Intrahepatic sarcomatoid cholangiocarcinoma.

Abstract

Intrahepatic sarcomatoid cholangiocarcinoma is a rare but an aggressive variant of cholangiocarcinoma with a very poor prognosis. We report the first caucasian patient who presented with a rapidly enlarging liver mass requiring hepatic resection. Detailed histopathological analyses including immunohistochemistry and electron microscopy confirmed sarcomatoid cholangiocarcinoma. The patient had early onset disease recurrence within 5 weeks of surgery. Here we demonstrate that combination chemotherapy with gemcitabine and cisplatin is a potential treatment option in patients with advanced sarcomatous cholangiocarcinoma. The patient achieved sustained partial remission with combination chemotherapy and remains alive and well more than 29 months since initial surgery.

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Hindawi Publishing Corporation
Journal of Oncology
Volume 2010, Article ID 701476, 4 pages
doi:10.1155/2010/701476
Case Report
IntrahepaticSarcomatoid Cholangiocarcinoma
ShaliniMalhotra,1JoannaWood,2Talal Mansy,2RajeevSingh,3Abed Zaitoun,1
andSrinivasanMadhusudan2
1Department of Histopathology, Nottingham University Hospitals, Queens Medical Centre Campus,
University of Nottingham, NG7 2UH Nottingham, UK
2Academic Unit of Oncology, Nottingham University Hospitals, City Hospital Campus, University of Nottingham,
NG5 1PB Nottingham, UK
3Department of Radiology, Derby City General Hospital, DE22 3NE Derby, UK
Correspondence should be addressed to Srinivasan Madhusudan, srinivasan.madhusudan@nottingham.ac.uk
Received 13 May 2009; Revised 4 February 2010; Accepted 16 February 2010
Academic Editor: Christos Dervenis
Copyright © 2010 Shalini Malhotra et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Intrahepatic sarcomatoid cholangiocarcinoma is a rare but an aggressive variant of cholangiocarcinoma with a very poor
prognosis. We report the first caucasian patient who presented with a rapidly enlarging liver mass requiring hepatic
resection. Detailed histopathological analyses including immunohistochemistry and electron microscopy confirmed sarcomatoid
cholangiocarcinoma. The patient had early onset disease recurrence within 5 weeks of surgery. Here we demonstrate that
combination chemotherapy with gemcitabine and cisplatin is a potential treatment option in patients with advanced sarcomatous
cholangiocarcinoma. Thepatientachieved sustainedpartialremissionwithcombinationchemotherapyandremainsaliveandwell
more than 29 months since initial surgery.
1.Introduction
Sarcomatoid changes of epithelial neoplasms are rare but
found occasionally in renal cell carcinoma, squamous cell
carcinoma (involving the lungs, oesophagus, and skin), and
adenocarcinoma of the lung [1]. In the liver, sarcomatoid
transformation has been reported in about 3.9 to 9.4% of
hepatocellular carcinomas at autopsy and in about 4.5% of
cholangiocarcinomas[2].Ithasbeenreportedthatprognosis
for intrahepatic sarcomatous cholangiocarcinoma is worse
than that for a conventional intrahepatic cholangiocarci-
noma. The factors that account for the poor prognosis may
be ascribed to the remarkable intrahepatic development,
especially the high potential of the sarcomatous component
to metastasize. Vascular invasion has been shown to be
more frequently present if there is a sarcomatous component
[3]. Here we report a case of intrahepatic sarcomatoid
cholangiocarcinoma in a caucasian patient and review the
literature.
2.CaseReport
A 60-year-old Caucasian woman presented with an acute
onset right upper abdominal pain and a rapidly enlarging
upper abdominal mass. She had a previous history
of resected early-stage melanoma. Clinical examination
revealed tender hepatomegaly, and a contrasted computed
tomography (CT) scan of the thorax, abdomen, and pelvis
showed a large solitary heterogeneous mass in segment
V1 of the liver with evidence of intratumoural bleeding
(Figure 1(a)). She proceeded to laparotomy and at operation
a large liver mass was evident and the tumour was found to
be grossly adherent to a number of intraabdominal organs
with evidence of tumour perforation and intraabdominal
spillage. A lateral segmentectomy of the liver along with
cholecystectomy was performed and she made an uneventful
postoperative recovery.
The tumour measured 15 × 11 × 20cm and cut sec-
tion revealed massive necrosis and haemorrhage consistent

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2Journal of Oncology
(a)
30cm
(b)(c)
Figure 1: Radiological and histopathological features are shown here. Figure 1(a): preoperative CT-scan, Figure 1(b): gross histopathology
and Figure 1(c): microscopy features. See text for details.
(a)(b)
Figure 2: Postoperative CT-scan showing early disease recurrence (indicated with an arrow) within the liver (Figure 2(a)). Partial response
after completion of chemotherapy is shown in Figure 2(b).
with the preoperative CT scan (Figure 1(b)). The tumour
extendedtothelivercapsuleandtowithin2cmofthemargin
of excision. There was extensive vascular and perineural
invasion. Histological examination of the tumour showed
a malignant biphasic neoplasm consisting of a moder-
ately differentiated adenocarcinoma intermingled with a
malignantmesenchymalcomponent(Figure 1(c)).Thelatter
consisted of pleomorphic spindle cells arranged in sheets
intermixed with bizarre multinucleate osteoclast like giant
cells. Reams of osteoid surrounded by osteoblasts were also
characteristically seen. The sarcomatous component made
up to 70% of the whole tumour. The adenocarcinoma cells
showed apparent mucus production as demonstrated by PAS
and alcian blue staining. They neither displayed trabecular
arrangement nor bile production, which are characteristics
of a hepatocellular carcinoma. Immunohistochemical study
of carcinomatous component revealed positive staining for
Cam5.2, EMA, AE1/AE3, CK7, CK19, and CEA and negative
staining for HePAR1. This immunoprofile was in keeping
with cholangiocarcinoma. The sarcomatous component was
positive for vimentin but negative for epithelial markers.
S100, HMB45, MELAN A, desmin, inhibin, and CD117
were negative in both components. Both MiB1 and p 53
showed strong positivity in both epithelial and sarcomatous
component (>80%). Electron microscopy showed presence
of basement membrane and microvilli in the tumour cells
which excluded their hepatocyte origin. It also demonstrated
presence of tight junctions and desmosomes in the sarcoma-
tous component indicating their epithelial origin. Based on
histological, immunohistochemical and electron microscopy
findings, a diagnosis of sarcomatoid cholangiocarcinoma
was made and the patient was referred for consideration of
adjuvant chemotherapy.
A postoperative contrasted CT scan at 5 weeks con-
firmed rapid onset disease recurrence with multiple peri-
toneal deposits and multifocal liver metastasis (Figure 2(a)).
Patient was started on gemcitabine (1000mg perm2on
days 1 and 8) and cisplatin (60mg perm2on day 1)
chemotherapy in a 21-day cycle which she tolerated well
with minimal side effects. Patient received a total of six
cycles of chemotherapy and a restaging CT scan at the
end of 6 cycles confirmed partial response (Figure 2(b)).
Apart from grade 1 nausea that settled with antisickness
medications, the patient tolerated chemotherapy very well.
The patient reported improvement in appetite, weight gain,
and resolution of abdominal swelling during chemotherapy.
Following completion of treatment, she was started on
clinical follow-up. A reassessment CT scan after 3 months
of follow up showed further marginal disease size reduction.
She continued under regular clinical follow-up until 10
months later; she developed further disease progression was
rechallenged with gemcitabine and cisplatin at the same

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Journal of Oncology3
Table 1: Clinicopathological features of previously published patients with sarcomatoid cholangiocarcinoma.
no. of patients
Sarcomatoid component
Pleomorphic and spindle
cells
TreatmentSurvival
Patient died ≤3 months after
surgery with recurrence
Patient died within 2 months after
diagnosis
Patient died within 3 months of
diagnosis
- Patient died ≤3 months after
diagnosis (4)
- Patient died 3–6 months after
diagnosis (2)
- Patient alive beyond 6 months (1)
Kaibori et al. [7]1
Surgery
Sumiyoshi et al. [8]1
Spindle cellNone
Sato et al. [2]1
Round cell variantNone
Nakajima et al. [5]7
Spindle cell (5) Surgery (2)
Pleomorphic and spindle
cell (2)
TAE (2)
Chemotherapy∗(1)
None (2)
Aishima et al. [3]7
Not availableSurgery (7)
5 patients died of disease
recurrence. 3 year survival (17.9%)
TAE (Trans arterial chemoembolisation),∗details of chemotherapy not available.
doses. A reassessment CT scan after chemotherapy showed
partialresponse.Sheremainswellandisnow29monthspost
initial presentation.
3.Discussion
Sarcomatoid cholangiocarcinoma is an uncommon vari-
ant of intrahepatic cholangiocarcinoma and in the previ-
ously reported series, the sarcomatoid component exhibited
mainly spindle cell morphology. To the best of our knowl-
edge osteoid differentiation and osteosarcoma like features
in a sarcomatoid cholangiocarcinoma are very rare. Here,
we describe the first case of such an entity in a Caucasian
patient along with ultrastructural features. Sarcomatoid
transformation has been reported to occur in a hepatocel-
lular carcinoma previously treated with transcatheter arterial
chemo embolisation regimes [4]. However, there have been
no reports concerning the relationship between sarcomatoid
cholangiocarcinoma and anticancer therapy. It is therefore
reasonable to consider that sarcomatoid transformation
is a natural course of tumour progression as far as a
cholangiocarcinoma is concerned [2]. Most of the previ-
ously reported cases of sarcomatoid cholangiocarcinoma
showed cytokeratin expression in both carcinomatous and
sarcomatous components [2]. In our case, the sarcomatous
component was negative for cytokeratins. This may be
related to possible anaplastic dedifferentiation of tumour
cells during sarcomatous transformation as occurred in 2
out of 7 cases reported by Nakajima et al. [5]. However
we did confirm the epithelial derivation of the sarcomatous
component in our case by electron microscopy. Though
controversy has surrounded the histogenesis of sarcomatoid
cholangiocarcinoma, we favour the concept of metaplastic
transformationashasbeenwellacceptedforsimilartumours
of other organs [6].
Aggressive biology is highlighted by the fact that our
patient had an early onset rapid recurrence of disease
within a few weeks of surgery. The rapid recurrence is also
indicative of early microscopic metastatic seedlings prior to
surgery. In view of widespread recurrence, further surgical
interventionwasnotperformedandthepatientproceededto
palliative chemotherapy. Kaibori et al. reviewed sixteen cases
of sarcomatous cholangiocarcinomas previously reported in
the literature. Seven patients had not had surgery and all had
died within five months of diagnosis. Nine patients had liver
resectionbutfourofthesepatientsdiedwithinsevenmonths
of surgery [7]. The survival rates of patients with surgically
resected disease were significantly higher than in patients
without resection [7, 8]. There is however, no information
available about the optimal adjunctive treatment after initial
surgical resection. Table 1 summarises clinicopathological
characteristics of patients with sarcomatoid cholangiocar-
cinoma previously published in the literature. To the best
of our knowledge, there is also no published report in
Caucasian patients demonstrating response and survival
benefit to systemic chemotherapy. A combination of gemc-
itabine and cisplatin has been shown to produce antitumour
responses in metastatic biliary tract cancer [9] and sarcoma
[10]. Based on this evidence, our patient received this
combination which was well tolerated. Patient achieved
partial response after 6 cycles of chemotherapy confirming
the clinical activity of this combination in this disease. In
addition, patient demonstrated improvements in clinical
symptoms during chemotherapy which was sustained after
completion and at follow-up. The patient remains alive and
well sixteen months since initial presentation. Given the fact
that she presented with rapidly progressive liver mass and
a rapid onset disease recurrence, it is very likely that this
combination chemotherapy resulted in a survival benefit for
this patient associated with improvement in quality of life.
In conclusion, we have demonstrated that combination
chemotherapy with gemcitabine and cisplatin is a potential
treatment option in patients with advanced sarcomatous
cholangiocarcinoma. Review of previous reports suggests
that radical surgery is the treatment of choice in those with
limited disease. However, the role of adjuvant chemotherapy
is unknown. As the prognosis of this tumour type is very

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4 Journal of Oncology
poor, and the amount of reported clinical data is limited,
our report raises the need to consider the potential benefit
of adjuvant gemcitabine/cisplatin chemotherapy in patients
withresectedintrahepaticsarcomatoidcholangiocarcinoma.
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