Lester Daron Robert Thompson, MD
Mucinous cystic neoplasm (mucinous
cystadenocarcinoma of low-grade malignant potential) of the
pancreas: a clinicopathologic study of 130 cases.
Thompson LD, Becker RC, Przygodzki RM, Adair CF, Heffess CS.
Am J Surg Pathol. 1999 Jan;23(1):1-16.
Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon
tumors. The classification and biologic potential of these neoplasms
remain the subject of controversy. Attempts to classify these tumors
in a similar manner to ovarian MCNs remains controversial, as even
histologically benign-appearing pancreatic MCNs metastasize and are
lethal. One hundred thirty cases of MCNs were identified in the
files of the Endocrine Pathology Tumor Registry of the Armed Forces
Institute of Pathology from the years 1979 to 1993. The pathologic
features, including hematoxylin and eosin staining, histochemistry,
immunohistochemistry (IHC), cell cycle analysis, and K-ras oncogene
determination were reviewed. These findings were correlated with the
clinical follow-up obtained in all cases. There were 130 women, aged
20-95 years (mean age at the outset, 44.6 years). The patients had
vague abdominal pain, fullness, or abdominal masses. More than 95%
of the tumors were in the pancreatic tail or body and were
predominantly multilocular. The tumors ranged in size from 1.5 to 36
cm in greatest dimension, with the average tumor measuring >10 cm. A
spectrum of histomorphologic changes were present within the same
case and from case to case. A single layer of bland-appearing,
sialomucin-producing columnar epithelium lining the cyst wall would
abruptly change to a complex papillary architecture, with and
without cytologic atypia, and with and without stromal invasion.
Ovarian-type stroma was a characteristic and requisite feature.
Focal sclerotic hyalinization of the stroma was noted. This
ovarian-type stroma reacted with vimentin, smooth muscle actin,
progesterone, or estrogen receptors by IHC analysis. There was no
specific or unique epithelial IHC. K-ras mutations by sequence
analysis were wild type in all 52 cases tested. Ninety percent of
patients were alive or had died without evidence of disease (average
follow-up 9.5 years), irrespective of histologic appearance; 3.8%
were alive with recurrent disease (average 10 years after
diagnosis); and 6.2% died of disseminated disease (average 2.5 years
from diagnosis). Irrespective of the histologic appearance of the
epithelial component, with or without stromal invasion, pancreatic
MCNs should all be considered as mucinous cystadenocarcinomas of
low-grade malignant potential. Pancreatic MCNs cannot be reliably or
reproducibly separated into benign, borderline, or malignant
See full article (4 MB .pdf)
A clinicopathologic and
immunohistochemical study of 22 intraductal papillary mucinous
neoplasms of the pancreas, with a review of the literature.
Paal E, Thompson LD, Przygodzki RM, Bratthauer GL, Heffess
Mod Pathol. 1999 May;12(5):518-28.
Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are
rare lesions. We undertook this study to analyze these tumors by
focusing on the diagnostic criteria and correlating the histologic
features with clinical prognosis. Twenty-two cases of IPMN were
retrieved from the Endocrine Tumor Registry of the Armed Forces
Institute of Pathology. Blocks or unstained slides were available
for histochemical and immunohistochemical studies (including
proliferative markers and cell cycle regulators) and K-ras oncogene
mutations in 15 cases. Patient follow-up was obtained in all of the
cases. IPMN occurs in both genders with a slight male predominance,
with a mean age at presentation of 64.4 years (range, 48-85 yr). The
patients presented with abdominal pain. The neoplasms were
radiologically and grossly cystic, usually (18 cases of 22) located
in the head of the pancreas. Histologically, the tumors consisted of
intraductal papillary proliferations protruding into and expanding
the pancreatic ducts. Invasion into the surrounding pancreatic
parenchyma was detected in 15 cases. Chronic pancreatitis was
present in all of the cases. p27 immunoreactivity always exceeded
the immunoreactivity of cyclin E. K-ras oncogene mutations were
detected in two cases. Patients were treated with a complete
surgical resection (n = 7) or a Whipple procedure (n = 13). Only 2
of 22 patients died of disease (3 died immediately postoperatively
and 3 died of unrelated causes), whereas the remaining 14 patients
were alive at last follow-up, without evidence of disease, an
average of 58.2 months after initial presentation. IPMNs are rare,
distinctive neoplasms, with complex intraductal papillae, that can
be easily separated from in situ ductal adenocarcinoma and mucinous
cystic neoplasms. The high ratio of p27 protein to cyclin E supports
the excellent prognosis of these neoplasms, despite the presence of
invasion and K-ras oncogene mutation.
See full article (2 MB .pdf)
Adenosquamous carcinoma of the pancreas:
a clinicopathologic series of 25 cases.
Kardon DE, Thompson LD, Przygodzki RM, Heffess CS.
Mod Pathol. 2001 May;14(5):443-51.
BACKGROUND: Adenosquamous carcinoma is a rare aggressive subtype of
pancreatic adenocarcinoma. We describe the clinical, pathologic, and
molecular characteristics of 25 of these lesions, the largest series
METHODS: Twenty-five cases of adenosquamous carcinoma of the
pancreas diagnosed between 1961 and 1994 were retrieved from the
files of the Endocrine Registry of the Armed Forces Institute of
Pathology. Histologic features were reviewed, histochemical,
immunohistochemical, and molecular (k-ras) studies were performed,
and patient follow-up was obtained.
RESULTS: The patients included 17 men and eight women, aged 28 to 82
years (mean, 65.4 y). The patients usually experienced weight loss
(n = 17) or painless jaundice (n = 11), while also presenting with
other abdominal symptoms. The tumors affected the head most
frequently (n = 17), followed by the tail (n = 9) or body (n = 4).
Five cases involved more than one anatomic region of the pancreas.
Microscopically, all tumors demonstrated dual differentiation toward
adenocarcinoma and squamous cell carcinoma. All cases tested were
immunoreactive with keratin (AE1:AE3 and CK1), whereas other keratin
markers were variably expressed: CK5/6 (88%), CK7 (68%), Cam5.2
(41%), and CK20(26%). CA-19-9 (84%) and CEA (74%) were positive in
the majority of the cases. K-ras oncogene mutations were identified
in seven of 13 cases. All patients died from their disease an
average of 5.8 months after diagnosis (range, 1 to 33 months).
CONCLUSIONS: Adenosquamous carcinoma of the pancreas represents a
distinct clinical and pathologic entity, demonstrating the expected
immunoprofile and k-ras oncogene mutation of a ductal origin, with a
worse prognosis than ductal adenocarcinoma.
See full article (2 MB .pdf)
A clinicopathologic and
immunohistochemical study of 35 anaplastic carcinomas of the
pancreas with a review of the literature.
Paal E, Thompson LD, Frommelt RA, Przygodzki RM, Heffess CS.
Ann Diagn Pathol. 2001 Jun;5(3):129-40.
Anaplastic pancreatic carcinomas are rare tumors, frequently
displaying a variety of growth patterns. The literature lacks a
comprehensive study of this tumor. Thirty-five cases of anaplastic
carcinoma of the pancreas diagnosed between 1955 and 1997 were
retrieved from the Endocrine Registry at the Armed Forces Institute
of Pathology. Histology, immunophenotype, molecular analysis, and
patient follow-up were analyzed. The tumors of 10 women and 25 men,
aged 34 to 85 years (mean age at presentation, 62.5 years), were
studied. Patients had vague symptoms (weight loss, pain, and
fatigue, nausea, or vomiting), lasting an average of 13.2 weeks. The
tumors, of an average size of 9.2 cm, were usually in the head or
tail of the pancreas. The tumors were widely infiltrative,
histomorphologically separated into predominantly large, pleomorphic
cell, or spindle cell groups. Tumor phagocytosis and necrosis were
noted. Immunohistochemical studies confirmed an epithelial origin
with at least one epithelial marker in 78% of the tumors. K-ras
mutations by sequence analysis were found in eight of 12 cases
tested. Surgical biopsy/excision was used in all patients.
Twenty-nine of 35 patients died of disease (average, 5.2 months),
three died with no evidence of disease (average, 56.9 months), and
three patients were alive at last follow-up (average, 94.0 months),
one with residual disease. There was no statistically significant
difference in survival between patients with and without a K-ras
mutation. Anaplastic carcinoma of the pancreas usually occurs in the
head of the pancreas in older men. The epithelial nature of the
pleomorphic cells (giant or spindled) can usually be documented.
Patients with K-ras mutations have a shorter survival time, even
though the overall prognosis for all anaplastic carcinomas is fatal
(93% fatality; average survival, 448 days). Ann Diagn Pathol 5:
129-140, 2001. This is a US government work. There are no
restriction on its use.
See full article (<1 MB .pdf)
Renal cell carcinoma to the pancreas in
surgical pathology material.
Thompson LD, Heffess CS.
Cancer. 2000 Sep 1;89(5):1076-88.
BACKGROUND: Clear cell carcinomas of the pancreas are rare and more
likely represent metastatic renal cell carcinoma (RCC).
METHODS: Twenty-one cases of metastatic RCC to the pancreas were
retrieved from the files of the Endocrine Registry of the Armed
Forces Institute of Pathology. Histologic features were reviewed,
special stains and immunohistochemical studies were performed, and
patient follow-up data were obtained.
RESULTS: The patients included 9 women and 12 men ages 47-76 years
(mean, 64.4 years). Patients experienced weight loss, abdominal
pain, or a mass lesion. The tumors occurred anywhere within the
pancreas. The mean size of the tumors was 4.0 cm. Histologically,
the tumors were comprised of clear cells with a rich vascular
network. The RCC was diagnosed before (n = 17 patients; ages up to
32.7 years) or after (n = 4 patients; ages up to 13.2 years) the
pancreatic metastases were discovered. Surgery was used in all
patients. Adjuvant chemotherapy was used in 4 patients. From the
date of the diagnosis of pancreatic metastasis, 13 patients were
dead with disseminated disease (DD) (mean, 4.5 years), and 8
patients were without disease (mean, 9.0 years). From the date of
the diagnosis of primary RCC, 13 patients were DD (mean, 12.7
years), and 8 patients were without disease (mean, 24.7 years).
CONCLUSIONS: Although histochemical and immunohistochemical studies
may help in the distinction between patients with primary versus
metastatic clear cell tumors of the pancreas, clinical confirmation
should be obtained. Surgical resection of the pancreatic metastatic
disease is suggested, because the patient may still have a prolonged
See full article (1 MB .pdf)
A clinicopathologic and
immunohistochemical study of ten pancreatic lymphangiomas and a
review of the literature.
Paal E, Thompson LD, Heffess CS.
Cancer. 1998 Jun 1;82(11):2150-8. -- Erratum in: Cancer 1998 Aug
BACKGROUND: Pancreatic lymphangiomas are rare benign tumors, of
which only a few cases have been reported in the literature. In this
study, the authors present a series of primary pancreatic
METHODS: Cases of nonepithelial pancreatic cystic tumors
(lymphangiomas) diagnosed between 1966 and 1994 were retrieved from
the Endocrine Pathology Registry of the Armed Forces Institute of
Pathology. Histologic features (in 10 cases) as well as
histochemical and immunohistochemical studies (in 6 cases) were
reviewed. Long term patient follow-up data were obtained in 9 cases.
RESULTS: The patients included 8 females and 2 males ages 2-61 years
(mean age, 28.9 years) at initial presentation. The tumors were
circumscribed and occurred predominantly (in 6 of 10 cases) in the
tail of the pancreas. The multicystic, serous, or chylous
fluid-filled cystic tumors ranged from 3 to 20 cm (average, 12.7 cm)
in greatest dimension. Histologically, the tumors consisted of
multilocular cystic spaces of various sizes, lined by endothelial
cells. The stroma contained smooth muscle and mature lymphocytes.
Immunohistochemistry determined the endothelial lining cells to be
factor VIII-R antigen and CD31 positive (in all cases tested) but
usually CD34 negative. All patients for whom follow-up data were
obtained (n=9) were alive without evidence of disease an average of
7.2 years after initial diagnosis.
CONCLUSIONS: Pancreatic lymphangiomas occur predominantly in females
within a wide age range. Multilocular, fluid-filled cysts, with
endothelial immunoreactivity for factor VIII-R antigen and CD31, are
characteristic of these tumors. Complete surgical excision of these
benign tumors resulted in excellent long term prognoses for all
See full article (<1 MB .pdf)
cystic neoplasms of the pancreas: radiologic-pathologic correlation.
Buetow PC, Rao P, Thompson LD.
Radiographics. 1998 Mar-Apr;18(2):433-49.
Mucinous cystic neoplasms of the pancreas are rare primary tumors.
They have pathologic and clinical similarities to biliary
cystadenomas of the liver and mucinous cystic tumors of the ovary.
Mucinous cystic neoplasms of the pancreas typically affect
middle-aged women and arise in the tail of the pancreas. Gross
pathologic and imaging features usually are those of a large,
multilocular cystic mass. There is, however, a spectrum of
radiologic findings that overlaps with those of other entities
including pancreatic pseudocyst, other primary epithelial and
nonepithelial tumors of the pancreas, and metastases. In most cases,
ultrasound and computed tomography are the mainstays for radiologic
evaluation, with magnetic resonance imaging having a complementary
role. All mucinous cystic neoplasms should be considered as mucinous
cystadenocarcinomas of low-grade malignant potential. Complete
surgical excision alone results in an excellent clinical outcome and
disease-free survival, irrespective of histologic or radiologic
parameters in over 90% of cases studied.
See full article (1.5 MB .pdf)
Monoclonal origins of malignant mixed
tumors (carcinosarcomas): Evidence of a divergent histogenesis.
Thompson L, Cheng B, Barsky S
Am J Surg Pathol 1996;20:277-85
Malignant mixed tumors (carcinosarcomas) are examples of unusual
neoplasms whose occurrences have been observed in increasingly
diverse sites but whose pathogenesis remains a complete mystery. Two
antithetical hypotheses that have been advanced to explain the
histogenesis of these tumors include the convergence hypothesis,
which proposes an origin from two or more stem cells (multiclonal
hypothesis), and the divergence hypothesis, which proposes an origin
from a single totipotential stem cell that differentiates into
separate epithelial and mesenchymal directions (monoclonal
hypothesis). To test these hypotheses, a novel strategy for the
determination of clonality from as few as 100 tumor cells obtained
by enzymatic digestion of either fresh or formalin-fixed,
paraffin-embedded tissues and cell sorting was used that exhibited
the polymerase chain reaction (PCR) in amplifying a 511-bp region
located within the first intron of the human hypoxanthine
phosphoribosyl transferase gene, a site that contains inactive X
chromosomal obligately methylated HpaII/MspI sites and single-base
allelic polymorphisms in 5% females. Carcinoma cells gated on the
basis of fluorescein isothiocyanate (FITC)-anti-cytokeratin and
sarcoma cells gated on the basis of FITC-antivimentin or
FITC-anti-desmin were sorted to homogeneity on FACSTAR and then
subjected to genomic DNA extraction and Hpa II digestion before PCR
amplification and subsequent analysis of the product on denaturing
gradient gel electrophoresis. The comigrations of the single
homoduplexes generated from both the carcinoma cells and sarcoma
cells in six different malignant mixed tumors obtained from four
different organs indicated clonal identity and monoclonality in all
cases. These findings of monoclonality were confirmed independently
by two other methods of clonality determination. The findings of a
monoclonal origin of carcinosarcomas support the single
totipotential stem-cell-divergence hypothesis.
See full article (2.5 MB .pdf)