| Keywords
EUS, small cell carcinoma, fine needle aspiration,
pancreatic cancer
Introduction
Case Report:
A 19 year-old college junior presented
to the gastroenterology clinic with abdominal pain. He had
intermittent cramps, mainly in the epigastric region, lasting
4-6 hours at a time, with nausea, occasional emesis, particularly
in the postprandial period. His history dated back to 12 years
of age when he had presented first with similar symptoms.
An EGD at age 14 had revealed an edematous duodenum, thought
to be due to bile reflux, and treatment with sucralfate led
to an interval improvement in his symptoms.
The patient has no other medical problems,
no drug allergies, was not taking any medications, he did
not smoke, drink alcohol, or use recreational drugs, and his
family history did not reveal any intestinal disease.
On physical exam, the patient was thin,
anicteric, and in no acute distress. His abdomen was soft,
mildly tender in the peri-umbilical region, without hepatomegaly
or splenomegaly. Rectal exam revealed guaiac-negative stool,
and there was no lymphadenopathy.
Laboratory evaluation included serum electrolytes,
liver and pancreas enzyme tests and a complete blood count,
all of which were normal, and an outside abdominal computed
tomography showed a prominent pancreatic head with mild pancreatic
ductal dilatation.
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Figure
1 |
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Figure
2A |
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Figure
2B |
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Figure
3 |
Methods for EUS Capture
Linear EUS (Pentax video-endosonoscope at
5MHz) images are captured with a Matrox video capture card
using a commercial endoscopic reporting system (cMore Medical
Systems, Minneapolis, MN).
Case/Body
Endoscopic ultrasound revealed a heterogeneously
enlarged pancreatic head with a moderately dilated pancreatic
duct (Figure 1). The patient was given the diagnosis of idiopathic
pancreatitis and treated with omeprazole, ursodeoxycholic
acid, and pancreatic enzymes. However his symptoms persisted
and he also developed weight loss and lower back pain. He
underwent a repeat endoscopic ultrasound 6 months after the
initial one, at which time incidental gallstones were seen.
The previously noted enlarged pancreatic head and newly found
peripancreatic lymph nodes were identified and biopsied (Figure
2A and B). Cytology from the pancreatic mass revealed a neuroendocrine
carcinoma with small cell features, with immunohistochemistry
showing positive staining for keratin AE1/AE3, chromogranin,
synaptophysin, and negative for neuron specific enolase, leukocyte
common antigen, and placental alkaline phosphatase. Cytogenetic
analysis was unremarkable. An abdominal computed tomography
showed a 5.7cm pancreatic head mass encasing the superior
mesenteric artery and vein, peripancreatic and retroperitoneal
lymphadenopathy, as well as numerous lesions in the liver
(Figure 3). Bone scan also revealed multiple skeletal lesions,
mainly in the vertebrae and ribs. Head and chest computed
tomography did not reveal any abnormalities.
Discussion / Summary Statement
Extrapulmonary Small Cell Cancer
of the Pancreas
Extrapulmonary small cell cancer was first
described by Duguid and Kennedy in 1930 (1), only a few years
after the original description of oat cell carcinoma. It is
defined by the presence of a small cell cancer in the absence
of any evidence of lung primary, with normal chest CT and
normal sputum cytology or bronchoscopy. Histologically, the
diagnosis is made by the presence of "small blue cells"
in conjunction with immunohistochemical markers: the tumor
typically stains for cytokeratin and neuroendocrine markers.
However, as seen in this case, neuron-specific enolase, may
be negative. Thyroid transcription factor 1 has been recently
shown to be helpful in the identification of small cell lung
cancer, but it also indicates extrapulmonary small cell cancer,
thereby not guiding in the origin of disease (2,3).
Extrapulmonary small cell cancer is thought to be of endocrine
origin, likely arising from cells of the APUD system, or alternatively,
from a totipotent stem cell. It is a very rare entity, accounting
for approximately 1000 new cases each year in the U.S., or
for 0.1-0.4% of all malignancies. It typically affects elderly
men, with a mean age of 63 years, but cases as young as 24
years have been reported (4-6). A smoking history can be found
in the majority of patients. Extrapulmonary small cell cancer
can affect any organ system; in a recent review from the Mayo
Clinic, involvement of the gastrointestinal tract accounted
for 38% of all cases, occurring mainly in the colon, esophagus,
and pancreas, but the head and neck region (17%), as well
as the genitourinary tract (15%) and gynecologic organs (12%)
are also more commonly involved (6). Involvement of the pancreas
has only been described in a few case reports (7-9). The occurrence
of paraneoplastic syndromes in these patients has been reported
anecdotally with Cushing's syndrome due to ACTH overproduction
(10,11) and hypercalcemia (12).
The clinical staging is similar to that
of small cell lung cancer, with limited disease being mainly
organ confined, including all patients whose tumor can fit
into a radiation port, and extensive disease being what extends
beyond the radiation port (6). The clinical course is comparable
to that of small cell lung cancer, with a very aggressive
course and short survival times. Survival is dependent on
the extent of disease at presentation, with patients with
localized disease doing much better than those with extensive
disease. The treatment of extrapulmonary small cell cancer
is also based on small cell lung cancer regimen, with cisplatin/etoposide
chemotherapy being most widely used as first-line agents (6).
As typical for small cell lung cancer, the majority of patients
will experience a good response to chemotherapy followed by
disease progression after a brief interval, necessitating
the use of second and third line agents.
Patient Follow-Up
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Figure
4A |
Figure 4B |
Our patient underwent six cycles of cisplatin/etoposide
chemotherapy with excellent clinical improvement and resolution
of his hepatic masses (Figures 4A and 4B). He remains asymptomatic
3 months after completion of chemotherapy. The etiologic factors
in this very young patient remain unknown: he clearly did
not have small cell cancer for the 7 years of the duration
of his symptoms, and one can only speculate whether a chronically
inflamed pancreas favored tumorigenesis.
References
1. Duguid JB, Kennedy AM. Oat-cell tumours
of mediastinal glands. J Pathology Bacteriology
1930; 33:93-99.
2. Cheuk W, Chan JK. Thyroid transcription factor-1 is
of limited value in practical distinction between pulmonary
and extrapulmonary small cell carcinomas. Am
J Surg Pathol 2001; 25:545-6.
3. Kaufmann O, Dietel M. Expression of thyroid transcription
factor-1 in pulmonary and extrapulmonary small cell carcinomas
and other neuroendocrine carcinomas of various primary sites.
Histopathology 2000; 36:415-20.
4. Remick SC, Hafez GR, Carbone PP. Extrapulmonary small-cell
carcinoma. A review of the literature with emphasis on therapy
and outcome. Medicine (Baltimore) 1987; 66:457-71.
5. Richardson RL, Weiland LH. Undifferentiated small cell
carcinomas in extrapulmonary sites. Semin Oncol
1982; 9:484-96.
6. Galanis E, Frytak S, Lloyd RV. Extrapulmonary small
cell carcinoma. Cancer 1997; 79:1729-36.
7. Chetty R, Clark SP, Pitson GA. Primary small cell carcinoma
of the pancreas. Pathology 1993; 25:240-2.
8. Reyes CV, Wang T. Undifferentiated small cell carcinoma
of the pancreas: a report of five cases. Cancer
1981; 47:2500-2.
9. Ordonez NG, Cleary KR, Mackay B. Small cell undifferentiated
carcinoma of the pancreas. Ultrastruct Pathol
1997; 21:467-74.
10. Sandler M, Rubin PC, Reid JL, Smith GD. Oat cell carcinoma
in the pancreas: an unusual cause of Cushing's syndrome.
Br J Hosp Med 1992; 47:537-8.
11. Corrin B, Gilby ED, Jones NF, Patrick J. Oat cell
carcinoma of the pancreas with ectopic ACTH secretion.
Cancer 1973; 31:1523-7.
12. Hobbs RD, Stewart AF, Ravin ND, Carter D. Hypercalcemia
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