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2010—February Case of the Month

Posted March 11, 2011

CLINICAL SUMMARY: PANCREAS  

CAP Foundation February 2010 Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 62-year-old woman presented with abdominal pain and dyspepsia. CT revealed a multicystic mass in the tail of the pancreas; the other organs were normal and there was no lymphadenopathy. The pancreatic mass, 6.5 x 2.5 x 2.5 cm, was well demarcated, composed of multiple small cysts, and contained a central stellate scar. The neoplastic cells were found to have PAS positive, diastase digestible, cytoplasmic material. The spleen and lymph nodes were unremarkable.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2008, and Case 7 is microcystic serous cystadenoma.

Criteria for Diagnosis and Comments: The tumor is composed of variably sized cysts lined by cuboidal cells with clear cytoplasm. The clear cytoplasm is due to abundant glycogen, as demonstrated by the PAS stain. The nuclei are uniform, small, round, and hyperchromatic; mitoses are absent. The stroma between the cysts is collagenous and unremarkable, except for occasional entrapped islets of Langerhans, other normal structures, and inflammatory cells. Focally, there are degenerative changes with debris, histiocytes, and calcification. The gross and microscoping findings are consistent with microcystic serous cystadenoma

Microcystic serous cystadenoma accounts for only 1 to 2 percent of tumors of the exocrine pancreas. The age range of patients is wide, with an average of 65 years, and the tumor is seen more often in women (7F:3M). The most common presenting symptoms include abdominal pain and dyspepsia, but a significant number of tumors are found incidentally. At least half of all patients with von Hippel-Lindau syndrome develop serous cystadenoma, which is often multifocal in these non-sporadic cases. Microcystic serous cystadenomas are benign, but are generally resected when large and symptomatic.

Microcystic serous cystadenomas are found throughout the pancreas, with approximately one half located in the head. They are generally well demarcated, have an average size of 6 cm, and are made up of multiple, small, thin-walled cysts that contain straw-colored fluid. Often there is a central stellate scar. Variants of the tumor include macrocystic serous cystadenoma, solid serous adenoma, combined well differentiated endocrine neoplasm-serous cystadenoma and von Hippel-Lindau associated cystic neoplasm. The macrocystic type is not as well circumscribed as the usual microcystic type, lacks a central scar, and contains fewer, larger cysts; however, the microscopic features of the lining cells are the same. The solid serous adenoma is a solid mass composed of clear polygonal cells forming nests, acini, cords, and sheets. The third variant contains components of both well differentiated pancreatic endocrine neoplasm and serous cystadenoma, either mixed or adjacent to each other. This variant is seen in patients with von Hippel-Lindau syndrome. Von Hippel-Lindau associated cystic neoplasms are often macrocystic and tend to be multifocal. The lining cells are the same as those in non-syndromic tumors.

Because the cells of microcystic serous cystadenoma contain abundant glycogen, they are PAS positive and PAS/diastase sensitive. Mucicarmine and Alcian blue stains are negative. By immunohistochemistry, they can be positive for AE1/AE3, CAM5.2, CK7, CK8, CK18, CK19, EMA, MUC6, alpha-inhibin, and NSE. Calretinin, CEA, CK20, chromogranin, synaptophysin, insulin, glucagon, somatostatin, VIP, PP, MUC2, MUC5AC, S-100, HMB-45, CD31, and vimentin are usually negative. These tumors have been reported to have loss of heterozygosity on chromosome 3p25 and somatic VHL gene mutations.

Serous cystadenocarcinoma of the pancreas is a rare neoplasm that is histologically identical to serous cystadenoma, but is distinguished by the presence of metastases in extra-pancreatic sites, most typically the liver, lymph nodes, and peritoneum.

Mucinous cystic neoplasms of the pancreas are lined by columnar cells with intracytoplasmic mucin. The cysts are usually larger than those in serous tumors (with the exception of macrocystic serous cystadenoma), and the cyst walls are thicker and contain ovarian-type stroma. These tumors are mucicarmine positive.

Lymphangiomas may mimic pancreatic serous neoplasms as they are multicystic, thin-walled and contain serous fluid. However, the endothelial lining cells are flat, rather than cuboidal, and the cyst walls contain smooth muscle and aggregates of lymphocytes. These tumors are positive for CD31.

Renal cell carcinoma, similar to serous neoplasms of the pancreas, can contain clear cells and arise in patients with von Hippel-Lindau syndrome. These tumors, however, usually have nuclear atypia and mitotic activity. The presence of a renal mass or a history of renal cell carcinoma, together with staining for CD10 and RCC, may also be useful in establishing a diagnosis of metastatic renal cell carcinoma.

Supplementary Questions:
For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which multicystic tumor is positive for CD31? A.  Lymphangioma
B.  Metastatic renal cell carcinoma
C.  Microcystic serous cystadenoma
D.  Mucinous cystic neoplasm
E.  Serous cystadenocarcinoma
2. Which tumor is associated with von Hippel-Lindau syndrome, can have VHL gene mutations, and is a primary pancreatic neoplasm? A.  Lymphangioma
B.  Metastatic renal cell carcinoma
C.  Microcystic serous cystadenoma
D.  Mucinous cystic neoplasm
E.  Serous cystadenocarcinoma
3. Which multicystic tumor contains ovarian-type stroma in the cyst walls? A.  Lymphangioma
B.  Metastatic renal cell carcinoma
C.  Microcystic serous cystadenoma
D.  Mucinous cystic neoplasm
E.  Serous cystadenocarcinoma

References

  1. Alpert LC, Truong LD, Bossart MI, Spjut HJ. Microcystic adenoma (serous cystadenoma) of the pancreas. A study of 14 cases with immunohistochemical and electron-microscopic correlation. Am J Surg Pathol. 1988; 12:251-263.
  2. George DH, Murphy F, Michalski R, Ulmer BG. Serous Cystadenocarcinoma of the pancreas: a new entity? Am J Surg Pathol. 1989; 13:61-66
  3. Hruban RH, Pitman MB, Klimstra DS. Tumors of the Pancreas. AFIP Atlas of Tumor Pathology. 4th Series, Fascicle 6. Washington DC: Armed Forces Institute of Pathology; 2007; 33-45.
  4. Huang P, Staerkel G, Sneige N, Gong Y. Fine-needle aspiration of pancreatic serous cystadenoma: cytologic features and diagnostic pitfalls. Cancer. 2006; 108:239-249.
  5. Perez-Ordonez B, Naseem A, Lieberman P, Klimstra DS. Solid serous adenoma of the pancreas: the solid variant of serous cystadenoma? Am J Surg Pathol. 1996; 20:1401-1405.

Author:
2008
Michael Deavers, MD, FCAP
Surgical Pathology Committee
The University of Texas MD Anderson Cancer Center
Houston, Texas