Rare Malignant and Semimalignant

Epithelial Neoplasms of the Biliary

Tract

Contents Tumors with Rhabdoid Features of the Biliary

Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Small Cell Carcinomas of the Hepatobiliary Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Intrahepatic Cholangiocarcinoma with Rhabdoid
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Primary Rhabdoid Tumor of the Gallbladder . . . . . . . . . . 8
Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Small Cell Carcinoma of the Liver References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
and Bile Ducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Clinical and Imaging Features . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Hepatic PSCC of the Neuroendocrine Type . . . . . . . . . . 3
Hepatic PSCC, Mixed Types . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
PSCC, Non-neuroendocrine Type or with Unknown
Neuroendocrine Features . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Small Cell Hepatoid Carcinoma of the Liver . . . . . . . . . . 4
Small Cell Carcinoma of the Bile Ducts . . . . . . . . . . . . . . . 4
Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Undifferentiated Carcinomas of the Bile Ducts . . . . . 5
Spindle Cell-Type Carcinoma of Bile Ducts . . . . . . . . . 5
Primary Hepatoid Carcinoma of the Bile Ducts . . . . 5
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Hepatoid Carcinoma of the Bile Ducts . . . . . . . . . . . . . . . . . 6
Hepatoid Carcinoma of the Gallbladder . . . . . . . . . . . . . . . 6
Solid Pseudopapillary Tumor (Papillary Cystic
Tumor) of the Liver/Bile Duct . . . . . . . . . . . . . . . . . . . . 6
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Solid Pseudopapillary Tumor Primary to the Liver . . . . 6
Morphologic and Biologic Features of Solid
Pseudopapillary Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

# Springer International Publishing Switzerland 2016 1

A. Zimmermann, Tumors and Tumor-Like Lesions of the Hepatobiliary Tract,
DOI 10.1007/978-3-319-26587-2_44-1
2 Rare Malignant and Semimalignant Epithelial Neoplasms of the Biliary Tract
Abstract
The hepatobiliary tract is the site of an intriguing
group of malignancies occurring in several
other organs, extrapulmonary small cell carci-
noma. In contrast to its bronchopulmonary
counterpart, extrapulmonary small cell carcino-
mas occur with similar rates in female and male
patients. With the exception of the gallbladder,
the biliary tract is very rarely involved. Small
cell carcinomas of the hepatobiliary tract belong
to several categories, i.e., neuroendocrine type,
mixed type, non-neuroendocrine type, and
not otherwise specified types. Small cell
carcinomas are highly aggressive neoplasms.
Diagnosis and classification require immuno-
histochemical and molecular methods. Poorly
differentiated or undifferentiated carcinomas of
the bile ducts also include spindle cell carci-
noma and carcinomas with rhabdoid features.
Unusual neoplasms primary to the bile ducts
also comprise hepatoid carcinoma and solid
pseudopapillary tumor, a neoplasm better
known from the pancreas.
Small Cell Carcinomas
of the Hepatobiliary Tract
Introduction
Extrapulmonary small cell carcinoma is a dis-
tinct category of high-grade malignancies dis-
tinct from bronchopulmonary small cell
carcinoma. In the United States, the estimated
incidence is between 0.1 % and 0.4 % of all
cancers (Levenson et al. 1981; Richardson and
Weiland 1982; Remick and Ruckdeschel 1992;
Walenkamp et al. 2009). In a study from South
East England, covering the years 1970–2004, the
incidence of extrapulmonary SCC was much
lower than for SCC of the lung, similar in males
and females, with incidence rates of 0.45 per
100,000 in males and 0.37 in females (Wong
et al. 2009). The pathology of extrapulmonary
SCC has been reviewed (Frazier et al. 2007).
Poorly differentiated or undifferentiated small
cell carcinomas also arise in the gastrointestinal
tract, including the hepatobiliary tract.
Epidemiology
In the entire gastrointestinal tract, 0.1–1 % of all
malignancies are small cell carcinomas, with the
esophagus being the most common primary site
(Galanis et al. 1997; Fenoglio-Preiser 2001;
Brenner et al. 2004a; Brenner et al. 2007; Lee
et al. 2007). With the exception of the gallbladder,
the biliary tract is very rarely involved by this
malignancy. Among 544 reviewed gastrointestinal
cases, 46 were located to the gallbladder (8.4 %),
6 in the ampulla (1.1 %), 3 in the common bile
duct (0.5 %), and 7 in the liver (1.3 %) (Brenner
et al. 2004b). In a study of 52 patients with
extrapulmonary SCC, 33 (62.3 %) were detected
in the esophagus, 5 in the cervix, 4 in the larynx,
3 in the pharynx, 2 in the upper sinus, 2 in the
rectum and sublingual gland, 1 in the thyroid gland,
1 in the pleura, and 1 in the liver (Yuan et al. 2006).
Classification
Primary small cell carcinomas (PSCC) of the
hepatobiliary tract can come in five basically dif-
ferent forms, i.e., (1) PSCC of the neuroendocrine
type, (2) PSCC of mixed type, (3) PSCC of
non-neuroendocrine type, (4) PSCC of hepatoid
type, and (5) PSCC of unknown type (PSCC, not
otherwise specified (NOS)) (Table 1). Part of
PSCC described in the older literature are usually
PSCC-NOS, owing to the lack of immunohisto-
chemical examinations.
Table 1 Types of primary small cell carcinomas (PSCC)
of the hepatobiliary tract
PSCC of the neuroendocrine type
PSCC of mixed type
PSCC of non-neuroendocrine type
PSCC of hepatoid type
PSCC, not otherwise specified
Small Cell Carcinoma of the Liver and Bile Ducts
Small Cell Carcinoma of the Liver and
Bile Ducts
Introduction
Small cell carcinoma can develop as a very rare
primary or apparently primary malignancy within
the liver substance, without proven connection to
intrahepatic bile ducts. PSCC of the liver forms a
heterogeneous group of lesions, as part of the
cases in the old literature were reported without
immunohistochemical and/or ultrastructural
examinations and are therefore difficult to clas-
sify. Based on what we know today, most of the
reported cases probably were undifferentiated
neuroendocrine tumors. As bronchopulmonary
small cell carcinoma can be small even in the
metastasizing phase of disease, some small cell
carcinomas purported to be liver tumors may in
fact have been a metastasis of a missed lung
primary.
Clinical and Imaging Features
Similar to other aggressive primary liver malig-
nancies, PSCC present with hepatomegaly, upper
abdominal discomfort or pain, fever, and jaundice
in part of the patients (Sengoz et al. 2003; Yuan
et al. 2006; Otten et al. 2013). Serum AFP is, in
most patients, not elevated, with the exception of
the very uncommon PSCC with AFP secretion
(Walshauser et al. 2013). Imaging reveals solitary
or multiple, sometimes lobulated masses, predom-
inantly in the right liver lobe. On CT scans, inva-
sion of the portal vein and the hepatic artery had
been detected (Jo et al. 2013).
Hepatic PSCC of the
Neuroendocrine Type
Extrapulmonary PSCC shares many features with
bronchopulmonary small cell undifferentiated
carcinoma (Remick et al. 1987; Vrouvas and
3
Ash 1995). This includes the cytological and his-
tological appearance, an aggressive behavior, and
the frequent short-lasting response to either che-
motherapy or radiotherapy. Very few PSCC of the
neuroendocrine type have been reported.
Selected References Nakasuka et al. (1998),
Kim et al. (2004, 2006a, b), Ryu et al. (2005),
Choi et al. (2007), Balta et al. (2008), Iwasa
et al. (2010), Kaman et al. (2010), and Jo
et al. (2013).
In one patient, neuroendocrine PSCC was
associated with adenoid cystic carcinoma of a
salivary gland (Premkumar et al. 2013). In a
review of the few published cases (Choi
et al. 2007), most patients were elderly to old
males, and tumor diameters ranged from 6.7 to
12 cm. It is assumed that these neoplasms arise
from the neuroendocrine cell system of the liver.
The neoplasms usually present as large and soli-
tary, highly invasive and advanced-stage lesions
at diagnosis, although multiple synchronous
hepatic tumors have also been reported (Nakasuka
et al. 1998). In part of the reported cases, immu-
nohistochemistry clearly proved the neuroendo-
crine features of these neoplasms (Kim et al. 2004;
Ryu et al. 2005; Choi et al. 2007).
Hepatic PSCC, Mixed Types
In some rare PSCC of the liver, a second carci-
nomatous component was found in addition to
the small cell neuroendocrine lineage. In one
patient, PSCC had arisen from combined hepa-
tocellular and cholangiocarcinoma (Khaw
et al. 2011). Very rare cases of hepatocellular
carcinomas can contain a small cell tumor com-
ponent with neuroendocrine features, the HCC
component expressing hepatocyte markers and
AFP, and the SCC component reactive for
chromogranin A and synaptophysin (Yamaguchi
et al. 2004; Garcia et al. 2006; Yang et al. 2009).
Composite small cell and mucinous
4 Rare Malignant and Semimalignant Epithelial Neoplasms of the Biliary Tract
adenocarcinoma can also originate from
intrahepatic bile ducts (see below; Ikegami
et al. 2013). Combined SCC and adenocarci-
nomas have been observed in the stomach (Jang
et al. 2007) and the colon (Scherwitz et al. 2002)
and found to have metastasized to the liver.
Malignant neoplasms with such a mixed pheno-
types involving at least two different cell line-
ages may originate from progenitor cells having
two cell fating strategies.
PSCC, Non-neuroendocrine Type or
with Unknown Neuroendocrine
Features
In few examples of PSCC primary to the liver, the
neuroendocrine status was negative or not known,
although the cytologic and histopathologic fea-
tures were those of bronchopulmonary small cell
or oat cell carcinoma (Sengoz et al. 2003;
Morikawa et al. 2008; Ochsenreither et al. 2009;
Groeschl et al. 2013).
Small Cell Hepatoid Carcinoma
of the Liver
This is a still ill-defined category of primary liver
tumors characterized by a small cell neoplasm
arising in non-cirrhotic livers, composed of
broad nests of small epithelial cells with little
supporting tissue. The tumor cells were
immunohistochemically positive for low molecu-
lar weight keratins and alpha-fetoprotein and
erratically for neuroendocrine markers. Such neo-
plasms were suggested to be a variant of hepato-
cellular carcinoma (Zanconati et al. 1996).
Small Cell Carcinoma of the Bile Ducts
Relatively few cases of small cell carcinoma pri-
mary to the common bile duct have been
published. These neoplasms clinically present as
other malignancies developing in this anatomical
compartment, i.e., with abdominal pain and
obstructive jaundice. Probably caused by massive
necrosis, the tumor may cause hemobilia (Cho
et al. 2009). On CT, an intraluminal mass is
detectable (Park et al. 2004; Okamura
et al. 2009), and MRI has shown a tumor mass
surrounding the common bile duct wall, with
ERCP showing a smooth narrowing of the bile
duct (Arakura et al. 2008). In one case, the tumor
was associated with clonorchiasis (Thomas
et al. 2005). Identical p53 gene mutation has
been identified in small cell carcinoma of the
bile duct and malignant proliferating trichilemmal
tumor in the same patient (Nakai et al. 2008).
Histology and immunohistochemistry are the
same as with small cell gallbladder carcinomas
(Kuraoka et al. 2003). Mucinous adenocarcinoma
of intrahepatic bile ducts can rarely be combined
with small carcinoma, the tumors showing CK
19-positive and chromogranin A-positive cell
populations (Ikegami et al. 2013). Small cell car-
cinoma of the bile ducts exhibits an aggressive
biology (Jeon et al. 2006), the longest reported
survival after multidisciplinary management
being 23 months (Okamura et al. 2009).
Selected References Sabanathan et al. (1988),
Motojima et al. (1990), Van der Wal
et al. (1990), Miyashita et al. (2001), Arakura
et al. (2003, 2008), Hazama et al. (2003), Kuraoka
et al. (2003), Park et al. (2004), Kaiho
et al. (2005), Thomas et al. (2005), Jeon
et al. (2006), Viana Miguel et al. (2006), Nakai
et al. (2008), Cho et al. (2009), Okamura
et al. (2009), and Groeschl et al. (2013).
Differential Diagnosis
The main differential diagnosis of hepatobiliary
PSCC is metastasis of bronchopulmonary small
cell undifferentiated carcinoma (Vaideeswar
et al. 2012; Sato et al. 2013), followed by metas-
tasis of extrapulmonary SCCs (mainly the esoph-
agus, the pancreas, and the lower digestive tube;
Akiyama et al. 2011; Al-Jiffry and Al-Malki
2013), several types of other anaplastic neuroen-
docrine and PNET tumors (O’Byrne et al. 1994),
and other small cell undifferentiated neoplasms
(Khalbuss et al. 2005). Another small cell tumor
Primary Hepatoid Carcinoma of the Bile Ducts
of poor differentiation metastasizing to the liver is
Merkel cell carcinoma (Bottles et al. 1984; Gollub
et al. 1996).
Undifferentiated Carcinomas
of the Bile Ducts
There are bile duct carcinomas with a low to very
low level of cell differentiation. This is a typical
feature of lymphoepithelial carcinomas, treated in
a separate chapter. In addition, a very small frac-
tion of intrahepatic cholangiocarcinomas show an
undifferentiated phenotype. These neoplasms
consist of medium-sized to large cells showing a
solid growth pattern in the absence of any glan-
dular structures. In the light of these morphologic
features, diagnosis of cholangiocarcinoma is dif-
ficult, apart from a close spatial relation to
intrahepatic ducts. A derivation from
cholangiocytes is suggested by the positivity for
cytokeratin 7 and CAM5.2 (Fujikawa et al. 2011).
Spindle Cell-Type Carcinoma of Bile
Ducts
Apart from carcinosarcomas with a spindle cell
component, rare variants of cholangiocarcinoma
partially or entirely consist of spindle cells, which
are only attributable to an epithelial cell lineage
after performing immunohistochemistry. These
lesions are of theoretical interest insofar as they
may represent examples of epithelial-
mesenchymal transition.
Spindle cell carcinoma also develops in the
region of the hepatic hilus and may then mimic
classical Klatskin tumor. In one 59-year-old
patient, the tumor had led to complete obliteration
of the left hepatic duct and stenosis of the bile duct
from the superior to the right hepatic duct. Histo-
logically, the tumor was a mixture of tubular ade-
nocarcinoma and spindle cell carcinoma, the
spindle cells being immunoreactive for CAM5.2
and AE1/AE3 (Nakanishi et al. 2007). Generally,
spindle cell carcinoma developing in other organs
co-expresses epithelial and mesenchymal
markers, positivity for epithelial markers being
5
somewhat more often expressed than vimentin
(Lewis et al. 2005).
The differential diagnosis of hepatobiliary
spindle cell carcinoma mainly includes sarcoma-
tous cholangiocarcinomas (Imazu et al. 1995;
Matsuo et al. 1999) and other malignant
sarcomatoid liver tumors (Eriguchi et al. 2001;
Matsui et al. 2010), which may also contain spin-
dle cell components. Very rarely, primary liver
carcinomas entirely consist of spindle cells
(Grigsby et al. 1987).
Primary Hepatoid Carcinoma
of the Bile Ducts
Introduction
Hepatoid carcinomas have a distinct and unique
immunophenotype, characterized by reactivity
for cytokeratins 7, 8, 18, 19, and 20, alpha-
fetoprotein (AFP), and p-CEA (Terracciano
et al. 2003). The immunoreactivity for AFP is
variable, ranging from the absence of staining
to massive staining, illustrating that not all
carcinomas with a hepatoid morphology are
producing AFP (Nagai et al. 1993). Many
hepatoid carcinomas of the gastrointestinal
tract show, similar to hepatocellular carcino-
mas, reactivity for hepatocyte paraffin 1 (Hep
Par 1) antibody, underscoring the fact that Hep
Par 1 expression is not unique to primary hepa-
tocellular neoplasms (Maitra et al. 2001).
Hepatoid carcinomas are reactive for glypican-
3, a cell surface heparin sulfate proteoglycan
expressed specifically in the fetal liver and
malignant neoplasms of the hepatocyte lineage
(Hishinuma et al. 2006).
Histologically, hepatoid carcinomas consist of
large polygonal cells that are arranged in trabecu-
lar fashion or solid nests separated by narrow
fibrous stroma bands and sinusoid-like vascular
channels. The differential diagnosis between
manifestations of hepatocellular carcinoma and
hepatoid carcinoma is often difficult, owing to
the almost identical histology and part of the
immunohistochemical findings. Co-expression of
antigens not found in a liver cell lineage may be
6 Rare Malignant and Semimalignant Epithelial Neoplasms of the Biliary Tract
helpful, e.g., in the stomach, where hepatoid car-
cinoma expresses the fetal gut differentiation stem
cell marker, SALL4, lacking in HCCs and
hepatoblastomas (Ushiku et al. 2010). Hepatoid
adenocarcinoma of the stomach expresses the pal-
ate, lung, and nasal epithelium carcinoma-
associated protein (PLUNC) gene, and PLUNC
immunostaining differentiates hepatoid carcino-
mas from ordinary adenocarcinomas (Sentani
et al. 2008).
Hepatoid Carcinoma of the Bile Ducts
Hepatoid carcinoma is an exceptional neoplasm
of the biliary tract. Hepatoid carcinoma was
observed in the common hepatic duct where it
mimicked Klatskin tumor, causing bile duct ste-
nosis and obstructive jaundice (Abdullah
et al. 2010).
Hepatoid Carcinoma of the Gallbladder
Few cases of hepatoid carcinoma of the gallbladder
have been reported (Nakashima et al. 2000; Maitra
et al. 2001; Sakamoto et al. 2004, 2005;
Gakiopoulou et al. 2007; Koswara et al. 2007; van
den Bos et al. 2007; Kao et al. 2009). The tumors
may be associated with elevated serum AFP (van
den Bos et al. 2007). They show the same histologic
features as those in other locations, but may show
cholangiocarcinoma-like components, which also
immunostain for AFP (Koswara et al. 2007).
Solid Pseudopapillary Tumor
(Papillary Cystic Tumor) of the Liver/
Bile Duct
Introduction
Solid pseudopapillary tumor (SPPT; papillary
cystic tumor; Frantz tumor) is a rare pancreatic
tumor clinico-radiologically belonging to the cys-
tic tumor group (Adams et al. 2008; Lee
et al. 2008; Chakhachiro and Zaatari 2009). The
neoplasm typically occurs in females and only
rarely in males: an analysis of 1014 patients
reported in the literature revealed only
137 (13.5 %) males (Lin and Stabile 2010).
SPPT is usually an expandingly growing mass
lesion, but a solid, infiltrating variety also exists
(Matsunou et al. 1990). The biology of disease is
that of benign or low-grade malignant behavior,
metastases (mostly to the liver) being uncommon
(Gonzalez-Campora et al 1995; Nagri et al. 2007).
Males had a twofold higher incidence of metasta-
ses and a threefold higher death rate, and SPPT
therefore has an atypically aggressive biology in
males (Lin and Stabile 2010). The cell of origin is
not known, but suspected to be a pancreatic
stem cell.
Solid Pseudopapillary Tumor Primary
to the Liver
A case of a primary tumor of the liver with path-
ologic features strikingly similar to pancreatic
SPPT has been observed in a 41-year-old female
patient (Kim et al. 1990). In this patient, two large,
solid and cystic tumors with extensive hemor-
rhage and necrosis were detected in the right and
left liver lobes, measuring 30 cm and 5.5 cm,
respectively, in diameter. The pancreas was free
of tumor.
Morphologic and Biologic Features
of Solid Pseudopapillary Tumor
Histologically, SPPTs are characterized by loosely
cohesive, relatively uniform polygonal cells with
a slightly eosinophilic or pale cytoplasm, some-
times with vacuolization. The nuclei exhibit
grooving and have a finely stippled chromatin.
These cells surround delicate capillary-sized
blood vessels. As an artifact, cell layers around
vessels may separate from each other, hence
resulting in a pseudopapillary pattern (Santini
et al. 2006; Fig. 1).
There are few very rare histologic variants of
SPPT, including clear cell SPPT (Hav et al. 2009),
pigmented SPPT (Daum et al. 2005), a spindle cell
variant (El-Bahrawy et al. 2010), and ossifying
Tumors with Rhabdoid Features of the Biliary Tract
Fig. 1 Solid
pseudopapillary tumor
(papillary cystic tumor) of
the liver (hematoxylin and
eosin stain)
SPPT (Kim et al. 2005). Immunohistochemically,
the tumor is complex and polyphenotypic, posi-
tive marker including vimentin, CD10, CD56,
alpha-1-antichymotrypsin, neuron-specific eno-
lase, synaptophysin, estrogen receptor beta, and
progesterone receptor (Pettinato et al. 1992;
Morales et al. 2003; Santini et al. 2006; Serra
and Chetty 2008). SPPT shows a peculiar claudin
expression profile and the highly specific pattern
of claudins 5 and 7 differentiates SPPT from other
pancreatic tumors (Comper et al. 2009).
SPPTs of the pancreas almost always harbor
mutations of the beta-catenin gene, with nuclear
accumulation of beta-catenin being present in
95 % of the cases (Abraham et al. 2002;
El-Bahrawy et al 2008; Kang et al 2009; reviews:
Antonello et al. 2008; Serra and Chetty 2008).
Nuclear expression of beta-catenin and loss of
E-cadherin are important diagnostic features of
SPPT (Kim et al. 2008; Burford et al. 2009).
Nuclear relocalization of beta-catenin in SPPT is
associated with loss of E-cadherin and decrease or
loss of p120, a protein which regulates E-cadherin
and is responsible for its degradation (Audard
et al. 2008; Chetty et al. 2008). In the pathogene-
sis of SPPT, the Notch signaling pathway is also
involved (Cavard et al. 2009).
7
Tumors with Rhabdoid Features
of the Biliary Tract
Introduction
Malignant tumors containing variable amounts
of rhabdoid cells commonly exhibit a more
aggressive biology. Therefore, the identification
of rhabdoid features is an important diagnostic
element. The nomenclature of these lesions is
not yet standardized. Several terms have been
employed to denote the presence of rhabdoid
cells in neoplasm, including rhabdoid features,
rhabdoid phenotype, rhabdoid differentiation,
rhabdoid transformation, rhabdoid areas, and
rhabdoid as an adjective preceding the name
of the tumor (such as rhabdoid adenocarci-
noma). Carcinomas and adenocarcinomas with
rhabdoid features occur in most organs and
tissue derived from the foregut. They comprise
the thyroid (including follicular carcinoma), the
lung, the esophagus, the stomach, the pancreas
(including neuroendocrine carcinoma), the
small intestine, and the colon. In the liver,
tumors with rhabdoid features chiefly comprise
a distinct lesion mostly occurring in the pedi-
atric age group, i.e., malignant extrarenal
rhabdoid tumor.
8 Rare Malignant and Semimalignant Epithelial Neoplasms of the Biliary Tract
Intrahepatic Cholangiocarcinoma
with Rhabdoid Features
Intrahepatic CC with rhabdoid features
(synonyms: intrahepatic CC with rhabdoid trans-
formation; rhabdoid cholangiocarcinoma) is a
very rare malignant neoplasm of the intrahepatic
biliary tree, characterized by a variable compo-
nent of cells with a rhabdoid phenotype (Honda
et al. 1996; Lim et al. 2004; Sugano et al. 2013).
The patient reported by Honda and coworkers, a
61-year-old female, showed multiple liver masses
at imaging. Histologically, these tumors exhibited
both sarcomatous and ordinary tubular adenocar-
cinomas, the sarcomatous areas being occupied
by rhabdoid cells expressing both vimentin and
cytokeratin (Honda et al. 1996). In the case of Lim
and coworkers (a 41-year-old female), a left
hepatic lobectomy showed a huge mass (up to
17 cm) with extensive necrosis and an infiltrative
border. The viable tumor, found only in the
peripheral portion of the mass, was reddish yellow
to tan and hemorrhagic. Histologically, the entire
tumor was composed of loosely cohesive, round
to polygonal cells with abundant eosinophilic,
glassy cytoplasm. The vesicular nuclei were
eccentrically placed. Close to the nuclei, the cyto-
plasmic body typical for rhabdoid cells was noted.
Some of the cells had mucin-containing vacuoles.
Immunohistochemically, the cells expressed both
vimentin and epithelial markers (Lim et al. 2004).
Differential diagnostically, peritoneal spread of
adenocarcinomas with rhabdoid features should
be distinguished from malignant peritoneal meso-
thelioma containing rhabdoid cells (Matsukuma
et al. 1996).
Primary Rhabdoid Tumor
of the Gallbladder
In a 46-year-old male patient, the gallbladder
showed a slight thickening in the body wall, mea-
suring 1 cm. The lesion was located on the peri-
toneal side, i.e., away from the liver bed. Sections
from this area revealed collections of loosely
arranged plump cells with the features of rhabdoid
cells, which showed the typical eccentric,
paranuclear positivity for vimentin (Suri
et al. 2003). A second case of gallbladder carci-
noma with a rhabdoid component, but associated
with sarcomatoid features, was reported in a
61-year-old female patient. This tumor of 4.5 cm
size was located in the neck portion of the gall-
bladder (Kim et al. 2003).
Pathogenesis
At least in part of rhabdoid tumors and tumors
with rhabdoid features, genetic alterations of the
INI1 gene are well established (see the chapter on
▶ Malignant Rhabdoid Tumors and Tumors with
Rhabdoid Features). In mucinous carcinoma with
rhabdoid features, INI1/SMARCB1 missense
mutations (codon 116) have been identified (Cho
et al. 2006).
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type tumor. Cancer Imaging 10:198–201
Abraham SC, Klinstra DS, Wilentz RE, Yeo CJ, Conlon K,
Brennan M, Cameron JL et al (2002) Solid-
pseudopapillary tumors of the pancreas are genetically
distinct from pancreatic ductal adenocarcinomas and
almost always harbor beta-catenin mutations. Am J
Pathol 160:1361–1369
Adams AL, Siegal GP, Jhala NC (2008) Solid
pseudopapillary tumor of the pancreas: a review of
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