Postgraduate Medicine

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A rare case of intraductal tubulopapillary

neoplasm of the pancreas – case report (with
video)

Ankit Dalal, Gaurav Patil, Amol Vadgaonkar & Amit Maydeo

To cite this article: Ankit Dalal, Gaurav Patil, Amol Vadgaonkar & Amit Maydeo (2019): A
rare case of intraductal tubulopapillary neoplasm of the pancreas – case report (with video),
Postgraduate Medicine, DOI: 10.1080/00325481.2019.1669058

To link to this article: https://doi.org/10.1080/00325481.2019.1669058

Accepted author version posted online: 15

Sep 2019.

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 Publisher: Taylor & Francis & Informa UK Limited, trading as Taylor & Francis Group

Journal: Postgraduate Medicine

DOI: 10.1080/00325481.2019.1669058
A rare case of intraductal tubulopapillary neoplasm of the pancreas – case
report (with video)

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Ankit Dalal, Gaurav Patil, Amol Vadgaonkar, Amit Maydeo

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Affiliation:

Baldota Institute of Digestive Sciences, Global Hospitals, Mumbai, Maharashtra, India

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Correspondence:
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Dr. Ankit Dalal, Consultant Gastroenterologist

Baldota Institute of Digestive Sciences, Global Hospitals, Mumbai, Maharashtra, India - 400012
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Email: ankit.dalal@gmail.com
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Intraductal tubulopapillary neoplasm (ITPN) is a premalignant epithelial tumor of the pancreas.

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We report a case of ITPN detected incidentally during histopathology examination (HPE) from a
specimen taken at the time of endosonography in a patient with pancreatitis. A 53-year-old
man presented with severe recurrent epigastric pain, associated with episodic non bilious
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vomiting, with a weight loss of about 7 Kg since 15 days. He underwent Magnetic resonance
cholangiopancreatography which showed an ovoid soft tissue lesion in the Pancreatic duct (PD)
reported as possible intraductal neoplasm. Patient underwent Endoscopic Ultrasound, whereby
the PD was dilated and a large hypoechoic lesion was noted in the PD (head region) causing
upstream dilatation. Lesion did not show any vascularity on Doppler. Fine needle biopsy was
sent from the intraductal lesion for histopathology examination (HPE). Patient then underwent

Information Classification: General

 an ERCP. After performing a pancreatic sphincterotomy, pancreaticoscopy was done using
SPYGLASS DS system which showed a nodular intraluminal lesion in the head region with
irregular and abnormal vascularity and papillary fronds. Biopsies were taken from this lesion
using SpyBite biopsy forceps. To our surprise this HPE report came out to be ITPN. Patient was
then referred for surgery. There is often difference of opinion in distinguishing and classifying
such tumors when compared to the subtypes of mucinous neoplasm. Identification of this

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neoplasm is often challenging for pathologists as well as radiologists. We present this case since
it is infrequent and atypical in routine medical practice.

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Key words: Intraductal, Neoplasm, Pancreas, Surgery

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INTRODUCTION

Pancreatic cancer is the eleventh most common cancer around the world [1], and sixth most
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common among the gastrointestinal tract. The incidence of pancreatic cancer in India is 0.5 -
2.4 per 100,000 in men and 0.2 - 1.8 per 100,000 in women [2]. The long term outcomes for
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pancreatic cancer are unsatisfactory. It is a deadly disease due to its high mortality and low
survival rates [3]. It rarely presents with symptoms during the early stages. Chemotherapy and
radiation are often not that effective. Surgery remains the only option, unfortunately the
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survival rate is 5 years for 7% of the people post which it is known to recur again. Lack of
standardized screening tools make the diagnosis difficult in the early stages of cancer when it is
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most likely to be cured. About 95% of pancreatic tumors are adenocarcinomas and are
commonly seen in the head of pancreas [4]. Intraductal tubulopapillary neoplasm (ITPN) is an
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uncommon tumor that accounts for < 1% of pancreatic exocrine neoplasms and 3% of
intraductal pancreatic neoplasms [5]. It manifests as a solid mass impeding the main pancreatic
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duct (MPD) causing upstream duct dilation. Endoscopic Ultrasound is a useful tool to indirectly
visualize the pancreas and to obtain a biopsy for histopathological examination.
Immunohistochemical workup helps in appropriate diagnoses. Being malignant, it is always
wise to surgically resect it as per the oncology criterion. Pancreaticoduodenectomy is the
preferred surgical procedure [6]. Though histological and morphological features are well
documented little is known about its prognosis and surgical outcome.

Information Classification: General

 CASE REPORT

A 53-year-old man presented with severe recurrent epigastric pain, radiating towards
back and associated with episodic non bilious vomiting since 15 days. He had similar complaints
twice previously in the last, 2 months. He also complained of abdominal fullness and bloating
and had a weight loss of about 7 kg in past 15 days. He was a known diabetic and denied any

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recent drug history. On examination, his vitals were stable. At physical examination his

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abdomen was soft, but no abdominal tenderness. Lab investigations were normal except for
raised serum amylase (709 U/L) and lipase (7911U/L). His lipid profile, serum calcium and serum

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parathormone levels were normal. His cancer antigen 19-9 was normal. Viral markers were

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negative. He underwent a computed tomography scan of the abdomen and pelvis with
intravenous contrast which was reported as acute interstitial pancreatitis, MPD was dilated to
11 mm. Magnetic resonance cholangiopancreatography (MRCP) (Fig. 1) was also done which
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was reported as bulky head of pancreas and uncinate process with an ovoid soft tissue lesion in
PD in neck region reported as possible intraductal neoplasm. He was admitted for further
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workup and management.

Patient was managed conservatively with nil per os, intravenous fluids and analgesics.
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He was planned for an EUS guided fine needle aspiration biopsy and if need be an Endoscopic
retrograde cholangiopancreatography. A linear echoendoscope was used to perform the EUS,
Pancreatic parenchyma appeared heterogeneous with peripancreatic inflammatory stranding
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and PD was dilated measuring 11.3mm. A large 1.2x1.6cm hypoechoic lesion in the PD was
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noted in the head region causing upstream dilatation (Fig. 2). Lesion did not show any
vascularity on Doppler. Fine-needle aspiration was taken from the intraductal lesion during EUS
and sent for HPE which was reported as paucicellular nondiagnostic aspirate. Aspirated ductal
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fluid showed a CEA of 26.3ng/ml and amylase of 68814 U/L. ERP was performed which showed
a dilated MPD with a filling defect in the head region. After performing a pancreatic
sphincterotomy, pancreaticoscopy was done using SPYGLASS DS system (Fig. 3). It showed a
nodular intraluminal lesion in the head region with irregular and abnormal vascularity and
papillary fronds. Biopsies were taken from this lesion using SpyBite biopsy forceps. A 5F
pancreatic stent was placed.

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 The biopsy specimen consisted of sheets and papillary structures composed of uniform cuboidal
cells which in the sheet like areas showed closely packed acini with central lumina. There were
no secretions in the lumina. The nuclei were round, dark and stippled. Nucleoli were not
apparent. Mitoses was not very obvious. There were no squamous morules. The tumor cells
expressed Mic-2, CK-7(Fig. 4), glypican 3 (Fig.5) and cytoplasmic beta catenin (Fig.6). They were
immunonegative for CK 20, CA-19-9, synaptophysin, chromogranin (repeated twice), CD 56,

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Pax-8, PSA, NKX 2.2, NKX 3.1 and, AFP. The Mib-1 labelling index was 50%. On histological
grounds this tumor appeared as a nodular, noncystic mass within a duct (Fig. 7) hence final

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diagnosis was termed to be ITPN. Prognosis was discussed with the patient relatives and then
referred for surgery. The entire procedure is shown in supplementary Video 1. Patient is

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planned for a Whipple’s surgery after 4 weeks once the episode of pancreatitis settles down.

DISCUSSION
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ITPN is an intraductal, tubule-forming epithelial neoplasm without apparent production of
mucin [7]. Intraductal papillary mucinous neoplasm (IPMN) is mucinous neoplasm, while ITPN is
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a solid intraductal neoplasm with no or minimal mucin. There can be histological overlap
between the two leading to an erroneous diagnosis. Use of molecular tests help to distinguish
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between the two [6]. There have been very few cases of ITPN hence long term follow-up is
inadequate to guide for routine management. Abdominal pain in our patient is likely
contributed to ITPN. To this date, reports of ITPN are rarely mentioned in routine
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gastroenterology practice and little is known about its potential for malignancy.
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The lesion at the head of pancreas causes ductal obstruction which leads to repeated attacks of
pancreatitis. CEA levels were done as the lesion resembled IPMN morphologically during EUS.
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However, histopathology proved otherwise. ITPN are premalignant and have demonstrated its
potential for progression to invasive carcinoma. The first case was recognized in 1990s, named
as intraductal tubular carcinoma in 2002, renamed as ITPN in 2009 [6]. There is no gender
predominance and is equally seen among males and females. The mean age at diagnosis is 61
years (range 35–78 years) [7]. Two-thirds of patients usually exhibit nonspecific symptoms
including abdominal pain, weight loss, vomiting, exacerbation of diabetes, jaundice, and fever.

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 While the remaining one-third are often asymptomatic. Nearly half of these neoplasms are
located in the head of pancreas. However, it has been seen in other parts as well including head
and body, body and tail with diffuse involvement [7]. They grow slowly and become large at the
time of diagnosis. Size of the tumor varies and can range approximately from 1 to 15 cm
(average of 3 cm). Laboratory investigations are often negative including tumor specific
antigens. Surgery is the treatment option in most cases with the commonly performed being

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pylorus preserving pancreatoduodenectomy and distal pancreatectomy.

Plain abdominal radiographs yield minimal results. One needs to make use of advanced

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radiological screening tools. ITPN are usually visualized as poorly enhancing lesions throughout

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the scanned phase. Motosugi et al [8] described a 2-tone duct sign in ITPNs on the CT and MR
images with a higher and lower density area with the former representing the tumor in the
MPD and the latter representing dilated upstream duct respectively. Most ITPNs are known to
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arise in the MPD with ductal dilation. A ‘‘cork-of-wine-bottle sign’’ is usually seen on MRCP and
ERCP images, indicating intraductal growth [8]. Sometimes they can have coarse calcification
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which is usually mistaken for neuroendocrine tumor. Insertion of pancreatoscopy with spyglass
was feasible in this case as the pancreatic duct was massively dilated. Pancreatoscopy using the
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SpyGlass allows direct visualization of lesion within the dilated pancreatic duct and allows direct
biopsy with SpyBite forceps.

ITPN typically have uniform high grade dysplasia and frequent mitotic figures. Approximately
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40- 50% of ITPN cases are usually invasive in nature [9] and a high-grade cytologic atypia of the
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tumor cells, the invasive component is limited in extent [10]. This explains the less aggressive
outcome of ITPN in comparison to IPMN [11]. Kolby et al described that 14 (46%) were alive
post-surgery and tumor-free at the last follow-up visit between 7 months to 6 years [7]. To
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improve prognosis radical surgery is recommended before the neoplasm evolves into an
invasive carcinoma. With 37 patients of ITPN post-surgery, the overall 1, 3, and 5-year survival
rates were 97.3, 80.7, and 80.7%, respectively. With ITPN associated carcinoma, patients had an
overall 5-year survival of 81.5% [12,13]. A higher risk of invasion is seen with male sex, larger
tumor size, and high Ki-67 proliferation. ITPNs are positive for cytokeratin (CK), CK19, MUC1
and MUC6, negative for MUC2, MUC5AC, trypsin and b-catenin. However, rare cases of

Information Classification: General

 MUC5AC-positive ITPNs have been reported. There might be possible mutations on β-catenin
which can result in diverse effects on cell growth and metabolism due to which it may be
negative in some patients. β-catenin was negative in 94% of the cases [7]. Mutational analysis
revealed TP53 mutations in 27%, PIK3CA mutations in 18%, BRAF mutation in 15%, and KRAS
mutation in 10% of the ITPN cases [14]. KRAS mutations are much more common in IPMN,
whereas PIK3CA mutations are much more common in ITPN.

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The histopathology in our case did not show any aggressive features. Also no necrotic areas
were identified possibly as the biopsy sample was taken at endoscopy and is not a completely

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resected specimen. Lack of aggressive features suggests that the lesion in our case was at the
lower end of the spectrum but as the patient was symptomatic with recurrent episodes of

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pancreatitis, resection of the lesion was indicated as it results in better outcomes. There have
been cases of death from multiple ITPN liver metastases. Therefore, surgery remains the gold
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standard to treat patients with ITPN to prevent malignant transformation. These tumors can
recur years after surgery, which is thought to be due to intraductal colonization [5]. However,
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other cases of ITPN resected via distal pancreatectomy did not have recurrence in the follow-up
period, suggesting that total pancreatectomy is not always necessary.
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Diabetic patients and those with a positive family history need to review their condition
regularly and if need be, should undergo a genetic screening test so as to ensure that they are
not at risk for developing pancreatic cancer. Future studies need to focus on various biological
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parameters and genetics of ITPN for an appropriate understanding of the prognostic factors so
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that adequate treatment options are discovered.

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Declaration of Funding

None

Declaration of financial/other interests

The authors have no relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the subject matter or materials

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 discussed in the manuscript. This includes employment, consultancies, honoraria, stock
ownership or options, expert testimony, grants or patents received or pending, or royalties.

Peer reviewers on this manuscript have no conflicts of interest to declare.

Author Contributions Ankit Dalal, Gaurav Patil, and Amol Vadgaonkar collected data. Ankit
Dalal drafted the article. Amit Maydeo provided vital inputs. All the authors were involved in

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the clinical management of this case. All the authors reviewed and approved the final version of

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the manuscript.

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Acknowledgements: We thank Mr. Sehajad Vora for acting as a chief technician and assisting
the procedure.

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 7. Kolby D, Thilen J, Andersson R, Sasor A, Ansari D. Multifocal intraductal tubulopapillary
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Figure legends

Fig 1 lesion seen in Magnetic resonance cholangiopancreatography

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Fig 2 lession seen in Endoscopicc ultrasound

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Fig 3 pancreaticosccopy done using SPYGLA

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Fig 4 hisstopathologgical image of CK-7

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 Fig 5 histopathological image of Glypican

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Fig 6 histopathological image Beta Catenin
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Fig 7 histopathological image of intraductal pancreatic mass

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Video legends

Supplementary Video 1 – procedural details are shown in Supplementary Video 1

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