Back to Homepage

Case 434 - Discussion

Uploaded: 2010-10-02, Updated: 2010-10-02

 

Serous Cystadenoma of the Pancreas

 

The Key Features

  • Associated with VHL syndrome;

  • Gross: numerous small, thin-walled cysts, central stellate scar, often calcified;

  • Histology: single layer of uniform clear cuboidal, glycogen-rich cells;

  • IPX: CAM5.2, CK7, CK8, CK18, CK19, alpha-inhibin and MUC6;

  • Serum CEA, CA19-9 and CD125, almost never increased;

  • Almost always benign.

 

CLINICAL FEATURES

  • Synonyms: microcystic serous cystadenoma, glycogen-rich cystadenoma, microcystic adenoma;

  • Women:Men = 2:1; mean age 65 years;

  • 1-2% of all neoplasms of the exocrine pancreas,10% of surgically resected cystic pancreatic lesions;

  • Most commonly in pancreatic head and body, rarely in main pancreatic duct.

  • Almost always benign;

  • Associated with VHL syndrome, especially multifocal;

  • Clinical image studies: well-defined mass with microlacunae separated by delicate septa, central stellate scar, 10-30% percent of these scars with a “sunburst” pattern of calcification, small cysts with“soap bubble” pattern;

  • Serum CEA, CA19-9 and CD125, almost never increased;

  • Surgical resection is curative.

GROSS FINDINGS

  • Large, mean 6 cm, well-demarcated, somewhat bosselated masses;

  • Numerous small (usually < 2 mm, up to 1 cm), thin-walled cysts, imparting a sponge-like or honeycomb appearance on cross section;

  • The cysts are filled with clear, watery, straw-colored (serous) fluid and are separated by thin fibrovascular septa;

  • Commonly has a central stellate scar, often calcified; toward the periphery of the neoplasm the cysts tend to be larger;

  • The cysts do not usually communicate with the pancreatic duct system.

MICROSCOPIC FINDINGS

  • Uniform clear cuboidal, glycogen-rich cells that form numerous small cysts containing serous fluid;

  • Tumor cells form single layer, flat sheets and rarely form microscopic papillae that project into the cysts;

  • Tumor cells: clear cytoplasm that contains abundant intracytoplasmic glycogen;

  • Nuclei: small and round, and have uniform hyperchromatic chromatin and inconspicuous nucleoli. Atypia and mitoses are usually absent;

  • The central stellate scar and the stroma separating the cysts are composed mostly of acellular collagenous connective tissue, but the stroma may contain entrapped islets of Langerhans and acini.

SUBTYPES

  • Macrocystic Serous Cystadenoma

    • Also known as oligocystic serous cystadenoma, serous oligocystic and ill-demarcated adenoma;

    • Cysts are larger, less well defined, and fewer in number, can be as few as one locule (unilocular variant); do not have a central stellate scar, and they tend to be poorly circumscribed, often extending into and entrapping adjacent pancreatic parenchyma between the cysts;

    • Involve the head of the gland more than the standard microcystic serous cystadenomas;

    • The epithelial cells of this lesion are identical to those in microcystic serous cystadenomas.

  • Solid Serous Adenoma

    • Grossly solid neoplasm;

    • Microscopically clear to pale polygonal to cuboidal cells form nests, sheets, and trabeculae, also form small acini, but macroscopic cyst formation is not seen; the nuclear features are identical to those of other serous neoplasms;

    • Strongly PAS positive and sensitive to diastase digestion.

  • Combined Well-Differentiated Endocrine Neoplasm/Serous Cystadenoma

    • Usually occurs in patients with VHL syndrome;

    • Two components: well-differentiated pancreatic endocrine neoplasm and a serous cystadenoma; the two components can be adjacent to each other, or intimately admixed.

  • VHL-Associated Cystic Neoplasms

    • younger age, mean 42 years;

    • Tend to be multifocal, may diffusely involve the entire gland, often have a macrocystic appearance;

    • The epithelial cells are identical to those in non-VHL-associated serous cystadenomas.

DIFFERENTIAL DIAGNOSES

  • Pancreatic Pseudocysts
    • Abnormal swellings after inflammation or injury;
    • Make up more than 75% of all pancreatic cysts;
    • Located most often behind the stomach;
    • Cyst wall - inflammatory tissue, no lining epithelial cells.
  • Mucinous Cystadenomas
    • Previously macrocystic cystadenomas;
    • Almost always in women;
    • Most common cystic pancreatic tumors, 45-50%;
    • Gross: larger, thicker walled, and filled with thick tenacious fluid, not the clear watery fluid; no central stellate scar;
    • Histology: tall columnar cells containing abundant mucin, ovarian-type stroma;
    • Mucicarmine +, CEA +;
    • Behavior ranges from benign to malignant.
  • Lymphangioma:

    • Lined with uniformly flat endothelial cells, no cuboidal clear cells;

    • Characteristically contain lymphoid aggregates in the cyst walls;

    • CD31+ and factor VIII +, cytokeratin -.

  • Pancreatic abscess: usually secondary to infection of a pseudocyst

  • Benign pancreatic cysts: congenital autosomal dominant polycystic kidney disease;

  • Parasitic cysts: echinococcus granulosis and multilocularis cysts;

  • Lymphoepithelial cysts: extremely rare, lined by lymphoid tissue;

  • Pancreatic dermoid cysts: Solid and papillary epithelial pancreatic tumors: pancreatic tail, hemorrhage and necrosis.

 

 

Amylase

CEA

Viscosity

Mucin

Cytology

Serous cystadenoma

Low

Low

Low

Negative

Glycogen-rich cells

Mucinous cystadenoma

Low

High

High

Positive

Mucinous cells

Pseudocyst

High

Low

Low

Negative

Inflammatory cells

 

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • Positive

    • CK AE1/AE3, CAM5.2, CK7, CK8, CK18, and CK19;

    • Alpha-inhibin and MUC6, in most cases;

    • EMA, in 1/3 cases.

  • Negative: CEA, MUC2, MUC5, chromogranin, synaptophysin, insulin, glucagon, somatostatin, VIP, CD31, factor VIII, HMB-45, S-100 protein, vimentin, CK20.

ELECTRON MICROSCOPIC FINDINGS

  • Single layer of cuboidal cells with centrally located round nuclei. These cells sit on a well-formed basement membrane, have short blunt microvilli, and show evidence of epithelial differentiation including well-formed desmosomes and tight junctions. Most organelles are sparse, and instead the neoplastic cells are filled with abundant intracytoplasmic glycogen. These ultrastructural findings suggest centroacinar ductal differentiation.

CYTOGENETIC STUDIES

  • Associated with VHL syndrome: hemangioblastomas, renal neoplasms and cysts, clear cell endocrine pancreatic neoplasms, clear cell papillary cystadenomas of the epididymis, clear cell carcinoid tumors of the biliary tree, endolymphatic sac tumors, and pheochromocytomas; VHL gene, chromosome 3p25, encodes a protein that promotes the degradation of hypoxia-inducible factor (HIF). Inactivation of the VHL gene increases HIF levels and thereby promotes the formation of blood vessels through the increased production of factors such as vascular endothelial growth factor (VEGF).

TREATMENT AND PROGNOSIS

  • Surgical resection is the treatment of choice with excellent prognosis.

REFERENCES

  • AFIP, tumor of the bone and joints, series 4.