Pancreatic Carcinosarcoma

Marcos Gelos
1
, Dirk Behringer
2
, Stathis Philippou
3
, Benno Mann
1
Departments of
1
General and Visceral Surgery,
2
Hematology and Oncology, and
3
Pathology,
Augusta-Kranken-Anstalt. Bochum, Germany
ABSTRACT
Context Carcinosarcoma (malignant mixed
tumor) is a rare variant of a pancreatic
neoplasm having a dismal prognosis; very
few clinical data and treatment options have
been published. Unlike adenocarcinoma of
the pancreas, there is nothing specific in the
literature for this variant regarding
postoperative treatment with chemo-
therapeutic agents.
Case report We report the case of a 61-year-
old woman presenting with anemia.
Examination revealed a mass in the pancreatic
head and she underwent a partial
pancreaticoduodenectomy. Histopathological
examination revealed a pancreatic neoplasm
with both adenomatous as well as
sarcomatous characteristics. Postoperatively,
the patient was treated with gemcitabine and
was in a good health for 9 months. Three
follow-up CT scans were done, showing
complete remission. Eleven months
postoperatively, the patient died from a
recurrence.
Conclusion Carcinosarcoma of the pancreas
is a very rare disease having a dismal
prognosis. In addition to reviewing the
literature on this entity, we present the first
published case where gemcitabine was
administered as a treatment modality in
combination with surgery.
INTRODUCTION
Carcinosarcoma of the pancreas is a rare
entity comprising a small subset of all
pancreatic neoplasms. The histogenesis is
unclear. To our knowledge, nine cases of this
entity have been published so far [1, 2, 3, 4, 5,
6, 7]. Diagnosis is usually established by
immunohistochemical examination of the
resected specimen. Prognosis is limited to
several months after resection [1, 2, 3, 4, 5, 6,
7]. We present the case of a 61-year-old
female patient, who underwent a partial
pancreaticoduodenectomy and was treated
postoperatively with gemcitabine as
chemotherapeutic agent. We review the
current literature on this rare type of
neoplasia, considering histopathological and
clinical features.
CASE REPORT
A 61-year-old white female was admitted to
our hospital suffering from anemia. Her past
medical history was not significant. She had
no nausea nor hematemesis or dark stools.
Laboratory investigation revealed a
hemoglobin value of 5.0 g/dL (reference
range: 12-16 g/dL). Other laboratory tests
including liver enzymes, alkaline phosphatase
and bilirubin were within the normal range.
Esophagogastroduodenoscopy revealed a
lesion within the duodenum, located orally to
the papilla of Vater. An abdominal computed
tomography scan showed a mass in the head

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51
of the pancreas with infiltration of the
duodenum (Figure 1). A radical pancreatico-
duodenectomy using the Whipple procedure
was performed with two hepatico-
jejunostomies due to the presence of an
aberrant bile duct.
Pathological Studies
The pathological specimen was composed of
the head of the pancreas, a portion of the
stomach and the duodenum, the distal portion
of the common bile duct, an aberrant bile duct
and the gallbladder. On gross examination,
the head of the pancreas revealed an
exophytically-growing tumor localized in the
duodenum 1 cm orally to the papilla of Vater
measuring 7x6x3.5 cm. Moreover, an
extraluminal growing tumor localized 3 cm
distally from the oral resection margin, 2 cm
in diameter, was detected in the stomach.
Paraffin-embedded sections of formalin-fixed
tissue were studied by routine morphological
histology using hematoxylin-eosin staining.
Immunohistochemistry was performed
applying monoclonal antibodies to CK7, pan-
cytokeratin, CK20, vimentin, PDGF, CD117,
CD34, beta-HCG, CD31 and Ki-67.
Microscopically, the tumor yielded two
components. The first one was a moderately
differentiated adenocarcinoma (Figure 2a).
The second component showed poorly
differentiated solid tissue with a focally
bizarre configuration of the nuclei (Figure
2b). Both components infiltrated the
peripancreatic fat with extension to the
resection margin, yielding an R1 situation.
One of eight peripancreatic lymph nodes
showed a metastasis of the adenoid
component. None of the perigastric lymph
nodes were malignant. The resection margins
of the pancreatic body, the common bile
ducts, the stomach, the duodenum and the
pancreatic duct were free from malignant
cells. Immunohistochemically, the epithelial
component was strongly reactive for
antibodies to CK7 and pan-cytokeratin
(Figure 2a). A moderate reaction was detected
for the antibody to CK20. The sarcomatoid
component was negative for all CK-
antibodies, but strongly reactive for the
antibody to vimentin (Figure 2b). Spindle
cells were found in the stomach tumor.
Immunohistochemically,
they
were
moderately positive for the antibody to
Figure 1. Axial contrast-enhanced CT image of the
pancreas. A low-density mass is present (arrow) which
involves the head of the pancreas.
Figure 2. Immunohistochemical staining of the
pancreatic tumor. a. Section with antibody against
cytokeratin demonstrating the epithelial component. b.
Section with antibody against vimentin demonstrating
the sarcomatous component.

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52
platelet-derived growth factor (PDGF). Ten
percent of the tumor cells were strongly
positive for Ki-67. All cells of this tumor
were negative for CD117 (Table 1). The
immunohistological features of this tumor
were concordant with the growth of a benign
gastrointestinal stromal tumor.
Clinical Course
On the first postoperative day, biliary liquid
appeared via the abdominal drain. The patient
underwent relaparotomy. Macroscopically, a
minimal
insufficiency
within
the
terminolateral hepaticojejunostomy was
visible. The anastomosis to the aberrant bile
duct was sufficient. As no major insufficiency
was detected and no obvious technical
problem was present, we decided to protect
both anastomoses by means of intraoperative
stenting using endoscopic cholangiography in
a random fashion. An inspectoral jejunal
stoma of the descending sling was applied.
Due to atonia and a prolonged need for
supportive parenteral substitution of volume
and weakness, she was in hospital for 6
weeks. After complete healing of
anastomoses, the stoma was reconnected
during the hospital stay 5 weeks
postoperatively. One week later, the patient
was discharged. After implantation of a
venous port system, additional therapy with
gemcitabine was initialized 8 weeks
postoperatively. Due to postoperative
complications, the start of the chemotherapy
was delayed by approximately 2 weeks. Six
cycles of gemcitabine with a dose of 1,000
mg/cm
2
were used and finished 7 months
postoperatively. The patient was well for
about 9 months after surgery and tolerated
chemotherapy without problems and without
evidence of disease. Three follow-up
abdominal and chest CT scans were done 2, 4,
and 8 months postoperatively, showing no
signs of tumor recurrence. Four months after
stopping gemcitabine (11 months post-
operatively), she was readmitted to our
hospital with diffuse abdominal pain and
anemia (hemoglobin 6.0 g/dL). An abdominal
CT showed a huge mass consistent with a
peritoneal carcinosis. The differential
diagnosis was a hematoma. To definitively
clarify the uncertain situation, a relaparotomy
was performed, and a diffuse intraperitoneal
tumor mass in the upper abdomen was
detected. The patient died 2 days
postoperatively.
DISCUSSION
Carcinosarcomas (malignant mixed tumors)
are rare neoplasms, predominantly located in
the uterus [8]. They are histologically
characterized by a carcinomatous and a
sarcomatous component. Immunohisto-
chemical diagnosis is established by reactivity
of the carcinomatous and sarcomatous
elements to cytokeratin and vimentin,
respectively. Carcinosarcomas must be
differentiated from sarcomatoid carcinomas,
which immunohistochemically show only
cytokeratin reactivity and are therefore
considered to be true carcinomas. However,
they have to be separated from epithelioid
sarcomas which are defined as sarcomas as
they lack cytokeratin reactivity [9]. So far,
Table 1. Applied antibodies and staining intensities.
Antibody against
Epithelial
component
Sarcomatous
component
Stomach
tumor
CK7
Strong staining
No staining
Not done
CK20
Moderate staining
No staining
Not done
CD117
Not done
Not done
No staining
Pan-cytokeratin
Strong staining
No staining
No staining
Vimentin
No staining
Strong staining
No staining
PDGF
Not done
Not done
Moderate staining
Ki-67
No staining
No staining
Strong staining
PDGF: platelet-derived growth factor

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53
only a handful of cases reporting true
pancreatic carcinosarcomas have been
published and the prognosis appears limited
with an average postoperative survival time of
6 months [1, 2, 3, 4, 5, 6, 7]. As a differential
diagnosis, a metastasis of a mixed malignant
ovarian Mullerian tumor may be considered,
as described previously [10]. A gynecological
primary tumor could be excluded in our case.
Remarkably, an independent benign gastro-
intestinal stromal tumor localized 3 cm distant
from the oral resection margin was detected in
the stomach of our patient.
The origin of mixed carcinosarcomas is
unknown. It has been postulated that these
neoplasms represent cellular elements derived
from two different histologic origins
proliferating in one tumor [9]. In contrast, van
den Berg et al. suggest a monoclonal origin
with subsequent divergence of the neoplastic
epithelial and sarcomatous portions [11].
Yamakazi proposed that carcinosarcomas
begin growing as adenocarcinomas and later
accumulate genetic alterations with
consequent transformation into carcino-
sarcomas having two different histological
patterns [5].
As detailed in Table 2, the cellular
composition of the sarcomatous components
varies. Wenig et al. report an association of
pancreatic mucinous cystic neoplasms with
sarcomatous stroma. They describe three
cases of pancreatic mucinous cystic
neoplasms with sarcomatous stroma making
the latter component responsible for their
aggressive clinical behavior. Only one of the
three patients was alive one year after surgical
therapy [3]. Also in the latest publication
regarding pancreatic carcinosarcoma [7], a
mucinous cystadenocarcinoma containing
sarcomatous components was found. The
patient, treated by pylorus-preserving
pancreaticoduodenectomy, died 4 months
after therapy from metastatic disease to the
liver and the peritoneum. In contrast to these
data, our patient had no cystic components in
her pancreatic tumor. In several reports, the
sarcomatous component of the mixed
neoplasms was composed of osteoclastic giant
cells [2, 6, 12]. We could not detect such
cellular components in our case. Millis et al.
[1] found leiomyosarcomatous areas in
regions of the tumor under examination.
Moreover, they made the observation that the
carcinomatous and sarcomatous areas of
differentiation showed a polar distribution
within the tumor. In contrast to this finding,
the invasion front in our case consisted of
epithelioid as well as sarcomatous cells. An
Darvishian et al. were the first to describe a
true pancreatic carcinosarcoma composed of
adenocarcinoma and a malignant fibrous
histiocytoma [4].
In our case, a residual tumor was detected in
the caudal resection margin. After an
interdisciplinary discussion held by the tumor
Table 2. Clinical and histological characteristics of published cases.
Author
Age Gender
Predominant histology of
non-epithelial component
Mucinous cystic
component
Survival
(months)
Millis et al. [1]
50 Female
Leiomyosarcoma
No
3
Watanabe et al. [2]
76
Male Osteoclastic giant cells; pleomorphic giant cells
No
3
Wenig et al. [3]
48 Female
Spindle-shaped stroma, (rhabdoid)
Yes
12
Wenig et al. [3]
65 Female
Spindle-shaped stroma
Yes
9
Wenig et al. [3]
67
Male
Spindle-shaped stroma
Yes
15
Darvishian et al. [4]
74
Male
Malignant fibrous histiocytoma
No
a
Yamazaki [5]
90
Male
Spindle-shaped stroma
No
b
Barkatullah et al. [6] 67 Female Spindle-shaped stroma; osteoclastic giant cells
No
8
Bloomston et al. [7]
67 Female
Spindle-shaped stroma
Yes
4
Alive and well 4 months after the surgery
Autopsy case report

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54
board and a second opinion (Prof. Issels,
Munich, Germany), we recommended
gemcitabine therapy. This drug has gained
importance in the treatment of pancreatic
adenocarcinoma in a neoadjuvant as well as in
an adjuvant setting. In adjuvantly-treated
patients who underwent resection for
pancreatic cancer with curative intent, it
delays the development of disease progression
[13]. Gemcitabine in combination with
cisplatin has been associated with a high
resection rate and improved survival in the
neoadjuvant setting in a preliminary study
[14].
In summary, we present the first case with a
rare manifestation of an incompletely resected
carcinosarcoma of the pancreas submitted to
treatment with gemcitabine as systemic
postoperative therapy. Though appearing to
be a feasible treatment option, the patient died
11 months postoperatively from recurrent
disease.
Received September 4
th
, 2007- Accepted
October 24
th
, 2007
Keywords
Carcinosarcoma; Combined
Modality Therapy; gemcitabine; Mixed
Tumor, Malignant; Pancreas
Abbreviations
PDGF: platelet-derived
growth factor
Conflict of interest The authors have no
potential conflicts of interest
Correspondence
Marcos Gelos
Department of General and Visceral Surgery
Augusta-Kranken-Anstalt
Bergstrasse 26
D-44791 Bochum
Germany
 
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