60 (continued)
a b
c d
Fig. 61 IPMN main-duct type: hemorrhagic changes. (a–h) MRI solid nodule. With T1 GRE fat-sat, the lesion appears markedly hyper-
study: a large MD-IPMN is visible at MRCP (a). With T2-weighted intense (e), such as in precontrast 3D GRE VIBE (f), thus appearing
HASTE (b), a small hypointense area is recognized within a small slightly hyperintense in the Gd-enhanced 3D GRE VIBE (g), thus simu-
dilated branch duct (arrow), which appears hyperintense on DWI b 800 lating enhancement of the nodule. Subtraction technique (h) allows to
(c), and with restricted diffusion on ADC map (d), thus simulating a eliminate to unenhancing signal (arrow in h)
e f
g h
Fig. 61 (continued)
b c
Fig. 62 IPMN main-duct type: double duct sign. (a) CEUS study: double duct sign with dilated main pancreatic duct (W in c) and com-
round shaped lesion in the pancreatic head (calipers) with intralesional mon bile duct (C in c). On dynamic phases (d), the enhancement of
small enhancing nodule (arrow). (b–f) MRI study: on coronal intralesional solid component is visible (arrow in d) and better appre-
T2-weighted images (b), a complex cystic lesion (long arrow in b) in ciable on sagittal image (e). On coronal dynamic images (f), solid inho-
the cranial portion of the pancreatic head is visible with solid compo- mogeneous enhancing extralesional neoplastic tissue (asterisk in f) is
nent inside (short arrow in b) and outside (asterisk in b) the lesion, the visible stopping the common bile duct
latter causing dilation of the common bile duct. MRCP (c) shows the
d f
Fig. 62 (continued)
a b
d
c
Fig. 63 IPMN with vessel infiltration. (a–d) MRI study: on duct (W in b). On DWI (c), at high b-value diffusion restriction of parts
T2-weighted images (a), a complex cystic mass (arrow in a) is visible of the mass is visible. On dynamic phases (d), the lesion shows enhance-
in the uncinate process of the pancreas. The lesion infiltrates the supe- ment of thick wall (arrow in d) and inner solid component and infil-
rior mesenteric vein (V in a) and artery (A in a). On MRCP (b), the trates the superior mesenteric vein (V in d) and artery (A in d)
lesion presents a small cystic portion and dilates the main pancreatic
a b
c
d
e
f
g h
Fig. 64 IPMN invading the duodenum. (a–h) MRI study: T2-weighted with massive solid component bulging from the major papilla and
images, axial (a) and coronal (b, c), show the massive filling of the invading the duodenum. On T1-weighted image (e), the solid endoduo-
duodenal lumen by solid, hypointense “frond-like” projections (arrow denal neoplastic tissue is hypointense showing clear enhancement in
in a, b), with associated dilation of the main pancreatic duct (W in b, c). the dynamic pancreatic (f) and venous (g) phases. On coronal dynamic
Multiple solid nodules (arrows in c) are visible in the lumen of the main phase image (h), the entire papillary projection (arrow in h) in the
pancreatic duct and in the region of the major papilla. MRCP (d) pan- lumen of the enlarged duodenum is visible
oramically shows the diffusely dilated main pancreatic duct (W in d)
a b
c
d
Fig. 65 Intraductal oncocytic papillary neoplasm. (a–d) Dynamic CT thickenings (arrow in a, arrows in b) along the internal wall, with better
study: on pancreatic phases (a, b), a huge cystic mass (asterisk in a) is conspicuity in the venous phase (c, d)
visible originating from pancreatic tail, with evident nodular enhancing
a b
Fig. 66 Intraductal oncocytic papillary neoplasm. (a–d) Surgical spec- cut (c) shows that the voluminous mass of the pancreatic body is mainly
imen (total pancreatectomy): huge mass (M in a) in the pancreatic body. cystic with irregular internal wall and multiple intralesional papillary
On longitudinal cut (b), the ductal system in the pancreatic head projections (arrow in c). Transverse cut at the level of the tail (d) shows
(Wirsung duct W in b) is dilated and entirely occupied by neoplastic dilated main pancreatic duct and branch ducts with irregular wall and
tissue. Common bile duct (C in b) is displaced by the mass. Transversal lumen filled by mucoid material and papillary vegetations
a b
c d
e f
g h
Fig. 67 Macrocystic uniloculated serous cystadenoma: differential ADC map (d), the signal intensity is high (n = 2.7). With Gd-enhanced
diagnosis. (a) MRI study: with T2-weighted HASTE (a), a uniloculate MRI (e), no pathological enhancement is appreciated. At MRCP (f), the
cyst in the body of the pancreas without solid component is appreciated. lesion shows a lobulated shape together with the absence of septa. (g, h)
The tight relationship between the cyst and the main pancreatic duct Surgical specimen: at macrosection (g), a large uniloculate cyst with
does not allow to exclude the presence of a communication. (b–f) MRI normal adjacent pancreatic parenchyma (asterisk in g) is visible. At
study at 3-year follow-up: with T2-weighted HASTE (b), the lesion is magnification (h), the Wirsung duct (W in h) is adjacent to the lesion
enlarged. No septa or solid component is visible with DWI b 800 (c). At (asterisk in h) but normal
a b
c d
Fig. 68 Chronic pancreatitis: differential diagnosis. (a–d) MRI study: intensity is high (n = 2.3). With Gd-enhanced MRI (d), no pathological
at MRCP (a), diffuse enlargement of the main pancreatic duct up the enhancement is appreciated. (e) Unenhanced CT study: a coarse calci-
papilla with slight involvement of branch ducts. With DWI b 800 (b), no fication is appreciated in the head of the pancreas
significant nodules are appreciated. With ADC map (c), the signal
a b
Fig. 69 Chronic pancreatitis with cystic lesions: differential diagnosis. dilation of the main pancreatic duct (W in c) together with dilation of
(a) Ultrasound study: dilated main pancreatic duct (long arrow) in the side branches diffusely on the entire gland. Cystic lesions (asterisk in c)
pancreatic body. Small pancreatic calcifications (short arrow) are pres- in the pancreatic head. Dilated common bile duct (C in c). (d) Surgical
ent. (b, c) MRI study: on coronal T2-weighted images (b), a dilated specimen (pancreaticoduodenectomy): retention cystic lesions (aster-
main pancreatic duct (W in b) is visible. Cystic lesions (asterisk in b) isk) in the pancreatic head that present chronic pancreatitis-related
very close to the main pancreatic duct are also detected. On MRCP (c), fibrotic changes
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Serous Neoplasms
Paola Capelli, Paolo Tinazzi Martini, Giovanni Morana,

Riccardo de Robertis, Claudio Luchini, Stefano Gobbo,
Introduction A series of 257 resected SCAs [6] has suggested that

more aggressive subtypes exist; in this series, 5.1% of SCAs
Serous pancreatic neoplasms are cystic tumors, usually were locally aggressive, with the invasion of the surrounding
detected in 50–60-years old females (sex ratio 2:1) as soli- structures or vasculature or by direct extension into the peri-
tary lesions. The most common is the serous cystadenoma pancreatic lymph nodes, and 0.8% were frankly malignant,
(SCA). These lesions can be multifocal in patients with Von given the presence of metastases.
Hippel–Lindau disease [1].
SCA typically presents as a solitary multilocular micro-
cystic lesion with a honeycomb architecture, because of the Pathology
presence of multiple microcysts (<20 mm), thin wall, and
thin multiple septa oriented toward the center of the lesion Serous neoplasms of the pancreas are cyst-forming epithelial
[2], without communication with the pancreatic ductal neoplasms composed of cuboidal, glycogen-rich, epithelial
system. cells, without any atypia. The cyst content is defined as “clear
In 15% of cases, a central scar, sometimes calcified, is watery.” They are relatively uncommon neoplasms, repre-
present [3]. senting about 1–2% of all pancreatic tumors.
Despite SCA being a benign tumor, it requires follow-up, Most serous neoplasms are benign and defined as serous
usually by means of US or MRI, because progressive growth cystadenomas (SCAs); only rare cases produce metastases,
has been reported [4]. Surgical treatment has to be consid- which characterize malignant serous cystadenocarcinomas
ered only for symptomatic patients with lesions usually (SCAKs); it must be noted that this latter group is repre-
larger than 4 cm [5]. sented by sporadic case reports in the recent literature.
Pancreatic serous neoplasms show a higher prevalence
among females. The mean age at diagnosis is 50–60 years.
P. Capelli (*) · C. Luchini They are mainly located in the body—tail and are typically
Department of Pathology, G.B. Rossi University Hospital, solitary [7, 8].
Verona, Italy
e-mail: paola.capelli@ospedaleuniverona.it
P. T. Martini
Department of Radiology, Casa di Cura Dott. Pederzoli, Macroscopy
Peschiera del Garda, Verona, Italy
G. Morana Grossly, the majority of serous neoplasms presents as a
Department of Radiology, S. Maria di Ca’ Foncello Hospital, microcystic serous cystadenoma: a well-demarcated lesion,
Treviso, Italy with plurilobular shapes; on cross-section, they show a hon-
e-mail: g.morana@ulss.tv.it eycomb pattern, characterized by the presence of numerous
R. de Robertis · M. D’Onofrio subcentimetric cysts separated by thin fibrous septa, which
Department of Radiology, G.B. Rossi University Hospital, usually converge toward a central fibrous scar; this latter may
Verona, Italy
e-mail: mirko.donofrio@univr.it; roberto.pozzimucelli@univr.it present calcifications. In addition to the most common
microcystic type, other less frequent variants have been
S. Gobbo
Department of Pathology, Casa di Cura Dott. Pederzoli, described: macrocystic, solid, Von Hippel–Lindau (VHL)
Peschiera del Garda, Verona, Italy associated [7, 8].
328 P. Capelli et al.
centrally oriented. In 15% of cases, a central solid echoic

Microscopy scar is recognizable, sometimes containing calcifications [9,
12]. The central scar is fibrovascular, and a contextual vessel
Tumor cysts are lined by monostratified epithelium com- can be visualized at Doppler study.
posed of cuboidal, glycogen-rich, epithelial cells, without At CEUS, typical microcystic SCA shows enhancement
any atypia. Mitoses are absent. Septa are characterized by of the intralesional septations with better identification of its
the presence of an abundant subepithelial microvessels net- microcystic feature. The central scar, when present, shows a
work [7, 8]. homogeneous enhancement [13, 14].
Imaging Computed Tomography
SCA typically presents as a solitary multilocular microcystic As for other cystic neoplasms of the pancreas, CT should not
lesion with honeycomb architecture, because of the presence be performed for the evaluation of SCAs.
of multiple microcysts (<20 mm), thin wall, and thin multi- At CT, a central calcified scar can be depicted in typical
ple septa, centrally oriented [2]. serous cystadenoma [15, 16].
The content of SCA usually appears homogeneously After the contrast medium administration, the vascular-
anechoic, hypodense, and homogeneously hypointense on ization of internal septa is clear, and, when extremely micro-
T1-weighted images. Fifteen percent of cases present a cen- cystic, SCA may even mimic a solid hypervascular lesion.
tral hypoechoic/hypodense/hypointense on T1-weighted The macrocystic type presents features that are indistin-
images scar [1, 9]. guishable from those of other macrocystic tumors of the pan-
At CEUS and contrast-enhanced CT, the vascularization creas [2, 16].
of internal septa is clear, but T2-weighted MR images are
more precise in the depiction of the honeycomb multilocular
structure, together with the lack of communication with the Magnetic Resonance Imaging
main pancreatic duct [3]. This latter finding is not demon-
strable with US, but is crucial for the differential diagnosis The typical microcystic serous cystadenoma is easily diag-
toward branch-duct IPMNs, which may present a similar nosed at MRI, owing to the good depiction of the “honey-
appearance. comb” multilocular architecture on T2-weighted sequences,
Sometimes, largest tumors can compress the ductal sys- where the cysts appear hyperintense, surrounded by hypoin-
tem, causing upstream dilatation. At US and CT, calcifica- tense septa and sometimes with a hypointense central scar
tions are well detected. [3]. SCA is homogeneously hypointense on T1-weighted
The diagnostic yield of EUS-FNA for SCA is usually sequences, presents a lobulated shape and thin wall, and does
poor, due to the small size of the cysts and to the relatively not communicate with the main pancreatic duct [1, 16].
high vascularization of the intercystic septa. Due to the dis- After gadolinium chelates administration, the vascular-
tinctive EUS appearance of microcystic SCA, cyst sampling ization of the central scar and of the internal septa may be
is generally not needed. If necessary, EUS-FNA of SCA seen, and, as at CEUS and CT, when extremely microcystic,
should target the largest cyst for fluid analysis. The content is SCA may mimic a solid hypervascular lesion with homoge-
often thin, nonviscous, and colorless. Cellularity is very low, neous enhancement, due to the enhancing thin septa and
and if any, cuboidal epithelial cells with a positive stain for absence of visualization of tiny cysts [3].
glycogen, but not mucin, have been described; CEA levels The macrocystic type presents features similar to other
are low, usually less than 20 ng/mL [10]. macrocystic tumors of the pancreas, but the lobulated con-
tours, together with the absence of wall enhancement and a
wall thickness less than 2 mm, should suggest the correct
Ultrasound diagnosis [1, 2, 16].
The typical microcystic type (70%) has a cloud-like mor-

phology, clearly demonstrable at US [9], characterized by Clinical Presentation
lobulated contours with thin walls and a “honeycomb” mul-
tilocular architecture due to the presence of anechoic micro- The presence of symptoms is mainly due to the lesion
cysts (≤20 mm) [11], separated by thin internal septa, growth.
Serous Neoplasms 329
Asymptomatic easily demonstrated at MRI, with a typical hyperintense sig-

nal on T2-weighted images.
Generally, SCAs are asymptomatic and incidentally found. Real solid SCAs have also been reported [7].
SCAs are usually sporadic, but they could also develop in the In addition to the most common microcystic type, other
setting of a Von Hippel–Lindau syndrome. This tumor is less frequent variants have been described: macrocystic,
present in 60–80% of VHL patients. Even if large in dimen- solid, Von Hippel–Lindau (VHL) associated [7, 8]. Besides
sions, SCAs are noninfiltrating tumors, which displace rather the above-mentioned subtypes of serous cystic neoplasm,
than infiltrate adjacent structures. For this reason, SCAs of mixed forms (microcystic and macrocystic) have been also
the pancreatic head are usually not associated with obstruc- identified.
tive jaundice [7, 8].
acrocystic Serous Cystic Neoplasms
M
This subtype represents 30% of cases. They are usually
Symptomatic located in the pancreatic head and have a slighter prevalence
for males. These tumors are characterized by a limited num-
SCA may cause abdominal discomfort and nonspecific ber of cysts, usually larger than 2 cm, up to 15–20 cm. They
abdominal pain when it reaches significant dimensions. can be also unilocular.
Grossly, these neoplasms present as a cystic mass with
sharp shapes, occasionally with a central septum. In oligo-
Behavior cystic cases, septa are thicker, and tumors usually lack the
central scar.
Typical In macrocystic unilocular tumors, the internal surface can
present large areas of dysepithelization, and cystic fluid can
As mentioned earlier, SCAs are usually incidentally discov- be brownish. Smaller tumors are usually poorly demarcated.
ered. A majority of SCAs are benign lesions, with a typical These cases are characterized by cysts and supporting fibrous
slow growth and a slow progression to malignant forms; tissue, which may extend into the adjacent pancreatic paren-
therefore, these lesions are usually simply followed-up with chyma [7, 8].
US or MRI. Though the rate of growth for serous cystadeno-
mas is unknown, previously reported data indicate that the olid Serous Neoplasms
S
average growth rate is about 4 mm per year [16]. They are extremely rare tumors, with anecdotic cases
reported in the literature. They are well-circumscribed
tumors, with solid appearance, made up by simple cuboidal
Atypical cells arranged in nests and microcystic structures. They are
usually of small dimensions (2–4 cm) and are grossly similar
Malignant degeneration with local infiltration and metastatic to NETs [7, 8, 18, 19].
spread is uncommon; Kashab [6] reported that 5.1% of SCAs
in his series were locally aggressive, with invasion of sur- on Hippel–Lindau (VHL)-Associated Serous
V
rounding structures or vasculature or direct extension into Cystic Neoplasms
peripancreatic lymph nodes, and 0.8% were frankly malig- Most VHL patients present this type of tumor. The main
nant, given the presence of metastases. characteristics are the multifocality or the involvement of the
entire organ [7, 8, 20, 21].
Variants
Pitfalls and Errors
Extremely microcystic SCAs are rare (5%) and may resem-
ble a solid lesion at conventional US (pseudo solid SCAs) [9, The macrocystic variant (25% of all SCAs) is often indistin-
13]. guishable from other macrocystic tumors of the pancreas.
After contrast medium administration, these forms may Macrocystic SCA can be divided into mixed type, with mul-
resemble a hypervascular solid lesion, owing to the homoge- tiple large (>20 mm) cysts, and unilocular type, which is
neous hyperenhancement of the extremely compacted inter- more difficult to differentiate from mucinous cystadenoma
nal septa [17]. The true cystic nature of the lesion can be [22].
In comparison with MCN, macrocystic SCA has a more (either adenocarcinomas or neuroendocrine neoplasms) with
anechoic content at conventional US. At MRI, the lobulated cystic degeneration, and lymphangiomas [16]. Mucinous
contours, together with the absence of wall enhancement and cystic neoplasms are more common among females and are
a wall thickness less than 2 mm, should prompt the correct usually located in the pancreatic body/tail [25]; as SCAs,
diagnosis [1, 2, 16]. they do not communicate with the pancreatic ductal system.
As previously reported, extremely microcystic SCA may The complex internal architecture of MCNs, including
resemble a solid lesion [9, 13], and after contrast agent mucin, septa, and eventually mural nodules, can be well
administration, it may resemble a hypervascular solid lesion, assessed with MRI and endoscopic US [16, 26, 27]. Another
as a neuroendocrine tumor, owing to the homogeneous specific finding of MCNs is the peripheral eggshell calcifica-
hyperenhancement of the extremely compacted internal tion, better seen at CT [28].
septa [17]. Side-branch or mixed IPMNs can be differentiated from a
macrocystic SCA and from a MCN through the identification
of a communication with the pancreatic ductal system.
Imaging-Pathologic Correlation Unilocular SCA must be differentiated from pseudocysts,
IPMNs, and lymphoepithelial cysts [16]. A clinical history of
The typical microcystic SCA is characterized by the pres- pancreatitis is crucial for the differential diagnosis with
ence of a fibrous central scar, well depictable if present at CT pseudocysts; this diagnosis is reinforced by imaging findings
or MRI; this scar is reported to be highly specific and virtu- of pancreatic inflammation, atrophy or calcifications of the
ally pathognomonic for SCA [16, 23, 24]. The vasculariza- pancreatic parenchyma, dilation, and presence of calculi in a
tion of the scar and the septa is related to the presence of typically thin-walled pancreatic duct [16]. The typical com-
small microvessels, and the use of a blood-pool contrast munication with the pancreatic ductal system of IPMNs can
agent, as the one used for CEUS, may provide a better iden- be found at MR cholangiopancreatography or CT, especially
tification for these structures. by using curved reformatted images [16, 29, 30].
With the exclusion of the above-mentioned findings, the
presence of a unilocular cyst, with a lobulated contour,
Differential Diagnosis located in the pancreatic head should be considered as a uni-
locular macrocystic serous cystadenoma, until otherwise
As previously mentioned, extremely microcystic SCAs may proven [31].
resemble a solid lesion at conventional US [9, 13]. After the Based on most recent estimated frequencies, SCAs repre-
administration of contrast agent, either at CEUS, CT, or MRI, sent about 20% of all cystic pancreatic lesions [32].
these forms may resemble a hypervascular solid lesion, as a
neuroendocrine tumor, owing to the homogeneous hyperen-
hancement of the extremely compacted internal septa [17]. Image Gallery
The macrocystic variant must be differentiated from other
macrocystic pancreatic lesions, such as mucinous cystic neo- See Figs. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,
plasms, side-branch and mixed-type IPMNs, solid tumors 18, 19, 20, 21, 22, 23, 24, 25, 26, and 27.
a b
Fig. 1 Serous cystadenoma. (a) Surgical specimen (pancreaticoduode- with typical microcystic appearance and very large central scar (arrow).
nectomy): serous cystadenoma with typical microcystic appearance and (d) Surgical specimen (distal pancreatectomy): serous cystadenoma
central scar (white arrow) with small calcification (black arrow). (b) with typical microcystic appearance with no macroscopically evident
Surgical specimen (pancreaticoduodenectomy): serous cystadenoma scar. (e) Histopathology: serous cystadenoma with typical single layer
with typical microcystic appearance and eccentric scar (arrow). (c) of clear cuboidal epithelial cells lining the cysts with typical subepithe-
Surgical specimen (pancreaticoduodenectomy): serous cystadenoma lial vessels (asterisks)
Fig. 2 Oligocystic serous a b

cystadenoma. (a, b) Surgical
specimen (distal
pancreatectomy): pancreatic
neoplasm (a) in the pancreatic
body, presenting as a
lobulated (arrow in a) cystic
mass delimitated by a very
thin wall. At cut section (b),
the lesion is oligocystic. The
Wirsung duct (W in b) is
slightly dislocated, but normal
in caliber. (c) Surgical
specimen (intermediate
pancreatectomy): oligocystic
serous cystadenoma with
typical very thin septa (arrow)
c
Fig. 3 Serous cystic neoplasm. (a–c) Ultrasound study: pancreatic head lobulated cystic lesion (arrow in a) with tiny vessels at Doppler (a, b),
along the septa, resulting centrally orientated and vascularized (arrow in c) at CEUS (c)
a b
c d
Fig. 4 Serous cystic neoplasm. (a, b) Ultrasound study: pancreatic (d) Surgical specimen (pancreaticoduodenectomy): oligocystic serous
head lobulated cystic lesion (arrow in a) with tiny vascularized septa cystadenoma with central scar (Courtesy of Piccin Editore, Milan,
(arrow in b) at CEUS (b) resulting centrally orientated. (c) MRI: the Italy)
cystic lesion is typical, hyperintense (arrow) on T2-weighted images.
a b
c d
Fig. 5 Serous cystic neoplasm. (a, b) CT study: serous microcystic study: pancreatic head serous oligocystic neoplasm presenting as a cys-
neoplasm, presenting as a hypodense mass in the baseline (a) and tic hypodense mass in the baseline (arrow in c) and dynamic (arrow d)
dynamic (b) scans, with central calcification (arrow in a). (c, d) CT scans
a b
Fig. 6 Serous cystadenoma. (a–c) CT study: serous microcystic neoplasm (arrow in a), better visible on coronal (b) and minimum-intensity pro-
jection (c) reconstructions, with typical lobulated contours (arrow in c)
Fig. 7 Big serous cystic neoplasm. Dynamic CT: pancreatic head big
serous cystadenoma with prevalent central microcystic appearance,
resulting hypodense, and with relatively larger cystic portions,
typically located at the periphery (arrow) of the mass
a b
Fig. 8 Small serous cystic neoplasm. (a) Ultrasound study: small lobulated microcystic lesion (calipers) of the pancreatic body. (b) CT: small
lobulated hypodense lesion (arrow) of the pancreatic body. (c) MRI: small lobulated microcystic lesion (arrow) of the pancreatic body
a b
c d
Fig. 9 Serous cystadenoma. (a–d) MRI study: small microcystic lesion lesion (arrow in c) and the Wirsung duct (W in c) is perfectly docu-
of the uncinate process of the pancreas, appearing hypointense on mented. In the dynamic phase (d), the lesion shows microcystic aspect
T1-weighted fat-saturated (a) images and hyperintense on T2-weighted with vascularized thin septa and lobulated contours (arrow in d)
(b) images. The lesion shows typically lobulated contours (arrow in b).
On MRCP (c), the absence of communication between the microcystic
Fig. 10 Lobulated contour of serous cystic neoplasm. (a, b) MRI

study: oligocystic serous cystadenoma with typical lobulated contours
(arrow in a) in the body of the pancreas. On MRCP (b), the typical
morphology of the cystic lesion with lobulated contours is visible. The
Wirsung duct (W in b) is normal and faintly visible through the cystic
lesion as an indirect sign of separation between the two structures
a b
Fig. 11 Serous cystadenoma. (a, b) MRI study: microcystic mass, fibrovascular small scar are well vascularized in the dynamic phase (b).
hyperintense on T2-weighted images with small central hypointense (c) Surgical specimen (distal pancreatectomy) of different case: micro-
scar (arrow in a). The multiple microcystic lesion septa and also the cystic serous cystadenoma with central scar (arrow)
a b
d
c
Fig. 12 Serous cystadenoma. (a–g) MRI study: microcystic mass, well vascularized with progressive accumulation of contrast medium in
hyperintense on T2-weighted axial (a) and coronal (b) images, with big the scar, resulting less visible (arrow in g) in the late phase. (h) Surgical
central hypointense scar (arrow in b). At DWI, the cystic lesion shows specimen (distal pancreatectomy): microcystic serous cystadenoma
drop of signal intensity moving from low (c) to high (d) b value. In the with big central scar (arrow)
dynamic pancreatic (e), venous (f), and late (g) phases, the lesion is
e f
h
g
Fig. 12 (continued)
a b
Fig. 13 Serous cystic neoplasm. (a) Ultrasound study: microcystic Surgical specimen (distal pancreatectomy) of different case: cystic
serous cystadenoma of the pancreatic body, appearing mainly hyper- mass with larger cyst (arrow in c) bulging the inferior profile of the
echoic (arrow), with the larger cystic portion (asterisk) typically located pancreas. The cut section confirms a mixed microcystic–oligocystic
at the periphery of the lesion. (b) MRI study: microcystic appearance of serous cystadenoma with larger cyst (asterisk in d) in the periphery of
the mass on T2-weighted images with central scar and larger cystic por- the mass
tion (asterisk) typically located at the periphery of the lesion. (c, d)
a b
c d
Fig. 14 Huge serous cystadenoma. (a, b) MRI study: huge microcystic (M in c) involving completely the body and tail of the pancreas with
mass, hyperintense on T2-weighted images (a) with central scar and typical microcystic aspect on the cut section (d) in which the central
evident septa vascularization in the dynamic phase (b). (c, d) Surgical scar is evident
specimen (distal pancreatectomy) of different case: huge cystic mass
a b
c d
Fig. 15 Massive serous cystadenoma. (a–d) MRI study: massive noma, confirming a common bile duct (arrow in c) regular in caliber. At
microcystic mass hyperintense on coronal T2-weighted images (a, b) dynamic MRI (d), multiple intralesional extremely thin septa enhance-
with central scar (arrow in a) and normal common bile duct (C in b). ment is visible
MRCP (c) highlights the massive dimensions of the serous cystade-
a b
c
d
Fig. 16 Huge serous cystadenoma with double-duct sign. (a) mass, is completely documented. In the dynamic phases (e and f) are
Ultrasound study: huge hyperechoic mass (calipers). (b–f) MRI study: well visible the septal vascularization on the coronal (e) and axial (f)
huge microcystic mass, hyperintense on T2-weighted axial (b) and acquisitions, and the scar enhancement on the axial (f) acquisition. (g–
coronal (c) images, with evident central scar, causing dilation of the h) Surgical specimen (pancreaticoduodenectomy) of different case:
common bile duct (C in c) and the Wirsung duct (W in c). At MRCP (d), huge microcystic serous cystadenoma (arrow in g) involving the com-
the double-duct sign with dilation of the common bile duct (C in d) and mon bile duct (C in g). Involvement of the Wirsung duct (probe in h)
the Wirsung duct (W in d), due to the pancreatic head huge microcystic entrapped in a microcystic serous cystadenoma
e f
Fig. 16 (continued)
a b
c d
Fig. 17 Serous cystadenoma with chronic obstructive pancreatitis. (a, enlarged. At CT (e), a small calcification can be appreciated in the cen-
b) On T2-weighted MR image (a), a microcystic lesion is appreciated ter of the lesion (arrow). (f) One year later, the calcification is signifi-
in the uncinate process. With MRCP (b), the close relationship between cantly enlarged at CT, not visible at T2-weighted HASTE (g). At MRCP
the lesion and the main pancreatic duct does not allow to exclude the (h), significant changes of chronic obstructive pancreatitis are appre-
communication. Initial signs of chronic pancreatitis are appreciable, ciable. (i) Surgical specimen (distal pancreatectomy) of different case:
with slight dilation of the main pancreatic duct and small branch ducts microcystic serous cystadenoma (arrow), involving the main pancreatic
in the body–tail. (c) With contrast-enhanced CT, no calcifications are duct (W) upstream-dilated
visible. (d) On MRCP, 2 years later, the Wirsung duct is slightly more
e f
g h
Fig. 17 (continued)
a b
c
d
Fig. 18 Small pseudo solid serous cystadenoma. (a, b) Ultrasound vs inhomogeneous hypoechoic oval lesion (arrow in c) is detected in the
MRI: on conventional ultrasound (a), small hypoechoic rounded lesion pancreatic head. On MRI (d), the lesion is typically microcystic, hyper-
(arrow in a) is detected in the pancreatic body–tail. On MRI (b), the intense on MRCP (arrow in d); no communication of the microcystic
lesion is typically microcystic, hyperintense on T2-weighted (arrow in lesion with the Wirsung duct (W in d) is clearly demonstrated
b) images. (c, d) Ultrasound vs MRI: on conventional ultrasound (c),
Fig. 19 Small pseudo solid hypervascular serous cystadenoma. (a, b)

Ultrasound study: on conventional ultrasound (a), small hypoechoic
oval lesion (arrow in a) is detected in the pancreatic head, resulting
hypervascular at CEUS (arrow in b). (c) MRI: the lesion is typically
microcystic, hyperintense on T2-weighted (arrow) images
a b
c d
Fig. 20 Small pseudo solid serous cystadenoma. (a, b) Ultrasound septa. (c, d) MRI: the lesion is confirmed to be microcystic with typi-
study: on conventional ultrasound (a), small hypoechoic lesion (arrow cally hyperintense (arrow in c) aspect on T2-weighted images. On
in a) is detected in the pancreatic body. At CEUS (b), the lesion (cali- MRCP (d), no communication of the microcystic lesion (arrow in d)
pers in b) shows microcystic pattern with numerous thin vascularized with the Wirsung duct (W in d) is clearly demonstrated
a b
Fig. 21 Huge pseudo solid hypervascular serous cystadenoma. (a) cally hyperintense (arrow in b) aspect on T2-weighted images, causing
Dynamic CT: huge inhomogeneously rounded hypervascular mass dilation of the Wirsung duct (W in b). MRCP (c) evidently shows that
(arrow) in the pancreatic head, with upstream chronic obstructive pan- huge microcystic mass involves the Wirsung duct (W in c) upstream
creatitis. (b, c) MRI study: the lesion is clearly microcystic with typi- dilated
a b
c d
Fig. 22 Microcystic solid serous cystic neoplasm. (a) Ultrasound b) with cranial microcystic portion (arrow in c). (d) Surgical specimen
study: inhomogeneously hypoechoic pancreatic head mass (calipers). (pancreaticoduodenectomy): microcystic serous cystadenoma with
(b, c) Dynamic CT: pancreatic head solid hypervascular mass (arrow in microcystic aspect (black arrow) and solid portion (white arrow)
a b
c d
Fig. 23 Solid serous adenoma. (a–c) Ultrasound study: hyperechoic (e) Surgical specimen (pancreaticoduodenectomy): solid serous ade-
mass (asterisk in a) in the pancreatic head showing numerous vessels at noma (arrow) dislocating the main pancreatic duct (W). Probe in the
color Doppler (b). At CEUS (c), the mass is hypervascular (asterisk in common bile duct (C)
c). (d) Dynamic CT: pancreatic head solid hypervascular mass (arrow).
Fig. 24 Macrocystic serous cystadenoma. Surgical specimen (distal

pancreatectomy): unilocular serous neoplasm
a b
d
c
Fig. 25 Macrocystic serous cystadenoma. (a–d) MRI study: unilocular caliber. The common bile duct (C in c) is normal. In the dynamic phase
cystic mass, hypointense (arrow in a) on T1-weighted fat-saturated (d), the lesion is internally avascular. (e) Surgical specimen (pancreati-
images and hyperintense (arrow in b) on T2-weighted axial images. On coduodenectomy) of different case: unilocular cystic serous cystade-
MRCP (c), the cystic lesion shapes the Wirsung duct (W in c) regular in noma. The big cyst occupies all the pancreatic head
a b
c d
Fig. 26 Bifocal serous cystadenoma. (a–c) MRI study: microcystic shows the two (arrows in c) microcystic lesions. (d) Surgical specimen
serous cystadenoma, hyperintense on T2-weighted (a, b) images in the (distal pancreatectomy) of different case: two (arrows) microcystic
head (arrow in a) and in the tail (arrow in b) of the pancreas. MRCP (c) cystadenomas. Between the two lesions, the pancreas (P) is normal
a b
Fig. 27 Multiple serous cystadenomas in Von Hippel–Lindau syn- fuse cystic lesions (arrows in b) of the pancreas. On the cut section (c),
drome. (a) MRI study: multiple small pancreatic serous cystadenomas. the body and tail of the pancreas are diffusely involved by multiple
(b, c) Surgical specimen (distal pancreatectomy) of different case: dif- (arrows) serous cystic cystadenomas
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Mucinous Neoplasms
Mirko D’Onofrio, Paola Capelli, Claudio Luchini,

Paolo Tinazzi Martini, Emilio Barbi,
Introduction The differential diagnosis mainly includes other cystic

pancreatic neoplasms and pseudocysts. The best way to
Mucinous cystic neoplasms (MCNs) are thick-walled, uni- reach a correct diagnosis is a combined evaluation of clini-
or multilocular tumors composed of mucin-containing cysts cal, imaging, and pathologic data.
that represent about 8% of surgically resected cystic lesions
of the pancreas [1] and about 10% of all cystic pancreatic
lesions [2]. Pathology
These neoplasms occur almost exclusively in women and
are mainly located in the body-tail of the pancreas. Mucinous cystic neoplasms (MCNs) are cyst-forming epi-
Given that MCNs encompass a spectrum of lesions from thelial tumors that do not communicate with the pancreatic
benign (i.e., mucinous cystadenoma, MCA) to invasive ductal system; they are composed of columnar, mucin-
mucinous cystadenocarcinoma, they always require surgical producing epithelial cells associated with ovarian-type sub-
resection, even if asymptomatic. epithelial stroma.
As a consequence, the differential diagnosis between These neoplasms occur almost exclusively in females
mucinous and non-mucinous cystic lesions of the pancreas is (female-to-male ratio is about 20:1). MCNs are classified as
fundamental for management and treatment. noninvasive or MCNs with an associated invasive carcinoma.
If completely resected, the prognosis of noninvasive Noninvasive MCNs are furthermore divided on the basis of
MCN is excellent despite the level of dysplasia [3]. the grade of epithelial dysplasia in low-, intermediate-, or
A MCN should be suspected when a cystic lesion is seen high-grade dysplasia [5].
by imaging in the pancreatic body/tail of a young or middle- MCNs represent less of 10% of surgically resected cystic
aged woman, especially in the absence of a history of lesions of the pancreas [6, 7].
pancreatitis. The mean age at diagnosis is usually 40–50 years. Patients
Staging follows the protocol for ductal adenocarcinoma [4]. affected by MCNs associated with invasive carcinoma are
usually 5–10 years older than patients with noninvasive
MCNs, supporting the hypothesis of a slow progression in
these tumors [7].
MCNs are typically solitary; most cases (>95%) occur in
the body and in the tail of the pancreas. Pancreatic head
M. D’Onofrio (*) · C. Luchini · R. De Robertis involvement is very rare.
Verona, Italy
Clinical features are usually correlated with the size. Most
e-mail: mirko.donofrio@univr.it patients with large MCNs have undefined abdominal symp-
P. Capelli
toms, such as epigastric pain or sense of abdominal fullness,
Department of Pathology, G.B. Rossi University Hospital, due to compression of adjacent anatomical structures. Other
Verona, Italy symptoms, like vomiting, diarrhea, anorexia, and weight
e-mail: paola.capelli@ospedaleuniverona.it loss, are not so common [8–10].
P. T. Martini · E. Barbi In case of MCNs with an associated invasive carci-
Department of Radiology, Casa di Cura Dott. Pederzoli, noma, the patients may present with symptoms due to
Verona, Italy
infiltration of adjacent structures. Almost 25% of MCNs,
especially those below 3 cm, are asymptomatic and nuclear pleomorphism; furthermore, mitosis are often
“incidentalomas.” evident and atypical.
The specific clinical-histopathological features of MCNs The associated invasive component is generally very sim-
(i.e., female prevalence, body-tail localization, and presence ilar to the common infiltrating ductal adenocarcinoma, with
of subepithelial ovarian-like stroma) support the hypothesis duct-like and/or glandular structures [6].
of a derivation of the stromal component from the ovarian The pathognomonic ovarian-like stroma below the epi-
primordium. Embryologically, the left primordial gonad and thelial coating is formed by densely packed spindle cells
the dorsal pancreatic anlage, which give rise to the pancre- with elongated nuclei and scanty cytoplasm; the presence of
atic body and tail and a small portion of the pancreatic head, this type of stroma is a specific element required for the diag-
lie side by side at an early stage of development (4–5th week nosis of MCNs and represents a fundamental finding in case
of gestation) [3]. of cysts with denudated epithelium.
Typically, this stroma is located within septa.
Macroscopy
Imaging
MCNs usually present as a single rounded mass with
smooth surface, fibrous pseudocapsule of variable thick- Mucinous cystadenoma (MCA) tends to be a unilocular or
ness, and frequent calcifications. The average size of the oligo-locular (≤6 cysts) cystic lesion, with a rounded ball-
neoplasms ranges between 6 and 10 cm. MCNs are usually like morphology.
multilocular but can be also unilocular. In multilocular It presents corpusculated complex content that can be par-
MCNs, the individual cysts are typically small and have ticled, viscous, and dense owing to mucin and hemorrhage;
usually thin walls. However, cyst’s size can grow up to this content very often makes the lesion heterogeneously
several centimeters in diameter. Some cysts are rich in hypoechoic at US, inhomogeneously hypodense at CT, and
mucus, while others contain hemorrhagic or watery fluid; slightly hyperintense on T2-weighted images at MRI [11].
the most common report is a viscous, mucinous liquid. In MCNs show irregular thick wall (>2 mm) and internal
some cases, papillary projections and necrohemorrhagic septa that enhance after contrast medium administration and,
material can be observed. Unilocular tumors usually have occasionally, peripheral calcifications [12, 13].
a smooth and glossy internal surface. When de-epithelized, The detection of vascularized vegetations is fundamental
the internal surface is irregular and brownish. In high- for the differential diagnosis between MCA and pseudocyst
grade neoplasms, papillary vegetations are often recog- [14, 15].
nized. MCNs with an associated invasive carcinoma are MCNs are typically located in the body-tail of the pan-
generally larger and multilocular, with a higher structural creas and do not communicate with the ductal system, which
disarrangement with thick septa and mural nodules. Tumor is generally not dilated [13, 16].
prognosis is based on the location of the infiltrating com- Aggressive forms (i.e., mucinous cystadenocarcinoma)
ponent, which usually resembles the common ductal ade- present thicker and more irregular internal enhancing septa
nocarcinoma [3]. and parietal nodules and may metastasize [17].
The imaging modalities routinely used to evaluate muci-
nous cystic neoplasms are magnetic resonance imaging
Microscopy (MRI) and endoscopic ultrasound (EUS).
Ultrasonography (US) with harmonic US, Doppler study,
MCNs are usually circumscribed by a thick fibrous band, and nowadays elastosonography are however usually the first
which separates the extralesional pancreas from the cysts. diagnostic step for the study of pancreatic tumors, especially
The epithelium presents typical mucin-producing cells, in European and Asian countries [11].
which are columnar and tall, with basal/pseudostratified The introduction of sonographic contrast agents has
nuclei and abundant intracytoplasmatic mucin. Epithelial improved the characterization of pancreatic mucinous tumors
cells usually form flat sheets or papillae. too [11, 18–20].
The grading of epithelial dysplasia is based on architec- However, the detection of a suspect MCN requires an
tural and cytological atypias and presents three degrees: MRI study with magnetic resonance cholangiopancreatogra-
low-, intermediate-, and high-grade dysplasia. phy (MRCP) sequences. MRI with MRCP in fact still
Papillary projections, crypt-like invaginations, and cellu- remains the imaging modality of choice for the study of cys-
lar pseudostratification are features of at least intermediate- tic neoplasms, as it provides excellent contrast resolution
grade dysplasia. In high-grade dysplasia are usually present and allows an accurate noninvasive evaluation of the pancre-
papillary vegetations with irregular budding and branching atic ductal system [16, 17, 21–24].
Mucinous Neoplasms 363
Despite this, in recent years, MDCT with postprocessing CEUS may significantly improve the identification of
reconstructions has been reported to have a similar accuracy septa and parietal nodules, mainly detecting their vascular-
to MRI in detecting and characterizing cystic lesions of the ization [15, 19, 39–42]. For example, some lesions that are
pancreas [25–28]. perfectly unilocular and without septa at CT may show
EUS permits a closer view of the pancreas, with a higher septa at transabdominal or endoscopical CEUS [15, 43].
resolution imaging of MCNs. Diagnostic accuracy of EUS Owing to its special technical features, as the dynamic eval-
alone for detecting malignant or premalignant lesions is uation of perfusion by using a blood pool contrast agent,
reported to be 82–96% [29–33]. Several EUS features of CEUS can sometimes better demonstrate the enhancement
pancreatic cysts associated with increased malignancy risk, than other imaging examinations, showing single micro-
including thick wall, presence of nodule or mass, and thick bubbles passing through the septa with a perfect correlation
septa, have been described in literature [29, 30]. More recent with resected specimens. Moreover, owing to the deletion
studies, however, have uncovered the shortcomings of of background tissues and of all the echogenic intracystic
relying on EUS alone in differentiating benign from malig- content (i.e., mucin, clots, or debris), the detection rate of
nant cystic lesions [32, 34]. septa and nodules at CEUS is absolutely superior as com-
EUS morphology alone is generally considered inade- pared to B-mode US, thus improving the characterization
quate for a definitive characterization of cystic pancreatic of cystic tumors; at unenhanced US, the viscosity of mucin
lesions; EUS-guided fine-needle aspiration has been shown causes an increased echogenicity, which can obscure inter-
to be an effective and safe sampling method for cystic pan- nal septa [12, 19, 44].
creatic lesions [33]. CEUS results can be sometimes even better than MRI,
Despite this, an MCA with concordant and typical find- because septa and nodules may be seen only on T2-weighted
ings at noninvasive imaging (US, CEUS, and MRI) should images and not on contrast-enhanced images, thus explain-
undergo resection without fluid analysis [11, 35]. ing possible MRI false-positive results [20]. As a result,
CEUS is reported to be an accurate method for the character-
ization of cystic pancreatic lesions. CEUS can reach 97.1%
Ultrasound accuracy for the diagnosis of pancreatic cystic tumors [18].
US is a good imaging method for the first assessment of cys-

tic pancreatic lesions, but sometimes, their content can be Computed Tomography
modified by hemorrhage or dehydration, leading to the loss
of their typical US appearance: cysts can become complex Mucinous cystadenoma has a variable inhomogeneous con-
heterogeneous lesions characterized by internal echoes. tent at unenhanced CT, depending on mucin concentration.
Mucin is a complex, corpuscular, and viscous fluid, which Peripheral calcifications are seen in 10–25% of cases and
produces inhomogeneous echoes at US study. represent an important feature to differentiate MCA from
Hence, mucinous tumors appear as cystic lesions with serous cystadenoma [11].
fine internal echoes due to the presence of mucin or hemor- Owing to the inhomogeneous density, during dynamic
rhagic fluid-fluid levels. study, the vascularization of thin septa and small nodules is
The heterogeneous echoes may impair the detection of not always easily detectable [13, 25, 45].
intralesional septa and/or parietal nodules, which is funda- As previously reported, CT must not be performed for the
mental for the differential diagnosis between cystic tumors characterization of a suspect MCN, being MRI the preferred
and pseudocysts. second-line exam for these cystic lesions; despite this, CT
Elastography with quantification by using ARFI seems to obviously plays a fundamental role for the staging of muci-
be able to noninvasively study the fluid content of pancreatic nous cystadenocarcinomas, which can metastasize.
cystic lesions, potentially improving lesion characterization
differentiating complex (mucinous) from simple (serous)
fluid content of pancreatic cystic lesions. As reported, this Magnetic Resonance Imaging
can be obtained with recurring numerical results, which
reflect the complex, viscous, dense, and corpuscular content Mucinous cystadenoma may show variable signal intensity
in respect to serous fluids [36–38]. In particular, the reported on T1-weighted images, ranging from hypointensity to slight
high sensitivity and positive predictive values could confer to hyperintensity [46].
ARFI a potential role in the screening of mucinous content On T2-weighted sequences, it typically presents as a fluid,
of cystic pancreatic lesions, if these findings will be con- hyperintense, grossly round lesion, with irregular thick wall
firmed in larger series [36]. and hypointense septations and mural nodules.
MRCP clearly demonstrates the lack of communication noninvasive cases is excellent despite the level of dyspla-
with the pancreatic ductal system, which usually shows a sia [3].
regular caliber [17, 46].
After gadolinium chelates contrast medium administra-
tion, the enhancement of wall, septa, and nodules is charac- Atypical
teristic. Unlike SCA, intralesional septa with disorganized
distribution are usually peripherally located, often describing Less frequently, MCNs present as frank malignant neo-
a bridge along the cystic wall with a pseudonodular appear- plasms, with local and metastatic diffusion, involving lymph
ance. It is known that sometimes septa and nodules may be nodes and other organs such as the liver [17].
seen only on T2-weighted images and not on contrast-
enhanced images, thus explaining possible false-positive
results [20]. Moreover, unlike SCA, septa in MCN are vari- Variants
able in thickness.
Mucinous cystic neoplasms may present at imaging with a
more or less complex aspect, due to multiple septa and wall
Clinical Presentation irregularity.
Gastric or intestinal differentiation of the mucin-
Clinical presentation of MCNs mainly depends on their size. producing epithelium with goblet cells represents an uncom-
mon report, and a clear radiological differentiation between
these variants is not possible.
Asymptomatic In larger cysts, the epithelial layer is often extensively
absent. In these cases, a detailed pathologic examination of
MCNs are usually incidentally found. The detection of a the epithelial cells of the locules/accessory cysts localized
single grossly rounded cystic lesion, located in the body/ within the wall is mandatory, because the small locules are
tail of the pancreas, with heterogeneous content, irregular the last to lose epithelial coating. If epithelium is absent, the
thick wall, and sometimes peripheral septa and/or calcifi- final diagnosis should be based on the presence of the
cations, should be considered a MCN until otherwise ovarian-like stroma.
proven.
Pitfalls and Errors

Symptomatic
Unilocular MCNs may be identical to unilocular serous cyst-
MCNs can rarely be symptomatic, when they reach signifi- adenoma and to pseudocysts: all these entities are rounded,
cant dimensions producing mass effect, resulting in abdomi- well-defined lesions, with heterogeneous content. The pres-
nal discomfort or epigastric pain. ence of internal vascularized septa/nodules and the absence
of a clinical history of acute pancreatitis are fundamental to
diagnose MCNs.
Behavior Huge de-epithelized MCNs are particularly difficult to
differentiate, both at imaging and at pathology, from pseudo-
Typical cysts, because of the lack of an epithelial lining.
Due to advances in imaging, MCNs are usually incidentally

found, so generally, they present as a localized and resect- Imaging-Pathologic Correlation
able mass, without metastatic spread.
Despite this, given the fact that the progression to malig- MCNs contain viscous mucin with different degrees of
nancy is possible and expected, even if slow, MCNs always hydration; at MRI, which is the most accurate imaging tech-
require surgical resection, also if asymptomatic. nique for fluid characterization, this produces a variable sig-
As a consequence, the differential diagnosis between nal intensity, especially on T1-weighted images.
mucinous and non-mucinous cystic lesions of the pancreas is Intratumoral septa and nodules have blood vessels, and
fundamental. this can be evaluated with CD34 immunostaining; the radio-
As previously stated, patients with invasive carcinoma logical consequence is that contrast medium, and particu-
are 5–10 years older, on average, than those with a nonin- larly blood-pool microbubbles, flows within these portions,
vasive tumor. If completely resected, the prognosis of thus producing their classical hyper-enhancing appearance.
Differential Diagnosis Conversely, intralesional blood clots and debris, which

are easily detectable on baseline sonograms, are completely
Pseudocysts and MCNs may have a similar radiological invisible during CEUS [15, 18, 19, 47]. Therefore, CEUS
aspect. For their differentiation, an accurate anamnestic col- improves the differential diagnosis [32] between pseudo-
lection is primarily necessary; in fact, no pseudocyst can cysts and cystic tumors of the pancreas by accurately reveal-
develop if there is no story of pancreatitis. As previously ing the vascularization of intralesional vegetations.
mentioned, the content of MCNs is usually heterogeneous MCNs must then be differentiated from the macrocystic
due to the presence of mucin or intralesional hemorrhage. variant of serous cystadenoma, side-branch and mixed-type
Pseudocysts also usually show heterogeneous content, with IPMNs, and solid tumors with cystic degeneration [48].
debris and internal echoes. Mucinous cystic neoplasms are usually located in pancreatic
The viable portions of MCNs enhance after contrast body/tail [49] and, as serous cystadenomas, do not commu-
medium administration; unlike MDCT and MRI, harmonic nicate with the pancreatic ductal system. The complex inter-
microbubble-specific software filters all background signals, nal architecture of MCNs, including mucin, septa, and
and only vascularized tissues (where microbubbles are eventually mural nodules, can be well assessed with MRI
present) are visible at CEUS, thus providing an extremely and endoscopic US [48, 50, 51]. Other specific findings of
accurate examination. The viable vascularized portions of MCNs are peripheral eggshell calcifications, better seen at
cystic pancreatic tumors become progressively echogenic CT [52].
during CEUS as the contrast material passes through the cap-
illary vessels of the septa or nodules [11].
Image Gallery
a b
Fig. 1 Mucinous cystic neoplasm. (a–c) Surgical specimen (distal pan- epithelium (c) with typical subepithelial ovarian-like stroma (asterisks
createctomy): pancreatic huge neoplasm (a) in the body-tail of the pan- in c) (Courtesy of Piccin Editore, Milan, Italy)
creas presenting as a cystic mass (b); the cavity is lined by a mucinous
a b
Fig. 2 Mucinous cystic neoplasm. (a, b) Surgical specimen (distal Wirsung duct; in fact, no fluid leakage from the mass (M in b) is present
pancreatectomy): pancreatic neoplasm (a) in the tail of the pancreas after longitudinal cut of the main pancreatic duct (W in b)
presenting as a cystic mass. The lesion does not communicate with the
Fig. 3 Mucinous cystic neoplasm. Surgical specimen (distal pancre-

atectomy): pancreatic mucinous cystic neoplasm presenting as a cystic
mass with few intralesional septa (arrow)
a b
Fig. 4 Mucinous cystic neoplasm. (a, b) Surgical specimen (distal pancreatectomy): pancreatic neoplasm presenting as a cystic mass (a) with
numerous intralesional septa shown in the cut section (b)
Fig. 5 Multiloculated mucinous cystic neoplasm. Surgical specimen

(distal pancreatectomy): pancreatic mucinous cystic neoplasm present-
ing as a cystic mass with multiple intralesional septa, delineating mul-
tiple locules along the internal wall Fig. 6 Complex mucinous cystic neoplasm. Surgical specimen (distal
pancreatectomy): pancreatic mucinous cystic neoplasm presenting as a
complex cystic neoplasm with irregular thick wall and filled by thick
tenacious mucoid material (Courtesy of Piccin Editore, Milan, Italy)
a b
Fig. 7 De-epithelized mucinous cystic neoplasm. (a) Surgical speci- cut section. (b) Surgical specimen (distal pancreatectomy): pancreatic
men (distal pancreatectomy): pancreatic mucinous cystic neoplasm pre- mucinous cystic neoplasm presenting as a cystic unilocular mass with
senting as a cystic mass with few intralesional septa and focal amply de-epithelized internal wall, appearing as diffuse brown areas on
de-epithelized internal wall (arrow), appearing as a brown area on the the cut section, resembling a pseudocyst
a b
c d
Fig. 8 Mucinous cystic neoplasm. (a) Ultrasound study: cystic mass of neoplasm in the body-tail of the pancreas. (d) On the cut section, the
the pancreatic body with thick wall, intracystic septa (arrow), and neoplasm is cystic with thin septa (arrow) and deposits (D). (e) Cystic
echoic deposit (D). (b) Ultrasound study: huge cystic mass (calipers) of fluid: after the aspiration, the intracystic fluid is typical torpid and
the pancreatic body with cystic corpuscular content and echoic deposit opaque
(D). (c) Surgical specimen (distal pancreatectomy): pancreatic huge
a b
Fig. 9 Mucinous cystic neoplasm. (a, b) Ultrasound study: cystic mass small septa are better visible on the detail image (arrow in d).
in the pancreatic body with corpuscular content (asterisk in a). Only at Histological image (e) of small septa along the wall. Detail histological
CEUS (b), a small vascularized septum along intracystic wall (arrow in image of small septum at hematoxylin-eosin stain (f), showing muci-
b) is visible. (c–g) Surgical specimen (distal pancreatectomy) and his- nous epithelium with subepithelial ovarian-like stroma. Along the small
topathology: mucinous cystic neoplasm with thick wall and small septa, septum, multiple tiny vessels are marked (brown trace) on CD34 stain
delineating small locules along the internal wall at cut section (c). The (g) (Courtesy of Piccin Editore, Milan, Italy)
d e
f g
Fig. 9 (continued)
a
b
Fig. 10 Mucinous cystic neoplasm internal wall. (a, b) Histopathology: (arrow) delineating an internal cystic locule along the wall. (d)
mucinous cystic neoplasm with thick wall and irregular internal surface Histopathology: mucinous cystic neoplasm with internal vegetation
with trabecular projections (arrows in a) in which, at CD34 immuno- (arrow) along the internal wall, characterized by a cluster of irregular
histochemical stain (b), multiple thin vessels (brown trace in b) are septa delimiting small cysts.
visible. (c) Histopathology: mucinous cystic neoplasm with thin septum
a b
c d
Fig. 11 Mucinous cystic neoplasm. (a) Ultrasound study: incidental thin septa (arrow) in the cystic lesion are clearly visible. (d) Surgical
cystic lesion (asterisk) in the pancreatic body. (b) CT study: the cystic specimen (distal pancreatectomy): thin intralesional septa (arrow) are
lesion (asterisk) is confirmed in the pancreatic body; no septa are confirmed on the cut section
detected within the lesion. (c) CEUS: after contrast medium injection,
a b
c d
Fig. 12 Mucinous cystic neoplasm. (a, b) Ultrasound study: incidental b). (c, d) MRI and CT studies: both dynamic MRI (c) and CT (d) did
small cystic lesion in the pancreatic body-tail with thin intracystic septa not provide the same detailed representation of septa
visible at ultrasound (arrow in a) and vascularized at CEUS (arrow in
Fig. 13 Mucinous cystic

neoplasm and pathological a
correlation. (a) CEUS: cystic
mass with several
vascularized septa
(arrowheads) and enhancing
nodule (arrow). (b) Surgical
specimen: septa (arrowheads)
and nodule (arrow) are
confirmed
b
a b
Fig. 14 Mucinous cystic neoplasm with septa. (a) CT study: cystic ferent case: mucinous cystic neoplasm appearing as a cystic mass
mass (asterisk) with thick wall, containing lamellar calcifications, and (asterisk in b) with thick septa (arrow in c) on cut section
septa (arrow). (b, c) Surgical specimen (distal pancreatectomy) of dif-
a b
Fig. 15 Mucinous cystic neoplasm with nodule. (a) CT study: huge different case: huge mucinous cystic neoplasm appearing as a cystic
cystic mass (asterisk) with thick wall and nodule (arrow) hyperdense mass (asterisk in b) with septa and nodular solid projections (arrow in
on dynamic phase. (b, c) Surgical specimen (distal pancreatectomy) of c) on cut section
c d
Fig. 16 Mucinous cystic neoplasm and pathological correlation. (a, b) phase. (e) Surgical specimen (distal pancreatectomy): mucinous cystic
CT study: cystic mass (asterisk in a) with unclear vegetations (arrow in neoplasm with septa (arrow) delineating small cystic locule along the
b) hyperdense in the dynamic phase. (c, d) CEUS: cystic mass (asterisk internal wall on cut section
in c) with well-detailed septa (arrow in d) vascularized in the dynamic
a b
c d
Fig. 17 Mucinous cystic neoplasm and pathological correlation. (a) (arrow). (d) Surgical specimen (distal pancreatectomy): mucinous cys-
CT: small cystic mass (arrow) completely hypodense without any tic neoplasm with septa (arrow) dividing the cavity in three locules on
septa. (b) CEUS: small cystic mass with well-detailed vascularized cut section
septa (arrow). (c) MRI: small cystic mass with well-detailed septa
a b
Fig. 18 Mucinous cystic neoplasm and imaging correlation. (a) MRI: cystic mass with very small well-detailed septum (arrow). (b) CEUS: cystic
mass with very small well-detailed vascularized septum (arrow)
a b
c d
e f
Fig. 19 Imaging and pathological correlation of mucinous cystic neo- fat-saturated images showing thick wall and enhancing septa (arrow in
plasm. (a–d) CT study: large cystic mass in the pancreatic body appear- f and g) in the pancreatic (f), venous (g), and late (h) dynamic phases.
ing hypodense (asterisk in a) in the baseline scan with thick wall and (i, j) Surgical specimen (distal pancreatectomy): large neoplasm in the
septa (arrow in b and c) well visible in the pancreatic (b), venous (c), body of the pancreas appearing as a cystic mass (asterisk in i) with thick
and late (d) dynamic phases. (e–h) MRI study: large cystic mass in the wall and thick septa (arrow in j) on cut section
pancreatic body appearing hyperintense (asterisk in e) on T2-weighted
g h
i j
Fig. 19 (continued)
a b
c d
e f
Fig. 20 Mucinous cystic neoplasm with intracystic deposit. (a) CEUS: intracystic vegetations in the dynamic phases (d). (e, f) Surgical speci-
big cystic mass (asterisk) in the pancreatic body-tail with thick wall and men (distal pancreatectomy): big neoplasm in the body-tail of the pan-
echoic deposit (arrow) avascular at dynamic phases. (b–d) MRI study: creas appearing as a cystic mass (asterisk in e) with deposit (arrow in f)
big cystic mass in the pancreatic body-tail appearing hyperintense on on cut section
T1-weighted (b) and on T2-weighted (c) images with no enhancing
a b
c d
e f
Fig. 21 Mucinous cystic neoplasm with multiple septa. (a) CT study: bulging the superior margin of the pancreatic body with multiple septa
big cystic mass in the pancreatic body with thick wall and multiple (arrow in c and d) dividing multiple locules on cut section. (e, f)
septa (arrow) vascularized in the dynamic phase. (b) MRI study: big Surgical specimen (distal pancreatectomy) of different case: big neo-
cystic mass in the pancreatic body with thick wall and multiple septa plasm bulging the inferior margin of the pancreatic body-tail appearing
(arrow) vascularized in the dynamic phase. (c, d) Surgical specimen as a cystic mass (asterisk in e) with thick wall and multiple septa (f)
(distal pancreatectomy) of different case: big mucinous cystic neoplasm delineating locules with different fluid component on cut section
b c
Fig. 22 Pathological correlation of mucinous cystic neoplasm with perfused (red color) at perfusion quantification color map (b) analysis.
nodule. (a, b) CEUS: huge cystic mass in the pancreatic body (asterisk (c, d) Surgical specimen (distal pancreatectomy): huge neoplasm in the
in a) with thick wall and vascularized septum and nodule (arrow in a) body-tail of the pancreas appearing as a huge cystic mass (c) with a
at dynamic phase. The intracystic nodule (arrow in b) results highly nodule (arrow in d) along the intracystic wall at cut section
Fig. 22 (continued)
Fig. 23 Mucinous cystic neoplasm with associate invasive carcinoma.

Surgical specimen (distal pancreatectomy): mucinous cystic neoplasm
with focal wall thickening (circle), grossly suspected for invasion
Fig. 24 Mucinous cystic

neoplasm with abundant deposit. a
(a–c) US study: huge cystic mass
(calipers in a) in the pancreatic
body with septa (arrow in a) and
abundant deposit (D in a). At
CEUS (b), the septa enhance-
ment (arrow in b) is well visible,
but the deposit (D in b and c)
remains avascular. (d–h) MRI
study: huge cystic mass in the
pancreatic body appearing
hyperintense on T1-weighted
(asterisk in d) and on
T2-weighted (asterisk in e)
images. Antideclivous deposit
hyperintense on T1-weighted (D
in d) and hypointense on
T2-weighted (D in e) images is
visible. Moreover, small septa are b
visible (arrow in e). On DWI, the
fluid remains slightly hyperin-
tense moving from low (f) to
high (g) b value. In the dynamic
phase, no clear enhancement of
the septa (arrow in h) is visible
c
d e
f g
Fig. 24 (continued)
Fig. 24 (continued)
a b
c d
Fig. 25 Mucinous cystic neoplasm. (a, b) CT: huge cystic mass (aster- ent case: huge neoplasm in the body-tail of the pancreas appearing as a
isk in a) in the pancreatic body with regular internal wall on dynamic cystic mass (c) with thin mainly smooth intracystic wall at cut section
phases (b). (c, d) Surgical specimen (distal pancreatectomy) of differ- (d)
a b
Fig. 26 Mucinous cystic neoplasm of the head of the pancreas. (a) Surgical specimen (pancreaticoduodenectomy): mucinous cystic neo-
Surgical specimen (pancreaticoduodenectomy): pancreatic head muci- plasm uniloculated (asterisk) in the head of the pancreas dislocating the
nous cystic neoplasm (asterisk) with few intralesional septa. (b) Wirsung duct (W). Common bile duct (C)
a b
Fig. 27 Cystic neuroendocrine tumor resembling a mucinous cystic neoplasm. (a) Dynamic MRI: pancreatic body cystic lesion (arrow) with
vascularized thin wall and septa. (b) Histopathology: small cystic pancreatic neuroendocrine neoplasm with visible wall and thin internal septa
Fig. 29 Mucinous cystic neoplasm in a male patient. Surgical speci-

men (distal pancreatectomy): mucinous cystic neoplasm with intracys-
Fig. 28 Serous cystadenoma resembling a mucinous cystic neoplasm. tic septa (arrow)
Dynamic CT: pancreatic body cystic mass with few vascularized thin
septa (arrow)
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Pseudocysts and Other Cystic Lesions
Valentina Ciaravino, Roberto Calbi, Antonio Giugliano,

Luca Geraci, Luisa Tomaiuolo, Chiara Longo,
Riccardo De Robertis, and Mirko D’Onofrio
Introduction the previous classification, are no longer used, and their use
is now discouraged.
In the pancreatic gland, a large amount of lesions with cystic As attested by the revised Atlanta classification, for acute
features, both neoplastic and non-neoplastic, could be seen pancreatitis diagnosis there must be present at least two or
during an abdominal examination, many of these are inci- more of the following criteria: (a) abdominal pain suggestive
dental findings. Increased detection of cystic pancreatic of pancreatitis, (b) serum amylase or lipase level greater than
lesions at cross-sectional imaging has been reported, and it is three times the upper normal value, or (c) characteristic
a widespread everyday experience. imaging findings [1, 2]. Take note that the updated version of
The two large subgroups at the beginning evaluation are the Atlanta classification of acute pancreatitis is valid for
neoplastic and non-neoplastic. adults only (>18 years).
In studying pancreatic cystic lesions, the correct approach Imaging has a significant role in acute pancreatitis diag-
includes epidemiological factors, clinical presentation, and nosis in those cases where it clinically suspected but not con-
laboratory results. firmed by, for example, serum amylase and/or lipase increase;
In this chapter, non-neoplastic pancreatic and peripancre- imaging could also suggest differential diagnosis supplying
atic cystic lesions will be discussed, and then rare pancreatic alternative ones that cause abdominal pain.
cystic neoplasms will be presented. Imaging could have a role in determining causes of acute
pancreatitis, for example, biliary stones, grading disease
severity, and establishing pancreatic or peripancreatic com-
seudocysts and Fluid Collections
P plications. Moreover, imaging can be used to guide therapeu-
in Pancreatitis tic interventions, for example, collection drainages in
selected cases.
According to the 2012 revised Atlanta classification, pancre- The choice of proper imaging techniques depends on
atic and peripancreatic collection classification was updated investigation causes, symptoms, time of symptom onset, and
removing confusing and occasionally inaccurate terminol- laboratory values. Usually, transabdominal ultrasound (US)
ogy previously used to describe these local complications of is the first imaging method required in patients with abdomi-
acute pancreatitis. According to this recent classification, nal pain due to its wide availability, portability, and speed of
words like acute pseudocyst or pancreatic abscess, used in execution. A potential advantage of this imaging method is
the good visualization and evaluation of the biliary system
V. Ciaravino (*)
and, as a consequence, of biliary stones, one of the most fre-
Department of Radiology, Morgagni Pierantoni Hospital, quent causes of acute pancreatitis. Despite this, lots of limi-
Forlì, Italy tations can be funded in patients with acute pancreatitis, such
R. Calbi as abundant intestinal meteorism due to a paralytic ileus and
Department of Radiology, Miulli Hospital, Bari, Italy pronounced abdominal pain which makes probe compres-
A. Giugliano sion very difficult, with the result of an incomplete and inad-
Department of Radiology, Naples, Italy equate pancreatic gland visualization. Anyway, US is an
L. Geraci · L. Tomaiuolo · C. Longo · R. De Robertis · incomplete study for acute pancreatitis, due to the limited
M. D’Onofrio panoramic view and the inability in distinction between via-
Department of Radiology, G.B. Rossi University Hospital, ble and non-viable tissue. Nevertheless, transabdominal US
Verona, Italy
394 V. Ciaravino et al.
could be useful for short-term follow-up studies and also of pancreatic parenchyma should be judged to be a pancre-
integrate with a contrast-enhanced ultrasound (CEUS) and atic parenchymal necrotic area until otherwise proven.
can be used to guide interventional procedures [3]. In the peripancreatic necrosis alone, pancreatic gland
However, contrast-enhanced CT (CECT) is the imaging enhances normally, whereas the peripancreatic tissues dem-
modality used more often in acute pancreatitis evaluation, onstrate necrosis, with collections having inside variable
but it is very important doing it with the correct timing (at amounts of fluid and non-liquefied components and debris.
least 48–72 hours from symptom onset and at least after In the pancreatic necrosis alone, the rarer subtype,
1 week to really estimate the abdominal scenario). necrotic unenhanced areas without peripancreatic collec-
CECT has a high degree of accuracy in different clinical tions are present [1].
scenarios that could be related to pancreatitis causes or All of the described necrotic areas, pancreatic and peri-
abdominal pain, and also it is wide available and has rapid pancreatic ones, can remain sterile or turn into infected,
execution. MRI could supply diagnostic capabilities similar often after the first week, making very important the diagno-
to CECT with intrinsic advantages, including lack of ioniz- sis of infected pancreatic necrosis due to prompt requirement
ing radiation and soft tissue characterization with a high tis- of antibiotic treatment [2, 11]. Development of infection can
sue contrast resolution, allowing better depiction of stones be supposed when extraluminal gas is present in pancreatic
and a better evaluation of pancreaticobiliary ductal system. and/or peripancreatic tissues or when percutaneous image-
However, MRI should be used only in cases with suspected guided fine-needle aspiration is positive for bacteria and/or
choledocholithiasis but without stone detection at transab- fungi growth [2, 12].
dominal US. Nevertheless, MRI is less available, it has During pancreatitis, local complications, such as fluid
acquisition time longer than CT, so for this reason, it is very collections, could be occur. An important insertion by the
difficult to do it in suffering patients, and last but not the revised Atlanta classification is the fundamental distinction
least, it has spatial resolution lower than CT [4–6]. between collections containing alone clean fluid and collec-
Acute pancreatitis is divided into two sub-categories tions that arise from necrosis and containing solid compo-
based on imaging findings: interstitial edematous pancreati- nent, such as necrotic debris, added to varying amounts of
tis, which is more common, and necrotizing pancreatitis. fluid. Another important distinction supplied by the last clas-
In interstitial edematous pancreatitis, there is a diffuse, or sification is the classification of the pancreatic and peripan-
rarer localized, gland enlargement due to edema caused by creatic collections on the basis of the time passed from the
phlogosis, without evidence of necrosis within or outside the symptoms’ onset.
gland. After contrast media injection, the pancreatic enhance- The various types of collections identified in the new
ment will be relatively homogeneous or finely heteroge- revised classification are acute peripancreatic fluid collection
neous, although less avid in edematous gland portions better (APFC), acute necrotic collection (ANC), pseudocyst, and
depicted in the arterial phase, due to interstitial edema, than walled-off necrosis (WON), classified depending on the
that of the normal pancreas, with no evidence of unenhanced presence or absence of necrotic debris or necrotic tissue and
necrotic areas. Peripancreatic fat could usually appear foggy on the correct timing (less or more of 4 weeks), from abdom-
and with mild stranding, and there may also be present some inal pain onset. Any collection subtypes may become
peripancreatic fluid [1, 2]. infected, although this complication happens most usually in
Necrotizing pancreatitis is rarer than the edematous one, necrotic ones.
and it is subdivided in turn based on which anatomic areas Diagnosis of infection of collection could be suspected
are involved by necrosis in (a) pancreatic only, (b) peripan- based on the patient’s clinical course or on the basis of pres-
creatic only, and (c) combined pancreatic and peripancreatic ence of gas within the collection, better seen on CECT rather
involvement (the most common subtype). The most common than ultrasound and MRI. In case of doubt, due to the only
type shows non-enhancing pancreatic parenchyma areas imaging finding of an infected collection which is the pres-
associated with non-enhancing non-homogeneous peripan- ence of gas inside the collection, fine needle aspiration
creatic collections, typically gathered in omental bursa and (FNA) for culture may be performed, even though this last
anterior pararenal space. In the first few days, the pancreatic procedure is not done a priori but only if strictly necessary
gland can show edematous features and globally or focally during a drainage procedure.
hypo-enhancing areas, consequently often indistinguishable
from an interstitial edematous pancreatitis. Necrotic areas
and signs of peripancreatic necrosis develop gradually over Acute Peripancreatic Fluid Collection (APFC)
several days, which explains the reason why after 1 week, it
should be useful to re-evaluate again the abdominal scenario Acute peripancreatic fluid collections (APFCs) result within
to better evaluate and classify the type of pancreatitis [2, 7– 4 weeks from symptom onset in patients with interstitial
10]. After the first week from the onset, a non-enhanced area edematous pancreatitis without evidence of necrosis, so they
Pseudocysts and Other Cystic Lesions 395
are characterized by a purely fluid content. These fluid col- pancreatic parenchymal necrotic areas; this theory suggests
lections are characterized by an exudate from the inflamed that consequent leakage of pancreatic juice results in a per-
pancreatic parenchyma. Sometimes, there may be an associ- sistent, localized, fluid collection, usually after more than
ated rupture of a small peripheral pancreatic side branch 4 weeks. The connection of the pseudocyst with the pancre-
duct, but other times, there may be no connection to pancreatic duct could be recognizable at imaging, in particular at
atic duct [13]. These collections have a peripancreatic MRI cholangiography.
location and homogeneous fluid appearance without a well- A pseudocyst may also occur during an acute necrotizing
defined wall, conforming often to the retroperitoneal space. pancreatitis as a result of a “disconnected duct syndrome,”
They could be multiple and with multiloculate and anfractu- resulting in those cases where a parenchymal necrotic area
ous appearance. Usually, the majority of APFCs remain ster- produces the discontinuity of main pancreatic duct, leaving a
ile and resolve in a natural way without intervention, and portion of the gland with preserved drainage downstream of
their drainage is not recommended due to the high risk of the necrosis and a parenchyma area with impaired drainage
infecting the collection otherwise sterile [1, 10, 14]. upstream of the necrosis, therefore isolating a still viable
At transabdominal ultrasound, APFCs are anechoic and remnant pancreatic portion [1, 2, 16]. Thus, viable pancreatic
echo-poor fluid collections, lacking of wall, mainly distrib- parenchyma upstream of the necrotic pancreatic portion pro-
uted around the pancreas and usually extending into the duces normally pancreatic juices, which ends up either accu-
omental bursa and the pararenal space. Moreover, the mulating or fistulizing upstream of the necrotic area,
enzyme-rich fluid can penetrate into parenchymal organs, producing in this way a pseudocyst [15].
like the spleen or liver [3]. Pseudocysts are usually followed up if small and not com-
On contrast-enhanced CT (CECT), APFCs may be mul- plicated, without involvement of near organs, but drainage or
tiple, and they are homogeneous fluid-attenuation collec- surgical treatments could be considered in selected cases.
tions, without a defined wall and confined by normal fascial Surgical approach is recommended in case of open commu-
planes in the retroperitoneum [12]. nication between pseudocyst and pancreatic ductal system or
At MRI, APFCs have a clearly purely fluid intensity, in case of involvement of adjacent organs, especially the
hypointense on T1w sequences and hyperintense on T2w arteries, to avoid pseudoaneurysm development and, as a
sequences, without non-liquefied elements and a clear wall, consequence, hemorrhage. In some cases, fistulas between
mainly distributed around the pancreas. A diffuse edematous pseudocyst and bile duct system have been shown [3, 17,
imbibition of peripancreatic fat may be seen. 18].
Bleeding is a severe complication due to erosion of ves-
sels walls, and it may occur within the pseudocyst, or gastro-
Pseudocyst intestinal tract, or peritoneal cavity. In case of bleeding into
the pseudocyst, within the pseudocyst is a visible change
Pseudocysts are classified as APFCs not resolved after appearance due to the blood’s different characteristics in
4 weeks; meanwhile, these collections become more orga- respect to clear fluid; moreover, the cyst may enlarge causing
nized and develop a peripheric wall with contrast enhance- pain due to a pressure increase. In this case, blood could pass
ment after contrast media injection related to the presence of through the main pancreatic duct into the duodenum, an
a fibrotic capsule with no epithelial layer. The pseudocyst event called hemosuccus pancreaticus. An important event to
has no necrosis inside, and it is filled only by fluid, without remember is bleeding within pseudocysts caused by erosion
non-liquefied elements, due to its relationship with intersti- of vessel wall or by rupture of a pseudoaneurysm, in particu-
tial edematous pancreatitis and acute peripancreatic fluid lar the splenic artery, configuring an emergency setting [3,
collections. In fact, with small amount of fat or soft-tissue 19, 20].
attenuation within the collection after 4 weeks is not correct At transabdominal US, pseudocysts are oval or round
called it pseudocyst, because the correct diagnosis is walled- anechoic lesions, defined by a sharp wall, with distal acous-
off necrosis. tic enhancement due to the fluid content. In case of history of
These collections are usually arranged in the peripancre- acute or chronic pancreatitis, the diagnosis of pseudocysts
atic tissues, but occasionally they may be partly or wholly should be considered. But in case of detection of a cystic
intra-pancreatic, in case, for example, of prior necrosectomy lesion in patients with pancreatitis history, it is fundamental
with an enduring pancreatic duct leak into the necrosectomy to do an evaluation with color Doppler US, excluding the
cavity [1, 2, 15]. Usually, pseudocysts contain amylases, presence of vascular complications, such as a pseudoaneu-
confirmed by aspiration of cysts fluid content or by the anal- rysm [3, 17, 21, 22].
ysis of fluid collection from a drainage, because they are Ultrasound has a role in confirming the absence or the
thought to occur from interruption of the main pancreatic presence of solid components in a walled fluid collection
duct or its intra-pancreatic branches, without any perceptible funded at CT, due to the complexity at CT of seen solid com-
ponents and debris within fluid lesions. Also contrast- These ANCs are characterized by a combination of paren-
enhanced ultrasound could have a role in pseudocyst study, chymal and fat necrosis mixed with exudates from the pan-
improving differential diagnosis of cystic lesions, because creatic gland. The activated pancreatic enzymes released into
they must be differentiated from pancreatic cystic neoplasms, the peripancreatic and pancreatic areas cause a fat saponifi-
in particular mucinous cystadenoma, often with unilocular cation and necrosis.
shape such as pseudocyst [3, 23, 24], because with These collections could be multiple and multiloculated,
contrast-
enhanced ultrasound, it is possible to evaluate containing necrotic material.
potential vascularity of eventual intralesional inclusions and and pancreatic fluid to various degrees and with septa that
better evaluate wall morphology. Pseudocysts are always create loculations.
completely avascular and homogeneously anechoic during In the first days, acute necrotic collections may appear
CEUS study [3, 24], due to the harmonic microbubble- homogeneous but usually change to heterogeneous aspect
specific software that filters all background tissue signals, due to the appearance of necrotizing process [13], and this is
defining CEUS high accuracy [3, 23]. one of the reasons why the correct timing to do an CECT is
At CT study, pseudocysts are well-defined rounded or at least 48–72 hours, so as to not underestimate both the pan-
oval-shaped hypodense or isodense fluid homogeneous col- creatic gland involvement and the appearance of peripancre-
lections in peripancreatic tissue, without contrast enhance- atic collections.
ment inside lesions, within fluid or over-fluid density mean An important distinction with APFC is that ANC may
values within the collection, and with a well-defined enhanc- extend into the pancreatic gland within areas of pancreatic
ing wall with a complete encapsulation. An important limit necrosis. In fact, in case of collections seen within pancreatic
of CT imaging is the frequent inability to show if within col- parenchyma, these are by definition ANCs in necrotizing
lections are present debris, non-liquefied material, and inclu- pancreatitis.
sions. Occasionally, a connection to the pancreatic duct can These collections take up often the omental bursa, and
be visualized on CECT, especially with curvilinear recon- they place in pararenal spaces, with a multiloculated mor-
structions [13], but endoscopic ultrasound and MR cholan- phology, and they may extend caudally until the pelvis.
giopancreatography (MRCP) are more precise in showing Non- liquefied debris, solid-appearing components,
the eventual connection. necrotic components, and fat globules within a variable
At MRI, pseudocysts are usually rounded or oval-shaped amount of fluid are useful elements in the distinction
fluid collection, uniformly hypointense on T1-weighted between ANCs and APFCs. Moreover, peripancreatic col-
images and hyperintense on T2w sequences, with no solid lections concomitant to pancreatic parenchimal necrotic
components or debris submerged by clear fluid, surrounded area should be called acute necrotic collection, even if it
by an enough smooth wall. Usually, pseudocyst walls has a homogeneous appearance and it no contains non-
enhance slightly on early post-contrast images and show liquefied debris [1, 2].
gradually intense enhancement on 5 min post-contrast An acute necrotic collection may be combined with main
images, related to the presence of fibrous tissue in the wall, pancreatic duct interruption, caused by necrotic disruption,
without viable cells [4]. within the parenchymal necrotic area and could become
Magnetic resonance is often required to confirm absence infected.
of solid components in the fluid collection, for a correct dif- Such as in the first week, it could be difficult at CT with
ferential diagnosis with walled-off necrosis, within debris contrast enhancement to discern an interstitial edematous
lacking of enhancement, or cystic neoplasms, with enhanced pancreatitis from a necrotizing pancreatitis; also, the distinc-
solid neoplastic vegetations and often more irregular and tion between an APFC and an ANC could not be easier, so it
thicker wall. Magnetic resonance imaging and magnetic res- is better to have a new valuation with CECT after 2 weeks to
onance cholangiopancreatography (MRCP) may often show show the internal heterogeneity of an ANC [1, 2].
the potential connection between pseudocyst and pancreatic At ultrasound imaging, ACNs are more or less corpuscle
ductal system [1, 25]. These ductal connections can be inter- multiloculated collections, depicted as anechoic fluid collec-
rupted, often determining pseudocyst resolution. tions, lacking of fully definable wall surrounding collections,
mainly distributed around the pancreas and with possible
involvement of pancreatic parenchyma, in which are recog-
Acute Necrotic Collection (ANC) nizable multiple echoic unviable debris. Contrast-enhanced
ultrasound (CEUS) could be useful to discern between unvi-
Acute necrotic collections (ANCs) are collections visible able debris and eventual viable material, because the first one
within the first 4 weeks of. does not enhance.
symptom onset, occurring in necrotizing pancreatitis (all On CECT, these collections may be multiple and multi-
the three subtypes), and they are characterized by a poor loculate, characterized by a heterogeneous appearance due to
organization with necrotic components inside. liquid and non-liquid components, such as solid necrotic
material, of various attenuation and amounts and varying pancreatic, adjacent to pancreatic parenchyma, causing
degrees of loculations, without a complete mature wall sur- sometimes a parenchymal compression with a resulting
rounding collections. If contrast material could not be dilated pancreatic main duct, whereas in cases of WONs,
injected for some contraindications, the presence within the they are both intra- and extra-pancreatic, and pancreatic fluid
collection of fat attenuation areas at the basal CT could be drains into the collection directly without ductal dilation.
helpful to identify necrosis and diagnose ACNs, making dif- At transabdominal ultrasound, WONs are more or less
ferential diagnosis with APFCs. However, sometimes, CECT corpuscle multiloculated collections, depicted as anechoic
may not be able to detect necrotic components, due to the fluid collections surrounded by a capsule, often with irregu-
poor density differentiation among fluid and debris within lar shape, involving both pancreatic parenchyma and peri-
the collection, and so if a necrotizing process is clinically pancreatic areas, in which are recognizable multiple echoic
suspected, MRI or transabdominal ultrasound with or with- unviable debris. Contrast-enhanced ultrasound could be use-
out contrast material administration can be used to confirm ful to discern between unviable debris and eventual viable
the presence or the absence of necrotic material within col- material, because the first one does not enhance, making pos-
lections, above all if this information are considered relevant sible a differential diagnosis with cystic neoplastic lesions.
for treatment [13]. On CECT, these collections may be multiple and multi-
Magnetic resonance imaging may be helpful to confirm loculate, characterized by a heterogeneous appearance due to
the presence of solid contents in the collection, because with liquid and non-liquid components, such as solid necrotic
MRI, it is easier to appreciate solid debris in respect to material, of various attenuation and amounts and varying
CECT. With MRI, ANCs have heterogeneous appearance, degrees of loculations, with a mature well-defined wall sur-
due to the presence of multiple non-liquefied materials rounding the collections, completely encapsulated. If con-
within fluid intensity collections lacking of a defined com- trast material could not be injected for some contraindications,
plete wall surrounding fluids [13]. In a contest of a hypoin- the presence within the collection of fat attenuation areas at
tense on T1w sequences and hyperintense on T2w sequences the basal CT could be helpful to identify necrosis and diag-
that characterized fluid collections, multiple small non- nose WON, making differential diagnosis with pseudocyst,
viable debris are seen as irregularly shaped area hypointense although sometimes walled-off necrosis has usually a more
on both T1 and T2w sequences. These collections are present irregular appearance. Also, in case of WONs, sometimes,
within the pancreatic gland and peripancreatic regions. A dif- CECT may not be able to detect necrotic components, due to
fuse edematous imbibition of peripancreatic fat may be seen the poor density differentiation among fluid and debris
as hyperintense on T2w sequences fat stranding. within the collection, and so if a necrotizing process is clini-
cally suspected, MRI or transabdominal ultrasound with or
without contrast material administration can be used to con-
Walled-off Necrosis (WON) firm the presence or absence of necrotic material within col-
lections [2, 4, 13]. Knowing the presence of necrotic
Walled-off necrosis (WON) is the mature form of acute components within a collection is very important to choose
necrotic collection after 4 weeks, when ANC, containing the best management, and CECT or MRI is useful for plan-
fluid interspersed to necrotic fat and necrotic pancreatic tis- ning interventions, especially MRI because it allows deter-
sue, well shown at imaging as non-liquefied debris, typically mination of necrotic debris amount that must be removed by
develops a thick peripheric non-epithelialized inflammatory means of more aggressive interventions.
enhancing wall, with a recognized capsule at imaging. WON Magnetic resonance imaging may be helpful to confirm
usually involves together both pancreatic parenchyma and the presence of solid content in the collection, because with
peripancreatic space, but this involvement could be seen also MRI, it is easier to appreciate solid debris in respect to
as separate and distinct. Walled-off necrosis could be multi- CECT. With MRI, WONs have heterogeneous appearance,
ple and multiloculate and may be present at sites distant from due to the presence of multiple non-liquefied materials
the gland, and it could be infected. Demonstration of poten- within fluid intensity collections surrounded by a defined
tial pancreatic ductal communication is very important, complete wall [13]. In a contest of a hypointense on T1w
because it may affect patients’ management. sequences and hyperintense on T2w sequences that charac-
In some cases, pseudocysts and WONs can have a similar terized fluid collections surrounded by an enhanced wall,
appearance, and they could be often confused with each multiple small non-viable debris are seen as irregularly
other. Pseudocysts occur only in patients with interstitial shaped debris hypointense on both T1 and T2w sequences. A
edematous pancreatitis, except those cases post-necrosectomy diffuse edematous imbibition of peripancreatic fat may be
that could develop a pseudocyst, and they are usually extra- seen as hyperintense on T2w sequences fat stranding.
Other Non-neoplastic Cystic Lesions head, configuring in this last case the subtype 1B (the expans-
ile solid form). This last form described is particularly diffi-
Other non-neoplastic lesions with cystic appearance can be cult to make out from pancreatic ductal adenocarcinoma or
detected in the peripancreatic region. In this paragraph, the from a peripapillary neoplasm. Type 1A is usually a sheet-
most common peripancreatic cystic lesion will be like mass (“sandwich sign”), with a linear mass centered in
presented. the groove region, with or without visible cysts. Type 1B is
usually a solid round mass (“rice ball pattern”), and it is dif-
ficult to do a differential diagnosis with pancreatic ductal
Paraduodenal Pancreatitis (PDP) adenocarcinoma or peripapillary neoplasm, especially in
case of absence of cystic changes in the groove region.
Paraduodenal pancreatitis (PDP) is a disease that groups dif- Signs that could suggest paraduodenal pancreatitis rather
ferent entities, each one represents different facets of this that pancreatic ductal adenocarcinoma or periampullary neo-
pathology, such as cystic dystrophy of heterotopic pancreas plasms are absence of common bile duct and main pancreatic
(on duodenal wall), pancreatic hamartoma of duodenum, duct dilation, lack of considerable pancreatic parenchymal
myoadenomatosis, para-duodenal/duodenal wall cysts, atrophy, presence of the “duct-penetrating sign” at secretin-
groove pancreatitis, and even as simply “pseudotumors” enhanced MR cholangiopancreatography, thickening of duo-
[26]. Radiologically, all of these conditions manifest either denal medial wall and widening of the distance between
as a solid fibrotic mass (solid variant) around the minor ampulla and duodenal lumen, and displacement rather than
papilla or as cysts in duodenum wall and in the pancreatico- encasement of common bile duct and vessels, especially gas-
duodenal groove anatomic region (cystic variant). troduodenal artery. Moreover, in case of paraduodenal pan-
Paraduodenal pancreatitis is a disease being part of the big creatitis, usually, Ca 19.9 levels are within the limits, and
group of chronic pancreatitis, being an uncommon focal overt jaundice is uncommon, unlike with pancreatic ductal
form of chronic pancreatitis grounded on the anatomical adenocarcinoma [27, 36, 37]. Nevertheless, dilation of com-
region of pancreatic-duodenal groove, but it could extend mon bile duct and pancreatic main duct could be seen in
also into the pancreatic head region [27, 28]. The pancreatic- some cases, making more difficult the differential diagnosis
duodenal groove is a virtual space between the pancreatic with neoplasms.
head, medial duodenal wall, and distal common bile duct Type 2 is the cyst-forming subtype, much easier to recog-
[29]. Inflammation and/or fibrosis that occurs in paraduode- nize due to the presence of cystic change in the pancreatico-
nal pancreatitis can produce a pseudotumor in the grove duodenal groove; in fact, cysts account for greater than 80%
region that may extend into the adjacent pancreatic head, of the lesion. Type 2 is usually characterized by visible cysts
mimicking a locally invasive pancreatic ductal adenocarci- in the groove region and within duodenal thickened medial
noma of the head of the pancreas [27, 30]. wall.
The majority of patients with paraduodenal pancreatitis Type 3 is the ill-defined type, without a mass appearance,
are male, on average in the fourth or fifth decade, with a his- so it is less likely to mimic malignant diseases [27, 30].
tory of alcoholism and smoking. Paraduodenal pancreatitis Paraduodenal pancreatitis is usually shown as solid or
could manifest itself with chronic pancreatitis symptoms, mixed solid and cystic mass centered at the pancreatico-
such as severe chronic abdominal pain, post-prandial vomit- duodenal groove region, with involvement of the region of
ing, and weight loss, primarily due to duodenal outlet accessory ampulla and thickening of duodenal medial wall.
obstruction, with concomitant increase of serum amylase Cystic changes are often seen in this disease, but they are not
and lipase levels. Diarrhea and diabetes mellitus are usually always visible; in fact, up to 20% of patients with paraduode-
associated. These symptoms spread over the time, determin- nal pancreatitis have no visible cysts within the lesion [27,
ing paraduodenal pancreatitis a chronic disease. In many 28, 30, 38].
patients, especially those with alcohol abuse, obstructive At transabdominal ultrasound, the appearance of paradu-
jaundice could be observed in the course of chronic disease, odenal pancreatitis depends on the patient’s symptom dura-
due to common bile duct stenosis [26, 29, 31–35]. tion. In fact, in early stages of the pathologic process,
Paraduodenal pancreatitis is composed by three different characterized by superior inflammatory elements, rather than
subtypes, each with distinctive imaging and histopathologic fibrosis, a hypoechoic sheet-like mass thickening of the
characteristics. pancreatico-duodenal groove and a thickening of the adja-
Type 1 is the solid tumoral type, and it manifests as a solid cent medial duodenal wall (> 3 mm) could be seen; in case of
pseudotumor with minimal or absent cystic change; in fact, involvement of the pancreatic head, it could be
cysts may constitute less than 50% of the mass or. heterogeneously hypoechoic. Otherwise, in the chronic

may be completely absent. This type may show as a solid- stages of the disease, fibrotic process dominates over inflam-
appearing sheet-like mass in the pancreatico-duodenal mation, and the hypoechoic sheet-like thickening is substi-
groove or could be more rounded involving the pancreatic tuted by a hyperechoic band in the groove region, contiguous
with hyperechoic thickening of the duodenum, and in case of also consequently to extrinsic compression of the pancreatic
involvement of the pancreatic head, it should be increasingly head caused by the groove mass.
slightly hyperechoic [33, 39]. If present, background chronic In case of involvement of the cephalo-pancreatic region, a
calcific pancreatitis and pancreatic duct and common bile focal hypodense lesion in the pancreatic head in close prox-
duct dilatation may be seen [39, 40]. imity to the duodenal wall could be seen, and main pancre-
With transabdominal US, the differential diagnosis with atic duct upstream dilation and common bile duct smooth,
pancreatic ductal adenocarcinoma is very hard, whereas at regular, and tapered narrowing in the distal part with
endoscopic ultrasound, the identification of tiny cysts, if upstream biliary dilatation could be present [29].
present, in the pancreatico-duodenal groove region could be Despite the type of paraduodenal pancreatitis, peripancre-
easier than transabdominal US. Identification of small cystic atic and retroperitoneal phlogosis is not a dominant feature
in a thickened duodenal wall on the pancreatic side is a spe- seen at imaging [33, 47].
cific finding for paraduodenal pancreatitis. Endoscopic ultra- At CECT, paraduodenal pancreatitis may mimic pancre-
sound is one of the best tools to demonstrate hypoechoic atic adenocarcinoma that involves the pancreatico-duodenal
lesion between duodenal wall and pancreatic head paren- groove, in particular in those cases without visible cysts.
chyma; thickening and narrowing of duodenal lumen, even- Both diseases are hypodense in the arterial phase, with
tually with intramural cysts; and, in case of involvement of progressive late phase enhancement. The presence of a fat
cephalopancreatic region, heterogeneous hypoechoic mass plane separating the mass from the pancreatic head may help
with enlargement of pancreatic head. If present, with EUS, it exclude a pancreatic origin of the lesion. Moreover, with
is possible to demonstrate also pancreatic parenchyma calci- CECT, it is possible to see if distal common bile duct or adja-
fications, smooth reduction of caliber of distal common bile cent vessels, such as gastroduodenal artery, are encased, sup-
duct, and main pancreatic duct dilation. Furthermore, EUS porting a neoplasm diagnosis, or displaced, usually medially,
allows to do fine-needle aspiration, confirming or retracting without thrombosis signs or infiltration, supporting paraduo-
paraduodenal pancreatitis diagnosis [40]. denal pancreatitis diagnosis [27, 48, 49].
Usually, CECT shows loss of fat planes between head of Usually, findings associated more frequent with paraduo-
the pancreas and the duodenum with an ill-defined hypodense denal pancreatitis and less frequent with neoplastic diseases
crescentic sheet-like soft tissue mass in the groove region, include conspicuous duodenal wall thickening and stenosis
with a poor enhancement after contrast media injection, which with hyper-enhancement after contrast media injection, cys-
increases in late phases, according to the amount of fibrosis tic lesions in the groove region and in the duodenal wall,
within the lesion [29, 41, 42]. Enhancement after contrast smoothly tapered stricture of the intrapancreatic common
media injection could be more heterogeneous and patchy with bile duct (vs an irregular and abrupt narrowing of the stric-
respect to pancreatic ductal adenocarcinoma [37]. ture, founded in case of pancreatic adenocarcinoma), rare-
This soft tissue appears as sheet-like curvilinear crescen- ness of pancreatic double duct cutoff, upstream atrophy of
tic shape better evaluated on coronal multiplanar reformatted parenchymal gland and infiltration of the retroperitoneum
images, because on the coronal plane, large thickening of the posteriorly (contrary to pancreatic ductal adenocarcinoma),
duodenal wall and the groove and small cysts within the duo- vessel displacement (vs vessel encasement in case of neo-
denal thickened wall or the pancreatico-duodenal groove are plasms), and usually absence of lymphadenopathy [29, 32,
better shown [29, 43, 44]. 33, 50–53].
Duodenal wall is often diffuse or eccentric thickened (> MRI may well prove the characteristic pathological fea-
3 mm), but stenosis of duodenum lumen is uncommon to see, tures of paraduodenal pancreatitis, and it has good ability in
and usually it shows a hyper-enhancement after contrast showing cystic aspect. A sheet-like mass is seen in the groove
media administration relative to the proximal jejunal loops region, corresponding to the fibrous scar [32, 40, 54].
[40, 41, 45, 46]. The sheet-like mass is slightly isointense or hypointense
Cysts, which vary in size and shape, could be seen within compared to pancreatic parenchyma on T1-weighted images
duodenal wall and or within groove area. In case of enlarge- and isointense, hypointense, or slightly hyperintense on
ment of a single cyst, differential diagnosis could be intesti- T2-weighted images according to the time of disease onset
nal duplication, congenital cyst, or pancreatic pseudocyst. and usually without signal restriction on DWI. Appropriate
Cysts, being fluid-filled lesions, are isodense at unenhanced interpretation of the T2-weighted images is useful to deduce
CT, and they are hypodense after contrast media the degree of disease activity, due to the variation of the
administration. signal intensity on T2 sequences from hyperintense, in initial
In case of chronic pancreatitis disease, calcifications and phases, to iso-hypointense in advanced phases, due to the
pancreatic main duct and common bile duct dilation may be progressive collection of fibrous tissue. In fact, in the sub-
seen. Furthermore, pancreatic ductal dilation can be seen acute form, the mass shows higher signal on T2-weighted
images due to edema, while in the chronic form, it has a Gastrointestinal duplication cysts are divided into two
lower T2-weighted image signal due to fibrosis [29, 33, 51]. categories: cystic duplication (80%), round cystic lesions
After contrast media injection, a peripheral enhancement without any communication with the bowel lumen, and tubu-
of the fibrotic mass is seen in first sequence after injection lar duplication (20%), communicating directly with the
with progressive centripetal enhancement on delayed images, bowel lumen [57–59].
reflecting the fibrous nature of the tissue [40, 50, 52, 55]. The majority of these lesions manifest in the early life,
The involvement of medial duodenal wall is typical of especially during the first year.
paraduodenal pancreatitis, with duodenal wall thickening This pathology could be also a rare cause of acute pancre-
and multiple cysts in both the duodenal wall and pancreatico- atitis in case of duodenum interest [60]. Only occasionally,
duodenal groove. The medial duodenal wall can be hyperin- they could manifest in adults, which are usually found inci-
tense on T2-weighted images and hyper-enhancing after dentally, due to their rare symptomatic nature. Sometimes,
contrast media injection [33]. they could manifest directly with complications, although
At MRI, cystic lesions present in the groove region or in they are rare, such as obstruction by volvulus or intussuscep-
the duodenal wall are well demonstrated as rounded lesions tion, bleeding, infection, and perforation. Moreover, despite
with sharp margins, variable in size, hypointense on the extremely rarity, malignant changes could happen from
T1-weighted images and hyperintense on T2-weighted the mucosa, so surgical excision is the treatment [57–59, 61,
images. At T2-weighted image, microcysts within the mass 62].
in the grove region suggest diagnosis of paraduodenal pan- At imaging, transabdominal and endoscopic ultrasound
creatitis [27]. plays a critical role in the evaluation of duplication cysts, due
Compared to CT, MRI better visualizes the potential to the characteristic US appearance of these lesions. Usually,
involvement of the pancreatic head, showing a diffuse they are anechoic mass with good through transmission due
decreased of signal intensity on T1-weighted images, due to to clear fluid content or echogenic mass due to hemorrhage
parenchymal atrophy and fibrosis [29, 56]. and inspissated material within the duplication [63].
Magnetic resonance cholangiopancreatography (MRCP) Gastrointestinal duplication cysts usually show an echogenic
may show an expanding of the space between duodenal inner mucosa surrounded by a hypoechoic outer muscular
lumen and ampulla, third distal common bile duct, and pan- layer, known as the “double-wall” or “muscular rim” sign.
creatic duct, with intramural and paraduodenal cysts. A long Nevertheless, this sign may be seen also in other cystic
segmental smooth stenosis of the distal common bile duct lesions, so it can be not entirely true, and it is not completely
may be present, and it could be differentiated from an irregu- characteristic [57, 64].
lar stricture, which is most viewed in case of groove neo- In case of inconclusive US findings, CT and MRI could
plasms [40, 55]. be alternative imaging modalities.
In paraduodenal pancreatitis, a large amount of fibrosis in At CT, usually, they are smoothly rounded, fluid-filled
the medial duodenal wall can implicate a non-malignant cysts or tubular structures with thin,
cause of double duct sign. Moreover, in case of chronic pan- slightly enhancing wall located in or adjacent to the wall
creatitis, it could be seen subtle dilatation of side branches or of part of the interested gastrointestinal tract [63]. Due to its
collateral duct, suggesting a chronic inflammatory and inner panoramic views, CT may depict the location and
fibrotic process rather than malignancy [27]. extent of these lesions. Moreover, with CT, complications
and other associated anomalies could be studied. In fact, in
case of hemorrhage or proteinaceous material within the
Duodenal Cystic Duplication cyst, a hyperdense area is seen within the lesions. If the cys-
tic lesion has a thick enhancing wall or septa and it is sur-
Gastrointestinal duplication cyst is a rare congenital defect rounded by adipose inflammation, it may indicate a
that may happen anywhere along the mesenteric side of the duplication cyst complicated by infection, whereas in case of
gastrointestinal tract, in particular in order of presentation in solid foci within the cyst that enhance after contrast media
the distal ileum, esophagus, colon, jejunum, stomach, and administration, it is suggestive of malignant change of the
finally duodenum. duplication cyst [57–59, 61, 62].
As a consequence, duodenal cystic duplication is an At MRI, usually they are smoothly rounded, fluid-filled
uncommon disease and is part of the major group of mesen- cysts or tubular structures with thin,
teric cysts. slightly enhancing wall located in or adjacent to the wall
These cystic lesions usually are connected to the gastroin- of part of the interested gastrointestinal tract. The intra-cystic
testinal tract, and they present smooth muscle in their wall, fluid is heterogeneous on T1-weighted images and hyperin-
then lined by gastrointestinal epithelium. tense on T2-weighted images [63].
Mesenteric Pseudocyst Rare Neoplastic Cystic Pancreatic Lesions
Non-pancreatic pseudocyst is an uncommon lesion that Among the big group of cystic pancreatic lesions, beyond the
usually arises from the mesentery and omentum, devel- benign ones, there are enough cystic lesions with malignant
oping usually secondary to trauma, surgery, or infection, or borderline behavior, requiring surgical excision. These
and it is part of the major group of mesenteric cysts pancreatic cystic neoplasms can be originally primary cystic,
[65–68]. or they can develop secondary cystic aspects due to the lesion
These lesions used to have a thick, fibrous wall, without involution.
an epithelial lining, and they could contain different kinds of
fluid, such as hemorrhage, pus, serous fluid, or occasionally
chylous content. Solid Pseudopapillary Neoplasm (SPN)
Differently from pancreatic pseudocysts, in the fluid of
these lesions are not seen high levels of amylase or lipase. Solid pseudopapillary neoplasm is an uncommon low-grade
Non-pancreatic pseudocysts are well-defined masses, malignant pancreatic neoplasm, accounting for 1–2% of all
with a round or oval shape, uni- or multilocular fluid- pancreatic tumors. This lesion occurs mainly, but not exclu-
filled, with possible fluid-fluid level, surrounded by thick sively, in women (85–90%), chiefly in young adults, espe-
walls. Features of the fluid within the cysts vary among cially in the second to fourth decades of life, with a mean age
purely fluid, denser up to hemorrhagic, so at imaging, of 25 years (but with a range from 10 to 74 years) [72]. This
they could show different characteristics both at US, CT, kind of tumor has been described also in men, but usually at
and MRI. In particular, pus and hemorrhage could be bet- an older age than women. Moreover, a slightly predilection
ter detected at MRI with the help of T1- and T2-weighted is seen for African and Asian individuals.
images and DWI, and often a fluid-fluid level is seen [67, Solid pseudopapillary neoplasm should be taken into con-
69, 70]. sideration in the differential diagnosis of any solid and non-
completely cystic pancreatic or upper abdominal mass,
particularly in young women.
Retroperitoneal Lymphocele These neoplasms can show a completely cystic, mixed
cystic and solid, or a purely solid appearance. This wide vari-
Lymphocele is a fluid-filled lesion without an epithelial lin- ability of solid pseudopapillary neoplasm’s histological fea-
ing that could occur after lymphadenectomy or after nephrec- tures reflects on imaging presentation, causing an imaging
tomy surgery, respectively, usually in the pelvis or in the spectrum from completely solid tumors to almost completely
retroperitoneum. In 12%–24% of patients who undergo radi- cystic masses. Smaller lesions (≤ 30 mm) are usually com-
cal lymphadenectomy, this phenomenon could happen. In pletely or mainly solid, with features well depicted both at
case of retroperitoneal location, these cystic lesions may CT and MRI, while larger lesions usually present as large
manifest with compressive sign, in case of big dimension, well-encapsulated masses with varying solid and cystic com-
and they could cause venous obstruction, with subsequent ponents due to hemorrhagic degeneration, and MRI can be
edema and thromboembolic complications. useful in showing their features helpful for the diagnosis,
Usually, these lesions are well-defined masses, with round such as intra-tumoral hemorrhage and peripheral enhance-
or oval shape, with pure fluid surrounded by a very thin not- ment pattern [73]. Solid pseudopapillary neoplasms smaller
epithelialized wall. In case of superinfection, material within than 30 mm may present atypical imaging features, which
the cystic lesion becomes thicker. At imaging, lymphoceles may overlap those of other solid pancreatic tumors [74].
present as thin-walled simple fluid collections with possible Due to their wide multiple appearance, classification of
minimal wall enhancement after contrast material solid pseudopapillary neoplasms as cystic pancreatic lesions
administration. may lead to confusion at imaging because in different cases,
At CT, these lesions manifest as hypodense masses. lesions are completely solid. Cystic components derive to
Negative attenuation values due to fat within the fluid are tumor degeneration, and they vary in size and morphology
very rare, but highly suggestive of a lymphocele. [75]. These lesions usually develop as solid masses and then
At MRI, usually they are hypointense on T1-weighted undergo huge hemorrhagic/necrotic degeneration, appearing
images and hyperintense on T2-weighted images. Rarely it as large mass with cystic appearance [76–79].
could be possible to see calcification along the lymphocele These lesions vary widely in size, but at diagnosis, they
wall. could be solitary large lesions, with a mean diameter of 9 cm,
For the diagnosis of lymphocele, the clinical history can with round or ovoid morphology, well demarcated from the
be very helpful [69, 71]. surrounding pancreatic gland. Some neoplasms appear
grossly encapsulated by a pseudocapsule composed of com- an exam performed for other clinical reasons. Often, they
pressed pancreatic tissue and reactive fibrosis, and some- remain asymptomatic due to their slow growth.
times peripheral curvilinear and central, stippled, eggshell At transabdominal ultrasound, lesion characterization is
calcifications can be seen within the cyst wall. Calcifications not possible, due to the presence of non-typical features. In
tend to be more frequently among tumors with bigger dimen- case of small dimension, they appear as solid, hypoechoic
sions [74]. masses with well-defined margins. In case of bigger dimen-
These lesions have a tendency to displace rather than sion, hemorrhage and cystic degeneration changes could be
invade the surrounding structures, both vascular and paren- seen as large well-defined mass with heterogeneous appear-
chyma, and rarely cause obstruction of the bile duct or pan- ances, due to its solid and cystic composition. In both cases,
creatic duct [72]. usually, no upstream ductal dilation is present. In only very
Solid pseudopapillary neoplasms commonly occur in the rare cases, ductal obstruction and secondary pseudocyst for-
pancreatic tail, followed by the cephalon-pancreatic region mation are seen.
[72]. Tumor location is probably related to a delayed diagno- In case of ultrasound contrast media administration, a
sis compared with pancreatic head location, owing to the capsule rim enhancement, with un-enhancing areas within
possibility of a larger tumor growth without producing early lesions, would be seen. The rim enhancement is secondary to
obstructive symptoms [74]. the presence of the pseudocapsule. Lesions could be iso- or
Literature has affirmed that small tumors (≤ 30 mm) had hypo-enhancing in comparison with the normal gland paren-
a significantly older age at diagnosis and that large tumors chyma, both in the early and in the later phases [86, 87].
were more frequently located in the pancreatic body-tail At CT, SPNs could show an entire spectrum from a com-
compared with smaller tumors [74]. pletely solid to an almost completely cystic mass. These
Microscopic appearance is heterogeneous with solid areas lesions typically present as large well-encapsulated, hetero-
characterized by nets and sheets of uniform cells or pseudo- geneous masses with varying solid and cystic components,
papillae alternating with cystic spaces filled with hemor- due to hemorrhagic degeneration. In case of mixed form,
rhagic and necrotic debris. Pseudopapillae show a usually, solid areas are found in the periphery of the lesion,
fibrovascular stem surrounded by a rim of one or more layers while cystic areas are found centrally. Calcifications and
of tumor cells and are formed in the presence of degenerative enhancing solid areas may be present at the periphery of the
changes. Though these lesions are well demarcated, it is not mass [78, 88, 89].
so uncommon to find tumor cells intermingling within the Usually, on unenhanced images CT, SPNs are heteroge-
normal pancreatic tissue, without tissue reaction. It is also neous hypodense, and cysts with relatively recent hemor-
typical to find entrapped non-neoplastic acini and islet within rhagic content may be seen as hyperdense areas. After
the periphery of the tumor. Histologically, principally solid contrast media administration, enhancement is weaker than
lesions may be confused with neuroendocrine tumors and that of the normal adjacent pancreatic parenchyma in the
tumors with acinar differentiation: in these cases, immuno- pancreatic phase, and gradual enhancement is seen during
histochemistry is helpful in establishing the diagnosis. When the venous phase [90]. Instead, small tumors (<3 cm) most
hemorrhagic-cystic degeneration is prominent, these masses commonly appear at CT as purely solid, without hemor-
must be differentiated from other cystic neoplasms. rhage, necrosis, or cystic changes, and pancreatic lesions
Solid pseudopapillary neoplasm, having a low malignant with well-defined margins, even if they appear less sharply
potential, usually shows an indolent behavior with an excel- circumscribed than the bigger ones, because they are often
lent prognosis following complete resection, but there are unencapsulated. After contrast media administration, small
few cases of recurrence after surgery and/or metastasis. lesions usually demonstrate mild, gradually increasing
Metastases tend to occur late in the course of disease, mostly enhancement.
to the lymph nodes, liver, omentum, and peritoneum. In lit- Imaging features of small SPNs may overlay with those
erature, malignant SPNs have a reported frequency of of pancreatic ductal adenocarcinoma, apart from the well-
10–20% [74, 77, 80, 81]. defined margins, caused by an expansive rather than infiltra-
Capsular or parenchymal invasion, extracapsular inva- tive growing. This typical growth pattern causes a
sion, vascular and perineural, is associated with an increase development of peripheral pseudocapsule, explaining the
in malignancy potential [82–85]. typical rim enhancement that can be seen around SPN, and
Solid pseudopapillary neoplasms could present with can be useful for differential diagnosis with ductal adenocar-
vague abdominal distension and pain related to intra- cinoma [76, 87, 88, 91].
abdominal space-occupying mass, with a palpable abdomi- Some signs at CT could lead to suppose a malignant
nal mass. But they could also be an incidental finding during behavior, such as focal discontinuity of the capsule, and
p ancreatic tail location, while lesions with amorphous or In case of small SNPs, the differential diagnosis is with
scattered calcifications, and mostly solid, may have more small neuroendocrine neoplasms, because both have well-
likely a benign behavior, with homogeneous enhancement of defined margins, they are hypervascular lesions, and they
the solid components and the peripheral thick wall [92]. could be slightly hyperintense on T2-weighted images. A
MRI shows in a better way than CT hemorrhage, cystic support in the differential diagnosis could be that small SNPs
degeneration, and eventual presence of a capsule [75, 79]. usually show progressive enhancement, and its enhancement
At MRI, SPNs of bigger dimensions usually appear as should be inferior to that of the pancreatic parenchyma, con-
well-defined lesions with heterogeneous signal intensity, due trary to the usual hypervascularity on the arterial phase typi-
to a combination of high and low signal intensity areas both cal of neuroendocrine neoplasm.
on T1- and T2-weighted images. Predominantly solid lesions When SPNs have mixed composition, both solid and cys-
have a mildly increased T2 signal intensity, while those that tic, the most difficult differential diagnosis is with neuroen-
are mostly cystic have a high T2 intensity [93]. docrine neoplasm with cystic degeneration.
Identification of blood products could be very helpful and Some useful features in differential diagnosis between
specific for the diagnosis of solid pseudopapillary neo- solid pseudopapillary neoplasms and cystic neuroendocrine
plasms, due to intrinsic characteristics: subacute hemorrhage neoplasms are age at presentation (neuroendocrine neo-
may appear hyperintense areas on T1-weighted images and plasms rarely occur in patients younger than 30 years of
homogeneously or in-homogeneously hypointense areas on age); signal intensity at T1-weighted MR imaging, because
T2-weighted images, whereas chronic. neuroendocrine lesions are hypointense, whereas SPNs,
hemorrhage is hypointense in both sequences, although which contain hemorrhage, may be hyperintense; and tumor
the absence of hyperintense areas on T1-weighted images enhancement characteristics, due to the lack of hypervascu-
should not completely exclude the diagnosis of larity in the peripheral portions in SPNs, which instead is
SPN. Moreover, areas within a fluid-fluid or fluid-debris typical of cystic neuroendocrine neoplasms [72].
level may sometimes be seen. In case of predominately cystic solid pseudopapillary
These lesions, especially in case of bigger dimensions, neoplasms, with a unilocular pattern, the main differential
usually show a fibrous capsule of variable thickness, visible diagnosis is with mucinous cystic neoplasms and in particu-
as a rim of low signal intensity, both on T1- and T2-weighted lar with mucinous cystoadenocarcinomas due to the pres-
images [91, 94–97]. ence of solid components with enhancement. Presence of
After contrast media administration, the solid compo- blood products makes diagnosis of SNP easier, but it is not
nents of SPNs may show slow early enhancement during the completely kept out of the mucinous cystic neoplasms’
arterial phase and progressive fill-in and enhancement during diagnosis.
delayed phase, without enhancement of the hemorrhage or However, because all three described entities require sur-
cystic areas. The psuedocapsule-surrounded tumors show gical resection, their preoperative differentiation may not be
early and more intense enhancement compared with the fundamental in the clinical setting [75].
tumor [98].
Instead, the most common enhancement pattern of solid
pseudopapillary neoplasms comprises of early, peripheral, Pancreatic Cystic Lymphangioma
and heterogeneous enhancement during the arterial phase
with progressive but heterogeneous fill-in of the lesions dur- Lymphangiomas are benign slow-growing tumors resulting
ing the portal and equilibrium phases. The enhancement is from lymphatic flow obstruction leading to development of
usually poorer in comparison to the pancreatic parenchyma, lymphangiectasias, with often a cystic morphology. This cir-
and this can be helpful in distinguishing these lesions from cumstance could be related to congenital malformations or
other hypervascular pancreatic ones [81]. obstructions secondary to different causes, such as inflam-
The composition of these lesions determines the degree of matory process, trauma, surgery, or radiotherapy [99–101].
diffusion and the ADC values on DWI images. Solid compo- These lesions are part of the major group of mesenteric
nents may show relatively low ADC values, whereas cystic cysts, and they are more often seen in pediatric population
areas do not show restriction at DWI [98]. but less frequently could affect adults, and they have a female
Solid pseudopapillary neoplasms could enter in differen- predominance. The majority of these lesions are found in the
tial diagnosis mainly with neuroendocrine neoplasms, both neck (75%) and axilla (20%), but 5% of cases could be found
in the typical and cystic variants, and with mucinous cystic in many other sites, including the pleura, pericardium, groin,
neoplasms.
bones, liver, spleen, pancreas, colon, omentum, and genital An accurate diagnosis before surgery with imaging is
organs [100, 102–109]. very difficult because imaging studies are not sufficient to
Pancreatic lymphangiomas are very rare, representing characterize these lesions.
less than 1% of all lymphangiomas and 0.2% of pancreatic Fine needle aspiration (FNA) of the cyst fluid can be use-
lesions. The majority of these lesions are localized in the dis- ful for a diagnosis, and usually, it could be done with an
tal pancreas (body or tail), although they can arise from other endoscopic ultrasound (and not with a transabdominal
parts of the gland, and they also could be peripancreatic approach due to the risk of tumor seeding in case the lesion
lesions (connected to the pancreas by a pedicle that could be is malignant). EUS allows a detailed study of lesion mor-
liable to torsion in some cases) or retroperitoneal masses. phology, revealing internal detail. Pancreatic lymphangio-
These lesions usually are big, with an average size of 12 cm mas have a variable appearance on EUS, because they can be
(from 3 to 20 cm in diameter) [99, 100, 110, 111]. unilocular or multilocular, anechoic without debris or solid
Usually, these lesions are asymptomatic and incidentally components, with thin septa. These findings are not exclu-
founded. Only in case of bigger dimensions, they can become sive of cystic pancreatic lymphangioma, but with EUS, it is
symptomatic with abdominal pain and sometimes with pal- possible to make FNA. An aspirated fluid with chylous
pable abdominal masses. Although rarely, they can manifest aspect, a milky-white appearance, and an elevated triglycer-
as acute abdomen due to complications, such as cyst rupture, ide level are diagnostic of pancreatic lymphangioma.
volvulus of pedicle, infection, or intra-cystic hemorrhage Moreover, levels of amylase, CEA, and Ca 19.9 are low in
[99, 106, 112]. these lesions. Furthermore, the aspirated fluid cytological
Pancreatic cystic lymphangiomas are difficult to differen- examination shows a large population of small mature
tiate among cystic pancreatic lesions, such as pseudocyst, lymphocytes.
other congenital cysts, intraductal papillary mucinous neo- In considering that lymphangiomas are benign lesions, a
plasm, serous and mucinous cystadenoma, mucinous cystad- conservative approach with close follow-up is acceptable if
enocarcinoma, pancreatic ductal adenocarcinoma with cystic definitive diagnosis is made by EUS. Despite that, they could
degeneration, and echinococcal cysts. Imaging alone is not be symptomatic due to dimensions, and they could show
completely specific, and it is not able to exclude these other complications, so the decision of excision should be bal-
entities. anced with the operation risks.
At transabdominal ultrasound, these lesions are seen as In case of excision, diagnosis of lymphangioma can be
complex cystic mass with internal septa and/or internal pathologically confirmed. Lesions are made of dilated cystic
echoes, with very rare calcifications within lesions. spaces lined by endothelial cells and containing protein-
At CECT, a cystic lymphangioma will be shown as a aceous eosinophilic fluid. These cystic spaces are separated
well-circumscribed mass surrounded by a thin wall, with by thin septa composed of smooth muscle cells, mature lym-
homogeneous hypodense fluid content, with a unilocular or phocytes, and some histiocytes. At immunohistochemical
multilocular shape with thin septa within the lesion; after studies, there is positivity for markers of lymphatic and cap-
contrast media injection, thin wall and thin septa usually illary endothelial cells [99, 102, 113–115].
show enhancement. These lesions are similar to mucinous
cystadenoma, but cystic neoplasms are more frequent than
cystic lymphangioma. Usually, cystic lymphangioma does Lymphoepithelial Cyst
not show an infiltrating sign, whereas compression signs
could be seen related to cystic dimensions. Lymphoepithelial cysts (LECs) are rare true cysts, account-
On MRI, lesions will be hypointense on T1-weighted ing for 0,5% of all cystic pancreatic lesions. These cysts are
images and hyperintense on T2-weighted sequences, sur- enclosed by mature keratinizing squamous epithelium, sur-
rounded by a thin peripheric wall and with thin internal rounded by lymphoid tissue, and filled with keratinized
septa, provided by contrast enhancement. In case of these material. Unlikely cystic pancreatic lymphangioma, males
cystic lesions, no communication between lesions and pan- are predominantly affected in middle age (fifth to sixth
creatic duct system is seen at cholangiopancreatography decades). Usually, these lesions are asymptomatic and inci-
MRI. dentally discovered, but in relation to their dimensions, they
could manifest with symptoms due to the compression, such
as abdominal pain, nausea, vomiting, backpain, and anorexia. In these cases, EUS-FNA could not be relevant in the
However, the average size is 4,7 cm. diagnosis because a mucinous or glandular epithelial tissue
Usually, lymphoepithelial cysts can be seen in any part of from intestinal sources acquired by the needle during the
the pancreas, but often they are peripancreatic, and they are procedure could cause contamination and could make diffi-
well-demarcated or uni- or multilocular [102, 103, 116–118]. cult to rule out completely a cystic neoplasm [102, 116].
If these lesions are in the region of the pancreatico-duodenal The cyst contents can range from serous to caseous, which
groove, the differential diagnosis with para-duodenal pan- is composed of keratinized material and cholesterol clefts
creatitis could be difficult, mimicking the cystic changes [102, 116, 121]. Nevertheless, the preoperative diagnosis of
seen in the groove region in this focal chronic pancreatitis. pancreatic LEC remains a challenge.
At diagnostic imaging, these lesions appear as cystic
lesions, uni- or multilocular, with thin wall and septa. These
kinds of lesions have a variable MRI appearance, due to their Mesothelial Cyst
content; in fact, they can by hypo- to mildly hyperintense on
T1w sequences, due to proteinaceous keratin content of the Mesothelial cysts are part of the major group of mesenteric
cyst, and hypo- to hyperintense on T2w sequences, with no cysts. These cysts are uni- or multilocular, surrounded by a
enhancement to minimal rim enhancement peripheric. In mesothelial cell lining in their inner surface, and they contain
some cases, round filling defects hypointense surrounded by serous material. More commonly, they are located in the
peripheral hyperintensity are seen on T2w sequences, with a mesentery or omentum, and they do not have a perceptible
“cheerio-like” appearance [37, 119]. This sign is specific to wall or internal septations [65, 67, 68].
MRI, EUS, and US and might be caused by the keratin These lesions can vary in size and shape from a few cen-
granulomas within the cyst of LEC, which could help in dif- timeters to a size that can occupy most of the peritoneal cav-
ferential diagnosis with other pancreatic cysts [120]. ity [122].
A preoperatively diagnosis is difficult to establish, At ultrasound, mesothelial cysts are anechoic, thin-walled
because most cases cannot rule out the possibility of a cystic cysts.
neoplasm, but it could prevent an unnecessary surgical With CT, size and relationship with other neighboring
procedure. organs are better studied; moreover, CT allows to depict wall
calcifications [123].
Image Gallery
a b
Fig. 1 Acute pancreatitis. (a, b) CT: multiple peripancreatic fluid collections hypodense in pancreatic (a) and venous (b) dynamic phases
a b
c d
Fig. 2 Pseudocyst. (a, c) CT: pseudocyst at the body of the pancreas atic (a) and venous (b) phases. (d) MRI: the fluid content of the
with rounded morphology, well visible wall with inhomogeneous con- pseudocyst is well demonstrated on T2-weighted images
tent on pre-contrast scan (a) not changing on dynamic study on pancre-
Fig. 3 Walled-off pancreatic necrosis. CT: pancreatic necrosis with

markedly inhomogeneous density delimited by visible wall
a b
Fig. 4 Walled-off pancreatic necrosis. (a) CT: pancreatic necrosis with markedly inhomogeneous density delimited by visible wall. (b, c) MRI:
pancreatic necrosis with markedly inhomogeneous intensity and content on T1 (b) and T2 (c), delimited by visible wall
a b
c d
Fig. 5 Disconnected pancreatic duct syndrome. (a) CT: acute pancre- visible; a communication of the main pancreatic duct with the fluid
atitis with peripancreatic fluid collections and dilation of the main pan- lesion is clearly demonstrated on T2 coronal (c). On MRCP (d), the
creatic duct at the tail of the pancreas. (b, d) MRI: during the follow-up main pancreatic duct is now dilated
at the pancreatic body, a fluid content lesion hyperintense on T2 (b) is
a b
c d
e f
Fig. 6 Pseudocyst in chronic pancreatitis. (a, b) CT: pseudocystic venous (d) dynamic phases. On coronal T2-weighted images (e), small
lesion in the pancreatic head surrounded by calcifications (a) also visi- hypodense deposits in the main pancreatic. On MRCP (f), the main
ble in the main pancreatic duct in the coronal scan (b). (c, f) MRI: the pancreatic duct is dilated with clearly irregular contours
pancreatic head pseudocystic lesion is avascular in pancreatic (c) and
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Secondary Tumors and Lymphoma
Paolo Tinazzi Martini, Eda Bardhi, Antonia Maria Olivieri,

Marco Todesco, Daniele Autelitano, Luisa Tomaiuolo,
Luca Geraci, and Paola Capelli
Introduction True pancreatic metastases more commonly arise from

renal cell carcinoma (which are the most frequent), mela-
Pancreatic metastases are uncommon entities [1, 2]. noma, and breast and lung adenocarcinoma [2, 9, 10]. The
Metastases can occur through different ways: by direct dissemination route to the pancreas can be either lymphatic
invasion, from systemic malignancies such as lymphomas or or hematogenous; the first is pretty typical for colorectal can-
leukemias, or by metastatic spread from a distant tumor [3]. cer, due to the unique lymphatic drainage through the meso-
Primary pancreatic lymphoma is another rare pancreatic colon to the pancreas. In these cases, the most frequent site
neoplasm that accounts for less than 1% of all pancreatic of implantation of metastases is the inferior portion of the
tumors [4]. pancreatic head.
Compared to primary pancreatic lymphoma, the second- The exact prevalence of pancreatic metastases is not clear:
ary involvement of the pancreas by non-Hodgkin’s lym- the reported frequency in autoptic studies ranges between
phoma is more common and can occur in 30–40% of patients 1.6 and 5.9% [2, 11, 12], while pancreatic metastases have
with extranodal disease [5]. been observed in 0.7–10.7% of endoscopic ultrasound-
guided fine-needle aspirations [10, 12–14].
Regarding the location, 25% of metastases are reported to
Pathology be confined to the pancreatic head, but the vast majority
(75%) involve multiple segments of the organ [2].
Metastases
Tumors that directly invade the pancreatic parenchyma gen- Primary Pancreatic Lymphoma
erally arise from adjacent structures such as Vater’s papilla,
extrahepatic bile ducts, stomach, duodenum, or colon [6, 7]. Primary pancreatic lymphoma (PPL) is defined by the fol-
Pancreatic involvement by lymphomas and leukemias usu- lowing diagnostic criteria [8]: mass predominantly located in
ally derives from the involvement of peripancreatic lymph the pancreas; involved lymph nodes confined to the peripan-
nodes; overall, this condition can be seen in up to 30% of creatic region; no palpable superficial lymphadenopathies;
patients with widespread disease [8]. no mediastinal nodal enlargement; and no hepatic or splenic
involvement and normal white cell count. PPL shows a slight
male predominance and usually develops between the fifth
and sixth decade of life.
P. T. Martini (*)
Department of Radiology, Casa di Cura Dott. Pederzoli,
Verona, Italy
Macroscopy
E. Bardhi · A. M. Olivieri · M. Todesco · D. Autelitano · L. Geraci
Metastases
Verona, Italy
L. Tomaiuolo · P. Capelli
Pancreatic metastases can be focal, multifocal, or may pres-
Verona, Italy ent with a diffuse enlargement of the pancreas. Grossly, they
e-mail: paola.capelli@aovr.veneto.it may mimic primary pancreatic tumors, especially when they
416 P. T. Martini et al.
present as solitary masses. A detailed knowledge of the Metastatic adenocarcinomas to the pancreas can arise
patient’s medical history is crucial. Multiple lesions through- from different organs, and to obtain a clear distinction from
out the whole pancreatic gland have been more frequently primary ductal pancreatic adenocarcinoma, immunohisto-
detected in patients with renal cell carcinoma than in those chemical studies might be necessary, despite the typical ten-
with other primary tumors [15, 16]. Grossly metastatic renal dency of pancreatic ductal adenocarcinoma to form sheet-like
cell carcinoma presents as a well-circumscribed yellow– clusters that resemble normal ductal epithelium.
orange tumor with red–brown or white–gray areas and may
display hemorrhagic or cystic degeneration.
Primary Pancreatic Lymphoma
Primary Pancreatic Lymphoma The majority of primary pancreatic lymphomas are diffuse
large B-cell non-Hodgkin’s lymphomas, accounting for 80%
PPL can present in different ways: with a well-circumscribed of patients [6]. FNAB usually shows large singular atypical
solitary pancreatic mass; in a diffuse manner, causing pan- lymphocytes within a background of lymphoglandular bod-
creatic enlargement; with a peripheral lymphomatous ies, representing small cytoplasmatic fragments. In rare
involvement; and with multinodular appearance. The most cases, PPL can also present as follicular lymphoma, small
common appearance is that of a large, soft, nodular mass, lymphocytic lymphoma, and T-cell lymphoma, either of
even with big dimensions, most commonly in the head of the NHL or of Hodgkin’s lymphoma.
gland. The pancreatic ductal system is usually displaced but
not infiltrated.
Imaging
Microscopy Metastases
Metastases Pancreatic metastases can be solitary, multifocal, or may

present with a diffuse pancreatic involvement.
Metastases usually involve pancreatic lobules replacing nor- Although US is usually capable to correctly study the
mal acinar tissue and expanding the interlobular septa. pancreas, CT and MRI are more accurate to detect single
Clusters of acinar cells and small pancreatic ducts entrapped and, particularly, multifocal metastases, which tend to repro-
within the tumor cells are often observed. This growth pat- duce the imaging pattern of the primary neoplasm. For
tern, though not exclusive for metastases, is suggestive of a example, metastases from hypervascular tumors, such as
secondary lesion, especially when a primary pancreatic renal cell carcinoma, usually rapidly enhance during the
tumor has been excluded. arterial and pancreatic phases.
Metastatic clear-cell carcinoma is a cell-rich tumor; tumor At MRI, metastatic lesions are usually hypointense on
cells are organized in sheets, small nests, or cords of polygo- T1-weighted fat-sat images and slightly hyperintense on
nal clear cells, with abundant clear cytoplasm because of the T2-weighted images, with the same enhancement pattern of the
accumulation of glycogen, which can be easily demonstrated primary tumor. Larger metastases may present T2-hyperintense
with PAS staining. Intracytoplasmic lipids can be apprecia- central necrosis with peripheral enhancement.
ble on Papanicolaou’s stain. Cell blocks can be useful for Hypervascular metastases of the pancreas, such as renal
confirmatory immunostaining with a panel including CD10, cell carcinoma secondary lesions, may mimic neuroendo-
PAX-8, and the renal cell carcinoma antigen [9]. crine pancreatic neoplasms. Hypovascular metastases, espe-
Aspirates from melanoma metastases usually display cially if richly fibrotic and involving the main pancreatic
overtly malignant features such as anisonucleosis, nuclear duct such as breast cancer secondary lesions, may mimic
pleomorphism, and high nuclear-to-cytoplasmic ratio. Given ductal adenocarcinoma at imaging.
the morphological overlap of metastatic melanoma with
other entities, immunohistochemical staining for melanoma
antigens such as S-100, MITF, MEL-A, and HMB-45 can be
useful [9].
Secondary Tumors and Lymphoma 417
Primary Pancreatic Lymphoma Metastases can also invade pancreatic ductal epithelium
and thus may clinically mimic primary pancreatic adenocar-
Different radiological appearances of primary pancreatic cinoma [21]: in a review of 220 patients, the most common
lymphoma have been described: well-circumscribed nodular presenting symptoms were jaundice (25.2%) and abdominal
type with solitary pancreatic mass (most common); diffuse pain (11.4%), while 27.6% of patients were asymptomatic
type with pancreatic enlargement; peripheral lymphomatous [23].
involvement, mimicking autoimmune pancreatitis; and mul-
tinodular type [17].
Primary pancreatic lymphoma, presenting as a solitary Primary Pancreatic Lymphoma
pancreatic mass, is frequently heterogeneous at imaging,
being large at presentation; it can extend and infiltrate beyond Primary pancreatic lymphoma (PPL) rarely presents with
the pancreas, also encasing major peripancreatic vascular typical “B-related” symptoms such as fever, weight loss, or
structures, in a way similar to ductal adenocarcinoma. night sweats. The common presentations are vague abdomi-
However, the degree of ductal dilatation is minimal even nal symptoms such as dyspepsia, pain, nausea, vomiting,
with ductal invasion: this lesser degree of ductal dilatation flatulence, and abdominal mass and weight loss [5].
even in the presence of a bulky homogeneous tumor mass Laboratory values are nonspecific, but lactate dehydroge-
should raise the suspicion of a pancreatic lymphoma. nase (LDH) levels may be elevated, and this can be helpful in
Alternatively, diffuse infiltration and enlargement of the the distinction between PPL and ductal adenocarcinoma
pancreas without clinical signs of acute pancreatitis should when imaging is doubtful [24].
alert to the possibility of a pancreatic lymphoma.
The classic US appearance of a lymphoma is that of a
markedly hypoechoic bulky mass. Behavior
At CT, most lymphomatous lesions are reported to be
well-defined, sometimes bulky and infiltrating, homoge- Typical
neously low-attenuating with mild enhancement. Vascular
encasement or invasion is rarely seen with pancreatic lym- Metastases
phoma, despite the vessels that may be stretched because of The prognosis of pancreatic metastases is generally poor,
a mass effect [18]. since in most cases, they are a part of an advanced disease
At MRI, pancreatic lymphomas usually appear as [25].
homogeneous, low-signal-intensity, focal nodular areas However, due to the relatively indolent course of meta-
on T1-weighted images, with low or high signal intensity static renal cell carcinoma in the pancreas, these lesions are
on T2-weighted images, and a generally circumscribed, frequently resectable [26]: it is widely recognized that the
hypoenhancing area after contrast medium administration longer is the interval between nephrectomy and metastases,
[18, 19]. the better is the outcome of the patient; the reported overall
The characteristic imaging pattern of primary pancreatic survival for isolated solitary or multiple renal cell carcinoma
lymphoma at FDG PET/CT is focal or diffuse increased pancreatic metastases was 57% in an extensive review [15].
uptake in the pancreatic tissue [20].
rimary Pancreatic Lymphoma
P
The classic symptoms of NHL, such as fever, chills, and
Clinical Presentation night sweats, are rarely seen in primary pancreatic lym-
phoma, as the back pain that is typically encountered with
Metastases pancreatic adenocarcinoma [18].
A complete response rate of 100% and a long-term sur-
The symptoms produced by pancreatic metastases are vival rate of 94% have been reported with surgery and adju-
variable. vant chemotherapy, when compared with a 5-year survival
Most patients are free of organ-specific complaints such rate of less than 50% and an overall 3-year disease-free sur-
as abdominal pain or jaundice, and the metastases are inci- vival rate of 44% with current chemotherapy, radiotherapy,
dentally detected during imaging studies [21, 22]. or combined methods [27].
Atypical Renal cell metastases are unlikely to be confused with duc-

tal adenocarcinoma, which is usually hypovascular [32]. In
PPL causing dissemination into the peritoneal cavity and such cases, immunohistochemistry is a worthwhile diagnostic
omentum (peritoneal lymphomatosis) is an extremely rare tool, because metastatic renal cell carcinoma shows typical
and fatal evidence [28]. reactivity for CD10 and CD13, but it is negative for endocrine
markers such as chromogranin and synaptophysin.
Lung and some breast metastases are hypovascular, and,
if single, could be mistaken for ductal adenocarcinoma [32].
Variants
Metastases Primary Pancreatic Lymphoma
Renal cell carcinoma metastases are usually hypervascular; PPL may mimic ductal adenocarcinoma or mass-forming
despite this, it has been reported that up to 50% can be hypo- pancreatitis, especially when single and not well-defined
vascular at MRI [29]. lesions are present [5].
Less commonly, pancreatic lymphoma may present with a
diffuse enlargement of the gland that could mimic acute pancre-
Primary Pancreatic Lymphoma atitis: in this setting, other typical features of acute pancreatitis,
such as peripancreatic fat-stranding, are usually absent [17].
In rare cases, PPL can also present as follicular lymphoma, In many cases, imaging could not definitively provide the
small lymphocytic lymphoma, and T-cell lymphoma, either correct diagnosis; therefore, FNAB is needed.
of NHL or of Hodgkin’s lymphoma.
There is a single, anecdotal reported case of a pancreatic
collision tumor, comprising pancreatic adenocarcinoma and Imaging–Pathologic Correlation
mantle cell lymphoma [30].
Another rare tumor is primary lymphoma, causing perito- Metastases
neal lymphomatosis [28].
As previously stated, metastases resemble the primary tumor.
The hypervascularity of the lesions at imaging can be histo-
Pitfalls and Errors logically proved with the measurement of the microvessel
density with CD34 staining [33].
Metastases
Pancreatic metastases have imaging features that resemble Primary Pancreatic Lymphoma
those of the primary tumors. Metastases could roughly be
divided into hypervascular and hypovascular. Because of their high cellularity and high nuclear-to-
Metastases from renal cell carcinoma, melanoma, and cytoplasm ratio, diffuse large B-cell lymphoma tends to have
some breast metastases are hypervascular and can mimic relatively high signal intensity on diffusion-weighted images
neuroendocrine tumors, even if multifocal [31]. and low ADC values [34].
Differential Diagnosis findings to differentiate between these two entities: lym-

phoma usually presents with a bulky homogeneous mass
Metastases without cystic changes, necrosis, and alteration of the main
pancreatic duct; the envelopment of adjacent vessels does
The appearance of most pancreatic metastases is not specific, not show evidence of obstruction; peripancreatic and retro-
though renal cell carcinoma, melanoma, and some breast peritoneal lymphadenopathies are present [18].
metastases are hypervascular and can therefore resemble Diffuse pancreatic enlargement may closely mimic the
neuroendocrine tumors, even if multifocal [31], and are imaging findings of acute pancreatitis [37, 38], but peripan-
unlikely to be confused with ductal adenocarcinoma, which creatic inflammation is typically minimal or completely
is usually hypovascular [32]. absent as fluid collections in lymphoma. When enlarged
Lung and some breast metastases are hypovascular. The peripancreatic or retroperitoneal lymph nodes are present,
finding of hypovascular pancreatic mass, especially if multi- exclusion of acute pancreatitis is much easier [17].
focal, without significant biliary or pancreatic duct dilatation The peripheral lymphomatous involvement of the pan-
should prompt the hypothesis of metastases. Moreover, these creas may mimic autoimmune pancreatitis; moreover,
latter are often well-circumscribed, another finding that is lymphadenopathies can be seen in autoimmune pancreati-
atypical for pancreatic ductal adenocarcinoma [29]. tis, thus confounding the diagnosis [39], but lymphoma
There are no other definite imaging features that could tends to present a higher signal intensity on T2-weighted
differentiate between metastases and primitive lesions; images and delayed enhancement [19] and other character-
therefore, the history of a primary malignancy strongly raises istic extrapancreatic lesions (biliary tract, kidneys) are
the possibility of metastases. FNA could also be an option to absent [39].
obtain the correct diagnosis. The two main differential diagnoses of the multinodular-
type lymphoma are with multiple metastases from hypovas-
cular tumors [40] and with a multifocal autoimmune
Primary Pancreatic Lymphoma involvement [41]: necrosis and cystic changes are more com-
mon in metastases, and hypo−/iso-intensity with speckled/
Well-circumscribed nodular lymphoma with solitary pancre- dotted hyperintense areas on fat-sat T1-weighted images and
atic mass, especially if heterogeneous in appearance and speckled/dotted enhancing areas are more common in focal
with poor definition, can lead to the misdiagnosis of ductal autoimmune pancreatitis [42].
adenocarcinoma [5, 35, 36], but there are still some useful In all cases, biopsy is frequently necessary for diagnosis.
Image Gallery
a b
Fig. 1 Metastatic renal cell carcinoma. (a) Surgical specimen: gross two nodules of metastatic renal cell carcinoma with hemorrhaged cystic
appearance of metastatic renal cell carcinoma appearing as a well- degeneration
circumscribed yellow–orange to red–brown mass. (b) Macrosection:
a b
Fig. 2 Metastatic renal cell carcinoma. (a, b) Surgical specimen: multiple pancreatic lesions bulging the profiles of the gland (a). At cut section
(b), multiple masses are clearly visible
Fig. 3 Metastatic renal cell carcinoma. Histopathology: sheets, small

nests, and cords of clear cell, separated by rich sinusoidal vascular
network
a b
Fig. 4 Metastases of breast cancer. (a) Surgical specimen (pancreati- wall and common bile duct (C in a) infiltration. (b, c) Histopathology:
coduodenectomy): gross appearance of breast metastases with the neo- the neoplastic cells involve the duodenal wall (b) and pancreatic lob-
plasm (arrows in a) mimics pancreatic adenocarcinoma with duodenal ules, replacing normal acinar tissue (c)
a b
Fig. 5 Metastatic melanoma. (a) Surgical specimen (intermediate pancreatectomy): solid mass with black to brown area reflecting the presence
of melanin pigment. (b) Histopathology: pancreas (P) and melanoma (M)
a b
Fig. 6 Metastatic leiomyosarcoma. (a) Surgical specimen (pancreaticoduodenectomy): gross appearance of mesenchymal tumor with the mass
appearing composed by soft tissue. (b) Histopathology: the tumor exhibits high cellularity, and it is composed of spindle cells with atypia
a b
Fig. 7 Hypervascular mets: metastatic renal cell carcinoma. (a) (arrow in b). More than one lesion are visible; small hypervascular nod-
Ultrasound: single mass in the pancreatic head is visible, appearing ule (arrow in c) is in fact also detected. The Wirsung duct (W in c) is
solid and hypoechoic (arrow). The Wirsung duct (W) is dilated. (b, c) dilated
CT: the pancreatic head mass is confirmed and appears hypervascular
a b
Fig. 8 Hypervascular mets: metastatic renal cell carcinoma. (a) CEUS: double hypervascular masses (arrows) in the uncinate process of the pan-
creas. (b) CT: double hypervascular masses (arrows) in the uncinate process of the pancreas
a b
Fig. 9 Hypervascular mets: metastatic renal cell carcinoma. (a–l) MRI paraduodenal portion of the pancreatic head (f). On DWI, all the lesions
study: on T1-weighted images (a–c), three hypointense nodules are vis- show diffusion restriction at high b-value, appearing hyperintense
ible; one in the pancreatic tail (arrow in a), one in the pancreatic head (arrow in g–i). In the dynamic phase, the lesions are hypervascular with
(arrow in b), and one very small in the caudal paraduodenal portion of good conspicuity (arrow in j and k), except for the smallest one in the
the pancreatic head (arrow in c). On T2-weighted images (d–f), the caudal paraduodenal portion of the pancreatic head (l)
lesions are visible as hyperintense, except the smallest in the caudal
c d
e f
Fig. 9 (continued)
g h
i j
k l
Fig. 9 (continued)
a b
c d
Fig. 10 Hypervascular mets: metastatic renal cell carcinoma. (a, b) CT geneously hyperintense while the nodule visible in the uncinate process
study: in the baseline scan (a), enlargement of the pancreatic gland is of the pancreas is homogeneously hyperintense. In the dynamic phases,
immediately visible. In the pancreatic phase (b), a huge mass, inhomo- pancreatic (e) and venous (f), the mass is inhomogeneously hypervas-
geneously hypervascular, occupies the entire gland; moreover, another cular with intralesional necrotic areas, and the nodule visible in the
hypervascular nodule is visible in the uncinate process of the pancreas. uncinate process of the pancreas is hypervascular with small intrale-
(c–f) MRI study: on T1-weighted images (c), the mass is inhomoge- sional central necrosis
neously hypointense. On T2-weighted images (d), the mass is inhomo-
e f
Fig. 10 (continued)
a b
Fig. 11 Hypovascular met: metastatic lung cancer. (a, b) CT study: in the pancreatic (a) and venous (b) phases, a hypovascular mass (arrow in a
and b) in the pancreatic head is visible
a b
c d
Fig. 12 Hypovascular met: metastatic rhabdomyosarcoma. (a) CT T2-weighted images (c, d), the mass is inhomogeneously hyperintense.
study: hypovascular mass (arrow) in the pancreatic head. (b–d) MRI The Wirsung duct (W in d) is upstream-dilated. On MRCP (e), the mass
study: on T1-weighted images (b), the mass is hypointense. On stops (asterisk) the Wirsung duct (W in e) upstream-dilated
a b
c d
Fig. 13 Metastatic melanoma. (a–c) CT study: huge mass (arrow in a) detected. On T2-weighted images (e), the mass is inhomogeneously
in the pancreatic body, resulting inhomogeneously vascularized on the hyperintense, as on the T2-weighted fat-saturated images (f). In the
pancreatic (b) and venous (c) phases with intralesional diffuse necrotic dynamic phases, the mass results inhomogeneously vascularized on
areas. (d–i) MRI study: on T1-weighted chemical shift images (d), in pancreatic (g), venous (h), and late (i) phases, with intralesional diffuse
the mass (arrow in d), a hyperintense centrally located component is necrotic areas
e f
g h
Fig. 13 (continued)
Fig. 13 (continued)
a b
Fig. 14 Pancreatic lymphoma. (a–c) CT study: huge mass (arrow in a and b) at the pancreatic head resulting in well and homogeneously vascular-
ized in the pancreatic (b) and venous (c) phases. Numerous slightly enlarged lymph nodes (arrows in c) are also detectable
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Uncommon Presentations of Pancreatic
Neoplasms, Rare Neoplasms,
and Peripancreatic Masses
Riccardo De Robertis, Antonia Olivieri, Angela Calabrese,

Luca Geraci, Nicolò Cardobi, Paolo Tinazzi Martini,
Roberto Calbi, Paola Capelli, and Mirko D’Onofrio
Pancreatic lesions can be easily characterized if they have a and magnetic resonance imaging (MRI) a progressive con-
typical radiological appearance, although a certain degree of trast pooling within the tumor mass can be seen, reflecting
experience is necessary. Pancreatic lesions with an atypical the extensive fibrosis that characterizes this tumor: therefore,
radiological appearance have become more and more fre- on delayed phase images, PDAC may appear slightly hyper-
quent owing to the increasing use of imaging methods: in dense/−intense. Parenchymal atrophy and ductal dilation
this case the radiological characterization can be difficult and upstream to the tumor mass are usually present; moreover,
tissue sampling is required for a final diagnosis. Even though pancreatic head tumors are almost invariably associated with
the atypical presentations of pancreatic lesions are uncom- bile duct dilation.
mon, they are more frequent than rare pancreatic neoplasms,
a group of lesions that almost invariably pose a diagnostic
dilemma, even to experienced radiologists. Knowledge of Isodense Appearance
the wide range of intratumoral changes and pathological
variants of pancreatic neoplasms may help in the diagnosis About 11% of PDACs are isodense compared to the pancre-
of lesions with atypical radiological features. atic parenchyma during the late arterial phase of contrast-
enhanced CT [1], thereby not identifiable without the help of
secondary signs, such as upstream ductal dilation or paren-
Ductal Adenocarcinoma chymal atrophy (Fig. 1). This finding is typical of small
PDACs (i.e., ≤20 mm), which are isodense in up to about
Pancreatic ductal adenocarcinoma (PDAC) typically pres- 30% of cases, and well-differentiated tumors (more than
ents as a solid hypoenhancing lesion with poorly defined 50% of cases) [2, 3]. A missed diagnosis results in a diagnos-
margins. At contrast-enhanced computed tomography (CT) tic delay, and this is particularly important in resectable
PDACs; moreover, local staging of isodense PDACs may be
difficult, as the tumor-vessel interface cannot be adequately
R. De Robertis (*) · A. Olivieri · L. Geraci · M. D’Onofrio evaluated. Delayed post-contrast phase may be helpful to
Department of Radiology, G.B. Rossi University Hospital, identify isodense PDACs, as contrast pooling makes the
Verona, Italy lesion slightly hyperdense/−intense compared to the adja-
cent parenchyma. Magnetic resonance imaging, ultrasound
A. Calabrese · N. Cardobi (US), contrast-enhanced US (CEUS), and endoscopic ultra-
Department of Radiology, Oncologic Hospital, Bari, Italy
sound (EUS) may be useful to detect “invisible” lesions or if
P. Tinazzi Martini CT findings are inconclusive. In these cases, in fact, a “sim-
ple” US may be able to solve the problem, as the lesion is
R. Calbi frequently well detected owing to its hypoechoic appearance
compared to the slightly hyperechoic pancreatic paren-
P. Capelli chyma, with significant acoustic impedance difference and
Verona, Italy
subsequent high tumor conspicuity [4, 5].
Fig. 1 Isodense adenocarcinoma of the pancreatic head. On arterial phase CT images, dilatation of the pancreatic duct is present, while no lesions
are visible
a b
Fig. 2 “Cystic epiphenomenon”. On portal phase CT image (a), dilatation of the main pancreatic duct and a cystic lesion in the pancreatic body
are visible. 18FDG-PET CT (b) shows focal hypermetabolism consistent with a pancreatic adenocarcinoma proximal to the cyst
Cystic Appearance extensively necrotic PDAC can be misdiagnosed as a pseudo-

cyst [9]: the absence of a clinical history of acute pancreatitis
In most cases PDAC is a solid and firm mass. Nevertheless, helps in the correct diagnosis of PDAC. PDAC with a micro-
this tumor has a cystic appearance in up to 8% of cases. Fluid cystic appearance are even more uncommon; this form is his-
areas are not a rare occurrence in histologic specimens of tologically defined as “large duct type adenocarcinoma” or
PDAC and differ in nature and pathogenesis: they can be the “large gland type adenocarcinoma” and is similar to a micro-
consequence of extensive central necrosis, or a “true” neo- cystic serous cystadenoma (SCA) [9]. Finally, even if very
plastic component, or even a retention cyst or a pseudocyst at small, PDAC usually infiltrates and obstructs the pancreatic
tumor periphery [6]. Fluid areas associated with PDAC are ducts, leading to upstream dilation of peripheral branches
markedly hypodense on CT and hyperintense on T2-weighted (“cystic epiphenomenon”—Fig. 2). In this case, the tumor is
MR images [6, 7]. In less than 1% of cases PDAC undergoes similar to an intraductal papillary mucinous neoplasms
necrosis with development of a central fluid area: in this case, (IPMNs); interestingly, the dilated ducts may show epithelial
what appears at imaging to be a macro cyst filled by fluid is changes that can be indistinguishable from IPMNs or muci-
necrosis surrounded by a cuff of viable tumor cells [8]. An nous cystic neoplasms (MCNs) at histological analysis [9].
Uncommon Presentations of Pancreatic Neoplasms, Rare Neoplasms, and Peripancreatic Masses 437
Acute Pancreatitis Pancreatitis-Like Appearance
The most common clinical presentations of PDAC are jaun- Ductal adenocarcinoma usually presents as a focal lesion
dice, epigastric pain radiated to the back, and weight loss. In with ill-defined, infiltrating margins; in rare cases, PDAC has
about 3% of cases, PDAC may present with acute pancreatitis a “pancreatitis-like” appearance, both with a focal and a dif-
due to infiltration and obstruction of the Wirsung’s duct [10]. fuse extent. While a diffuse gland involvement makes the
In this case, imaging shows signs of acute pancreatitis (Fig. 3), radiological differentiation between PDAC and acute pancre-
with enlargement of the pancreas, decreased echogenicity/ atitis extremely difficult (Fig. 4), things may be easier for the
density/signal intensity, hypovascularization, and eventually focal mass-forming variant. CEUS can improve the differen-
local complications; the absence of a definite etiopathology tial diagnosis between PDAC, which is hypoechoic, and
should raise the suspicion of an obstructive neoplasm [11] and inflammatory masses, which enhance like the adjacent pan-
repetition of imaging, particularly EUS, after resolution of the creatic parenchyma (“parenchymographic” enhancement)
surrounding acute inflammation is mandatory [12]. [13]. A relative delineation of a focal mass with respect to
a b
Fig. 3 Ductal adenocarcinoma presenting with acute pancreatitis. a solid hypoechoic lesion consistent with a ductal adenocarcinoma
Arterial phase CT image (a) shows signs of acute pancreatitis, with causing upstream dilatation of the main pancreatic duct and decreased
enlargement of the pancreas, decreased vascularization, and peri- echogenicity of the gland (b)
pancreatic fat stranding; in the same patient transabdominal US revealed
a b
Fig. 4 “Pancreatitis-like” appearance of a ductal adenocarcinoma. and stranding of the peri-pancreatic fat; histology revealed a diffuse
Axial (a) and coronal reformatted (b) arterial phase CT images show involvement by a ductal adenocarcinoma
enlargement and hypovascularization of the body-tail of the pancreas
adjacent parenchyma on gadolinium-enhanced images of

MRI may favor the hypothesis of a PDAC [14]. Other signs
that favor the hypothesis of a PDAC are the “double-duct
sign,” with coexistent dilatation of the pancreatic and biliary
ducts [15], the absence of the “duct-penetrating sign,” defined
as a stenotic main pancreatic duct coursing through the mass
[16], and the presence of a single, abrupt interruption of the
pancreatic duct instead of multiple, gradual stenosis [17].
Neuroendocrine Neoplasms
Pancreatic neuroendocrine neoplasms (pNENs) typically

present as well-defined lesions, hypoechoic at US and
hypodense/isodense at unenhanced CT; on MRI, they have a
Fig. 5 Hypovascular neuroendocrine neoplasm. Arterial phase CT
homogeneously hypointense appearance on T1-weighted image shows a large, well-defined hypodense mass in the pancreatic
images and a slightly hyperintense aspect on T2-weighted head; multiple liver metastases are present. Ga68 PET-CT diagnosed a
images. Nonfunctioning and large pNENs frequently have an neuroendocrine neoplasm
inhomogeneous appearance due to necrosis and calcifica-
tions [18]. The feature that above all characterizes pNENs is may produce complete occlusion with portal hypertension.
hyperenhancement at contrast-enhanced examinations [19]. Tumor thrombi associated with pNENs often directly extend
from the tumor as an appendage into the lumen of adjacent
vessels, causing their enlargement; as pNENs themselves,
Hypoenhancing Neuroendocrine Neoplasms associated tumor thrombi usually enhance strongly after
intravenous contrast medium administration (Fig. 6) [29].
Several studies have reported an unexpectedly high rate of
pNENs lacking a clear hyperenhancement during the late
arterial phase of contrast-enhanced CT and MRI [20–25]; Cystic
several histopathologic features, such as tumor size, intratu-
moral fibrosis, cystic changes, tumor grade, and the size of As PDACs, pNENs usually present as solid lesions. Non-
the intratumoral vascular network may influence the degree hyperfunctioning pNENs are usually large at diagnosis and
of arterial phase enhancement (Fig. 5). The differentiation of may contain fluid areas that present as unilocular cysts located
hypoenhancing pNENs from PDACs may be difficult on ana- in the center of the tumor mass; these cystic areas are lined by
tomic imaging: in this context, Ga68 PET-CT is useful, as this a cuff of neoplastic endocrine cells, that show hyperenhance-
radionuclide fixes only to pNENs. Digital subtraction of MR ment on dynamic imaging, and filled with clear fluid rather
images allows better characterization of pNENs compared than necrosis; sometimes, a fluid-fluid level can be present
with native late arterial phase images by increasing both the [30]. Small pNENs can present as quite-exclusively cystic
subjective conspicuity and contrast-to-noise ratios of pNENs lesions that resemble MCNs or unilocular SCA (Fig. 7).
and the rate of clearly hyperenhancing pNENs [26].
Calcified
Intravascular Growth
Calcifications are not common within pancreatic tumors.
Surgical series revealed that gross tumor thrombosis may be Coarse and irregular calcifications can be found within
associated with about 5% of pNENs and literature data sug- pNENs in about 16% of cases (Fig. 8) [31]. Calcifications
gested that this finding is frequently underreported on pre- are more frequent in non-hyperfunctioning and large tumors,
operative imaging examinations [27, 28]. Among pancreatic in which they develop because of cystic necrosis [32].
neoplasms, tumor thrombi are almost exclusively encoun- However, insulinoma, which is usually very small at diagno-
tered with pNENs. Tumor thrombi may be clinically silent or sis, can contain calcifications in up to 20% of cases.
a b
Fig. 6 Intravascular growth of a neuroendocrine neoplasm. Axial (a) and coronal (b) portal phase CT images show a pancreatic head neuroendo-
crine tumor directly extending into the superior mesenteric vein through a vascularized appendage
a b
Fig. 7 Cystic neuroendocrine neoplasm. Axial T2-weighted image (a) seen on the axial post-contrast image (b); Ga68 PET-CT scan confirmed
shows a well-defined, fluid-containing lesion in the pancreatic tail, with the diagnosis of a neuroendocrine neoplasm
tiny septa; peripheral enhancement and vascularization of the septa is
a b
Fig. 8 Calcified neuroendocrine tumor. Bone windowing (a) of CT image shows dystrophic calcifications within a inhomogeneously vascularized
tumor of the pancreatic body (b) which revealed to be a neuroendocrine tumor at histology
a b
Fig. 9 Pancreatic carcinoid. Extensive dilatation of the ductal system ductal dilatation on post-contrast axial image (b). Surgical resection
at the pancreatic body-tail is visible on MR cholangiopancreatography revealed the presence of a carcinoid tumor
(a); a very small, slightly hypointense lesion is seen proximal to the
Pancreatic Carcinoid pancreatic duct resulting in a disproportionate dilation of

the upstream ducts and parenchymal atrophy (Fig. 9) [36];
Carcinoids are serotonin-producing tumors usually found sometimes ductal obstruction leads to acute pancreatitis
in the appendix and the small intestine; pancreatic carci- [37]. Imaging findings in pancreatic carcinoids are poorly
noids are a separate and extremely rare entity with a described: enhancement is variable according to the
malignant behavior [33–35]. The local secretion of sero- degree of intratumoral fibrosis; internal calcifications,
tonin induces the formation of fibrosis, therefore these cystic changes, and liver metastases may be present
tumors, even if small, commonly cause a stenosis of the [38–40].
Serous Cystadenoma contain a central scar. Unilocular SCA is composed by a

single, large cyst, without a central scar. While MR imaging
Serous cystadenoma (SCA) is a benign cystic neoplasm con- can differentiate a macrocystic SCA from a mucinous cystic
taining serum, with a typical multilocular, “honeycomb” neoplasm (MCA), as the first presents thin wall and septa
architecture due to the presence of multiple microcysts and do not contain internal vascularized nodules, the non-
(<20 mm), thin walls, and multiple thin septa oriented toward invasive differentiation of unilocular SCAs from a pseudo-
a central scar, that may contain calcifications. The typical cyst is difficult [41]; moreover, in large, unilocular SCAs,
“cloud-like” morphology of SCA is usually clearly depict- the internal epithelial lining may be lost and the histologic
able at imaging. The content of the tumor is anechoic at US, differentiation with a pseudocyst may be difficult. A clinical
hypodense at CT, hypointense on T1-weighted images, and history negative for acute pancreatitis favors the hypothesis
hyperintense on T2-weighted images at MRI; T2-weighted of a SCA.
MR images usually well demonstrate the microcystic pattern
of the lesion. On post-contrast images, the central scar is
usually hypo- or non-enhancing, while internal septa may Pseudo-Solid Appearance
demonstrate enhancement [41].
Serous cystadenomas with an extremely microcystic appear-
ance may mimic a solid hypervascular lesion at US/CEUS
Macrocystic and Unilocular and CT, owing to the presence of multiple and compact
enhancing septa, thereby resembling a pNEN [42]. MR
Serous cystadenoma may present a macrocystic or unilocu- imaging is extremely useful in these cases as it displays the
lar appearance. Macrocystic SCA is composed of few cysts “true” cystic nature of this lesion, owing to the detection of
larger than 2 cm, which can reach 15–20 cm, and do not the fluid content on T2-weighted images (Fig. 10) [43].
a b
Fig. 10 Serous cystadenoma with a pseudo-solid appearance. Arterial tent and the microcystic appearance of the tumor, consistent with a
phase CT image (a) shows an inhomogeneously vascularized lesion in serous cystadenoma
the pancreatic head; axial T2-weighted image (b) displays the fluid con-
ovary during embryogenesis; because of the exposure of

the endodermal stroma to female sex hormones or the
presence of ectopic primary yolk cells MCNs can rarely
arise in different sites within the pancreatic gland [45].
MCNs can rarely develop in males: there is no certain
explanation for this, but hormonal and/or sexual dysfunc-
tion was found in most patients affected by hormone-
related pancreatic tumors [46]; moreover, ovarian stroma
may be a secondary modification during the growth of the
tumor [47, 48].
Disepithelized Walls
As may happen in SCAs, the internal epithelial lining

within large MCNs may be lost during the growth of the
tumor. Disepithelized MCNs are lined only by a fibrous
capsule and the distinction with pseudocysts may be diffi-
Fig. 11 Giant serous cystadenoma. Coronal T2-weighted MR image
shows a huge multicystic tumor occupying the whole abdomen, dis- cult at imaging and pathology; the absence of a clinical
placing the bowels, and compressing the hepatic hilum with coexistent history of acute pancreatitis favors the hypothesis of a
bile duct dilatation. The patient underwent surgery with histological MCN [45].
diagnosis of serous cystadenoma
I ntraductal Papillary Mucinous Neoplasms
“Giant” SCA Intraductal papillary mucinous neoplasms (IPMNs) are
mucin-producing cystic neoplasms that arise from the pan-
Serous cystadenomas are slow-growing tumors [44] inciden- creatic ducts. There are three variants of IPMN: the branch-
tally found as small lesions. In rare instances they can grow up duct (BD), characterized by multiple cystic lesions
to a significant size, causing compressive symptoms (Fig. 11); throughout the gland, expression of dilated peripheral
this is one of the few indications for surgical resection. ducts; the main duct (MD), characterized by diffuse or
focal dilatation of the main pancreatic duct; and the mixed-
type, in which both the main duct and the secondary ducts
Mucinous Cystic Neoplasms are dilated. The most important diagnostic criteria for BD-
and mixed-IPMNs is the connection of the cystic lesions to
Mucinous cystic neoplasms (MCNs) are tumor-producing the main pancreatic duct, a feature that can be easily evalu-
mucin that harbor a potential of malignancy, therefore they ated by MR cholangiopancreatography (MRCP). Among
should be resected when discovered. MCNs are usually diag- several features that should raise the suspicion of malig-
nosed in young women and present as a rounded, uni- or oli- nancy associated with IPMNs, the presence of solid vascu-
golocular cystic lesion with thick walls and septa; they are larized nodules within the cysts is one of the most important
usually located in the body-tail of the gland and do not com- feature. Even though vascularized nodules may be identi-
municate with the ductal system. The content of the tumor is fied by CEUS and contrast- enhanced CT, contrast-
heterogeneously echoic at US, hypodense or slightly hyper- enhanced MRI is the gold standard to evaluate this
dense at CT, hypo- or slightly hyperintense on T1-weighted feature.
images, and hyperintense on T2-weighted images at MRI. On
post-contrast images, enhancement of the walls and septa can
be seen, and intracystic vascularized nodules can be depicted. Pan-Ductal-Ectasia
When extensive dilatation of the whole ductal system is pres-

Uncommon Site and Gender ent, the differentiation between MD- or mixed-type IPMN
and ductal dilatation secondary to mucin hyperproduction
Pancreatic body-tail is the most common site for MCNs, with secondary duct overfilling is difficult to achieve
probably because these areas are close to the rudimental (Fig. 12).
Solid Pseudopapillary Neoplasms
Solid pseudopapillary neoplasms (SPNs) are epithelial

tumors with low malignant potential. They usually develop
as solid tumors and then undergo massive hemorrhage or
necrosis, so at diagnosis they usually present as a large mass
with a predominantly cystic appearance [51]. The content of
the tumor is usually hyperdense at CT and hyperintense on
T1-weighted MR images, reflecting the presence of blood
degradation products. Enhancement of the solid components
of the tumor and the peripheral wall is usually appreciated
[52–54].
Small
Solid pseudopapillary neoplasms that are 30 mm or smaller

may present atypical imaging features, as a completely solid
Fig. 12 Pan-ductal ectasia. MR cholangiopancreatography shows a
diffuse dilatation of the pancreatic ductal system and biliary dilatation
appearance, the absence of a well-defined capsule and a
in a patient with mixed-type IPMN homogeneous enhancement. In this case, the differential
diagnosis with other solid tumors of the pancreas, in particu-
lar pNENs, may be difficult [55, 56].
Rare Pancreatic Neoplasms
Acinar cell carcinoma (ACC) is a rare primary pancreatic

tumor (1% of pancreatic neoplasms) [57–61] usually diag-
nosed in men around 60 years of age and has a less aggres-
sive behavior compared to PDAC, allowing long-term
survival after surgical resection [62, 63]. The signs and
symptoms associated with ACC are nonspecific, as abdomi-
nal pain and weight loss [61]; sometimes the “Schmid’s
triad,” a syndrome characterized by necrosis of the subcuta-
neous fat, polyarthralgia, and eosinophilia, can occur due to
the excessive production of serum lipase [59]. Less fre-
quently ACC presents with acute pancreatitis [64] or sponta-
neous rupture [65]. They can metastasize, mainly to the liver
[62], or directly invade adjacent organs [65]. Acinar cell car-
cinoma most commonly develops in the head of the pancreas
Fig. 13 Intraductal papillary mucinous neoplasm with a “colonizing” [66] as a large (on average 10 cm), well-defined solid lesion
growth. Axial T2-weighted MR image shows a large pancreatic head with a thin capsule (60% of cases) [67–69]. Intraductal and
IPMN with internal “frond-like” papillae infiltrating and erupting into
the first portion of the duodenum
cystic variants have also been described. On contrast-
enhanced CT, the lesion is slightly hypodense and has a
hyperdense peripheral capsule; an inhomogeneous appear-
“Colonizing” Appearance ance owing to necrosis, hemorrhage, or hypovascular neo-
plastic tissue can be present [68–72]. This tumor has a
The high pressure produced by mucin, or the enzymatic ero- variable appearance on MRI: necrosis is slightly hypointense
sion of the epithelial lining may result in perforation and fis- on T1-weighted images and hyperintense on T2-weighted
tulization of the IPMN into peri-pancreatic organs, such as images, while hemorrhage is hyperintense on T1-weighted
the duodenum, the stomach, and the bile ducts, with a “colo- images and heterogeneous on T2-weighted images [68, 71–
nizing” appearance (Fig. 13) [49, 50]. 73]; on post-contrast images ACC is slightly hypointense
compared to the pancreatic parenchyma, with a peripheral The differential diagnosis of pancreatoblastoma includes
enhancement [67–69]. Microscopically, ACC is character- pNEN and SPN [99, 100]. Pancreatoblastoma is character-
ized by a high number of cells with round nuclei and abun- ized histologically by the presence of “squamoid nests”:
dant PAS-positive granular eosinophilic cytoplasm, lacking large tissue lobules of epithelial cells, acinar structures, and
the desmoplastic stroma typical of PDAC. The cell growth occasional semiglandular structures, separated by stromal
pattern can be solid, trabecular, or glandular. Acinar cell car- bands between cells, composed of hypercellular spindle
cinoma frequently shows mutations of the APC/β-catenin cells with variable collagenization; in rare cases a neoplas-
pathway [74]. Multiple lines of differentiation may coexist, tic mesenchymal component is also present [101].
presenting as acino-endocrine, acino-ductal, and acino- Molecular alterations very often involve the β-catenin gene.
endocrine-ductal tumors [75–77]. Acinar cell carcinoma Hepatoid carcinoma of the pancreas is an extremely rare
usually differs from PDAC both at imaging, as it is usually tumor with less than 20 cases reported in the literature [102,
larger and present well-defined margins, and histology, 103]; this tumor can present in pure forms or with morpho-
because it is highly cellulated. If the tumor capsule is absent, logical features typical of other pancreatic tumors [104]. The
ACC has poorly defined margins and an aggressive behavior pure form has morphological and immunohistochemical fea-
[78], being similar to a PDAC. Acinar cell carcinomas are tures of hepatocellular carcinomas: it is an expansive tumor,
similar to nonfunctioning pNENs, which may present as composed of large eosinophilic or clear cells, sometimes
large lesions with fluid areas; immunohistochemistry usually with granular cytoplasm, growing in a sheet-like or trabecu-
demonstrates the acinar differentiation with positivity for lar pattern with sinusoidal vascular channels, with glycogen
pancreatic enzymes, most frequently trypsin, chymotrypsin, abundant cytoplasmic, hyaline blood cells and especially
and amylase or the anti-BCL10 antibody [79]; large SPNs bile production; typically, an increase in AFP in serum or in
may also resemble ACCs, but they are seen almost exclu- tumor cells can be appreciated [105, 106].
sively in young women, in whom ACC occurs rarely [21]; Primary non-epithelial tumors originate from adjacent
thick-walled pseudocysts may resemble an ACC and the organ and involve the pancreas. Vascular tumors include
patient’s medical history is fundamental to reach the correct hemangioendothelioma [107, 108], hemangioma [109],
diagnosis [78]. lymphangioma [110–112], and infiltrating cavernous lymph-
Pancreatoblastoma is an extremely rare tumor that angiomyoma [113]. Neural tumors include schwannoma
mainly affects male children, with a mean age at diagnosis [114], neurofibroma [115], and paraganglioma [116, 117].
of 4 years, although it has been described also in adults Teratoma usually affects the elderly, has a variable
[80]. The clinical presentation includes abdominal pain and radiological appearance due to the different tissues that
a palpable epigastric mass [81, 82]; less frequently, pancre- coexist within the tumor mass, and presents with non-spe-
atoblastoma causes weight loss due to mechanical obstruc- cific symptoms, such as abdominal pain and nausea [118,
tion of the duodenum or stomach, with reduced nutritional 119]. At US teratomas are uni- or multi-locular cysts
supply. Pancreatoblastoma is typically associated with ele- delimited by a thin capsule [120] with an echoic appear-
vated serum levels of alpha-fetoproteine (AFP) [83]. ance due to keratinous and sebaceous content [121]. On
Congenital pancreatoblastoma is associated with the CT teratomas have a variable appearance owing to coexis-
Beckwith- Wiedemann syndrome [84]. Most tumors are tence of fluid, calcifications, and fat (Fig. 14); MRI allows
resectable at diagnosis; metastases occur in 30% of cases, to better characterize the tumor components [121–123].
mainly to the liver but also to the lymph nodes, lungs, and The role of fine-needle aspiration (FNA) for the preopera-
peritoneum [85–90]. Pancreatoblastomas are usually found tive diagnosis of teratomas is uncertain, as false positives
in the head or tail of the gland and typically present as large (0.3%) and false negatives (14.3%) have been reported
lesions (about 10 cm), with well-defined borders and lobu- [124–126]. Teratomas differ histologically from lympho-
lated contours [88], with internal calcifications and hetero- epithelial cysts, as the latter has a well-differentiated strat-
geneous appearance due to the presence of necrotic and ified squamous epithelium with subepithelial lymphoid
hemorrhagic areas [91, 92]. At US it usually appears as a tissue, even though if the teratoma is predominantly com-
hypoechoic mass with hyperechoic septae [93]; Doppler posed of epidermal elements the differential diagnosis can
signals are present at the periphery of the tumor. On CT, be difficult [126, 127]. Other possible differential diagno-
pancreatoblastoma is usually a heterogeneous mass consis includes foregut-derived fat-containing cyst and lipo-
taining septa, calcifications, and fluid. At MRI, pancreato- sarcoma with cystic degeneration [127].
blastoma presents as a solid T1-hypointense and The solitary fibrous tumor of the pancreas is composed by
T2-hyperintense mass; internal hemorrhage may present spindle cells; at immunohistochemistry there may be positiv-
with T1-hyperintensity. Diffuse enhancement is typical; the ity for CD34, BCL-2, B-catenin, and a weak staining for
enhancement is poor in largely necrotic tumors [94–98]. CD-99. On MR, solitary fibrous tumor is a well-circumscribed
Peripancreatic Masses
The pancreas lies in the anterior para-renal space, near sev-

eral peritoneal and retroperitoneal structures. Due to the
complex anatomical relationships between the pancreas and
the peri-pancreatic structures, several non-neoplastic and
neoplastic lesions belonging to the latter can involve or
adhere to the pancreatic gland [143].
Duodenal duplication cysts and diverticula can be misin-
terpreted as pancreatic lesions, especially if their content is
purely fluid. Duodenal duplication cyst is a rare congenital
anomaly that occurs during embryonic development. They
are mostly located in the second and third portion of the duo-
denum and may communicate with the duodenum lumen or
the pancreatic or biliary duct. The noninvasive diagnosis of a
duodenal duplication cyst is difficult, as it presents as a fluid-
filled cyst located on the medial border of the second portion
of the duodenum, and the differential diagnosis includes any
Fig. 14 Pancreatic teratoma. Coronal-reformatted portal phase CT cystic lesion in the pancreaticoduodenal region, in particular
image shows a well-defined, rounded lesion with peripheral enhance-
ment and inhomogeneous internal density in the pancreatic head; slight groove pancreatitis, pseudocysts, and pancreatic cystic neo-
upstream dilatation of the main pancreatic duct is present plasms [144]. Duodenal diverticula are a relatively common
incidental finding at barium examinations. Intraluminal
diverticula are mainly located within the second portion of
mass predominantly hypointense on T2 images; on post- the duodenum and may mimic a cystic pancreatic neoplasm;
contrast images the tumor mass shows a progressive enhance- at barium examination, intraluminal diverticula show a
ment; smaller tumors show early homogeneous “windsock” deformity, with the contrast-filled diverticulum
enhancement. projecting into the true lumen [145].
Malignant mesenchymal tumors include malignant sarco- Choledochal cysts are a rare congenital anomaly of the
mas arising from the retroperitoneum, as leiomyosarcoma bile ducts that appear as a cystic dilatation of the common
[128–130], malignant fibrous histiocytoma [131], liposar- bile duct and may simulate a cystic lesion of the pancreatic
coma [132, 133], and malignant nerve sheath tumor [134]. head; hepatobiliary phase MR images may be useful for dif-
Pancreatic lipoma is usually asymptomatic and inciden- ferential diagnosis by demonstrating contrast filling into the
tally discovered [135]. At US, lipoma presents as a well- choledochal cyst; EUS and ERCP may be required for diag-
defined, hyperechoic, homogeneous lesion [136]; on CT, nosis [146].
lipoma is well-defined [137], with lobulated contours, homo- A peri- and intra-pancreatic accessory spleen and spleno-
geneously hypodense as composed almost entirely by fat, sis may mimic a hypervascular pancreatic lesion; the differ-
with few vessels or sometimes interlobular septa [138–140], ential diagnosis with a pNEN can be difficult basing only on
without enhancement. Chemical-shift MR imaging improves imaging and nuclear medicine is usually necessary for a final
the detection of the lesion capsule [141]; on MRI, the lipoma diagnosis [147].
follows the signal intensity of fat. The Wirsung’s duct is usu- Enlarged portocaval, portal, peripancreatic, and celiac
ally normal. The differential diagnosis includes localized nodes may mimic pancreatic lesions. Coexistence of enlarged
pancreatic lipomatosis, which generally does not present a lymph nodes above and below the level of the renal veins
capsule; cystic teratoma, which contains calcifications and favors the diagnosis of lymphoma [148] or inflammatory dis-
various tissues with heterogeneous densities; and other fat- orders such as sarcoidosis and Castleman disease [149, 150].
containing neoplasms such as liposarcoma, which is usually Pancreatic and nodal involvement by tuberculosis is
larger (>5 cm) and more heterogeneous, containing areas of extremely rare [151, 152]. Metastatic disease from esopha-
soft tissue; radiologic differentiation between lipoma and geal, gastric, and renal cancer can manifest with isolated,
lipogenic liposarcoma can be difficult [142]. Pancreatic lipo- peri-pancreatic nodal involvement.
mas that are larger than 5 cm, those that increase in size over Aberrant vessels or pseudoaneurysms may mimic a pan-
follow-up or with an inhomogeneous structure are at risk of creatic mass at imaging. Pseudoaneurysms of the pancreati-
transformation into liposarcoma [142] and should therefore coduodenal, hepatic, or mesenteric artery secondary may be
be surgically resected. confused with a hypervascular pancreatic lesion [153]:
Doppler US shows turbulent flow within a pseudoaneurysm, guished from pseudocyst and mucinous cystadenocarcinoma. Int J
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Pancreatic Surgery and Post-Operative
Complications
Riccardo De Robertis, Luca Geraci, Nicolò Cardobi,

Luisa Tomaiuolo, Antonia Maria Olivieri,
Francesco Verrengia, Francesco Cicalò, Filippo Moro,
Roberto Calbi, and Mirko D’Onofrio
Eat when you can, pancreatectomy) and parenchyma-sparing resections (i.e.,

Sleep when you can,
enucleation and middle pancreatectomy). Although major
Don’t mess with pancreas
pancreatic resections are still usually performed during open
laparotomy, minimally invasive approaches, such as laparos-
These three “unwritten rules” well represent surgeons’ copy and robotic surgery, have become increasingly used
reverence and fear for pancreatic surgery. Surgery is the only over the last years and, in selected cases, represent a valid
potentially curative treatment for pancreatic cancer, but it is alternative to the conventional surgical approach.
known that pancreatic surgery is technically demanding:
despite advances in decreasing post-operative mortality
below 2% after pancreatic resection in specialized centers,
specific morbidity remains high (35%–50%) [1]. A clear Pancreaticoduodenectomy
volume-outcome correlation has been demonstrated in pan-
creatic surgery: according to a previous report, mortality Pancreaticoduodenectomy (PD) is performed for pancreatic
after pancreaticoduodenectomy was 16.3% in low-volume head and periampullary neoplasms and consists of resection
institutions, and 3.8% in high-volume institutions [2]. For of the head of the pancreas, the duodenum and a short seg-
these reasons, pancreatic surgery should be performed only ment of the jejunum beyond the duodenum, the gallbladder
at high-volume, reference centers, where there are the surgi- and the common bile duct, and regional lymph nodes. There
cal, clinical, radiological, and endoscopic skills necessary are two variants of PD: the Kausch-Whipple operation, in
for the optimal pre- and post-operative management of which the pylorus and the distal stomach are removed, and
patients with a pancreatic tumor. the Longmire-Traverso operation, also known as pylorus-
preserving (pp-PD), a modified Whipple’s operation in
which the stomach and the pylorus are preserved (Fig. 1).
Types of Pancreatic Surgery Pylorus-preserving PD was developed to decrease the inci-
dence of post-gastrectomy complications, with a potential
Different types of surgery are possible to treat pancreatic improvement in long-term gastrointestinal function [3]; nev-
neoplasms, and the choice is based both on the type of lesion ertheless, further studies [4, 5] concluded that this technique
and its location within the pancreatic gland. Pancreatic does not have a clear superiority of over Whipple’s PD in
surgery can be divided into major resections (i.e., terms of overall perioperative morbidity or mortality, tumor
pancreaticoduodenectomy, distal pancreatectomy, and total recurrence or long-term survival; nevertheless, pp-PD has
advantages over Whipple’s operation in terms of lower risk
of biliary reflux, reduced operating time, and intraoperative
R. De Robertis (*) · L. Geraci · L. Tomaiuolo · A. M. Olivieri ·
F. Verrengia · F. Cicalò · F. Moro · M. D’Onofrio blood loss.
Department of Radiology, G.B. Rossi University Hospital, After the surgical median incision of the abdominal wall,
Verona, Italy the entire abdomen is explored in search of any micrometas-
tases, with particular regard to the liver. The second step is to
N. Cardobi confirm the resectability of the mass: the duodenum and the
Department of Radiology, Ospedale Borgo Trento, Verona, Italy
pancreatic head are mobilized to search for any neoplastic
R. Calbi infiltration of the artery and/or superior mesenteric vein.
a b
Fig. 1 (a, b) CT images in a patient with a resectable pancreatic head cancer scheduled for PD. The structures that will be resected during surgery
are outlined in red (T tumor, D duodenum, GB gallbladder, CHD common hepatic duct, PH pancreatic head)
a b
Fig. 2 (a, b) Surgical anastomoses after PP-PD. (a) The CT image common hepatic duct remnant (CHD, outlined in green). (b) Coronal
shows the anastomoses created on a single jejunal loop (J, outlined in CT image showing the anastomosis between the residual duodenum (D,
orange) with the pancreatic remnant (P, outlined in yellow) and the outlined in blue) and the anastomotic jejunal loop (J, outlined in orange)
Once resectability has been verified, the duodenum is enteric anastomosis, which, in Whipple’s PD, is constructed
resected immediately distal to the pylorus; the next steps are between the stomach and the jejunum, while in PP-PD is cre-
the detachment of the pancreatic head from the superior mes- ated between the duodenum remnant and a jejunal loop. The
enteric vein, the isolation of the common hepatic duct, and enteric anastomosis can be constructed either anteriorly or
the section of the pancreas at the passage head-body. posteriorly to the transverse colon. For the antecolic recon-
After resection, three anastomoses are created during PD struction, the jejunal loop about 30 cm distal to the hepatico-
(Fig. 2): one between the pancreatic remnant and the jeju- jejunostomy is brought up anterior to the transverse colon
num (pancreaticojejunostomy) or the posterior wall of the and anastomosed to the duodenum or stomach, while for the
stomach (pancreaticogastrostomy); a hepaticojejunostomy, retrocolic reconstruction the jejunal loop is anastomosed to
performed between the common hepatic duct remnant and the duodenum or stomach through a separate mesocolic win-
the jejunum distal to the pancreaticojejunostomy; and an dow on the left of the middle colic vessels.
Pancreatic Surgery and Post-Operative Complications 453
Distal Pancreatectomy also be necessary after an initial partial pancreatectomy

because of positive resection margins on intraoperative fro-
Distal (or left) pancreatectomy (DP) is performed for body- zen section; moreover, a two-stage TP (a.k.a. completion
tail tumors; because of the lower incidence of pancreatic pancreatectomy) can be performed because of severe post-
tumor and later appearance of clinical symptoms in these operative complications or neoplastic recurrence in the pan-
parts of the organ, DP is performed less often than PD. creatic remnant after previous pancreatic resection [6]. Total
Distal pancreatectomy involves surgical resection of the pancreatectomy involves the resection of the whole pancreas,
body and tail of the pancreas to the left of the superior the common bile duct, the gallbladder, the duodenum, a short
mesenteric-portal vein confluence; DP can be carried out segment of jejunum beyond the duodenum, the pylorus, the
with or without associated splenectomy, depending upon the distal part of the stomach, the spleen, and regional lymph
disease process and the characteristics of the lesion: spleen- nodes. After resection, two anastomoses are constructed: a
preserving DP is reserved for benign/borderline pancreatic hepaticojejunostomy and a gastrojejunostomy distal to the
lesions and cysts, and for localized neuroendocrine tumors, hepaticojejunostomy.
while splenectomy must be carried out in malignant lesions
of the pancreatic body-tail (Fig. 3).
As with PD, the abdominal organs are explored in search Parenchyma-Sparing Resections
of any micrometastases before resection. In case of resect-
able neoplasm, the great curvature of the stomach is detached Middle pancreatectomy (MP), also known as central or
to separate it from the transverse colon and the spleen. This medial pancreatectomy, is a limited resection of the midpor-
exposes the body-tail of the pancreas. If the spleen must be tion of the pancreas that allows to preserve endocrine and
removed, after ligating the splenic vessels, the spleen and the exocrine pancreatic function, that can be proposed for benign
body-tail of the pancreas are mobilized, and their en bloc and borderline neoplasms of the pancreatic body [7]. During
resection is carried out. No anastomoses are created after DP, MP, the segment of the pancreas with the tumor is transected
and the pancreatic stump can be either hand-sutured, closed to the left and to the right of the lesion. After resection, the
with a stapler, or sealed with a harmonic scalpel. cephalic pancreatic stump is sutured, while the distal pancre-
atic remnant is anastomosed to a jejunal Roux-en-Y loop
(pancreaticojejunostomy) or to the posterior wall of the
Total Pancreatectomy stomach (pancreaticogastrostomy); after pancreaticojejunos-
tomy, the Roux loop is connected to the distal jejunum.
Total pancreatectomy (TP) is indicated for a multifocal neo- Enucleation is designed to remove small (around 2 cm)
plasm, as intraductal papillary mucinous neoplasia or neuro- tumors of the pancreas which have a likely benign biological
endocrine tumors in the setting of MEN1 syndrome, but may behavior while preserving almost all the pancreatic
a b
Fig. 3 (a, b) CT images in a patient with a pancreatic body carcinoma scheduled for DP. The structures that will be resected during surgery are
outlined in red (T tumor, P pancreatic tail, S spleen)
a b
Fig. 4 (a–c). Patient with a pancreatic head neuroendocrine neoplasm trast medium (arrowhead) during retrograde injection into the main
scheduled for enucleation. (a) T2-weighted MR image shows a fluid- pancreatic duct (arrow) as a consequence of the iatrogenic damage of
containing lesion with thick wall in the ventral portion of the pancreatic the duct. (c) The complication was successfully treated by endoscopic
head (arrow). (b) After enucleation, the patient developed a high-flow placement of a plastic endoprosthesis in the lumen of the main pancre-
pancreatic fistula; the ERCP image demonstrated the spilling of con- atic duct (arrow)
parenchyma, thereby minimizing the risk of long-term exo- ascular Resection During Pancreatic
V
crine and endocrine insufficiency [8]. Enucleation involves Resection
shelling out the tumor from the surrounding pancreas (Fig. 4).
The lesion should be at least 2–3 mm distant from the main Infiltration of major peri-pancreatic vessels frequently deter-
pancreatic duct and not too deep in the parenchyma in order mines unresectability. Nevertheless, in selected cases, surgi-
to prevent ductal damage with subsequent pancreatic fistula; cal resection of infiltrated veins and—less often—arteries
magnetic resonance (MR) with cholangiopancreatography is could be attempted. Vascular resection during pancreatic sur-
particularly helpful to evaluate the distance and the relation- gery is technically demanding, as complete tumor e radication
ship between the tumor and the ductal system. (R0 resection) must be achieved to obtain curative strategy.
Several studies have shown equivalence in terms of morbidity, tions and to guide percutaneous intervention, contrast-
mortality, and survival of pancreatectomy with versus without enhanced computed tomography (CT) is the most important
venous resection and reconstruction [9–11]; for this reason, vein imaging method to evaluate post-operative complications, as
resection and reconstruction should be considered, if technically it is widely available, it has high spatial resolution and
feasible, to achieve curative resection in patients with tumor enables a rapid diagnosis. Magnetic resonance (MR) imag-
involvement of the portal and superior mesenteric veins [12]. ing and fluoroscopy are used in specific cases to better evalu-
On the other hand, arterial resection and reconstruction ate the biliary and pancreatic ducts, the gastrointestinal
during pancreatectomy remains debatable, as literature data function, and the evolution of post-operative collections.
did not show a clear improvement in terms of long-term sur-
vival of patients who underwent pancreatectomy with com-
bined arterial resection; moreover, careful patient selection is Post-Operative Pancreatic Fistula
critical to define the patients who may benefit from this
highly aggressive surgery. Surgical resection of the neck, Clinically relevant post-operative pancreatic fistula (POPF)
body, and tail of the pancreas with en bloc resection of the remains the most troublesome complication after PD. A pan-
celiac artery, an intervention known as Appleby procedure creatic fistula is clinically defined as the output via a drain or
(or DP with celiac artery resection) has been increasingly a surgical wound, on or after post-operative day 3, of any
performed at select centers of excellence to treat locally fluid containing pancreatic juice [14, 15]. The origin and
advanced pancreatic neck or body tumors. Tumor thrombo- incidence of POPF vary according to the type of resection:
sis does not represent per se a contraindication to surgery in the incidence of pancreatic fistula after PD is between 10 and
patients with pancreatic neuroendocrine neoplasms. Surgical 20% and represents the failure of the pancreaticojejunos-
treatment of such condition should be adopted when techni- tomy or the pancreaticogastrostomy. In DP (incidence
cally feasible to treat or prevent complications related to por- 20–25%), the pancreatic juice leaks from the surface of the
tal hypertension. Tumor thrombosis associated with pancreatic remnant. In MP (incidence 40–50%), pancreatic
neuroendocrine neoplasms can be treated through the extrac- fistula derives from the failure of the distal pancreoenteric
tion of the thrombus or with a proper vascular resection [13]. anastomosis and/or it may originate from the proximal
stump. Finally, the incidence of pancreatic fistula after enu-
cleation is 35–40% and represents a leak from the resection
Post-Operative Complications bed because of inadvertent damage of the ductal system. The
potential consequences of pancreatic fistula are intra-
Despite technical advancements, post-operative complica- abdominal collections, delayed gastric emptying, reopera-
tions after pancreatic surgery remain a major issue, even in tion, post-pancreatectomy hemorrhage, increased hospital
specialized centers. Most post-operative complications are stay, readmission, and increased mortality risk. The most
diagnosed upon the clinical course and laboratory parame- common imaging finding in patients with a POPF is a fluid
ters; nevertheless, imaging is necessary to confirm the diag- collection around the pancreatic anastomosis [16, 17]
nostic hypothesis and to evaluate the severity. While (Figs. 5 and 6); nevertheless, this finding is not specific, and
ultrasound (US) is helpful to evaluate post-operative collec- the final diagnosis relies on clinical and laboratory findings.
a b
Fig. 5 (a, b). Patient with a pancreatic fistula after PD secondary to pancreojejunal failure. CT images show a clear separation of the pancreatic
remnant from the anastomotic jejunal loop, with the interposition of a thin fluid layer (arrow); a peri-pancreatic collection coexists (arrowhead)
a b
Fig. 6 (a, b) Patient with a pancreatic fistula secondary to dehiscence of the pancreogastric anastomosis after PD. On CT images the pancreatic
remnant (P) and the stomach (S) are separated (arrow in a); a fluid layer surrounds the pancreatic remnant and the anastomosis (arrowhead)
Other imaging features suggestive of POPF in PD include air may be helpful to confirm the suspicion of hepaticojejunos-
bubbles in a peripancreatic collection and a clear disruption tomy failure (Fig. 8) by demonstrating the passage of the
of the pancreatic anastomosis, with separation of the anasto- contrast medium injected through drainage tubes into the
mosis’ sides. MR imaging may be helpful in diagnosing pan- bile ducts, the anastomotic loop, or both. Some authors advo-
creatic duct disruption as a cause of pancreatic fistula [18], cated the use of MR imaging with hepatobiliary contrast
especially after pancreatic enucleation; nevertheless, patients agents to identify a bile leak by demonstrating extravasation
with a post-operative pancreatic fistula are frequently too of contrast material from the hepaticojejunostomy on delayed
sick to undergo a proper MRI examination. Conventional fis- hepatocyte phase T1-weighted MR images [21].
tulography can confirm the suspicion of pancreoenteric
dehiscence by demonstrating the passage of the contrast
medium injected through surgical drainage tubes into the Post-Pancreatectomy Hemorrhage
enteric lumen, the remnant of the pancreatic ductal system,
or both [19]. Post-pancreatectomy hemorrhage (PPH) is the most severe
complication of pancreatic surgery, with an incidence
between 2% and 8% [22]. Early post-operative hemorrhage
Post-Operative Biliary Fistula occurs within 24 h after surgery, while delayed post-operative
hemorrhage—which is a serious event associated with mor-
Biliary fistula is less frequent than pancreatic fistula, as it tality rates of 15–20%—may occur several days or even
occurs in 3–8% of patients following PD and is defined as weeks after surgery. Early hemorrhage frequently results
the output via a drain of any measurable volume of fluid con- from a technical failure of surgery or from vasospasm of
taining bile [20]. Bile leakage may occur after PD or TP and small vessels on the surface of the pancreatic resection, while
represents the failure of hepaticojejunostomy. As for pancre- delayed bleeding is associated with vessel erosion and pseu-
atic fistula, the most typical imaging finding is the presence doaneurysm rupture caused by a pancreatic fistula, infection,
of a para-anastomotic fluid collection (Fig. 7); fistulography or intra-abdominal abscess. Post-operative hemorrhage can
a b
Fig. 7 (a–c). Patient with a biliary fistula after PD secondary to dehis- remnant (CHD) and the anastomotic jejunal loop (J); the collections are
cence of the biliodigestive anastomosis. CT images show a gas- directly connected to the disrupted anastomosis (arrow in c)
containing collection (arrowhead) next to the common hepatic duct
a b
Fig. 8 (a, b) Patient with a biliary fistula after PD secondary to dehis- of a large collection (arrow in b) along with retrograde opacification of
cence of the biliodigestive anastomosis. (a) CT image shows a fluid the bile ducts and absent opacification of the jejunal loop, consistent
collection (arrow) next to the common hepatic duct remnant (CHD) and with complete failure of the hepaticojejunostomy
the anastomotic jejunal loop (J). (b) Fistulography shows opacification
a b
Fig. 9 (a, b) Intragastric bleeding after PD with pancreogastric anastomosis. CT images show active contrast medium extravasation into the gas-
tric lumen (arrows)
be intraluminal or extraluminal; however, if anastomotic on the pancreatic stump surface of a pancreoenteric anasto-
dehiscence is present, extraluminal blood can present as mosis secondary to a pancreatic leak, by gastric or duodenal
intraluminal and vice versa [23]. Intraluminal bleeding ulcers or by diffuse gastritis. Extraluminal bleeding occurs in
(Figs. 9 and 10) occurs into the bowel lumen and can be the abdominal cavity and may originate from surgical dam-
caused either by enzymatic digestion of the blood vessel wall age of arterial or venous vessels in the areas of resection or
a b
Fig. 10 (a, b) Intrajejunal bleeding after PD with pancreojejunal anastomosis. CT images show a contrast blush into the lumen of the anastomotic
jejunal loop consistent with an active extravasation of contrast medium (arrows)
a b
Fig. 11 (a, b) Extraluminal bleeding after DP. CT images show active contrast medium extravasation from the splenic artery remnant (arrows)
within a large collection next to the pancreatic remnant (P) (arrowhead)
from eroded and ruptured pseudoaneurysms secondary to early PPH; on the other hand, when the patient is hemody-
intra-abdominal collections (Figs. 11 and 12). According to namically stable, it is generally recommended to perform a
a recent meta-analysis, the gastroduodenal artery stump is CT examination. Subsequent treatment depends upon the
the most frequent origin of extraluminal hemorrhage (29%), cause, nature, and site of bleeding: endovascular treatment is
followed by the common hepatic artery (19%) and splenic recommended as the first choice for most patients with arte-
artery (12%) [24]. When post-operative hemorrhage occurs, rial bleeding after pancreatectomy. If the source of bleeding
patient’s management is based on the timing of onset, the remains uncertain after CT, or if CT does not show any clear
hemodynamic status, and CT findings: in case of hemody- bleeding despite a clinically defined PPH, angiography of
namic instability, regardless of the timing of bleeding, imme- the celiac axis, superior mesenteric artery, and their branches
diate reoperation is usually indicated, especially for very should be performed to better evaluate the site of bleeding.
a b
Fig. 12 (a–c) Extraluminal bleeding after PD. CT images (a, b) show active contrast medium extravasation next to the gastroduodenal stump
(arrow in a and b). Selective celiac angiogram confirmed a massive hemorrhage from the gastroduodenal stump (arrow in c)
Delayed Gastric Emptying imaging usually shows dilation of the stomach; the enteric
anastomosis may appear thickened and edematous. A gastro-
Delayed gastric emptying is a functional gastroparesis that grafin x-ray study is usually performed in patients with
frequently complicates pancreatic resections, especially PD, delayed gastric emptying, aiming to exclude gastric outlet
with an incidence comprised between 14 and 61% [25]. obstruction. The most frequent findings are a decreased or
Several factors, including disruption of pylorus innervation, absent gastric peristalsis, gastric dilation and delayed or
motilin deficiency due to duodenum resection, and technical absent emptying of the contrast agent (Fig. 13).
aspects of the surgical intervention, may cause delayed
gastric emptying. The incidence of DGE does not appear to
be related to other technical factors, such as the type of pro- Post-Operative Pancreatitis
cedure performed (classical Whipple’s vs pp-PD) and the
type of reconstruction of the duodenojejunostomy or gastro- Post-operative pancreatitis is triggered by enzymatic acti-
jejunostomy (antecolic vs retrocolic) [25]. Cross-sectional vation in the pancreatic remnant with local inflammation.
a b
Fig. 13 Patient with delayed gastric emptying after pylorus-preserving gastrografin study (c), the stomach (S) is markedly dilated, with poor
PD. CT images show circumferential wall thickening of the duodenoje- and delayed emptying of the contrast agent
junal anastomosis (arrow in a and b) and dilation of the stomach (S); at
There exists significant evidence to support the hypothesis tion of the pancreatic remnant and peri-glandular edema or
that the pathophysiology of a significant proportion of fluid collections (Fig. 14). Peripancreatic soft-tissue strand-
POPF following PD is due to post-operative acute pancre- ing is also a common finding during the immediate post-
atitis [26]. operative period. Because the appearance of peripancreatic
The diagnosis relies on elevated serum amylase levels; soft-tissue stranding is similar to that of acute pancreatitis, a
imaging may demonstrate enlargement and hypovasculariza- clinical diagnosis is required [27].
artery-first approach for superior mesenteric-portal vein resection

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11. Kleive D, Sahakyan MA, Berstad AE, Verbeke CS, Gladhaug IP,
Edwin B, et al. Trends in indications, complications and outcomes
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2017;104(11):1558–67.
12. Hartwig W, Gluth A, Hinz U, Koliogiannis D, Strobel O, Hackert
T, et al. Outcomes after extended pancreatectomy in patients with
borderline resectable and locally advanced pancreatic cancer. Br J
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13. De Robertis R, Paiella S, Cardobi N, Landoni L, Tinazzi Martini
P, Ortolani S, et al. Tumor thrombosis: a peculiar finding associ-
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et al. Postoperative pancreatic fistula: an international study group
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Risk-adjusted outcomes of clinically relevant pancreatic fistula fol-
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Fig. 14 Acute inflammation of the pancreatic remnant. Increased
16. Raman SP, Horton KM, Cameron JL, Fishman EK. CT after pan-
serum amylase and lipase levels were found on post-operative day 8.
creaticoduodenectomy: spectrum of normal findings and complica-
On coronal CT image, inhomogeneous appearance of the pancreatic
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17. Malleo G, Pulvirenti A, Marchegiani G, Butturini G, Salvia R,
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Imaging Methods for Pancreatic
Neoplasms
Alessandro Beleù , Fabrizio Urraro, Roberto Calbi,

Chiara Longo, Annalisa Cominziolli, Riccardo De Robertis,
Nicolò Cardobi, and Mirko D’Onofrio
Introduction impossible without invasive methods. In any case, no radio-

logical evaluation of the pancreas can be separated from a
Despite many technological and medical improvements, deep knowledge of pancreatic pathology, its risk factors, its
imaging of the pancreas still represents a challenging evalu- clinical and laboratory characteristics, its evolution, compli-
ation even for the most experienced radiologist. However, cations, treatments, and outcomes.
modern imaging techniques can provide a solid aid to diag- Ultrasound is often the first approach to the pancreas,
nose different pancreatic diseases, both neoplastic and not being easy to be performed and low-cost, but it suffers from
neoplastic. The strengths and weaknesses of each radiologi- a limited field of view and could be limited from the physical
cal technique must be well known and mastered by the radi- conformation of the patient or the interposition of abdominal
ologist because the evaluation of pancreatic disorders often gas. CT and MRI, despite the larger field of view and the dif-
derives from the careful and expert interpolation of radio- ferent contrast resolution, are more complex and expensive
logical findings deriving from different imaging methods. examinations, but often indispensable for a correct charac-
There is no single best method to evaluate the pancreas, but terization of pancreatic neoplasms.
often it is the global consideration of ultrasound (US), com- In this chapter, an in-depth technical explanation of the
puted tomography (CT), and magnetic resonance (MRI) functioning of each method will not be provided, assuming
findings, as well as endoscopic ultrasound (EUS) or rarely that every radiologist already knows it well, as well as any
angiography, to lead to the correct radiological diagnosis of non-radiologist physician can deepen it in other specific
pancreatic disease, or at least to raise the probability of its texts. Rather, an overview of pancreatic imaging techniques
correctness. In fact, like all medical diagnoses, the radiologi- will be provided, highlighting the strengths and weaknesses
cal diagnosis of pancreatic pathology is probabilistic; it is the of each one, also focusing on the innovations that the flour-
duty of the expert radiologist to choose the appropriate imag- ishing world of modern radiology is increasingly making
ing methods, consider the results obtained globally, interpret available and that in the not-too-distant future could become
them in the light of clinical and anamnestic information, to part of normal clinical practice.
raise the probability of a correct diagnosis as much as pos-
sible, which, however, can be very difficult and sometimes
Ultrasound
A. Beleù (*)
Department of Diagnostic and Interventional Radiology, Conventional US represents the first-line examination for the
“Ca’ Foncello” Hospital, Treviso, Italy evaluation of the pancreas, as it is a low expensive, widely
Department of Diagnostic and Interventional Radiology, available, and quite fast technique. Despite the limited field
“P. Pederzoli” Hospital, Verona, Italy of view compared to other methods, the US allows perform-
e-mail: alessandro.beleu@aulss2.veneto.it
ing examinations by orienting the scan in infinite planes of
F. Urraro space, counting on an excellent spatial resolution. US is also
Department of Precision Medicine, University of Campania “Luigi
the only non-invasive radiological method that allows a real-
Vanvitelli”, Naples, Italy
time assessment of the target organ, and the only one that
R. Calbi · C. Longo · A. Cominziolli · R. De Robertis
allows at the same time not only to “look” but also to “visit”
N. Cardobi · M. D’Onofrio
Department of Radiology, “G.B. Rossi” Hospital, the patient, performing compressions on the abdomen,
University of Verona, Verona, Italy displacing some interposed organs, evaluating the
464 A. Beleù et al.
modifications with the breath, with position changes, with blood-pool microbubble contrast agent, CEUS is the only
forced maneuvers such as Valsalva, understanding what imaging method that allows a real-time evaluation of small
evokes pain and what provides its relief. In short, US is per- vessels’ blood flow during the entire dynamic phases [3].
haps the most “clinical” method of radiology. Exalting the pure vascularization of a pancreatic tumor, this
In the evaluation of the pancreas, US allows to investigate technique can improve the characterization of pancreatic
the parenchyma and its echo-structure, understanding if it is lesions seen on conventional US, accurately differentiating
normal or if the pancreas is atrophic or in adipose involution between solid and cystic lesions with an accuracy of 87–97%
(typically hyperechoic); it also allows to evaluate the bile and discerning benign from malignant masses with good
duct and the main pancreatic duct, evaluating its course, sensitivity and specificity [4, 5]. While a hypovascular pat-
diameter, regularity, and any cystic dilatation of the branch tern at CEUS identifies a pancreatic ductal adenocarcinoma
ducts. However, the US evaluation of cystic lesions of the (PDAC) with an accuracy close to 90%, and a sensitivity and
pancreas often does not establish with certainty its commu- specificity of 95%, a hypervascular pattern is associated with
nication with the main pancreatic duct, which is key infor- a pancreatic neuroendocrine tumor (pNET) with an accu-
mation for the differential diagnosis of pancreatic cystic racy, sensitivity, and specificity of more than 90% [2–4, 6].
neoplasms; therefore higher level methods such as MRI or In some cases, pNETs could be hypovascular; well-
EUS is often needed [1]. demarcated margins and expansive growth may help differ-
The use of color-Doppler can also help to recognize the entiate them from PDAC [7, 8], but they always should be
main vessels and give a rough estimate of the proximity of a considered as PDAC until otherwise proven [3]. Solid pan-
neoplasm with the portal venous system and with the mesen- creatic tumors of the pancreas could also be distinguished
teric arteries, although the infiltration judgment is better del- from different tissues based on their specific consistency;
egated to CT or intraoperative US. since malignant tumors tend to be harder than benign ones
However, US has some limitations; being the pancreas a and parenchyma, US-elastography (USE) can help to differ-
retroperitoneal organ, the interposition of gas in the bowel entiate solid pancreatic tumors, especially when <30 mm [9].
and the transverse colon can partially or completely obscure However, both strain-USE and shear-wave USE are rela-
the pancreas. Also, the presence of abdominal obesity can tively new techniques and their role in pancreatic diagnostic
limit the evaluation, even if the introduction of new technolo- imaging must be fully validated in literature and introduced
gies such as Tissue Harmonic Imaging (THI) can eventually in daily clinical practice at the moment [9, 10].
help in this case. Sometimes, even with strong compression Cystic tumors are correctly diagnosed with CEUS with an
with the probe, it is still not possible to visualize the pancreas accuracy of 97% [4], providing information on their charac-
correctly. Moreover, the pancreatic tail, called the “pancreatic teristics of complexity (septa, vascularized wall nodules,
blind area”, is often invisible for anatomical reasons, or at etc.) comparable to MRI [11, 12]. The complete absence of
least only partially visible with the trans-splenic approach. vascularization at CEUS in patients with previous pancreati-
Although pancreatic cystic neoplasms are classically tis episodes supports the diagnosis of a pseudocyst with an
described as anechoic and solid ones as hypoechoic, this accuracy of 84–99% [4, 13]. Even if is still reserved only for
generalization may be inaccurate. The judgment of echo- selected cases [14], the use of EUS, using high-frequency
genicity always derives from the comparison with the sur- probes with a direct approach, even combined with the
rounding parenchyma, which can be very different from administration of US-contrast agent, improves the accuracy
patient to patient. It is therefore important to orient a diagno- particularly for smaller cysts [15], permitting also the analy-
sis not only on the echogenicity of a tumor, but on its mor- sis of the cystic fluid with EUS-fine-needle aspiration which
phological characteristics, on its relationship with the helps to differentiate serous cystic neoplasm and non-
surrounding vessels and with the main pancreatic duct and neoplastic cystic lesions from mucinous neoplasms with
their relative modifications, but above all on the vasculariza- malignant potential [16].
tion of the tumor. In pancreatic interventional radiology, US is certainly the
For this reason, contrast-enhanced ultrasound (CEUS), most used guidance technique, both for invasive diagnostic
introduced in the last decades, allows a more complete US percutaneous procedures or the positioning of peri-pancreatic
evaluation of the pancreas. The US contrast agent is com- drainages, and for the rarer and more complex ablative meth-
posed of microbubbles of sulfur hexafluoride which resonate ods that currently play a niche role in a few specialized cen-
when excited by the ultrasound, returning a signal propor- ters, with purely palliative purposes at the moment [17–19].
tional to their spatial concentration. Unlike the contrast For US-guided interventional procedures, Fusion
agents used for CT and MRI, the US contrast agent is an Imaging technology (US-FI) has recently been imple-
exclusively intravascular drug, therefore lacks a distribution mented in many high-end ultrasound scanners. This tech-
phase in the extravascular tissues. Compared to CT, CEUS is nology allows the synchronous association of B-mode US
cheaper and there is no renal failure contraindication, avoid- images with one or more other cross-sectional studies such
ing also the use of ionizing radiations [2]. Exploiting a as CT, MRI, or PET-CT, which are instantly reconstructed
Imaging Methods for Pancreatic Neoplasms 465
in real-time in the corresponding plane. Real-time US-FI staging therapy. In this latter case, the PDACs evaluation
exploits the strengths of all imaging modalities simultane- after chemotherapy is challenging and it must be kept in
ously, minimizing the weaknesses of every single modality. mind that CT tends to underestimate its resectability, espe-
Therefore, US-FI provides benefits from both the dynamic cially for tumors <25 mm [33].
information and spatial resolution of the common US and The advent on the market of the new Dual-Energy CT
the high-contrast resolution and wide field of view of CT (DECT) has revolutionized the future prospects of pancreatic
and MRI [20]. With US-FI it is possible to guide pancreatic imaging. DECT simultaneously acquires data from two dif-
interventional procedures with greater safety, even in ferent X-ray spectra, generally low energy at 80–100 kV and
poorly visible areas such as the “pancreatic blind area”, high energy at 140 kV [34]. In this way, DECT allows mate-
increasing the confidence of the operator, reducing the time rials with differential X-ray absorption at high and low kVp
of the procedure, and allowing to choose more accurately (e.g., iodine, calcium) to be quantified or removed in post-
the path of insertion of the needles to avoid dangerous vas- processing [35]. The post-processing of a DECT acquisition
cular structures [21, 22]. permits the creation of a virtual non-contrast scan (then
reducing the overall radiation dose) and a virtual monoener-
getic image, as well as an advanced evaluation of the
Computed Tomography enhancement through the creation of iodine maps. The use of
DECT also allows reducing the volume of iodine contrast
Contrast-enhanced multidetector CT is considered the gold administered and to reduce metal artifacts, an important fea-
standard for the evaluation of focal solid pancreatic tumors ture when there are metallic stents in the common bile duct
due to its high spatial resolution and accuracy. The multipha- or in the duodenum that limit the evaluation of surrounding
sic imaging classically includes a baseline, a pancreatic arte- tumor [36]. In the pancreatic field, DECT can significantly
rial, and a portal venous phase acquired before and after improve the image quality and the tumor-to-parenchyma
intravenous injection of an iodinated non-ionic contrast [23]. contrast, reducing the noise and improving an eventual
The baseline phase is the gold standard for the evaluation of CT-perfusion evaluation [37–39].
duct stones and calcifications, which are key findings for the
diagnosis of many pancreatic lesions; moreover, this scan
permits to measure the baseline Hounsfield Units (HU) Magnetic Resonance Imaging
which is useful to measure the enhancement after contrast
injection. The pancreatic arterial phase usually starts about MRI is a high-level, multiplanar, multiparametric radiologi-
35–40s after contrast injection; being the pancreas a mixed cal method with the highest tissue resolution. Despite the
exocrine-endocrine gland, the parenchyma usually shows a high cost and the presence of some well-known absolute
vivid enhancement in this phase, which permits to better contraindications (e.g., pacemaker, etc.), MRI allows to
allows hypovascular tumors detection and their local staging accurately characterize the components of a specific neo-
[24–27], with a sensitivity of 75–100% and a specificity of plasm, refining its diagnosis, accurately evaluating both the
70–100% [28]; even hypervascular tumors (e.g., pNET, renal solid components and the fluid components. Associated with
cell carcinoma metastases, etc.) or diffuse pancreatic neo- the intravenous administration of contrast agents based on
plasms (e.g., diffuse form of pancreatic lymphoma) are bet- gadolinium chelates, MRI allows to dynamically evaluate
ter detectable in this phase. Finally, the portal venous phase the enhancement of a tumor.
permits the assessment of tumor relationship with the portal The introduction of diffusion-weighted imaging (DWI)
venous system, to increase the contrast resolution between drastically improved the MRI detection performance. DWI is
abdominal organs, and to better detect eventual hepatic a method of signal contrast generation that exploits differ-
metastases and metastatic lymph nodes. ences in the Brownian motion of water molecules, allowing
CT also permits to discover eventual secondary signs of to evaluate the micro-architecture of the human tissues [40].
PDAC such as main pancreatic duct and common bile duct Nowadays, DWI represents an integral part of modern state-
dilatation or interruption (“double-duct” sign), distal atrophy of-art MRI [41, 42]. Combined with the use of hepatospe-
of the parenchyma, and morphological abnormalities of pan- cific contrast (e.g., Gd-BOPTA, Gd-EOB-DTPA), which is
creatic margins, which are essential finding to be evaluated actively captured and excreted by hepatocytes, MRI with
for the detection of isoattenuating PDAC [29, 30]; in litera- DWI is the method of choice for the study of the liver; in the
ture, the reported prevalence of secondary signs is 76% for staging of pancreatic neoplasms, this is particularly impor-
PDACs smaller than 20 mm and 99% for tumors between 21 tant for the identification of occult hepatic metastases, whose
and 30 mm [31, 32]. early detection is essential for the decision of the correct
Tumor staging is crucial for the correct management of therapeutic management [41–46]. Moreover, the new intra-
the patient; in this sense, CT is essential to define if a tumor voxel incoherent motion (IVIM) DWI enables to separate the
is primary resectable, unresectable, or suitable for a down- perfusion-from diffusion-related parameters, permitting to
differentiate pancreatic PDAC from the normal pancreas, Golden-angle Radial Sparse Parallel sequences can be
chronic pancreatitis, and pNETs with more precision [47]. applied in the post-contrast phase, obtaining a dynamic
The IVIM-derived perfusion-fraction and incoherent micro- acquisition that allows choosing the desired temporal reso-
circulation parameters may be helpful for the characteriza- lution, without artifacts. Finally, the implementation of
tion of focal pancreatic lesions, both solid and cystic, but Compressed Sensing allows the further reduction of acqui-
needs further investigation for large-scale application in sition times and motion artifacts, by combining incoherent
clinical practice [47–49]. undersampling techniques with post-acquisition balancing
MRI with cholangiopancreatography (MRCP) is the gold iterative algorithms.
standard for the characterization of pancreatic cystic tumors.
The accuracy is excellent, owing to the ability of MRI to
detect fluid contents and simultaneously evaluate the ductal Future Prospective in Pancreatic Imaging
system and the surrounding parenchyma. In particular,
MRCP accurately depicts the relationship between cystic The world of pancreatic radiology is not only evolving in
tumor and ductal system [50, 51]. terms of improvements in acquisition technologies. The use
The typical microcystic pattern of serous cystadenoma of computerized radiological image processing techniques
with multiple septa, sometimes with a central scar, is appre- makes it possible to extract more and more information from
ciable with MRI; the absence of connection with the main radiological images that are invisible to the human eye.
pancreatic duct is a key diagnostic feature to be easily dem- Through advanced Texture Analysis methods, it is possible
onstrated with MRCP. Likewise, MRI is essential to charac- to extract information with an increasing potential for use as
terize mucinous cystadenomas, with their thick enhancing a biomarker for the diagnosis, prognosis, and evaluation of
walls and their malignant potential [52–55]. MRI with the response of pancreatic neoplasms [67, 68]. The modern
MRCP can distinguish benign pancreatic cystic lesions from radiological image is digital, therefore made up of pixel
malignant ones with a sensitivity, specificity, and accuracy of matrices that are nothing more than numerical matrices.
94%, 75%, and 73–81% respectively. Furthermore, it is pos- These matrices can be described according to innumerable
sible to differentiate mucinous from non-mucinous tumors mathematical parameters of different orders, from the sim-
with a sensitivity of 91% and an accuracy of 79–82% [56– plest ones (e.g., entropy, skewness, kurtosis, etc.) to the more
59]. In particular, MRI with MRCP is the gold standard for complex ones (e.g., gray-level run-length matrix, size-zone
the evaluation of intraductal papillary mucinous neoplasms matrix, neighboring gray-level tone difference matrix, etc.)
(IPMN) arising from the epithelium of the main and/or side- [69]. All these parameters could have an important diagnos-
branch pancreatic ducts [60–62], reaching a high sensitivity, tic and prognostic significance [70]. However, research is
specificity, and accuracy (91–100%, 89%, and 90%, respec- still in its infancy in this field, first of all, requiring standard-
tively) in demonstrating the communication with the pancre- ization methods of radiological images between the various
atic duct system and in the differential diagnosis between research centers [71, 72], and then moving on to large-scale
benign and malignant behavior, slightly higher accuracy than validation and large clinical trials.
CT and similar to endoscopic retrograde cholangiopancrea- With the aid of Artificial Intelligence, trained on huge
tography, thanks to curved multiplanar post-processing shared databases, and the use of automatic or semi-automatic
reconstructions [56, 57, 63–66]. segmentation techniques, the radiologist of the future will be
Finally, thanks to technological progress, MRI is also able to benefit always more from new technologies to com-
making more and more steps in the improvement of diag- plement normal clinical activity [73].
nostic sequences that allow to shorten the duration of the We are entering the era of computer-assisted medicine,
exam and increase its accuracy. The use of post-processing and radiology is certainly one of the most thriving and
algorithms, image fusion techniques, and ultra-fast promising research fields. The role of Radiomics, which is
sequences is rapidly changing the world of modern MRI. In the science that aims to extract multiple quantitative
particular, the use of modern ultra-fast sequences further parameters from radiological images to achieve increas-
extends the indications for MRI also to non-cooperative ingly precise and less invasive diagnosis, is increasingly
patients. These sequences, based on the oversampling of promising in the clinical setting [74–78]. Radiogenomics
the central portions of the k-space in a radial scheme, is the next step to radiomics. Radiogenomics relates quan-
allow to greatly increase the signal-to-noise ratio and the titative data obtained with radiomics to tumor genomic
contrast-to-noise ratio, both in fast spin-echo and gradient- data. Radiomics and radiogenomics of the pancreas are
echo acquisitions. Oversampling also creates redundancy promising tools for the quantitative assessment of both
of information that can be compared and post-processed pancreatic neoplasms and non-neoplastic diseases, that in
by iterative algorithms, limiting motion artifacts and mak- the future can drastically revolutionize the world of radiol-
ing the sequence “motionless”. In the same way, the new ogy and medicine [74, 78].
Image Gallery
a b
c d
Fig. 1 MRI (1.5 T) of a 77-year-old female patient, occasional finding lesion. (e) Venous phase post-contrast VIBE-GRASP sequence acquired
during US of a cystic lesion of the pancreatic tail. (a, b) Axial and coro- in free-breathing in a not cooperative patient. The next-generation
nal T2-HASTE sequence; the lesion has fluid content and thickened motionless sequence made it possible to clearly visualize the hypervas-
walls, with a solid portion more represented at the distal side. (c, d) cularization of the lesion. The radiological diagnosis of cystic pNET
DWI and ADC map; diffusion restricted in the solid portion of the was then confirmed with histology (G1 pNET)
a b
Fig. 2 CT study of a 74-year-old female patient with a pancreatic splenic vein. The radiological diagnosis of high-grade pNET was con-
body-tail abdominal mass. The neoplasm presents intense enhancement firmed by 68Ga-DOTATOC PET-CT and by cytological analysis per-
in the arterial phase (a) and rapid washout in the venous phase (b, c), formed by EUS
where it is possible to appreciate the growth inside the lumen of the
b c
Fig. 3 US and MRI study (1.5 T) of a 50-year-old female patient with with small septa. (c–e) Post-contrast T1-VIBE sequences demonstrate
an occasional finding of pancreatic expansive lesions. (a) CEUS study minimal septa enhancement. (f) MRCP shows the absence of connec-
demonstrates hypovascularization of the lesion, with sharp margins and tion with the main pancreatic duct. The findings are indicative of multi-
with expansive growth, however with the presence of very fine vascu- focal serous cystadenoma. The tumor is kept in follow-up and is
larized septa. (b) T2-HASTE sequence demonstrates the presence of currently stable for 4 years
three large microcystic lesions on the head and body of the pancreas,
d e
Fig. 3 (continued)
a b
c d
Fig. 4 MRI (1.5 T) follow-up of a 77-year-old male patient previously vascularized nodules such as the previously resected original tumor. (d,
operated by splenopancreatectomy for symptomatic low-grade pNET. e) DWI and ADC map showing the presence of a nodule with marked
(a) T2-HASTE sequence showing the pancreatic residue, with the diffusion restriction, referable to local recurrence on the resection mar-
absence of clear signs of local recurrence. (b, c) arterial and venous gin, subsequently confirmed at biopsy (hypovascular recurrence of
post-contrast T1-VIBE sequence demonstrating the absence of hyper- pNET, G2)
a b
c d
Fig. 5 MRI study (1.5 T) of a 59-year-old female patient with evidence in clear communication with the pancreatic ductal system, confirmed
of pancreatic cystic formations. (a–c) T2-HASTE sequences showing with MRCP (d), and therefore compatible with IPMN without worri-
the presence of multicystic lesions to the head and tail of the pancreas, some features
a b
c d
e f
Fig. 6 CT and MRI study (3 T) of a 20-year-old patient with a painful contrast T1-VIBE sequence demonstrating enhancement of most of the
abdominal mass in the left hypochondrium. (a) CT scan showing the lesion, except for the necrotic components. The CT and MRI character-
presence of an expansive polylobulated lesion with coarse calcifica- istics, combined with the young age and sex of the patient, clearly sug-
tions. (b) T2-HASTE sequence which confirms the presence of volumi- gested the diagnosis of a pseudopapillary tumor of the pancreatic tail,
nous polylobulated expansive neoplasm of the pancreatic tail, partly which was subsequently confirmed with histology on the operative
cystic-necrotic with some fluid-fluid levels. (c, d) DWI and ADC map specimen after splenopancreatectomy
demonstrating intense restriction of diffusion of the tumor. (e, f) Post-
a b
c d
Fig. 7 50-year-old male patient arrived in the emergency room for compatible with arteriovenous malformation of the pancreas. (d, e) The
worsening abdominal pain. (a) Arterial phase of the CT scan demon- angiographic study demonstrated the presence of tangles of arteriove-
strates intense enhancement of an expansive lesion in the pancreatic nous shunts with direct drainage in the portal flow. Small intralesional
head, with no effect on vessels profile, with the presence of early venous bleeding was also recognized which was immediately embolized with
drainage in the superior mesenteric vein that runs nearby. (b) Venous coils. No massive embolization of the malformation was performed to
phase which demonstrates homogenization of the lesion. (c) Coronal avoid dangerous ischemic pancreatitis. The patient was discharged
venous phase reconstruction showing aberrant venous discharge in the asymptomatic after few days and kept in follow-up
superior mesenteric vein through a large tributary vessel. The finding is
a b
c d
e f
Fig. 8 MRI study (3 T) of a 44-year-old female patient with previous intense focal restriction of pancreatic body diffusion. (e) Post-contrast
membranous glomerulonephritis, with recent hospitalization for intense arterial T1-VIBE sequence demonstrating delayed enhancement of the
epigastric pain associated with lipase and amylase elevation. (a) arterial parenchyma. (f) MRCP showing interruption of the main pan-
T2-HASTE sequence demonstrating the presence of focal hyperinten- creatic duct, slightly dilated in the tail, with a very irregular profile. (g)
sity of the pancreatic parenchyma determining upstream dilation of the Late post-contrast T1-VIBE sequence demonstrating delayed enhance-
main pancreatic duct, without signs of chronic atrophic pancreatitis. (b) ment of the pancreatic body. The radiological diagnosis of autoimmune
Pre-contrast T1-VIBE sequence demonstrating “sausage-like” appear- focal pancreatitis was subsequently confirmed with IgG4 assay and suc-
ance of the pancreatic body with loss of spontaneous physiological cessfully treated with high-dose corticosteroids
hyperintensity of the parenchyma. (c, d) DWI and ADC maps showing
Fig. 8 (continued)
a b
c d
Fig. 9 CT and MRI study (3 T) of an 80-year-old male patient under- plasm demonstrates intense restriction of diffusion in DWI and in the
going chemotherapy for pNET G3 of the pancreatic body-tail. (a) The ADC map (e, f). (g, h) Post-contrast T1-VIBE sequences confirm what
arterial phase CT scan demonstrates the presence of hypervascularized was seen on CT. (i) At the 3-months follow-up the neoplasm progressed
tumor with calcifications that also grows inside the lumen of the splenic despite the treatment, with further intraluminal growth towards the por-
vein, reaching the spleno-mesenteric-portal confluence (b, c). The find- tal vein
ing is also confirmed in the T2-HASTE MRI sequence (d). The neo-
e f
g h
Fig. 9 (continued)
a b
c d
Fig. 10 MRI study (3 T) of a 62-year-old female patient with a previ- sequences demonstrate inhomogeneous enhancement of the neoplasm.
ous diagnosis of serous cystadenoma in follow-up. The patient is In the suspicion of malignancy, biopsy and evaluation of tumor markers
asymptomatic and comes to the specialized high-volume center to con- (elevated) have been recommended. The neoplasm is therefore resected
tinue her follow-up. (a, b) A microcystic lesion is recognized in the and the histological examination confirmed the presence of infiltrating
T2-HASTE sequence, with however the presence of unusual thickening carcinoma of the pancreas with “osteoclast-like” plurinucleate giant
of the external margins and apparent obstruction of the main pancreatic cells associated with a component of ductal adenocarcinoma both in
duct, which is initially dilated upstream. (c, d) Post-contrast T1-VIBE situ and micro-infiltrating
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Advanced Imaging of Pancreatic
Neoplasms
Nicolò Cardobi, Riccardo De Robertis,

Introduction last paragraph, we also shortly discuss the impact of

radiomics and artificial intelligence (AI) in pancreatic
Imaging has a pivotal role in pancreatic neoplasms, ranging neoplasms evaluation.
from diagnosis to treatment monitoring. It is crucial, espe-
cially for pancreatic ductal adenocarcinoma (PDAC), to
obtain an early diagnosis since the therapeutic approach is Computed Tomography
mainly surgical and may be curative only in early-stage dis-
ease. For this reason, every advance in imaging should be Multidetector CT vs Dual-Energy CT
evaluated and tested to produce a step forward in lesion
identification. Computed tomography is still considered the primary imag-
On the other hand, once detected a pancreatic neo- ing modality to evaluate pancreatic neoplasms, especially
plasm, the role of imaging is not over. Radiologists have the solid ones. There are two acquisition techniques: multi-
to formulate a diagnostic hypothesis to select patients, detector CT (MDCT) and dual-energy CT (either dual-tube,
together with pancreatic surgeons and clinicians, that dual-current, or single-tube with rapid switching current
may require immediate surgical evaluation from those configuration, DECT). DECT provides the possibility to per-
who may be inserted in a follow-up evaluation. form virtual non-contrast imaging, which demonstrated to be
Moreover, radiologists should be as precise as possible almost as effective as traditional non-contrast acquisition,
in some parameters evaluation, such as vascular inva- together with associated dose reduction [1]. In the detection
sion in PDAC, which may have surgical and prognostic of solid lesions, DECT is superior to MDCT due to the pos-
drawbacks. On these bases, better and advanced imag- sibility of generating iodine map (Fig. 1) and the low kilo-
ing may optimize radiologists’ workflow and introduce electronvolt (KeV) monochromatic images. These images
new quantitative parameters, which may lead to a step are generated as if acquired at around 55 KeV [2] (or 40–50
forward in the radiological diagnosis of pancreatic neo- KeV with a noise-optimized algorithm [3]), which improves
plasms. This chapter briefly analyses and reports most the contrast-to-noise (CNR) ratio since the iodine k-edge is
of the advances in imaging, focusing on computed around 33 KeV.
tomography (CT) and magnetic resonance (MR). In the This translates into greater lesions conspicuity, it is par-
ticularly useful in small iso-attenuating pancreatic adenocar-
cinoma [4–7]. The low KeV images of DECT were also
N. Cardobi (*) useful in evaluating vascular invasion in the presurgical stag-
Radiology, Ospedale Maggiore, Verona, Italy ing of PDAC [8].
R. De Robertis · M. D’Onofrio DECT was also useful in small atypical and iso-attenuating
Radiology, University Hospital Policlinico GB Rossi, Verona, Italy pancreatic neuroendocrine tumours (PNETs) [9, 10].
482 N. Cardobi et al.
a b
c d
Fig. 1 Pancreatic head mass consistent with PDAC (arrowhead). the mass and normal pancreas (asterisk). The encasement of the pancre-
Delayed arterial phase (a) demonstrates the slight density difference aticoduodenal artery is also more evident than in (a). Venous iodine
between the mass and the normal pancreas (asterisk). In the venous map superimposed on standard CT scan (d) shows the progressive
phase (b), there is contact with the superior mesenteric vein (SMV, uptake of iodine by the mass, albeit still lower than the normal pan-
short arrow). The delayed arterial iodine map superimposed on standard creas. Partial involvement of SMV is still evident (short arrow)
CT scan (c) shows the marked differences in iodine distribution between
Moreover, PNETs and, in particular, insulinomas are better map evaluation [11, 12]. Moreover, DECT showed signifi-
visualized in iodine maps, which improve the detection rate cantly higher attenuation values and iodine concentration in
of this kind of lesion from 68.8% to 95.7% [9] (Fig. 2). mucinous cystic neoplasm (MCN) compared to olygocystic
About cystic lesions, DECT demonstrated to be useful in serous cystadenoma (SCA) [11], albeit it is reported that
differentiating between high attenuating cystic lesions from additional information provided by DECT did not improve
solid lesions, from different attenuating curves and iodine diagnostic performance [13].
Advanced Imaging of Pancreatic Neoplasms 483
a b
Fig. 2 Aorta normalized delayed arterial phase iodine map superim- The post-contrast MRI T1 VIBE Dixon acquisition (b) confirms the
posed on normal CT scan (a) shows a small rounded hypervascular lesion (arrow), although it appears almost isointense to normal pancre-
mass of the head of the pancreas, represented by an insulinoma (arrow). atic parenchyma
CT Perfusion iodine map may replace conventional CT perfusion, allow-

ing a dose reduction [23].
CT perfusion is a technique that allows functional evaluation
of tissue vascularization. With this technique is possible to
measure temporal density change on a target tissue after con- Magnetic Resonance
trast agent administration. A series of dynamic CT
acquisitions on the target organ allows to compute the tissue MRI is considered the first-choice imaging modality in cys-
time attenuation curve (TAC) and other parameters [14–16]. tic pancreatic neoplasms evaluation [24]. However, it retains
CT perfusion demonstrated to be useful in pancreatic neo- a diagnostic accuracy comparable with CT in local staging of
plasms, particularly in PNETs. PNETs are highly vascular PDAC [25, 26]. MRI is superior to MDCT in detecting of
neoplasms, usually even more than pancreatic parenchyma, PDAC liver metastasis, using a gadoxetic acid contrast agent
so their blood flow and blood volume much more than nor- [27]. MRI, with the use of diffusion-weighted imaging
mal pancreas [17]. A typical perfusion TAC with a fast wash- (DWI), is also useful in the detection of small pancreatic
in followed by a wash-out retains 100% sensitivity, 98.3% neuroendocrine tumours (PNETs) [28, 29] thus, it may be
specificity, 75% PPV and 100% NPV in diagnosing PNETs considered complementary to CT examination also in vari-
[18]. PNETs blood flow, measured by CT perfusion, was ous solid pancreatic neoplasms.
also significantly correlated with microvascular density Compared to CT, MRI acquisition time is longer, and it is
(MVD). The MVD is an important factor to consider in easier to experiment motion and or respiratory artefacts.
the case of anti-angiogenetic drug administration. A post- Moreover, despite higher contrast resolution than CT, MR
therapy decrease in blood flow in neuroendocrine liver imaging is usually acquired at lower spatial resolution.
metastasis was observed, compared with baseline, with Below we briefly discuss advanced MR imaging techniques
a persistent reduction over time [19, 20]. to obtain more accurate and consistent imaging and to intro-
Recently, some authors evaluated the combination of duce new parameters in the evaluation of pancreatic
DECT and perfusion focusing on pancreatic neoplasms. neoplasms.
Skornitzke et al. evaluated the utility of virtual low KeV per-
fusions in pancreatic cancer compared to traditional 80kVp
perfusion. The low-energy virtual monoenergetic perfusion T2-Weighted Imaging (T2WI)
improved the robustness and quality of quantitative measure-
ments, despite an increased patient dose [21]. Time-resolved Non-cartesian T2WI
DECT iodine map may also be used as a substitute for con- Usually, T2WI of the upper abdomen is performed with fast
ventional 80 kVp perfusion in pancreatic carcinoma. The dif- spin-echo sequences, either in breath-hold or with navigator/
ference in blood flow measured by the two techniques is respiratory trigger. Recently, a different type of T2WI has
negligible, but with an increased dose also in this case [22]. been introduced. This imaging is based on a different k-space-
However, since iodine concentration has a moderate positive filling method, namely non-Cartesian or radial [30]. The
correlation with blood flow and blood volume, a single sequences are named differently according to vendors,
respectively BLADE in Siemens, PROPELLER in GE, This kind of sequence, originally applied to DWI [36], allows
MultiVane in Philips, RADAR in Hitachi and JET in Canon. the acquisition of sub millimetric T2WI of the pancreatic
The non-Cartesian T2WI could reduce respiratory, peristalsis gland to highlight and study IPMN and its eventual MPD
and pulsation artefacts. Moreover, there was a significantly connection (Fig. 3).
better depiction of pancreas margins [31, 32]. These kinds of
sequences may come at the cost of increased acquisition time rtificial Intelligence Enhanced T2WI
A
and with the introduction of radial streak artefact [30, 33, 34]. To reduce noise and motion artefacts recently, an artificial
intelligence (AI) approach was proposed in upper abdominal
educe Field of View Imaging
R T2WI. Herrmann et al. investigate the use of single breath-
In the differential diagnosis of the cystic pancreatic lesion, it hold deep learning (DL) half-Fourier single-shot turbo spin
is useful to evaluate the presence or the absence of commu- echo (HASTE) compared to BLADE and conventional respi-
nication of cystic lesion with the main pancreatic duct ratory triggered HASTE. DL accelerated HASTE was supe-
(MPD). The communication with MPD allows the distinc- rior to conventional HASTE and non-inferior to BLADE in
tion between IPMN from other cystic lesions. MRCP acqui- lesion detectability and characterization, referring to
sition has a high sensitivity in main pancreatic duct the liver. Moreover, there was a significant reduction of
communication, ranging from 91.4% to 100% [35]. Despite acquisition time, respectively 2:30–6:00 min for BLADE,
this high sensitivity, some cysts may not exhibit clear com- 1:28–1:44 min for conventional HASTE and 16 s for DL
munication with MPD. To overcome this limitation, with 3D accelerated HASTE [37]. However, this paper focused on
MRCP, T2-weighted reduced FOV imaging may be applied. the liver and more evaluation on pancreas imaging is needed.
a b c
Fig. 3 Fat suppressed reduce FOV T2WI (a, b, c), 0.8 mm in-plane resolution, 2.5 mm slice thickness. MPD is shown by the long arrow, while
the short arrow highlights the communication with branch duct IPMN. The communication was also evident in MRCP (d, arrowhead)
1-Weighted Imaging (T1WI) and Dynamic

T which is sensitive to B0 and B1 magnetic field inhomogene-
Contrast-Enhanced Imaging (DCE) ity and thus prone to heterogeneous fat saturation [41].
Another fat saturation approach can be used in upper
Fat Saturation Techniques abdominal MRI only in recent years, the Dixon technique.
Normal pancreas has a low T1 relaxation time, lower than Dixon described this technique in 1984, and it is based on
other abdominal organs. As a consequence, pancreas has a chemical shift method [42, 43]. For this reason, it is rela-
high signal intensity in T1WI. The low T1 relaxation time is tively insensitive to B1 field inhomogeneities. Dixon-
due to a large quantity of protein and endoplasmic reticulum based T1WI improves fat suppression and reduces scan
in acinar cells and a high quantity of paramagnetic ions such time in pancreatic imaging [44]. Moreover, the Dixon
as manganese [38–40]. Every focal and diffuse pancreatic technique allows, in a single sequence, the acquisition of
disease increase T1 relaxation time and decrease T1WI pan- the in-phase, out-of-phase, fat and water sat imaging [45].
creatic signal intensity. While the acquisition of in-phase and out-of-phase imag-
Since also abdominal fat is bright in T1WI, fat suppres- ing eliminates the need for a dedicated sequence, the water
sion is mandatory to better delineate pancreatic margins. suppression images may be useful in fat-containing lesions
This is usually obtained using spectral fat saturation, (Fig. 4).
a b
c d
Fig. 4 T1 Dixon imaging, fat only (a), water only (b), in-phase (c) and demonstrating a fat-containing lesion. Fat continent was also confirmed
out of phase (d) respectively. Pancreatic head sharply rounded hypoin- by hypointensity in out-of-phase image
tense mass in the fat only image is hyperintense in water only image,
a b
c d
Fig. 5 Pre (a) and post (c) contrast breath hold VIBE Dixon, compared intra-pancreatic choledochal dilation is present (arrow). This is sus-
to pre (b) and post (b) contrast GRASP VIBE acquisition. In a and c, tained by a vascularized wall thickening of the distal common bile duct,
there are a lot of respiratory artefacts. In b, the image is artefact free and represented by neoplasia (d, arrowhead)
espiratory Artefact Reduction

R sity) and quantitative parameters like volume transfer con-
T1WI is generally acquired in breath hold. Despite rapid stant (KTrans), volume of extravascular extracellular space
acquisition time (below 20 s), this may lead to a respiratory (ve), volume of blood plasma (vp) and rate constant (kep).
artefact. To overcome this limitation, recently, a non- Both qualitative and quantitative parameters were useful in
cartesian T1WI approach has been developed. These order to improve diagnosis confidence between normal pan-
sequences, acquired in free breathing, reduce motion and creas, PDAC and PNET [50]. KTrans and kep were useful in
respiratory artefacts, improve image quality and, together PNET grading, especially G1 vs G2 PNET [51]. Finally,
with compressed sensing techniques, reduce acquisition time considering therapy response evaluation, KTrans was found to
[34, 46–49] (Fig. 5). be higher in responders to gemcitabine-based chemotherapy
Compressed sensing acquisition (CS), together with inco- in advance PDAC after chemotherapy [52]. Moreover, KTrans
herent radial sub-sampling of k-space, enabled the free- and kep were found to be lower in pancreatic adenocarci-
breathing acquisition of high temporal resolution noma compared to the normal pancreas and it showed a
post-contrast imaging, which may be useful in hypervascular negative correlation with tumour fibrosis [53].
pancreatic neoplasm (Fig. 6).
ancreatic Neoplasia MRI Perfusion

P Diffusion-Weighted Imaging (DWI)
Like CT, it is possible to estimate perfusion parameters in
MRI. It is usually done by the repetition of T1WI at short usion Between T2WI and DWI
F
intervals focused on the pancreas. This results in the estima- Since DWI is low-resolution functional imaging based on
tion of semiquantitative parameters extracted from the time/ the Brownian motion of water molecules, it may be useful to
signal intensity curve (e.g. slope, maximum signal inten- merge functional information with higher resolution anatom-
a b c
d e
Fig. 6 Pancreatic tail cystic mass in T2WI (a), DWI b800 (b) and ADC as demonstrated by time to signal intensity curves (e, purple curve nor-
map (c). The cystic mass has thickened vascularized and asymmetric mal pancreas, yellow curve cystic wall). The histopathological exam
walls. ROIs are placed on the normal pancreas (d, purple) and cystic reveals a cystic neuroendocrine tumour
wall (d, yellow). The walls are more vascularized than normal pancreas,
ical T2WI. The imaging fusion was found to be useful by Computed DWI
Brenner et al., which investigated the impact of fusion imag- In normal diagnostic settings, DWI is associated with the
ing in PNET. Both readers found a significantly better detec- calculation of the apparent diffusion coefficient (ADC) map.
tion score in fusion imaging, with a better inter-reader This map assumed a mono-exponential diffusion model, in
agreement [54] (Fig. 7). which the signal decay linearly increases with the b-value.
a b
Fig. 7 Multiple PNETs in a patient with Von Hippel Lindau Syndrome. In a and b, axial DWI b800 superimposed to axial T2WI there are pan-
creatic tail and head small PNETs (arrows), with high DWI signal intensity. Multiple liver metastases are also evident (a, circles)
a b
c d
Fig. 8 DWI b = 800 s/mm2 (a), computed DWI b = 1200 s/mm2(b), (arrows). The computed DWI b = 1200 s/mm2 (b), compared to DWI
ADC map (c) and post-contrast T1 VIBE Dixon. A small, sharply b = 800 s/mm2 (a), demonstrates a slightly higher signal intensity of the
rounded mass of the pancreatic head consistent with PNET is evident mass
The slope of the line represented the ADC value. Since this superior to acquired b 1000 s/mm2 and effective as acquired
linear correlation between signal intensity and b-values, it is b 1500 s/mm2, with a substantial reduction of acquisition
possible to plot signal intensity at arbitrary b-values [55]. In time. Similar results may also be obtained in the evaluation
PDAC, a computed b-value of 1500 s/mm2 was found to be of PNETs (Fig. 8).
imultaneous Multi-Slice (SMS) Acquisition

S approach. However, a reduction in acquisition time may be
DWI of the upper abdomen is acquired with Echo Planar obtained with a lower spatial resolution (and thus higher
Imaging (EPI) technique. For the pancreas, despite different SNR), lower number of slices (i.e. focusing only on lesion)
hardware compositions and sequence implementation by and with sequence optimizations, like SMS acquisition [67].
different vendors, Barral et al. [56] reported general recom- Both mono-exponential and bi-exponential models
mendations about acquisition parameters. The increasing assume that the moving water molecules follow a Gaussian
scanner performance and the wider application of parallel or normal distribution. While this assumption may be true
imaging led to the introduction of SMS acquisition. In this for pure water, it is probably not suitable for biological tis-
sequence, more than one slice is simultaneously excited, sues, where complex structures such as cell membranes act
leading to an acceleration factor equal to the slices exited as a barrier to the diffusion of water molecules [68, 69]. This
[57–59]. SMS-DWI delivered a higher signal-to-noise ratio is responsible for a non-Gaussian distribution of water mol-
normalized to time unit than normal DWI-EPI acquisition, ecule movements, and this is more evident at high b-values
which may be used to acquire more or thinner slices [60]. (above 2000 mm/s2) and longer echo time [68]. At 3.0 Tesla,
An SMS factor of 2 was the best balance between acquisi- the acquisition of 4 b-values (0, 500, 1500 and 2000 mm/s2)
tion time and image quality. Moreover, lower ADC values was suggested, with no influence in DKI parameters calcula-
for SMS acquisition should be considered in a quantitative tion compared to 7 b-values sequences, thus reducing acqui-
DWI evaluation [61]. sition time [70]. There are a small number of papers regarding
DKI parameters and pancreatic cancer; however, these
I ntra-Voxel Incoherent Motion (IVIM) parameters may be useful in differentiating tumours from
and Diffusion Kurtosis Imaging (DKI) non-tumours tissue in PDAC [71, 72].
In normal diagnostic workflow, with the calculation of ADC
map, we assume a mono-exponential decay of the signal
increasing b-values. However, in normal tissue, the water Magnetic Resonance
molecular diffusion is also influenced by micro circulations, Cholangiopancreatography (MRCP)
which introduce fast-moving protons in voxels. Since these
protons have no specific orientation, they contribute to MRCP is a useful complementary sequence to evaluate cys-
pseudo diffusion (D*). At high b values, over 200 mm2/s, the tic pancreatic lesions, especially to discriminate whether a
signal of these protons becomes insignificant because flow- pancreatic cyst is communicating or not with the main pan-
ing blood protons cover a much greater distance than the pro- creatic duct. Initially, the MRCP acquisition was bidimen-
tons outside the vessels, so the signal decay at increasing sional, acquired in a single shot and during a breath hold. To
b-values is far more accentuated. For this reason, for date, there is the possibility to acquire 3D MRCP images.
b > 200 mm2/s, the signal of protons outside vessels becomes However, if done with a respiratory triggering technique, it is
more evident, called diffusion (D). To fit this model, a differ- a time-consuming approach. With the advent of the CS tech-
ent mathematical approach is required, which was described nique, it is now possible to acquire high-resolution, high-
in 1988 by Le Bihan [62]. This bi-exponential model quality 3D MRCP in a single breath hold superior to
included the D, D* and perfusion fraction (f). So, through a single-shot 2D acquisition [73–76].
diffusion sequence, it is possible to estimate perfusion
derived parameters.
Focusing on perfusion fraction parameters, it was found adiomics and Artificial Intelligence Applied
R
to be reliable in the distinction between PDAC and normal to Pancreatic Neoplasm
pancreatic tissue [63]. Regarding the characterization of pan-
creatic lesions, De Robertis et al. found a higher perfusion From some years by now, radiology images are not consid-
fraction in autoimmune pancreatitis (AIP) compared to ered only pictures, but also as data. Every pixel/voxel, and
PDAC and a higher D* and f in AIP compared to PNET [64]. the relationships between their neighbouring pixels/voxels,
The low perfusion fraction of PDAC was also reported by may be represented as a number and used as data to extract
Concia et al., probably reflecting the high fibrous content of several features of a given region of interest (ROI) [77, 78].
this kind of tumour and its low vascularization [65]. IVIM- This approach is called generically radiomics and has
derived parameters may also be useful for therapy monitor- been demonstrated to be promising applied to both focal and
ing. Klauß et al. found f parameter modification during diffuse pancreatic pathologies [79]. Most of the papers focus
steroid treatment of AIP wich may serve as an imaging bio- on CT and MRI and solid focal lesions. In particular,
marker in therapy monitoring of AIP [66]. radiomics was found to be useful to distinguish PDAC from
Since the optimal model fit requires multiple b-values PNET [80–82], to stratify PNET grade [83–87] and to pre-
acquisitions (usually more than 10), it is a time-consuming dict prognosis in both resectable [88–91] and unresectable
PDAC [92, 93]. Radiomics was also applied to cystic pancre- nificantly increases lesion contrast. Clin Radiol. 2013; https://doi.
org/10.1016/j.crad.2012.06.108.
atic lesions, in particular to distinguish serous cystadenoma
5. Macari M, et al. Dual-source dual-energy MDCT of pancre-
from non-serous cystadenoma [94], SCA from MCA [95] atic adenocarcinoma: initial observations with data generated
and to distinguish low to high-grade IPMN [96]. at 80 kVp and at simulated weighted- average 120 kVp. Am J
About AI, there is growing attention in the literature about Roentgenol. 2010; https://doi.org/10.2214/AJR.09.2737.
6. McNamara MM, et al. Multireader evaluation of lesion con-
this topic applied to Pancreas imaging. AI-driven approaches
spicuity in small pancreatic adenocarcinomas: complimen-
are mainly oriented in the following topics: segmentation, tary value of iodine material density and low keV simulated
detection/classification and risk stratification. monoenergetic images using multiphasic rapid kVp-switching
There are several papers about pancreas segmentation dual energy CT. Abdom Imaging. 2015; https://doi.org/10.1007/
s00261-014-0274-y.
in both CT and MRI. The performance of this kind of
7. Li HO, et al. Assessment of pancreatic adenocarcinoma: use of
algorithm is rather good, with a Dice Sorensen coeffi- low-dose whole pancreatic CT perfusion and individualized dual-
cient (DCS) [97] in the range between 0.76 and 0.88 [98– energy CT scanning. J Med Imaging Radiat Oncol. 2015; https://
101]. AI-driven approach is usually less time-consuming doi.org/10.1111/1754-9485.12342.
8. Yu Y, Guo M, Han X. Comparison of multi-slice computed tomo-
than manual and semi-automatic approaches. Boers et al.
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Elastography and New Ultrasound
Techniques
Christoph F. Dietrich, Adrian Saftiou, Michael Hocke,

and Liliana Chiorean
Introduction promising results for the differential diagnosis of thyroid

nodules [21–29], pancreatic masses [7, 11, 12, 30, 31],
Elastography is a newly developed ultrasound (US) tech- chronic pancreatitis features [7, 32, 33], prostate cancer [34],
nique, the imaging equivalent of manual palpation intro- and lymph node assessment [35–39].
duced to medicine in ancient times by Hippocrates and others Because elastography is an imaging method that is per-
[1–3]. Elastography is able to provide additional clinically formed in real time during US examination (either using a
useful information based on tissue stiffness estimation. Since transcutaneous approach, or via an echoendoscope), it gives
many diseases induce changes in affected tissues stiffness, immediate information that can further influence patient
elastography is able to enhance their detection by providing management. This represents one of its most significant
differentiation between normal and diseased tissues and fur- advantages [40].
ther complementary characterization [4–6]. As a non- More recently, elastography has been also introduced to
invasive technique, US elastography complements endoscopic ultrasound (EUS) examinations [12, 41–54]. It
conventional US with minimal prolongation of the examina- brings an aid to the differential diagnosis between benign
tion time and minimal cost [7–9]. and malignant masses to one of the best diagnostic tools for
During the last years, many studies have assessed the assessment of the digestive tract and surrounding organs,
clinical value of US elastography in different clinical appli- which is EUS [38, 55].
cations. Information related to tissue stiffness obtained by
using elastography techniques may reflect histopathological
differences between normal and diseased tissues [10–12]. It Techniques, Methods, and Approaches
has been already proven to bring valuable information in
applications such as breast cancer diagnosis [13–15] and Various techniques for imaging tissue elasticity have been
assessment of liver fibrosis [16–20]. Also, it has shown investigated since the early 1990s. EFSUMB has prepared
recommendations on the use of elastography [3, 6] and the
techniques are gaining acceptance for many clinical applica-
tions [9, 47, 56–60].
Elastography techniques are largely separated into two
C. F. Dietrich (*)
main groups, strain elastography and shear-wave velocity
Department Allgemeine Innere Medizin (DAIM), Hirslanden Bern
Kliniken Beau Site, Salem und Permanence, Bern, Switzerland measurements. The qualitative one, called strain elastogra-
phy (SE), is based on tissues’ mechanical response to an
A. Saftiou
Department of Gastroenterology, Research Center of externally or internally generated force. The quantitative
Gastroenterology and Hepatology, Craiova, Romania one, called shear wave elastography (SWE), is based on
Gastrointestinal Unit, Department of Endoscopy, Copenhagen measurements of shear waves’ velocities generated by a
University Hospital, Herlev, Denmark “push-pulse” of low-frequency [4, 39, 47]. Both SE and
M. Hocke SWE are evaluating tissue stiffness, but the principles used
Helios Hospital Meiningen, Meiningen, Germany by each one of the methods are different, and so are their
L. Chiorean clinical applications [56].
Département d’imagerie médicale, Annonay, France
496 C. F. Dietrich et al.
Basic Principles of Elastography are displayed at frame rates up to the ultrasound frame rate,
the need to average over many frames while moving the tis-
As an imaging equivalent of manual palpation, elastography sue means that strain imaging is not as suitable as real-time
is able to give access to more deeply located masses not ultrasonography for observing tissue motion or for rapidly
available for clinical evaluation and more, it can exceed the exploring a volume. The latter problem may be solved by 3D
subjectivity of the physical exam [3]. It follows the supposi- elastography [3].
tion that, under compression, harder parts of the tissues The strain ratio is a way to semi-quantify the information
deform less than softer parts do, so the degree of deformation by computing the ratio of the strain from within the region of
is an indicator of tissues stiffness [10, 58, 59, 61]. Since dis- interest (ROI) to that of the normal surrounding tissues, at
eased tissues are most frequently associated with an increase the same depth. It is the measure of relative stiffness, the
in their consistency/stiffness, by means of elastography we absolute tissue stiffness being unknown [32, 55, 64–67].
can objectively differentiate between normal (softer) and
diseased (harder) tissues, being also able to quantify the stiff-
ness of a lesion [62]. Region of Interest
The area to be evaluated is defined by an ROI, in a similar

train Elastography (Quasi-Static Strain
S way to Doppler examination [40]. The necessary pressure
Imaging) can be applied by manipulating the probe, though very little
additional pressure is required as the forces from the pulsa-
With the SE technique, the operator manually exerts com- tion of adjacent vessels are usually sufficient [64]. The elas-
pression of the assessed tissues via the ultrasound transducer ticity ROI must be sufficiently large to encompass also the
or internal physiological movements such as heartbeats are lesion and enough surrounding normal tissue for compari-
used as compression generating forces. Pre- and post- son, ideally containing equal amounts of each. Comparing
compression data are then compared to measure tissues dis- two different tissues within the elasticity ROI (e.g. a focal
placement, from which a strain image is derived and pancreatic lesion and adjacent pancreatic parenchyma)
displayed as a cultured map. The generated map is superim- allows calculation of the strain ratio. New technical develop-
posed over the conventional sonographic image, in the same ments allow for averaging over several frames to calculate
way we are used with Doppler examination [63]. In quasi- the mean histogram value, which corresponds to the overall
static strain imaging, axial and lateral tracking is typically strain within a selected area.
applied between each pair of RF-echo frames and the lateral
displacements are discarded leaving a sequence of axial dis-
placement images. Each axial displacement image is then How to Achieve the Best Image Quality
converted to a strain image by passing a moving-window for Elastography?
(the strain estimator window) down each image line, to cal-
culate the local axial gradient of displacement at each win- Favorable conditions for obtaining good quasi-static strain
dow position. The size of the strain-estimating window is images representing tissue elasticity include [57, 68]:
chosen as a compromise between strain image resolution
(small window) and good strain signal-to-noise ratio • Close proximity of the target area to the transducer
(SNR = the ratio of mean strain to standard deviation of (<3–4 cm).
strain for an elastically homogeneous region). A high level of • No or minimal pre-compression.
persistence (time integration) is generally applied to strain • Surrounding homogeneous tissue (e.g., liver).
images to improve their SNR. The transducer may alterna- • Equivalence of region of interest and surrounding tissue.
tively be held stationary to image strain generated by internal • Little mobility of examined organs.
physiological pulsations (e.g., cardiovascular, respiratory) or • No structures present that would damp the shear stress
muscular contractions. However, when this is done, in gen- (e.g., large veins).
eral the origin and direction of the stress are unknown; there- • A broad stress source (in 2D) relative to the width of the
fore, only the axial component of displacement and strain are imaged region.
measured. There are also likely to be more sources of de- • Knowing the position of the stress source relative to the
correlation noise than when a simple uniaxial stress is imaged region.
applied by moving the transducer. Although strain images • A limited number of diagnostic targets.
Elastography and New Ultrasound Techniques 497
Shear Wave Elastography Safety Considerations
Shear wave elastography has been also introduced in clinical Quasi-static strain imaging and shear wave methods based
use mainly for the liver [20, 69]. Techniques used are sum- on force applied by dynamic surface displacement have
marized as follows (for more details refer to the EFSUMB identical ultrasound safety considerations to conventional
guidelines) [3, 6]: ultrasound imaging modes. Radiation force-based elastogra-
phy operates with higher TI but assured to be within
1. Acoustic radiation force impulse imaging (ARFI): imag- American Institute of Ultrasound in Medicine (AIUM) limits
ing tissue displacement induced by radiation force. and thus, the safety considerations are similar to Doppler
2. Transient elastography (TE): shear-wave speed measure- mode, i.e., normal due diligence should be employed con-
ment using a surface impulse. cerning sensitive tissues such as the eye and fetus, and when
3. Point shear wave elastography (pSWE): shear-wave bone may be present in the pushing beam [3].
speed measurement at a location using acoustic radiation
force.
4. Shear wave elastography: shear-wave speed imaging Limitations
(SWE, 2D SWE or 3D SWE) using acoustic radiation
force [3, 6]. Elastography techniques have several limitations that
include: high selection bias of the still image and lack of
For SWE, operator’s dependence is small although care is reproducibility in some cases, limited depth of penetration,
needed to minimize probe pressure and the level of pre- irregular (and especially excessive) application of pressure,
compression when imaging superficial tissues. This is impor- inadequate representation of the surrounding tissue struc-
tant in order to avoid a high shear-wave speed artifact near tures (vessels, fluid lesions including cysts, bone structures,
the surface plane due to localized pre-stress which would etc.), and insufficient contrast between the elastic properties
cause the superficial tissue to stiffen due to its nonlinear of the tissues [40]. Qualitative strain methods are limited
stress-strain character [3]. because they are displaying the relative elasticity from the
“Simple shear” results from a simple shearing force such sampled area, not giving an absolute scale of tissue stiffness
as that applied to displace a single location on or within the [71]. In addition, both qualitative and semi-quantitative
body—an object of square cross-section (dashed outline) is approaches of EUS elastography are associated with intra-
deformed to one that has a trapezoid cross-section (solid out- and inter-observer variability, because only relative values
line) without a change in its volume [3]. are measured and visualized through EUS elastography tech-
niques [9, 46]. Despite the subjectivity of the image acquisi-
tion and interpretation, good inter-observer results have been
Acoustic Radiation Force Impulse (ARFI) reported [76].
Acoustic radiation force impulse (ARFI) imaging is a shear

wave velocity measurement technology that utilizes sound Clinical Applications
waves to interrogate the mechanical stiffness properties of
tissues, without the need of an external compression [70, 71]. Introduction Into the Pancreas
ARFI elastography is integrated into an ultrasound machine
and can be performed with a conventional ultrasound probe The internal structure of the smoothly contoured organ in
during routine ultrasound examination [72]. Moreover, the young people is uniformly hypoechoic, finely granular, with
stiffness is measurable quantitatively wherever the ROI has similar ultrasound characteristics to the liver parenchyma.
been set [73]. The pancreas is mobile [77, 78]. Embryologically, the pan-
Briefly, an acoustic push pulse transmitted by the trans- creas develops from two primordia: the dorsal and the ven-
ducer through the tissue induces an elastic shear wave that tral. The latter can rise above the surrounding tissues as a
propagates through the tissues. This is followed by detection band-shaped hypoechoic structure and should not be con-
pulses that are used to measure the velocity of the shear wave fused with local inflammation, nor with a tumor. Its appear-
propagation. The velocity is expressed in meters per second ance on real-time elastography during endoscopic ultrasound
(m/s). The tissue elasticity is proportional to the square value (EUS) examinations is homogenously soft as compared to
of the shear wave velocity (SWV) [74, 75]. surrounding tissues. With advancing age, pancreatic
echogenicity increases significantly, because of fat and con- difference in the elasticity of the pancreas between healthy
nective tissue deposits. Consequently, the elastogram volunteers (HVs) and patients with definite CP is the first
becomes more heterogeneous. Depending on its fat content step to further studies. The elasticity of the pancreas mea-
and its demarcation against the surrounding connective and sured by ARFI has been shown to be higher in patients with
fatty tissues, the contour appears smooth or ill defined, some- CP as compared to the values obtained in HVs. The ARFI
times coarsely lobulated. Visualization of the outer boundar- measurements were noninvasive and reproducible [81].
ies is improved with elastography as compared to D’Onofrio et al. assessed the utility of ARFI ultrasound
conventional B-mode sonography. This is especially true in imaging in the evaluation of cystic pancreatic lesions as
early chronic pancreatitis with a honeycomb appearance [46, compared to phantom fluid models. They found that the tech-
77, 78]. nique might potentially be able to differentiate mucinous
Endosonography, in particular when combined with elas- from serous cysts if a quantification tool named Virtual
tography, is the procedure with the highest sensitivity for Touch is used. Thus, by means of a non-invasive method, the
detecting even very small pancreatic masses. In addition, the analysis of the fluid content of the pancreatic cystic lesion
method is helpful in staging pancreatic cancer and for guid- can be further characterized [82]. The study of Galotti et al.
ing biopsy to obtain samples for cytological or histological investigated the same Virtual Touch imaging procedure in
diagnosis [9, 46]. The method has been proven useful in the order to define normal values of shear wave speed for the
differential diagnosis of pancreatic tumors, and also in healthy pancreas, and for other healthy organs as well (liver,
chronic pancreatitis [6]. EUS allows the detection of very gallbladder, spleen, and kidneys). The method provided
small focal pancreatic lesions (Fig. 1). numerical measurements of tissue stiffness. The pancreas
had the lowest mean shear wave speed value as compared to
the liver and the kidney, while the highest value was obtained
Introduction into Pancreatic Elastography in normal splenic parenchyma [83].
The main purpose of pancreatic elastography is to clarify the

natural course of chronic pancreatitis (CP) by determining Endoscopic Ultrasound (EUS) Elastography
fibrotic changes within the pancreas, in a way that is similar
to detecting those changes in the liver. Although CP is one of EUS is currently the main imaging method for the diagnosis
the risk factors for pancreatic cancer, it has not yet been and staging of pancreato-biliary diseases. It is one of the
shown whether the development of this cancer is related to most accurate techniques for both inflammatory, as well as
the degree of pancreatic fibrosis, or whether any kind of for neoplastic pancreatic diseases [40, 55, 84–86].
endoscopic or medical intervention may delay the fibrotic Differentiation between inflammatory-related changes in
changes in the pancreas. Confirmation of a significant chronic pancreatitis and neoplastic changes in pancreatic
cancer remains challenging, requiring EUS–FNA to assure a
high overall diagnostic accuracy [30, 87–90].
EUS elastography is used for the in vivo characterization
of stiffness of pancreatic lesions and gastrointestinal wall
layers (especially in the anorectum). Solid tumors located
within or near the gastrointestinal tract can be visualized and
further characterized by this technique [7]. Though the tech-
nology needs further refinement, initial reports are demon-
strating proof-of-principle for the evaluation and staging of
subepithelial and epithelial gastrointestinal tumors. Only
strain elastography is currently available for EUS and it can
be used with longitudinal and radial echo-endoscopes, the
former having the advantage that suspicious regions can be
biopsied under direct visualization.
Interpretation
Fig. 1 B-mode imaging. Wirsungianus duct infiltration as a sign of
SE allows visualization of relative stiffness differences
malignancy. Dilation of the pancreatic duct without symptoms and an
identifiable pancreatic mass can precede the diagnosis of pancreatic between the tissues included in the assessed ROI.
cancer by several months [79, 80] Interobserver variability has been shown to be small for
qualitative or semi-quantitative elastographic characteriza- ROI (e.g., a pancreatic mass and adjacent pancreatic paren-
tion of solid pancreatic lesions. Nevertheless, more conflict- chyma) and facilitates calculation of a strain ratio between a
ing results were obtained for lymph nodes [38]. suspicious mass lesion and reference surrounding tissue
[55]. Another approach has been used to calculate the mean
hue histogram (strain histogram) value, which describes the
Limitations and Artifacts global tissue elasticity within a selected area inside the elas-
tography ROI [19]. Neither strain ratio nor strain histograms
A number of technical factors specific for EUS may adversely report absolute values; therefore, the method is better called
influence also the elastographic assessment in clinical prac- semi-quantitative instead of quantitative. The histogram
tice. The small size and penetration depth of EUS transduc- reports the values inside of a smaller ROI, i.e., the tumor
ers limits the applicability of EUS elastography for mass, but elastography calculations are still relative in the
characterizing large and deep-seated lesions. If the ROI is whole ROI area of elastography. New technical develop-
too small to adequately represent the tissue surrounding the ments allow averaging over several frames, in an attempt to
lesion or if there is size discrepancy between the lesion and minimize the bias derived from user-selection of the best
the ROI including surrounding tissue, assessment of relative single image from a dynamic sequence (movie) of EUS elas-
stiffness between the two may be also impaired. Moreover, tography [9, 46]. New ultrasound systems have all these
the reproducibility of elastography may be reduced in sev- options incorporated into the software, allowing the calcula-
eral anatomical sites in which the effects of physiological tion of elastography parameters in real-time, during the EUS
movement are too weak or too strong (heart, large arterial procedure [9, 46]. For more details of the examination tech-
vessels) or in which compression with the transducer is dif- nique of the pancreas we refer to current textbooks [92].
ficult (left adrenal gland, spleen, or parts of the liver).
Interposition of large vessels, cystic lesions, and dilated
ducts between the targeted lesion and the transducer may Normal Pancreas
also impair the strain assessments.
The utility of EUS elastography may be hampered by When using real-time elastography during EUS, the normal
tumoral necrosis (which is soft), by abundant fibrosis (e.g., pancreas has a homogenously green appearance in most
of lymph nodes in sarcoidosis), by similarity between tissues cases, representing intermediate stiffness. Elastography has
stiffness’s in cases of pancreatic cancer and chronic pancre- proven to be particularly helpful for the correct identification
atitis, and also by mucinous or semi-solid content of cystic of ventral and dorsal pancreas and exclusion of tumors [6,
lesions. 93]. In the study of Iglesias-Garcia et al., a homogeneous
green elastographic pattern has been shown in all 10 normal
pancreas controls [94]. It becomes heterogeneous with
Examination Technique advancing age due to fat and connective tissue deposits [6,
56, 71]. Moreover, semi-quantitative analysis has indicated
Pancreatic elastography can be performed using two differ- relatively high strain values on the average hue histogram [7,
ent approaches: endoscopic (SE) and percutaneous (e.g., 9, 46, 91].
ARFI). Pancreatic masses have been evaluated in different
studies using both approaches [56]. The EUS approach is the
most frequently used, based on its overall accuracy and diag- Acute Pancreatitis
nostic performance. Using EUS elastography, initial studies
have reported malignant masses as blue (stiff) and a benign Inflammation of the pancreas can be hard or soft on elasto-
mass as green (intermediate stiffness), although this simple gram, depending on the stage of the inflammation and on the
dichotomy has been contradicted by some other authors and amount of associated collections and necrosis [56]. In the
later articles. case of acute pancreatitis, necrosis appears softer as com-
Because different tissue elasticity (strain) patterns are pared to harder tumors [46, 94].
represented by a range of colors, in subsequent studies sev-
eral qualitative and semi-quantitative analysis methods have
been developed [67, 91]. Qualitative analysis has included a Chronic Pancreatitis
five-step score method based on the predominant color pat-
tern inside the elastography ROI: homogenously hard, het- A recent study indicated that EUS elastography might be
erogeneously hard, mixed, heterogeneously soft, and used to predict pancreatic exocrine insufficiency, through an
homogenously soft [45]. Semi-quantitative analysis has been indirect estimation of pancreatic fibrosis. Thus, pancreatic
based on comparing two different areas of tissue within the strain ratios are higher in patients with pancreatic exocrine
insufficiency [95]. The natural course of chronic pancreatitis, according to reported studies. In other words, the negative
as well as fibrotic-related changes, may be thus assessed by predictive value is usually higher than 90%. Both qualitative
elastographic techniques, one of the main aims being the and semi-quantitative approaches have been used in the lit-
prediction of the potential risk for pancreatic cancer accord- erature, showing high values for the sensitivity, specificity
ing to the degree of pancreatic fibrosis [33, 81, 94, 95]. and overall accuracy in the differential diagnosis of benign
Nevertheless, differential diagnosis between pancreatic and malignant focal pancreatic masses [66]. Besides indi-
cancer and mass forming chronic pancreatitis is challenging vidual reports, several multicentric studies have shown a
even for experienced gastroenterologists [7, 33]. Thus, high sensitivity, but lower specificity and accuracy for the
chronic pseudotumoral pancreatitis can be differentiated diagnosis of benign versus malignant focal pancreatic
from pancreatic adenocarcinoma by differences in elasto- masses. Computer-aided diagnostic techniques might also
graphic appearance in most of the cases, based on semi- improve the differential diagnosis of focal pancreatic
quantitative analysis, which shows high strain for the average masses, the most commonly used until now being based on
hue histograms in chronic pancreatitis as compared to pan- artificial neural networks [7]. Meta-analysis of 13 studies
creatic adenocarcinoma. However, in approximately half including a total of 1042 patients examined by EUS elastog-
cases of chronic pancreatitis, elastographic patterns are simi- raphy for differentiating benign and malignant solid pancre-
lar to the ones observed in pancreatic adenocarcinomas, atic masses showed an excellent pooled sensitivity of 95%
showing as homogeneously or heterogeneously blue pattern, (95% confidence interval [CI], 93%–96%) and moderate
highly influencing the specificity of the method for the diag- specificity 69% (95% CI, 63%–75%), respectively. The
nosis of adenocarcinomas [5, 43]. As studies have shown, pooled sensitivity, specificity, and diagnostic odds ratio of
ARFI elastography of the pancreas has proved higher stiff- EUS elastography in distinguishing benign from malignant
ness values in chronic pancreatitis as compared to findings in solid pancreatic masses were 0.95 (95% confidence interval
the normal pancreas [81]. Elastography might have a contri- [CI], 0.94–0.97), 0.67 (95% CI, 0.61–0.73), and 42.28 (95%
bution for the early diagnosis of pancreatic carcinoma in CI, 26.90–66.46), respectively [9, 46].
cases of chronic pancreatitis in some patients. Based on our However, one recently published large single-center
experience of elastography measurements, and the histologi- study found semi-quantitative elastography less accurate
cal characteristics outlined above, we do not believe that than in previously described studies and meta-analyses.
elastography can contribute to the early diagnosis of pancre- Sensitivity again was high, but specificity and negative pre-
atic carcinoma in cases of chronic pancreatitis (with the dictive value in this study were disappointingly low. It could
exception of the early stages of autoimmune pancreatitis) [9, be shown that the method is of most value in smaller lesions
46]. EUS elastography might be helpful in the diagnosis of <30 mm. Nevertheless, the study employed the same strain
early autoimmune pancreatitis due to the unique appearance ratio assessment that has certain flaws, with the values influ-
of universal stiff tissue in this disease [12]. enced by the distance of the reference area from the trans-
ducer [9, 46].
The presence of intratumoral necrosis may also influence
Focal Pancreatic Masses the appearance on elastogram, as well as the calculated rela-
tive or absolute stiffness. Necrotic areas appear softer as
A homogeneously green pancreatic appearance on elasto- compared to the viable tumor which is harder [56]. Strain
gram obtained using an EUS approach is indicative of inter- ratio obtained between the strain of a lesion and the strain of
mediate homogeneous stiffness and can be used to exclude the surrounding normal pancreatic tissue is higher for neo-
pancreatic malignancies, as some studies have suggested plastic pancreatic masses as compared to mass-forming pan-
[56]. A uniform elastographic pattern is usually seen in creatitis [96].
benign lesions, while malignant ones most frequently are
displaying a heterogeneous pattern [44, 55]. Pancreatic duc-
tal adenocarcinoma appears as a stiff mass, stiffer than the Neuroendocrine Tumors
adjacent parenchyma, owing to the presence of fibrosis and
marked desmoplasia. A heterogeneous blue-predominant, The elastographic appearance of neuroendocrine pancreatic
stiff pattern with a geographic appearance is usually seen in tumors varies according to different studies, from blue-
pancreatic adenocarcinomas and in metastatic tumors [94]. homogeneous or honeycomb pattern to homogeneous-green
However, there is no proof of a direct relationship between or central green surrounded by blue tissue [11, 31, 43, 76,
either tumor grading or collagenous fiber content on the one 96]. A pattern of slightly harder than normal pancreatic
hand, and the stiffness of the tumor on the other. Due to the parenchyma has been reported for small endocrine tumors,
tissue characteristics, malignancy can be excluded with high especially if malignant (Fig. 2). Most of the authors have
accuracy when a predominantly green pattern is seen consequently indicated that the method does not replace
Fig. 2 Strain elastography of the pancreas in a benign neuroendocrine rounded by normal pancreatic tissue. Elastography indicated blue color
tumor with soft to intermediate stiffness [11] (a). Solid tumor of 5 mm as a sign of stiffer tissue than the surrounding pancreas (b)
in the pancreatic tail in a patient with an insulinoma, the lesion is sur-
EUS-FNA, but may be very useful in negative or inconclu- SE has the potential to add value to B-mode US, particu-
sive EUS-FNA cases, if a strong suspicion for malignancy larly by better targeting lymph nodes or nodal invasion for
still persists [46]. biopsy. With an accuracy of >85% documented in several
large studies, EUS-guided fine needle aspiration (EUS-FNA)
delivers the most reproducible results in the diagnosis of
Cystic Pancreatic Tumors metastatic lymph node infiltration. However, sensitivity of
EUS-FNA depends on the appropriate selection of lymph
SWE can be useful in differentiating between serous and nodes and focal infiltration within lymph nodes for biopsy
mucinous malignancies, and showed good accuracy in dif- [46]. The lymph node architecture using elastography has
ferentiation of benign and malignant cystic pancreatic lesions not been studied in detail. To our experience some lymphoma
[82, 97]. may show typical infiltration of the cortex which is different
to the early circumscribed (Fig. 3) and later more diffuse and
homogenous infiltration of the entire lymph node by adeno-
Recommendations [6] carcinoma [46]. Elastography has the potential to further
improve the accuracy of EUS-FNA by targeting lymph nodes
• EUS elastography is useful as a complementary tool for for needle sampling. A recent meta-analysis calculated a
the characterization of focal pancreatic lesions. pooled sensitivity of 88% and a pooled specificity of 85%,
• When there is strong clinical suspicion of pancreatic can- respectively, with EUS elastography for the differentiation of
cer, but the biopsy is inconclusive or negative, a hard focal benign and malignant lymph nodes [8]. Intra- and inter-
lesion on elastography and/or suggestive endoscopic observer agreement was good in one recent study using
CEUS (hypovascular lesion) should guide clinical man- visual assessment of the elastography image to differentiate
agement by indicating repeated EUS-FNA or direct refer- between malignant and benign lymph nodes in a real-time
ral to surgery. technique [101]. However, the same group found that EUS
• EUS elastography cannot be currently recommended for elastography did not perform better than EUS morphology in
differentiating advanced chronic pancreatitis from pan- differentiating between malignant and benign lymph nodes
creatic carcinoma due to their similar tissue stiffness in a in patients with resectable upper gastrointestinal cancer
large proportion of cases. [102]. These findings conflict with the results of another
group, which showed superior accuracy of EUS elastogra-
phy strain ratio in comparison with conventional EUS crite-
Lymph Nodes ria in differentiating malignant and benign lymph nodes in
the nodal staging of esophageal cancer [36, 46].
The reliable classification of benign and malignant lymph
nodes is important for patient prognosis and selection of
appropriate therapy for many cancers, e.g., esophageal, Recommendations [6]
stomach, bronchial, and pancreatic carcinoma [38].
Endosonographic B-Mode criteria for detecting malignant • Complementing established B-mode criteria, EUS strain
lymph nodes (hypoechoic structure, round shape, sharp mar- elastography is useful as an additional tool for discrimina-
gins, >10 mm) vary in accuracy between 50% and 100% tion of benign and malignant lymph nodes.
[46]. Elastography can be recommended to support discrimi- • EUS elastography may be used for identifying the most
nation of benign and malignant lymph nodes by identifying suspicious lymph node and/or harder lymph node regions
malignant areas within lymph nodes and to target these areas suspicious of malignant invasion that should be targeted
by EUS-FNA [38, 46]. In particular, lymph node size is not a for EUS fine-needle aspiration biopsy.
reliable indicator for lymph node metastasis in gastrointesti-
nal and pulmonary cancers. Despite a significant difference
in lymph node size between malignant and benign lymph Gastrointestinal Tract
nodes in cancer patients, up to 50% of malignant lymph node
infiltration occurs in lymph nodes <5 mm [98–100]. Vice Just as with gray scale ultrasonography, elastography may
versa, in gastric cancer, lymph nodes with a diameter of also be used to show the layered gastrointestinal wall struc-
≥10 mm occur in as many patients without metastatic nodal ture. Also, the contractility of the gastrointestinal wall can be
involvement as in patients with lymph node metastases [46]. assessed using strain rate imaging [6, 103].
Fig. 3 Strain elastography of malignant peripancreatic lymph nodes
A major clinical challenge in Crohn’s disease is to evalu- • Characterizing bowel wall lesions and possibly discern-
ate whether a stenosis is caused by inflammation or fibrosis, ing the active phase of inflammation from fibrotic stenosis
since the latter requires surgical intervention while an inflam- using strain elastography.
matory stricture requires medical treatment. Strain elastogra- • Evaluation of gastric contractility and GI wall strain using
phy has been tested in this setting and helps differentiate SRI [103].
between these two conditions, since a fibrotic stenosis appears
stiffer while an inflammatory stenosis, softer [6, 104].
Strain imaging of the GI tract is normally performed with Hepatobiliary System
linear transducers. SE can be performed with many high-end
ultrasound scanners. Conversely, SRI is only available with In contrast to the well-known value of elastography of the
specifically dedicated software currently provided by one liver and pancreas as described above, the value of elastogra-
manufacturer [6]. phy for the diagnosis of biliary system disorders has not been
adequately evaluated. Hepatobiliary system elastography is
particularly useful for evaluation of the papilla and for stag-
Recommended Uses and Indications ing of papillary carcinoma and papillomatosis. In biliary
malignancies, malignant involvement of hepatoduodenal
According to EFSUMB guidelines [105] elastography is ligament lymph nodes can be evaluated by EUS elastogra-
indicated for [6, 104]: phy, being homogeneously or inhomogeneously harder than
the surrounding connective tissue [106]. In the case of (unex- Arterial and plaque stiffness has been studied in prelimi-
pected) choledocholithiasis, chronic inflammatory or scle- nary investigations and might form a clinically useful way to
rosing processes of the bile duct wall (with stiffer elasticity) assess vulnerable plaque.
can be diagnosed as a sign of chronic inflammation. The dif-
ferentiation of harder sclerosing bile duct wall changes from
softer, non-reactive changes is also important in the assess- Other New Ultrasound Techniques
ment of proximal changes in the biliary tree. Interesting
applications include the differential diagnosis of primary Compound Imaging
sclerosing cholangitis versus distal bile duct carcinoma and
the analysis of retro papillary tumors, which can be evalu- State-of-the-art ultrasonography produces images with great
ated analogously to elastography of the pancreas [46]. detail resolution owing to both amplitude and phase informa-
tion of the return echo and compound technology.
Compounding can improve contrast and spatial resolution in
Future Applications the B-mode image, reducing the intrinsic acoustic noise of
US imaging, called “speckle,” by generating several inde-
As a new method, elastography is being used in applications, pendent frames of data and then averaging them [108, 109].
which as yet lack sufficient strength of evidence for their rec- Different types of compounding technology are available,
ommended use, although they may prove to be of clinical such as frequency compounding and spatial compounding.
value once more experience is gained. The topics below are Compound acquisition may also generate volumetric images
an incomplete list of those that are of clinical interest but that are increasing the multiplanar capabilities of conven-
whose value is still to be confirmed. Elastography of superfi- tional US, opening new clinical opportunities for more com-
cial lymph nodes, for example in the neck or inguinal regions, plete evaluation of the organs [108, 110]. This is a relatively
is a promising application, where an increase in stiffness new technique based on the acquisition of a volume dataset
would be expected in malignancy but might also occur in of anatomical structures. Automated volumetric imaging
inflamed nodes. Future developments include the evaluation allows to overcome the low reproducibility of the previous
of elastography targeted biopsy techniques for pancreas and volume freehand sweep acquisition, owing to the possibility
lymph nodes. Combination with other techniques, like of a standardized and objective acquisition during the study:
contrast-enhancement techniques, including hybrid imaging the whole volume of a ROI is automatically acquired during
approaches or 3D elastography examinations might also be a breath hold of few seconds without moving the probe,
feasible [46]. because with the volumetric electro-mechanical transducers,
Intraoperative elastography has been applied to the brain such as 4D3C (GE Healthcare, Waukesha, W.I., USA), the
to guide the surgeon to stiffer regions that represent tumors acquisition is related to the internal movement of the piezo-
and improve the precision of their resection. electric elements inside the probe with an angle of acquisi-
Assessment of uterine cervix and of testicular tumors tion from 40° to 60°. Thus, the entire volume is uniformly
might be a useful application of elastography, which could and automatically acquired, and then reviewed and studied
also aid the distinction between the commoner malignancies by means of different applications: volume review, to review
and the rarer less invasive tumors such as Leydig cell tumors, the whole volume acquired to obtain a virtual scan of the
which can be managed, with tissue-sparing surgery. studied organ; tomographic imaging, to allow the multipla-
Anal incontinence, most commonly an obstetrical injury, nar vision of the ROI; volume rendering, to allow the volu-
leads to scarring, which is stiffer than the normal sphincter metric visualization of a lesion within the organ. Moreover,
muscles. There is a preliminary report focusing on the pre- studying the evaluation of the involvement of vessels by a
surgical findings, with promising results, whereas postopera- mass could be improved by using multiplanar reconstruc-
tive evaluation was disappointing [107]. Elastography has tions [108].
been used in rectal and anal carcinomas where it might
improve the discrimination between rectal adenoma and rec-
tal cancer and the differentiation of T2 and T3 stages of rec- Doppler Techniques
tal cancer.
Perineal ultrasound is an effective method for imaging Doppler imaging may be combined with new ultrasound
perianal inflammatory lesions (e.g., in Crohn’s disease) but techniques, such as CEUS, elastography, 3-D/4-D ultra-
is too rarely used. Generally speaking, acute inflammatory sound, allowing what is called “multiparametric ultrasound,”
lesions are softer, and chronic lesions, harder in comparison a term used to describe the complexity of the sonographic
to the surrounding tissue. examination [65]. Even more, new ultrafast sonographic
machines are now available for in vivo use. Their technique

allows, between other multiple applications, also the use of
ultrafast Doppler. Blood flow can be now imaged with high
precision and ultrasensitivity, with unprecedented spatial and
temporal resolution (Fig. 4). This has improved ultrasound
imaging, especially the functional applications for the char-
acterization of the brain activity [111]. Ultrafast Doppler
allows highly precise characterization of complex vascular
flows, even in very small vessels [112, 113]. Continuous
Doppler spectral analysis is helpful to differentiate benign
from malignant lesions [114] (Fig. 5).
Other new technologies have been developed in the past
in color-Doppler studies: wide-band Doppler which improves
both spatial and temporal resolution of the color-Doppler
signal with decreased artifacts [108, 115]; Power-like flow
Fig. 4 Color Doppler imaging. Hypervascular lesion (NET) as a sign systems as B-flow (General Electric) and e-flow (Aloka)
of no ductal adenocarcinoma. In contrast, a hypovascular lesion is imaging, able to suppress tissue untidiness and improve sen-
indicative for ductal adenocarcinoma
Fig. 5 Doppler spectrum, high resistive index (RI 0.86) as a sign of malignancy [114]
sitivity to directly visualize blood reflectors, consequently mation derived from power-Doppler, clearly differentiating
providing image characterized by better spatial resolution vascular anatomy from acoustic artifacts and surrounding
[108, 115]; color flow imaging (CFI), mostly used to image tissue [108, 116].
the blood movement through arteries and veins, but also to
represent the motion of solid tissues [108, 116]. The weak
signals from blood echoes are enhanced and correlated with Perfusion Imaging
the corresponding signals of the adjacent frames to suppress
non-moving tissues. The remaining of the data processing is Ultrasound contrast agents (UCAs), in conjunction with
essentially the same as in conventional grey-scale imaging. contrast-specific imaging modes, are increasingly accepted
In comparison with Doppler techniques, these new flow in clinical use for diagnostic imaging and pre- and post-
imaging US modalities are not affected by aliasing and have interventional work-up. Contrast-enhanced ultrasound
the advantages of a significantly lower angle dependency and (CEUS) has improved the detection and characterization of
better spatial resolution with reduced overwriting, with pathologies in comparison to conventional ultrasound
marked improvement of the evaluation of vessel profiles. (Figs. 6 and 7).
Other Doppler-based technologies are able to improve the Recently, new imaging techniques have been devel-
image quality, owing to the immediate identification of the oped to perform an ultrasound perfusion analysis of the
vascular structures in B-mode. In this field, the Clarify tumor vascularization [117, 118]. In addition, dynamic
Vascular Enhancement (Acuson, Siemens) allows the image contrast-enhanced ultrasound (DCE-US) overcomes sub-
optimization by enhancing the B-Mode display with infor- jective evaluation of the enhancement between normal
Fig. 6 CEUS. Hyperenhancing lesion as a sign of benign neuroendocrine tumor. Benign NET typically shows homogenous enhancement whereas
non-enhancing regions are indicative for malignancy (see next Figure)
Fig. 7 CEUS. Non-enhancing regions in a patient with NET are indicative for malignancy whereas benign NET often shows homogenous
enhancement
and abnormal parenchyma, or between a focal lesion and in adenocarcinoma than in inflammatory masses. There were
the surrounding tissue. Furthermore, DCE-US offers the no significant differences between IMAX and AUC. They
potential for a better understanding of the pathophysiol- concluded that cases of CP, PDAC, and focal masses have
ogy of angiogenesis of benign and malignant neoplasia of different perfusion patterns at a capillary level and that

the pancreas [119]. DCE-US offers a new instrument to facilitate the differential
Differentiation between an inflammatory focal lesion of diagnosis of focal lesions in pancreatic cancer and CP [126].
the pancreas and pancreatic carcinoma using DCE-US has Moreover, D’Onofrio et al., in a study about quantitative per-
been attempted [120–125]. Time-intensity curves (TICs) fusion analysis for an objective characterization of pancre-
were obtained for all examinations in two ROIs; one within atic ductal adenocarcinoma, assert that CEUS is a new
the lesion, and the other within the normal pancreatic tissue. imaging technique with lots of capabilities in the visualiza-
The following measurements were obtained: IMAX, arrival tion of vascularization and analysis of organs and neoplasms
time (AT), TPI, and AUC. Absolute values and differences perfusions. In particular, CEUS quantitative perfusion analy-
between the lesion and the normal tissue were evaluated. sis can provide objective parameters for the characterization
Histology analysis revealed 45 pancreatic ductal adenocarci- of pancreatic masses detected during a conventional ultra-
noma (PDACs) and 15 inflammatory masses in patients with sound study [117]. The technology has recently become
CP. Although markedly lower than in a healthy pancreas, the available for contrast-enhanced harmonic EUS [119, 127],
IMAX and AUC data were not significantly different between allowing examinations with a low mechanical index for char-
PDACs and focal lesions in patients with CP. They compared acterization of microvessels, but also differential diagnosis
the enhancement in the lesions to the representative paren- of focal pancreatic masses and enhanced staging or guidance
chyma and found significantly longer values for AT and TPI of therapy [128] (Fig. 8).
Fig. 8 Dynamic contrast-enhanced ultrasound using time-intensity curve analysis [91, 119, 127]
Second-generation blood pool UCAs are used in con- isovascular and respectively, with pancreatic neuroendocrine
junction with specific multi-pulse harmonic imaging tumors, which are hypervascular [131]. An initial pilot study
modes, which allow the depiction of the signal generated indicated good sensitivity (89%), specificity (88%), and
by the insonated microbubbles in the blood stream [129]. accuracy (88.5%) for hypoenhancement as an indicator of
Quantification techniques have been also developed in a pancreatic carcinoma [132]. The results of the published
similar manner to transabdominal ultrasound. Both using studies have been analyzed into a comprehensive meta-
specific software for measurements of intensity as a func- analysis, which showed a pooled sensitivity of 94% and a
tion of time (time-intensity curve analysis). Various pooled specificity of 89%, with an area under the ROC curve
parameters can be measured: peak enhancement (PE), of 0.9732, for hypoenhancement regarded as an indicator of
rise time (RT), mean transit time (mTT), time to peak pancreatic adenocarcinoma [133]. A prospective multicen-
(TTP), wash-in area under the curve (WiAUC), wash-in tric trial also showed a high sensitivity (96%), specificity
rate (WiR), wash-in perfusion index (WiPI), wash-out (94%), and accuracy (95%) for contrast EUS in order to
AUC (WoAUC) and wash-in and wash-out AUC diagnose pancreatic carcinoma [134]. The results have been
(WiWoAUC) [130]. confirmed in a recent multicentric study that included con-
Several studies of contrast-enhanced EUS have looked at secutive patients with chronic pancreatitis and pancreatic
the role of perfusion imaging for the differential diagnosis of cancer, indicating a similar sensitivity (87.5%) and specific-
focal pancreatic masses, based on the assumption that pan- ity (92.7%), while peak enhancement and wash-in area under
creatic adenocarcinoma is a hypovascular tumor, as com- the curve for the TIC analysis were completely different in
pared to chronic pseudotumoral pancreatic, which is between the two groups [91]. Besides the diagnostic role,
contrast-enhanced EUS might play a role in the guidance of method in this regard, offering valuable clinical information.
FNA in focal pancreatic masses, having an incremental effect It could confirm pathologic features and suspected diagnos-
for the conventional EUS-FNA technique, with a combined tic findings identified by other imaging methods in 100% of
accuracy reaching 94% [135]. the cases, in 86% of the cases highlighting new clinical rel-
Concerning neuroendocrine tumors (NETs), EUS has evant findings.
been used to better detect and characterize small insulinoma
[136]. Besides localization, EUS helps the characterization
and differential diagnosis of benign and malignant pancre- Three-Dimensional (3D) Sonography
atic NETs, with a sensitivity that exceeds 95% [137]. The
hypervascular pattern of NETs is thus consistent with hyper- While 3D sonography has been established in gynecology
enhancement, the sensitivity being 78.9%, with a very high and vascular applications, abdominal applications are less
specificity of 98.7%, in contrast with the hypoenhancement frequent. However, recent advances in computer technology
that appears in pancreatic ductal carcinomas, consistent with have supported the development of new systems with motion
a sensitivity of 95.1% and a specificity of 89.0% [138]. detection methods and image registration algorithms, making
Basically, an important role of perfusion ultrasound imag- it possible to acquire 3D data without position sensors, before
ing is the clinical application of dynamic contrast-enhanced and after administration of contrast-enhancing agents. The
ultrasound (DCE-US) for monitoring the response to antian- so-called freehand 3D method is a multistep procedure (data
giogenesis or antivascular drugs. Initially, such monitoring acquisition, correlation algorithms with segmentation, and
relied based only on qualitative analyses only; but more quantification) based on correlation algorithms, including the
recently, robust and quantitative features have been devel- display of the three-dimensional image. Today, modern tech-
oped [119, 139]. Since antiangiogenic treatment frequently niques for motion detection and image co-registration of
induces necrosis without causing tumor shrinkage, func- structures allow for 3D data acquisition without position sen-
tional imaging techniques are particularly suitable for the sors, which is true for CEUS and elastographic techniques.
early assessment of response. Studies of various types of As a basic requirement for correct 3D data acquisition, the
tumors treated with antiangiogenic therapies have confirmed transducer must be moved at a constant speed. Real-time
that DCE-US may enable early prediction of response to visualization of the acquired image data occurs in part through
treatment [119, 139–144]. Also a multicenter study has been instant reconstruction of a plane with appropriate corrective
published, underlining the importance of DCE-US for the functionality (e.g., motion artifacts, irregular movement pat-
evaluation of antiangiogenic therapies [145]. tern, etc.). B mode image data and flow data (power mode)
are acquired in a combined way. However, in post-processing
both modes can be visualized independently [148].
Indications 3D imaging facilitates the detection of pancreatic patho-
logic processes, allowing a better representation and volume
Transplant Medicine assessment of small masses and irregularly shaped tumoral
The method allows early identification of transplant rejection foci. It influences management and prognostic outcome by
in kidney allograft and pancreas transplant recipients. To providing the better evaluation tool of lesions and of their
predict early graft rejection by DCE-US, TICs were calcu- relations to surrounding pancreatic parenchyma and vessels
lated in 14 pancreas transplant recipients and the data were [149]. In addition, by dynamic vascular analysis in real time,
compared between normal pancreas transplants, grafts available by means of contrast-enhanced 3D sonographic
undergoing rejection, and grafts after successful treatment of techniques, differentiation between benign and malignant
the rejection episode by Kersting et al. [146]. The TICs masses can be made. Miwa et al. [150] investigated the use-
showed a significantly slower ascent and diminished IMAX fulness of 3D contrast-enhanced ultrasound for the differen-
in pancreas grafts during rejection, with significantly reduced tial diagnosis of solid pancreatic lesions. A number of 85
IMAX and TPI. After the successful treatment of rejection, patients have been retrospectively analyzed in this regard,
these measurements were almost restored to initial values. including 64 patients with ductal adenocarcinoma, 10
Thus, DCE-US seems to be a sensitive tool in the surveil- patients with mass forming pancreatitis, and 11 patients with
lance of pancreas grafts [126]. neuroendocrine tumors. They concluded that the method
Rennert et al. [147] evaluated the identification of acute could be used for differential diagnosis of solid pancreatic
and subacute complications following pancreatic transplant lesions based on direct detailed visualization of enhance-
by means of CEUS, as compared to other cross-sectional ment patterns. Ductal adenocarcinomas presented with
imaging techniques (MRI, CT, digital subtraction angiogra- hypovascular patterns during both arterial and venous phases,
phy, and ultrasound). CEUS proved to be a useful promising presenting also peritumoral, irregular vessels. Mass forming
Fig. 9 3D CEUS imaging in a patient with a very small hypoenhancing and, therefore, malignant pancreatic neoplasia [148]
pancreatitis was isoenhancing during all phases, with intral- Fusion

esional fine vessels. Neuroendocrine tumors were hypervas-
cular in both phases, with irregular intratumoral vessels. The The term “volume navigation” in ultrasonography refers to
method proved to have an accuracy of 90.5% for these diag- the technical capability of reproducibly determining the
nostic criteria. Pezzilli et al. [151] assessed the diagnostic exact position in space of a specific sectional plane or ana-
accuracy of 3D CEUS for the diagnosis of intraductal papil- tomic site and using that information for image fusion, posi-
lary mucinous neoplasms (IPMN) of the pancreas. Their tion marking, or the 3D guidance of interventions. Volume
study included a number of 30 consecutive patients, which navigation requires a tracking system that continuously
have been evaluated in a prospective manner and results have monitors the transducer position and beam direction in real
been compared with those of MRI. The two imaging meth- time with adequate precision, magnetic navigation being
ods showed similar results in lesions smaller than 1 cm or used for this purpose. The goal and purpose of this system
greater than 2 cm. Even if 3D ultrasound navigation for intra- are to align the images produced by ultrasound and a differ-
operative surgical guidance is a well-established technique ent sectional imaging modality in order to achieve additional
in orthopedic and neuro-surgery, its abdominal applications important anatomical information of the corresponding
are not as many. This is due in part to difficulties related to imaging procedure before the interventional procedure and
segmentation in cases of extensive inflammation or tumor of course exploit the advantages of ultrasound (higher spatial
growth [152] (Fig. 9). resolution, real-time imaging, and easier biopsy guidance).
Fig. 10 Anorectal fusion in a patient with rectal carcinoma. This is the first description and images using fusion of endoscopic ultrasound and
magnetic resonance imaging
Publications to date have described fusion applications for ities, magnetic navigation being further used to keep the co-
imaging the coronary arteries, liver, and anorectal region registration in between the two imaging modalities [153].
(Fig. 10) and for guiding neurosurgical procedures. Even if transabdominal ultrasound is a widespread tech-
One of the most important applications of volume naviga- nique for assessing biliopancreatic diseases, still the pan-
tion is the precise fusion of live ultrasound images with ana- creatic tail region is frequently difficult to be visualized.
tomically identical sections from a previously acquired CT, Sumi et al. [154] sonographically examined the pancreatic
MRI, or PET volume data set. Before the start of the ultra- tail region with spatial positional information obtained by
sound examination, the data sets are imported via a network using a GPS-related technology and visualization-related
or portable storage device (USB stick, CD, DVD) and loaded factors available by CT fusion imaging. The method proved
into the image memory of the ultrasound system. The data to be useful for the estimation of the pancreatic tail “‘blind”
transfer is done in standard DICOM format and generally area, which was not visible by means of sonographic obser-
takes less than 1 min. To ensure precise image fusion, the spa- vation from the splenic hilum in 33% of the subjects. Sofuni
tial coordinates of the tracking system must be matched to et al. [155] evaluated the usefulness of real-time virtual
those of the imported volume for each new patient. This sonography in pancreatic diseases by merging the ultra-
image co-registration can be done quickly and easily by sound image with an objective multiplanar reconstruction
selecting a salient image from the CT, MRI, or PET volume CT image. The relationships between the pancreatic lesions
and then imaging the same plane sonographically in the and surrounding organs and vessels could be easily inter-
patient. The identity of the sections is confirmed by clicking a preted, with a superior evaluation rate of 80% and a better
button, which matches the coordinate systems of both modal- visualization rate of 20%.
Conclusion 12. Dietrich CF, Hirche TO, Ott M, Ignee A. Real-time tissue elas-
tography in the diagnosis of autoimmune pancreatitis. Endoscopy.
2009;41:718–20.
Effective use of elastography requires knowledge of the 13. Berg WA, Cosgrove DO, Dore CJ, Schafer FK, Svensson WE,
underlying physics and technology, which is made difficult Hooley RJ, Ohlinger R, et al. Shear-wave elastography improves
by the complexity of the subject and the variety of technolo- the specificity of breast US: the BE1 multinational study of 939
masses. Radiology. 2012;262:435–49.
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ties, which the research community is pursuing with Yamakawa M, et al. Breast disease: clinical application of US
enthusiasm. As a result, the technology for elastography is elastography for diagnosis. Radiology. 2006;239:341–50.
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Percutaneous Interventional
Procedures in Pancreatic Cancer
Mirko D’Onofrio, Antonia Maria Olivieri,

Francesco Verrengia, Filippo Moro, Luca Geraci,
Luisa Tomaiuolo, Chiara Longo, Francesco Cicalò,
Cesare Cacciatore, Alice Parisi, Erminia Manfrin,
Interventional procedures dedicated to pancreatic cancer can The use of contrast media may be an additional value dur-
be performed percutaneously. Common procedures are per- ing the ultrasound examination. Contrast-enhanced ultrasound
formed to obtain pathological diagnoses. Ultrasound is fre- (CEUS) is able to provide a real-time dynamic evaluation of
quently used to guide interventional procedures on the tumor enhancement. The latest guidelines by the EFSUMB
pancreas. Differently from fluoroscopy and CT, when percu- [1] provided the following recommendations for the use of
taneous intervention is performed under ultrasound guidance CEUS before or during US-guided pancreatic intervention:
it is possible to compress the abdominal wall with the probe distinction between cystic neoplasms and pseudocysts (level
in order to displace the stomach and the bowels also reduc- of evidence 1a, grade of recommendation A); differentiation
ing, together with the obliquity manually arranged from case of vascular (solid) from avascular (e.g., liquid or necrotic)
to case, the length of the route from the skin to the target. components of a pancreatic lesion (level of evidence 1a, grade
Moreover, besides the diagnostic procedures, recently sev- of recommendation A); definition of dimensions and margins
eral percutaneous ablative treatments have been applied to of a pancreatic lesion and its vascular relationships (level of
pancreatic malignancies. evidence 2b, grade of recommendation A); diagnosis and fol-
low-up of acute necrotizing pancreatitis (level of evidence 1b,
grade of recommendation A); improvement of the accuracy of
ercutaneous Interventional Procedures
P percutaneous US-guided pancreatic procedures (level of evi-
Guidance dence 2a, grade of recommendation B). The CEUS-guided
biopsy may be helpful for pancreatic lesions that are barely
Transabdominal ultrasound is faster and cheaper than com- visible on B-mode US, thus improving accuracy [2]. Moreover,
puted tomography (CT), magnetic resonance imaging (MRI), by directing the biopsy needle toward solid, enhancing por-
and endoscopic US (EUS); however, ultrasound is strongly tions of the lesion, necrotic portions can be avoided, thus
dependent on operator expertise, in particular when used as a reducing the need for biopsy repetition [1].
guidance for interventional procedures for pancreatic dis- Fusion imaging is a new technique that allows a real-time
eases. In this latter case, transabdominal US is particularly fusion of ultrasound imaging with previously acquired cross-
helpful for minimally invasive procedures with a percutane- sectional images, including CT, MRI, and positron emission
ous approach, as it guarantees real-time imaging that allows tomography CT (PET-CT) [3]. This technique has a great
to precisely evaluate each step of the procedure. potential for interventional radiology, since it associates the
characteristics of two different types of imaging in a single
examination, thus increasing the amount of anatomical, func-
M. D’Onofrio (*) · A. M. Olivieri · F. Verrengia · F. Moro · tional, and metabolic information during ultrasound-guided
L. Geraci · L. Tomaiuolo · C. Longo · F. Cicalò · C. Cacciatore · procedures. Fusion imaging is usually used to assist percutane-
R. De Robertis ous procedures for challenging lesions, especially those char-
acterized by low conspicuity on B-ultrasound [4]. Theoretically,
Verona, Italy
e-mail: mirko.donofrio@univr.it the pancreas could benefit from this technique, since being a
retroperitoneal organ it is poorly affected by respiratory move-
A. Parisi · E. Manfrin
Department of Pathology, G.B. Rossi University Hospital, ments that could impair real-time image fusion and synchroni-
Verona, Italy zation of the images. Nevertheless, there are very few literature
reports on the use of fusion imaging for percutaneous interven- specificity, and accuracy values for CNB of pancreatic
tion in pancreatic diseases. Sofuni et al. [5] and Sumi et al. [6] masses, with a diagnostic rate that ranges between 92% and
reported the potential usefulness of fusion imaging for the 96% [14–17]. Percutaneous CNB has a higher risk of com-
evaluation of the pancreatic tail, a well-known “blind area” for plications than US-FNA [17]. Therefore, percutaneous
transabdominal US, and for pancreatic lesions with low conspi- US-FNA, especially when performed in the presence of an
cuity on ultrasound. Zhang et al. [7] compared the efficacy of experienced cytopathologist on site, could be preferable,
US guidance alone and ultrasound/CT image fusion guidance especially as a first approach for pathological evaluation.
in percutaneous drainage of infected walled-off necrosis fol-
lowing acute pancreatitis. The fusion imaging group achieved a
significantly higher imaging effective rate, and significantly Tumor Ablation
lower inflammatory response indexes and severity score, than
the ultrasound group; the fusion group required fewer puncture Radical resection is the only treatment capable of improving
times and drainage tubes and a lower rate of advanced treat- long-term survival in patients with pancreatic cancer. Surgical
ment, showing a higher operational success rate than the US resection is possible only in 20–30% of patients with pancre-
group. Moreover, the fusion imaging group exhibited signifi- atic cancer and the 5-year survival rate is still very low, even in
cantly lower complications and hospital stays. combination with chemo- and radio-therapy [18]. Tumor abla-
The fusion imaging applications with the percutaneous tion was first proposed under intraoperative US to debulk
approach for pancreatic intervention resides in the necessary tumors that were found to be unresectable during surgery,
compression with the probe on the abdomen which could based on previous effective experiences in other organs such
create discrepancies between ultrasound and previously as the liver or the kidney [19]; afterward, given the efficacy in
acquired images. terms of mass shrinkage, pain relief, CA 19.9 reduction, and
survival, this procedure has been introduced as a part of the
multidisciplinary approach to patients with pancreatic cancer
Pancreatic Cancer Biopsy in high-volume centers [20, 21]. As a consequence, there was
a need for minimally invasive (i.e., laparoscopic, percutane-
The most recent guidelines of the European Federation of ous, and endoscopic) approaches to avoid unnecessary lapa-
Society for Ultrasound in Medicine and Biology (EFSUMB) on rotomies. There are many ablative techniques for pancreatic
diagnostic ultrasound-guided interventional procedures [8] pro- cancer, which can be divided into three groups: invasive, ther-
vided the following indications for invasive diagnosis of pancre- mal techniques, such as radiofrequency ablation (RFA),
atic lesions: (a) characterization of a solid unresectable microwave ablation (MWA), laser ablation, and cryoablation;
pancreatic mass; (b) differential diagnosis between neoplasm invasive, non-thermal techniques, such as ethanol injection
and focal inflammatory conditions; (c) suspicion of an uncom- and irreversible electroporation (IRE); and non-invasive abla-
mon entity (i.e., metastases, lymphoma), even if resectable, tive techniques, as high-intensity focused US (HIFU). Among
which could be treated non-operatively; (d) Ki-67 quantification these techniques, RFA and IRE are the most used for the abla-
for the prognosis of neuroendocrine neoplasms; (e) cystic tion of pancreatic cancer; HIFU is an emerging alternative.
lesions that are undefined or suspicious for malignancy after Radiofrequency ablation induces coagulative necrosis within
MR imaging evaluation. The same guidelines recommended the tumor mass. While EUS is safer for lesions in the pancreatic
that unresectable, locally advanced pancreatic masses should be head, the percutaneous approach can be adopted for lesions
evaluated for percutaneous US-guided biopsy first, and if a per- located in the body of the pancreas [22]. The necrotic area pro-
cutaneous approach is not feasible then EUS should be consid- duced by RFA depends on the type of needle-electrode.
ered; moreover, cystic lesions that require pathological diagnosis Moreover, technical parameters, such as power, influence the
should be always sampled through an endoscopic approach. temperature and the volume of necrosis. In the pancreas, the use
Previous studies reported high sensitivity and accuracy of very high temperature (above 100 ° C) is related to a high risk
values of percutaneous US-FNA for the diagnosis of pancre- of complications without significant advantages, so several
atic masses, even above 98% [9–13]. Moreover, percutane- studies have shown that a temperature of about 90 °C is suffi-
ous FNA has a relatively low complication rate ranging cient for a successful procedure, with lower risk of complica-
between 0% and 5%, and is almost always limited to post- tions [20, 23, 24]. Previous studies reported that CA 19.9 blood
procedural pain or mild abdominal effusion [9–13]. levels are reduced after RFA of unresectable pancreatic cancer,
When a complete tissue analysis is needed for a correct thus indirectly suggesting effective cytolysis of the tumor after
histological diagnosis and for further pathological analyses, ablation [25]. It has been proven that RFA can provide a reduc-
such as Ki67 quantification in neuroendocrine neoplasms, tion in back pain and analgesia requirement in inoperable
FNA is not adequate. Core-needle biopsy provides preserved patients [26]. Overall survival is longer in patients treated with
tissue structures for histologic analysis and molecular char- RFA instead of classical supportive care, especially when com-
acterization. Coaxial cutting needles are commonly used for bined with chemotherapy, reaching up to 33 months in unresect-
CNB. Several studies have reported very high sensitivity, able pancreatic cancer [27]. Despite the successful results, there
Percutaneous Interventional Procedures in Pancreatic Cancer 519
are still few studies regarding percutaneous RFA of pancreatic Cryoablation is increasingly used for the ablation of unre-
lesions. However, all authors agreed on the safety and effective- sectable pancreatic cancer. This technique produces a rapid
ness of the procedure, not only for ductal adenocarcinoma [28] freezing of the lesion down to temperatures between −80°
but also in neuroendocrine tumors [29, 30] and pancreatic and − 160 ° C by using a cryoprobe. The biological mecha-
metastases [31]. Owing to the above-mentioned results, ultra- nisms underlying cryoablation are not still fully understood;
sound-guided RFA has been introduced in the multidisciplinary nevertheless, it is known that this technique leads to the destruc-
approach to pancreatic cancer in high-volume centers; neverthe- tion of cell membranes and tissues’ ultrastructure, leading to
less, randomized clinical trials on larger samples are needed in delayed cell necrosis and apoptosis [41]. Ultrasound can be
the future to validate this procedure. used to guide percutaneous cryoablation, but posterior acoustic
Microwave ablation (MWA) is based on tissue heating by shadowing limits visualization, while at CT the frozen lesion
mechanical agitation of water molecules induced by micro- appears as a hypodense “ice ball”. For these reasons, CT guid-
waves, which ultimately causes coagulative necrosis [32]. ance is more frequently adopted to guide percutaneous cryoab-
Microwaves can spread throughout tissues independently lation. Nevertheless, there have been reports on successful
from their electric impedance: this allows to produce faster US-guided percutaneous cryoablation for pancreatic cancer.
and larger ablation areas than RFA, thus requiring fewer Niu et al. [42] reported effective pain relief after cryoablation,
applications to obtain complete tumor necrosis. Although lit- with a ≥ 50% reduction in pain score in 84% of patients, a 50%
erature reports on percutaneous US-guided MWA of pancre- decrease in analgesic consumption in 69% of patients, and
atic lesions are few, this technique appears to be safe and a ≥ 20 increase in Karnofsky Performance Status score in 50%
promising for the treatment of unresectable pancreatic of patients. Xu et al. [43] reported complete tumor response in
tumors. Carrafiello et al. [33] reported that this procedure 20.4% of patients, partial response in 38.8%, and stable disease
was feasible in all patients of their series, with only one in 30.6% after percutaneous cryosurgery associated with
procedure-related complication. Ierardi et al. [34] reported 125-iodine seed implantation.
improvement in quality of life after US-guided percutaneous High-intensity focused ultrasound (HIFU) is a non-
MWA in 5 patients with pancreatic cancer. invasive ablation technique that delivers high-intensity
Irreversible electroporation (IRE) is the newest and most ultrasounds in a definite area in order to produce both ther-
promising invasive technique for pancreatic cancer ablation. mal and mechanical damage. The target region is heated up
IRE is based on the application of short high-voltage electric to 60–80 °C inducing protein denaturation and tissue necro-
pulses, in order to produce multiple micropores on cell mem- sis [44]. Both US and MR imaging can be used to guide the
branes causing irreversible permeabilization, which leads to procedure; while MR imaging is the most commonly used
disruption of cellular homeostasis, activating apoptotic path- technique, US has the advantage to identify and displace
ways in tumor cells [21]. The main advantage of IRE com- the bowels in order to improve the effectiveness of the pro-
pared with other ablative techniques is the ability to preserve cedure and reduce complications. HIFU has been proven to
the extracellular matrix, thus allowing ablation adjacent to be an effective treatment for patients with advanced pancre-
critical structures such as nerves, vessels, and biliary ducts; atic cancer, by reducing pain in more than 80% of the cases
IRE is, therefore, the safest ablative approach for tumors [45–47]. Marinova et al. [48] reported that US-guided
encasing major peripancreatic vessels [21]. Irreversible elec- HIFU induced significant early relief of cancer-induced
troporation has been proposed for palliation of unresectable abdominal pain in 84% of patients, with a tumor volume
tumors of the pancreas, as a bridge therapy before surgery, reduction of 37.8 ± 18.1% after 6 weeks and 57.9 ± 25.9%
and also as a technique for intraoperative “margin augmenta- 6 months after treatment. The median overall survival and
tion”, in order to reach R0 resection in technically unresect- progression-free survival were 8.3 and 6.8 months from
able pancreatic tumors [35]. Open, laparoscopic, and intervention.
percutaneous approaches have been evaluated for IRE. In
most cases, percutaneous IRE was performed under CT
guidance, with encouraging results in terms of feasibility, Conclusion
safety, and effectiveness [36, 37]. Preliminary studies [38,
39] reported successful percutaneous ultrasound-guided IRE Ultrasound-guided percutaneous intervention for pancreatic
of pancreatic cancer, without significant procedure-related diseases is increasingly used and could be considered part of
complications. Månsson et al. [40] reported a median sur- clinical practice in high-volume centers. Technical advances
vival of 7 months after percutaneous US-guided IRE of pan- allowed to develop and refine both diagnostic and therapeu-
creatic cancer; the median time from IRE was 6.1 months to tic procedures. The use of CEUS and fusion imaging allows
local progression and 2.7 months to observation of metasta- to increase the accuracy, safety, and feasibility of ultrasound-
ses. With larger studies, data on safety and overall survival guided percutaneous procedures. Ablative techniques can be
after percutaneous US-guided IRE could be obtained to con- used for cytoreduction of locally advanced non-metastatic
firm its long-term efficacy within a multidisciplinary pancreatic cancer within a multitreatment modality based on
approach to unresectable pancreatic cancer. a multidisciplinary approach for pancreatic cancer.
Image Gallery
Fig. 1 Ultrasound probe. Ultrasound probe with lateral guidance Fig. 2 Menghini needle. Fine needle for aspiration biopsy
system
a b
Fig. 3 Percutaneous ultrasound-guided fine-needle aspiration. Pancreatic head hypoechoic mass with well visible peripancreatic vessels at
Doppler (a). The pancreatic head mass is reachable from the left side along the track (b)
Fig. 4 Percutaneous ultrasound-guided fine-needle aspiration.

Pancreatic body hypoechoic mass reachable from the right side along
the track avoiding vessels well visible at Doppler Fig. 5 Percutaneous ultrasound-guided fine-needle aspiration.
Pancreatic head hypoechoic mass reachable from the right side along
the track avoiding vessels well visible at Doppler
a b
Fig. 6 Percutaneous ultrasound-guided fine-needle aspiration. Hypoechoic mass infiltrating the superior mesenteric artery (a). The artery is well
visible by using Doppler (b). The needle is inserted in the lesion avoiding vessels (c)
a b
Fig. 7 Contrast-enhanced ultrasound (CEUS). Necrotic metastasis at the body of the pancreas appearing hypoechoic at conventional ultrasound
(a). At CEUS well visible the viable portion of the lesion vascularized and enhanced during dynamic phases (b)
a b
c d
Fig. 8 Fine-needle aspiration (FNA). Material from a fine-needle aspiration (a). Slice preparation (b). On-site stain (c) for cyìytologist evaluation.
Cytological diagnosis of pancreatic adenocarcinoma (d)
a b
Fig. 9 Biopsy. Tru-cut needle (a) for biopsy. Biopsy specimen (b) of pancreatic adenocarcinoma
Fig. 10 CT fusion imaging. CT/US fusion imaging of a pancreatic head adenocarcinoma appearing as a hypoechoic mass infiltrating the superior
mesenteric vein
Fig. 11 CT fusion imaging. CT/US fusion imaging of an adenocarcinoma at the pancreatic isthmus appearing as a hypoechoic mass
Fig. 12 CT fusion imaging. CT/US fusion imaging of pancreatic body adenocarcinoma appearing as a hypoechoic mass
Fig. 13 CT fusion imaging. CT/Doppler fusion imaging of pancreatic body adenocarcinoma appearing as a hypoechoic mass with visible Doppler
signals superimposed on the celiac trunk
Fig. 14 CT fusion imaging. CT/Doppler fusion imaging of pancreatic head adenocarcinoma appearing as a hypoechoic mass with visible Doppler
signals superimposed on mesenteric vessels
Fig. 15 CT fusion imaging. CT/US fusion imaging (a) of pancreatic posed Doppler signals on peripancreatic vessels. CT/CEUS fusion
body adenocarcinoma appearing as a hypoechoic mass. CT/Doppler imaging (c) of markedly hypoenhancing pancreatic body
fusion imaging (b) of pancreatic body adenocarcinoma with superim- adenocarcinoma
Fig. 15 (continued)
Fig. 16 CT fusion imaging. CT/US fusion imaging with visible track to guide percutaneous interventional procedure to pancreatic body adenocarcinoma
Fig. 17 CT fusion imaging. CT/US fusion imaging to guide percutaneous interventional procedure to pancreatic body adenocarcinoma
Fig. 18 MRI fusion imaging. MRI/US fusion imaging to guide percutaneous interventional procedure to pancreatic body adenocarcinoma
Fig. 19 Radiofrequency ablation (RFA). Percutaneous RFA of pancre-

atic adenocarcinoma. The needle is inserted into the tumor under ultra-
sound guidance
a b
Fig. 20 Ultrasound-guided radiofrequency ablation (RFA). sels along the track. Starting the ablation a hyperechoic area (b) is
Percutaneous needle placement for RFA of pancreatic adenocarcinoma. developed within the tumor where the exposed part of the needle is
The needle is guided by using ultrasound and doppler (a) to avoid ves- placed
Fig. 21 Radiofrequency ablation (RFA). Percutaneous RFA of pancre-

atic adenocarcinoma. The needle is completely inside the tumor in the
body of the pancreas with a well hyperechoic area during the ablation
procedure
Fig. 22 Irrevesible elettroporation (IRE). Percutaneous IRE of pancre-

atic adenocarcinoma. Two-needle application
Fig. 23 Fusion imaging for radiofrequency ablation (RFA) of

pancreatic cancer. Percutaneous radiofrequency ablation of
pancreatic adenocarcinoma by using fusion imaging guidance
a b
c d
Fig. 24 CT control after radiofrequency ablation (RFA) of pancreatic cancer. The core of the intratumoral thermolesion is hyperintense in the
pre-contrast phase (a). On dynamic phases the ablation area is markedly hypodense and avascular in arterial (b), venous (c), and late (d) phases
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New Diagnostic and Interventional
Endoscopic Techniques
Michael Hocke
odern Diagnostic Tools of Endoscopic

M Doppler imaging can help diagnose high vascularized
Ultrasound in Detection and Differentiation lesions, which are rarely typical adenocarcinomas. Normal
of Pancreatic Neoplasms color Doppler applications are already incredible sensitive
for that matter, especially if the operator lowers the flow rate
Contrast-Enhanced Endoscopic Ultrasound to a minimum and increase the gain. Modern adaptations are
even more sensitive like power Doppler or capillary flow
Using endoscopic ultrasound, the pancreas can be examined Doppler versions (fine flow, etc.) [4]. The introduction of
with a high-resolution ultrasound transducer from the duode- color Doppler imaging into the diagnostic work flow can be
num and stomach in a very close distance. Currently, no very helpful in regard to neuroendocrine tumors, however is
other imaging method can provide a more detailed picture not specific enough to discriminate chronic inflammation
than this one [1]. Naturally, the fact of invasiveness and oper- from pancreatic ductal adenocarcinoma. This seems to be
ating the transducer on top of an endoscope requires a highly still a crux in modern diagnostic.
skilled investigator and the results are operator depended. To Since the introduction of ultrasound contrast enhancers,
make the method more broadly available, there are training the sensitivity of Doppler color imaging did increase even
programs provided on different skill levels from all ultra- more due to the fact that the contrast enhancer can be used as
sound societies worldwide [2]. a simple Doppler enhancing tool. This led to a totally new
The most difficult thing is to get the anatomical orienta- understanding of the meaning of Doppler images of pancre-
tion right and to learn typical images of certain tumors like atic adenocarcinoma [5, 6]. It could be observed that the neo-
the appearance of a serous microcystic cyst adenoma [3]. vascularization of pancreatic adenocarcinoma is
Once this is done, there are still diagnostic challenges left fundamentally different to chronic inflamed areas and this
B-mode ultrasound imaging cannot solve successfully and can be made visible using the combination of contrast
this is, when more modern imaging methods are required. enhancer and a simple Color Doppler technique [7]. To get
Most modern endoscopic ultrasound equipments provide the best results, the high powered and very close to the object
a variety of options. The most basic of those are color placed ultrasound transducer has to be powered down by
Doppler ultrasound on different levels. Using the informa- approximately half. This ensures that the gas bubbles (in
tion of color Doppler ultrasound to discriminate in between Europe most common Sonovue) do not disintegrate to fast
highly vascularized lesions and low vascularized lesions can and can work as a Doppler enhancer. The advantage of this
sometimes make all the difference. The typical image of a method is the possibility to discriminate in between venous
pancreatic cancer per example is an echopoor, poorly defined and arterial vessels by using additionally the pw-Doppler
and invasive lesion which very often involves the pancreatic mode. Looking at the lesions closely it is typical, that inflamed
duct and leads to a dilatation of the downstream pancreatic pancreatic tissue is determined by a rich netlike vessel system
duct. However neuroendocrine tumors or even inflamed pan- with arterial and venous vessels side by side whereas pancre-
creatic tissue can mimic this appearance and accordingly atic cancer shows only arterial vessels and no venous vessels
result in a wrong diagnosis, what could be fatal to the patient. can be displayed. This phenomenon can be explained by the
different neovascularization from those fundamentally differ-
ent entities. Adenocarcinoma grows invasive with lots of
M. Hocke (*)
Department of Internal Medicine 2, Helios Hospital Meiningen, fibroblastic areas, so venous vessels will be easily invaded
Meiningen, Germany and heavily compressed. The neovascularization of the tumor
536 M. Hocke
is marked by the feeding function of the tumor. This results in The major advantage of low MI CE-EUS comes up, if struc-
the missing detection in enhanced Doppler imaging. The tures are investigated which requires a high resolution of the
assumption is undermined by the increased resistance index perfusion of the capillary bed. This is mainly the case in cystic
of the tumorous arterial vessels and histology appearance of tumors. It is well known that cystic tumors can be differentiated
the tumor [8]. In chronic inflamed areas the neovasculariza- from pseudocysts and dysontogenetic cysts by the characteris-
tion serves a different purpose. Blood should approach the tic of perfusion of the cystic septae or wall [12]. High MI
inflamed area in big quantities and waste products of the CE-EUS is in this regard to artifact overloaded and not sensi-
inflammation process have to be removed effectively. The tive enough due to the limitation of the necessary vessel diam-
well-known effect of reddening and swelling of an inflamed eter. Low MI CE-EUS does not show motion artifacts and is
area is achieved by newly built arterial and venous vessels, highly sensitive and therefore excellent in that regard.
resulting in the typical imaging explained above [6]. Unfortunately, the discrimination of malign and benign cystic
This method is in place for 15 years now and is recom- tumors or different cystic tumor entities like serous cystade-
mended since 2011 in the EFSUMB guidelines for dis- noma or mucinous cystadenoma is still difficult. Nowadays
crimination of focal chronic pancreatitis and pancreatic there is evidence that contrast-enhanced endoscopic ultrasound
carcinoma [9]. can discriminate cystic nodules from mucinous clots and might
Still the technique of contrast-enhanced endosonography be helpful to estimate worrying signs [13, 14].
refined further and for approximately 10 years investigators
are able to use the technique of low mechanical index imag-
ing in endoscopic ultrasound accordingly to the percutane- Elastography
ous approach [10]. Although the image quality is still behind
the percutaneous approach, an incredible amount of informa- Elastography is used to determine tissue stiffness without
tion can be taken from it. To understand the difference of the touching it [15]. How important tissue stiffness in the diag-
Doppler enhanced imaging (or high mechanical index nostic of pancreatic tumors can be is plainly explained by the
contrast- enhanced endoscopic ultrasound – high MI method, a pancreatic surgeon looks for the estimation of area
CE-EUS) and the low mechanical index contrast-enhanced of resection of a pancreatic carcinoma. Due to tumor palpa-
endoscopic ultrasound (low MI CE-EUS) further, it is impor- tion, he is highly accurate able to resect the tumorous tissue
tant to analyze both methods more deeply. (later confirmed by the pathologist).
In high MI CE-EUS the resulting image shows only arte- It was always the wish of operators of endoscopic ultra-
rial or venous vessels bigger than the size of arteriolies and sound to use this simple tool as a discrimination tool for
venoulis with an estimated diameter bigger than 0.1 mm. In pancreatic carcinomas. Mostly strain elastography is used
low MI CE-EUS a display of the capillary field is possible for stiffness discrimination purposes in endoscopic ultra-
due to the fact that the size of a contrast enhancer bubble is sound. Strain elastography allows a continuous display of
roughly the size of an erythrocyte and can be individually the tissue stiffness during the investigation. Mostly used is a
displayed. Taken that into account it should be realized by color coding what displays stiff tissue with the color blue
the operator that those similar performed methods produce and soft tissue with the color green or red. Unfortunately,
fundamentally different results [6]. the tissue cannot be compressed with the transducer—like it
Most impressive is the difference in the discrimination of is the case in percutaneous ultrasound. Therefore the com-
focal chronic pancreatitis from pancreatic carcinoma. pression wave of the aortic pulsation is been used, what is
Although the low MI CE-EUS can produce perfusion videos not as accurate as manual compression of the tissue [16].
in a much higher resolution than high MI CE-EUS, that reso- Due to the fact that the estimation of the stiffness is made by
lution does not increase the sensitivity and specificity of the the impression of the operator, the method is fragile.
method. This can be easily explained if looked more deeply Recently operator- independent software analyzing tools
into the histology of the lesions. Unfortunately, in chronic have been developed to overcome the shortcoming. Most
pancreatitis inflammation processes lead to a fibrotic change successful seem to be postprocessing algorithms in this
of the inflamed areas. This heavily involves the capillary bed regard [17]. Whereas the method has a very high sensitivity
resulting into a diminished perfusion of the area in low MI to display any solid pancreatic tumor in the otherwise
CE-EUS, exactly the same as the pancreatic cancer does. unchanged pancreas, the specificity of discriminating
However, the neovascularization of the bigger vessels from chronic pancreatitis from pancreatic carcinomas drops sig-
0.1 mm up is not been involved and therefore still usable as nificantly [11, 18]. This is due to the fact that fibrotic altera-
a diagnostic tool [11]. A typical example of a pancreatic car- tion with increased stiffness occurs as well in pancreatic
cinoma is shown in Fig. 1. carcinoma as in chronic pancreatitis.
New Diagnostic and Interventional Endoscopic Techniques 537
a b
Fig. 1 (a) Example of a poor vascularized pancreatic carcinoma after area. (b) The same area in high mechanical index mode. A few vessels
injecting of 4.8 mL Sonovue (Bracco) in low mechanical index mode. are displayed within the tumor. Doppler analysis shows only arterial
The cancer is delineated with three red arrows in the contrast screen, signals in the vessels indicating pancreatic carcinoma
showing a dark brown color what indicates less contrast agent in the
Three-Dimensional Endoscopic Ultrasound In addition, the three-dimensional image can more easily
demonstrate the anatomy to a doctor, who is not trained in
Some endoscopic ultrasound machines are even able to dis- the method—per example showing the surgeon the position
play the ultrasound image three-dimensional. The short com- of a main duct IPMN (intrapapillary mucinous neoplasia) to
ing of the method is that the three-dimensions cannot be the rest of the pancreas.
displayed in a metric way. It would be a nice tool to use met-
ric three-dimensional pictures for follow-up tumor treat-
ments, however the technique seems not to be feasible these ndoscopic Fine Needle Puncture
E
days. in the Diagnostic Setup
However, three-dimensional display of pancreatic tumors
can still have an advantage. The technique is easy to apply— Although endoscopic fine-needle puncture is not a recent
more easily with a longitudinal transducer by a simple tool, the understanding of the importance of combining
sweep, than a radial transducer by pushing or pulling—and it ultrasound images with pathological results and the advan-
could make the analyzation of the tumor borders easier. In tages of different handlings of the resulting material as well
clinical practice, the endoscopic ultrasound operator has to as the advantages and disadvantages of various pathological
keep attention to multiple things: the ultrasound picture, the methods increased a lot lately [22].
movement of the ultrasound probe, the reaction of the patient, In the beginning of endoscopic ultrasound fine-needle
the movement of the ultrasound tip due to breathing move- aspiration only cytological analysis of the resulting spec-
ments and motion artifacts. The advantage of a three- imen could be performed. Due to the fact that pancreatic
dimensional sweep is the post-processing analysis on the cytology was not a common method before the introduc-
ultrasound machine. The operator can countless times cut tion of endoscopic ultrasound, the learning curve was
through the data block in any dimension. He can analyse dif- two-fold in the beginning. It was hard for the ultrasound
ficult areas without the stress of the actual investigation [19– operator to handle the resulting specimen the right way
21]. 3 dimensional pictures of a pancreatic carcinoma are and hard for the pathologist to diagnose different
shown in Fig. 2. diseases accordingly. Up to this time, pathology was
538 M. Hocke
a b
Fig. 2 (a) Example of a 3D reconstruction of a pancreatic carcinoma in cancer to the surrounding area visible. (b) The same area displayed in
low mechanical index mode after application of 4.8 mL Sonovue high mechanical index mode with help of 3D reconstruction. The feed-
(Bracco). The carcinomatous area is delineated with three red arrows. ing arterial vessels are displayed within the tumor
The cube can be cut through in any direction to make the relation of the
based on histology and cytology was a niche diagnostic material from the tumor included but not from the sur-
method [23]. rounding tissue, what makes the histology analysis even
The problem has been mainly overcome these days, but harder.
the aim for histologic specimens—more driven by patholo- Nevertheless, a major development has taken place from
gists—still stands. many companies to refine the tip of the endoscopic ultra-
Cytology has the major advantage, that diagnosis can sound needle to collect tissue instead of single cells from the
be made with very little material because the diagnosis is lesion in order to make histology analysis of the material
made of the cell appearance rather than the cell behavior. rather than cytologic analysis [24].
A cancerous cell shows certain signs of malignancy and If this development is really necessary still stands to prove,
different cancer types produce different cell appearances. because even the more advanced pathological methods like
The most important fact is that cytological specimen immunohistology or gene analysis can be made as well from
should be carefully handled without destroying the cell histologic specimen as cytologic specimen [25, 26].
structure. The easiest way to achieve that is simple air The newest development for collecting material from the
drying of loaded slides. For histological specimen a pancreatic area is to use a thick needle as a transporter for a
Formalin fixation is necessary. However, Formalin fixa- histological forceps. This method was developed for wall
tion leads to a degeneration and shrinking of proteins, analysis of pancreatic cysts. In theory, it should be an advan-
what makes the analysis of the cell appearance hard to tage over the different collecting methods with a cytology or
impossible. Per example a small cell carcinoma has in histology needle [27]. The disadvantage is the small diame-
cytology pathognomonic signs which cannot be spotted in ter of the forceps and that the collection can only take place
Formalin fixated specimens anymore. Cytological smears on the opposite side of the puncture. If the method is able to
of a pancreatic carcinoma and a neuroendocrine tumor are increase the diagnostic accuracy of endoscopic fine-needle
shown in Fig. 3. puncture has to be still proven.
One major diagnostic criterion of cancer in histology is
the proof of the invasiveness of cancer cell complexes into
healthy tissue. Unfortunately, this border will be rarely dis- Interventional Endoscopic Ultrasound
played in a specimen resulting from endoscopic ultrasound
fine-needle aspiration. The principle of puncture is to Tumor Destructive Methods
advance the needle tip into the lesion and start collecting
the material from this position from the tumor without leav- Using the possibility of advancing a needle very accurate
ing it anymore. In this way the resulting specimen has only into the pancreas opens multiple opportunities. One is the
a b
Fig. 3 (a) A typical example of pancreatic cancer cells in a smear cally enlarged and inhomogenous formed nuclei. (b) A typical example
stained with QuikStain (Polysciences Inc.) 1000× with oil immersion. of cells of a well differentiated neuroendocrine tumor of the pancreas.
The five cancer cells are visible in the centre of the picture with typi- Note the smaller and more homogenous formed nuclei
possibility of tumor ablation. First performed on an insulin- transhepatic cholangiography with drainage—PTCD) is the
oma in an otherwise inoperable state using poor ethanol it disturbed body integrity of the patient, if a permanent percu-
had a very good effect on the symptomatic [28]. Since then taneous drainage cannot be avoided. Another problem arises
multiple case reports have been published and among a vari- if the patient developed ascites or if metastasis blocks the
ety of possibilities the technique of radio-frequency therapy way into the dilated bile ducts.
with a special endoscopic ultrasound needle has been devel- Endoscopic ultrasound provides an interesting alterna-
oped [29, 30]. tive because dilated bile ducts can be displayed from vari-
It has to be considered that tumor ablation in general ous positions out of the duodenum and the stomach. If they
serves a palliative purpose and side effects like bleeding or can be displayed, they can also be punctured and therefore
inducing an acute pancreatitis have to be considered. a guide wire can easily be placed. Over the guidewire the
However, in otherwise inoperable patients it can provide a way can be dilatated and it is possible to introduce a plastic
real alternative to surgery. or metal stent to create a short cut from the liver into the
Based on the same principle there are other developments gastrointestinal tract without being hampered by the tumor
like ethanol or chemotherapy-based ablation of pancreatic [34]. Meanwhile the method developed in such a way, that
cystic tumors, but those methods did not pass the experimen- results can be produced, who are comparable or even better
tal stage yet [31]. than the drainage via ERCP [35]. It has to be mentioned
that the side effect of the endoscopic ultrasound-based
drainage is higher regarding bleeding or perforation, but
Therapeutic Endoscopic Ultrasound the long-term success is higher, once the drainage is in
place. The main advantage of the method is the remained
Advanced and inoperable tumors can lead to a variety of body integrity of the patient, what is of utmost importance
complications. Mostly those complications arise from the in a palliative stage [36, 37]. An internal drainage from the
invasive and compressive behavior of the tumor. The liver into the stomach is shown in Fig. 4.
most common complication is the blockade of the com- As well as the bile duct, the pancreatic duct can be drained
mon bile duct due to a pancreatic carcinoma located in by the same approach. Mostly a dilated pancreatic duct has
the pancreatic head. Normally those blockades can be no direct clinical significance. However, in some cases it
treated by ERCP with implantation of a plastic or metal could produce a fistula or pain due to an ongoing pancreati-
prothesis [32]. tis. The drainage of the pancreatic duct into the stomach
In some cases, however, the Papilla vateri cannot be should be reserved for highly skilled endoscopists due to
reached due to the compression of the duodenum. In those procedural difficulties and a higher complication rate. This
cases, a percutaneous approach was commonly used [33]. arises from mostly instable guidewire positions and the usu-
The problem of the percutaneous approach (percutaneous ally hard pancreatic tissue, especially in patients with chronic
540 M. Hocke
a b
Fig. 4 (a) Endoscopic ultrasound guided cholangiodrainage in a (Hanarostent, Olympus Medical) for internal drainage was placed over
patient with a pancreatic cancer and closure of a biliary metal stent after the guidewire to drain the bile duct into the stomach. (c) View of the end
implantation of two duodenal metal stents. The EUS transducer is of the stent within the stomach. Bile and pus is draining out of the inner
placed in the stomach and a guidewire is introduced into the enlarged part of the partly covered metal stent
intrahepatic bile duct over the left liver lobe. (b) A special biliary stent
b
a
Fig. 5 (a) Endoscopic ultrasound guided pancreatic duct drainage in a atic duct. (b) A double pigtail plastic stent is introduced over the guide-
patient with chronic calcificated pancreatitis and complete closure of wire into the enlarged pancreatic duct ensuring the stable stent position
the pancreatic duct by pancreatic stones. The EUS transducer is placed within the duct and the stomach. The contrast agent did drain already
in the stomach and a guidewire is introduced into the enlarged pancre- out by the introduced stent
pancreatitis. If the procedure cannot be finished successfully, Conclusion

postinterventional pancreatitis, sometimes severe, is basi-
cally a certainty. If the procedure is successful, it can be a It can be safely said that endoscopic ultrasound developed in
great relief for the patient and can avoid further complica- the past years into the main diagnostic and therapeutic
tions like the development of peripancreatic pseudocysts or method of many pancreas diseases. The technological
walled of necrosis [38, 39]. A typical example of an internal improvements are astonishing and the available methods
drainage of the pancreatic Duct is shown in Fig. 5. should be broadly used to diagnose and treat patients with
If peripancreatic pseudocysts or walled of necrosis pancreatic tumors more efficiently. Although not all meth-
develop, the complication can also be treated endoscopically. ods, like the 3-D imaging, are part of clinical routine yet, but
Meanwhile, special metal stents with an electrocautery deliv- if they will be developed further, they might as well turn into
ering system have been developed which can easily be major diagnostic tools like the contrast-enhanced endoscopic
applied and made the method broadly available basically in ultrasound already has.
every endoscopy suite [40]. An example is given in Fig. 6.
542 M. Hocke
a b
Fig. 6 (a) Endoscopic view of the inner part of a HotAxios stent tific) in place for treatment of a massive walled off necrosis after acute
(Boston scientific) with an additional introduced double pigtail plastic pancreatitis. The upper stent has two double pigtail plastic stents intro-
stent to prevent closure of the stent by pancreatic necrosis. (b) duced to ensure the drainage of pus from two different areas of the
Endoscopic view into the cavity partly filled with necrotic material of a necrotic cavity
walled off necrosis. (c) Two HotAxios stents systems (Boston scien-
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Mirko D'Onofrio, Paola Capelli, Paolo Pederzoli - Imaging and Pathology of Pancreatic Neoplasms - A Pictorial Atlas-Springer (2022)

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Mirko D’Onofrio

Imaging and Pathology

Imaging and Pathology of

ISBN 978-3-031-09830-7 ISBN 978-3-031-09831-4 (eBook)

Verona, Italy Claudio Bassi

Mirko D’Onofrio, Riccardo De Robertis,

Introduction artery, as well as for circumferential extension to the superior

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 1

Rarely, ductal adenocarcinoma of the pancreas is inciden- Pathology

Fig. 14 Ductal adenocarcinoma with double-duct sign.

Fig. 25 Ductal adenocarcinoma and inflammatory

Fig. 32 Ductal adenocarcinoma a

Fig. 34 Ductal adenocarcinoma with

Fig. 50 Isodense ductal

Fig. 75 Autoimmune pancreatitis. (a)

Riccardo De Robertis, Paola Capelli, Chiara Longo,

Introduction be performed before biliary stenting, while restaging should

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022 99

Riccardo De Robertis, Mirko D’Onofrio,

Introduction complex (TSC), glucagon cell hyperplasia and neoplasia [4,

R. De Robertis (*) · M. D’Onofrio · L. Geraci

Table 1 Neuroendocrine neoplasms classification

Fig. 18 Nonfunctioning neuroendocrine neoplasm. (a) Surgical speci-

Fig. 24 Nonfunctioning neuroendocrine neoplasm at DWI. (a, b) MRI

Fig. 41 Wirsungocele caused

Fig. 67 Neuroendocrine tumor growing in the main pancreatic duct.

Fig. 71 Neuroendocrine tumor in Von Hippel–Lindau syndrome.

References 5. Crona J, Skogseid B. Genetics of neuroendocrine tumors. Eur J

Mirko D’Onofrio, Antonio Giugliano, Gregorio Aluffi,

Introduction images and are usually characterized by poor enhancement

Unlike PDAC, it causes a long and smooth narrowing of Peripancreatic Structures

Fig. 7 Autoimmune pancreatitis. CT: diffuse enlargement of the

Fig. 14 Peripancreatic accessory spleen. CT: a small nodule

14. Hough TJ, Raptopoulos V, Siewert B, Matthews JB. Teardrop supe-

Giovanni Morana, Mirko D’Onofrio, Paolo Tinazzi Martini,

Introduction cant differences in frequencies of malignancy in IPMNs

Ultrasound Accurate post-processing is needed in order to obtain

Clinical Presentation Atypical

Asymptomatic Rarely, atypical appearances of complicated IPMNs have

In MD-IPMNs, total or segmental ductal dilation is observed,

Fig. 2 IPMN branch-duct type: site. Whole

Fig. 10 IPMN branch-duct type. (a)

Fig. 12 IPMN branch-duct type. EUS

Fig. 24 Multifocal branch-

Fig. 28 IPMN branch-duct type: stable at follow-up. (a) MRCP study

Fig. 34 IPMN main-duct type. (a–c) a

Fig. 36 IPMN main-duct and branch-duct type: content.

Fig. 40 IPMN. EUS study: branch-duct

Fig. 42 IPMN mixed type. MRCP:

Fig. 56 IPMN main-duct

References 19. Zamboni G, Hirabayashi K, Castelli P, et al. Precancerous

Paola Capelli, Paolo Tinazzi Martini, Giovanni Morana,

Introduction A series of 257 resected SCAs [6] has suggested that

centrally oriented. In 15% of cases, a central solid echoic

Imaging Computed Tomography

The typical microcystic type (70%) has a cloud-like mor-

Asymptomatic easily demonstrated at MRI, with a typical hyperintense sig-

Fig. 2 Oligocystic serous a b

Verona, Italy Claudio Bassi

Introduction artery, as well as for circumferential extension to the superior

Rarely, ductal adenocarcinoma of the pancreas is inciden- Pathology

Introduction be performed before biliary stenting, while restaging should

Introduction complex (TSC), glucagon cell hyperplasia and neoplasia [4,

Introduction images and are usually characterized by poor enhancement

Unlike PDAC, it causes a long and smooth narrowing of Peripancreatic Structures

Introduction cant differences in frequencies of malignancy in IPMNs

Ultrasound Accurate post-processing is needed in order to obtain

Clinical Presentation Atypical

Asymptomatic Rarely, atypical appearances of complicated IPMNs have

Introduction A series of 257 resected SCAs [6] has suggested that

Imaging Computed Tomography

Asymptomatic easily demonstrated at MRI, with a typical hyperintense sig-

Introduction The differential diagnosis mainly includes other cystic

Pitfalls and Errors

Differential Diagnosis Conversely, intralesional blood clots and debris, which

Mesenteric Pseudocyst Rare Neoplastic Cystic Pancreatic Lesions

Introduction True pancreatic metastases more commonly arise from

Metastases Pancreatic metastases can be solitary, multifocal, or may

Atypical Renal cell metastases are unlikely to be confused with duc-

Metastases Primary Pancreatic Lymphoma

Differential Diagnosis findings to differentiate between these two entities: lym-

Cystic Appearance extensively necrotic PDAC can be misdiagnosed as a pseudo-

Acute Pancreatitis Pancreatitis-Like Appearance

Pancreatic Carcinoid pancreatic duct resulting in a disproportionate dilation of

Serous Cystadenoma contain a central scar. Unilocular SCA is composed by a

Solid Pseudopapillary Neoplasms

Rare Pancreatic Neoplasms

Distal Pancreatectomy also be necessary after an initial partial pancreatectomy

Introduction impossible without invasive methods. In any case, no radio-

Introduction last paragraph, we also shortly discuss the impact of

CT Perfusion iodine map may replace conventional CT perfusion, allow-

1-Weighted Imaging (T1WI) and Dynamic

espiratory Artefact Reduction

ancreatic Neoplasia MRI Perfusion

imultaneous Multi-Slice (SMS) Acquisition

Introduction promising results for the differential diagnosis of thyroid

Shear Wave Elastography Safety Considerations

pancreatitis was isoenhancing during all phases, with intral- Fusion