Answer: Serous cystadenoma

Histology: The lesion is grossly solid and well circumscribed, located within the pancreatic parenchyma. Microscopically, the lesion consists of small nests or tubules of uniform cells with bland nuclei and water-clear cytoplasm. No mitoses or necrosis are evident. Immunostains are performed and show the lesional cells to be negative for synaptophysin, chromogranin and CD56, with a low Ki67 proliferation index (<2%).

Discussion: Serous cystadenomas of the pancreas are benign neoplasms comprised of clear (glycogen-containing) cuboidal cells with bland nuclei. They are typically well-circumscribed and may contain a central scar. If the cysts are large enough, the cysts may be seen grossly, and the microcysts may appear “sponge-like” on cut section. Microcystic serous cystadenomas with small individual cysts can appear solid on imaging, mimicking other solid, well-circumscribed lesions of the pancreas (most often mimicking pancreatic neuroendocrine tumors). A variant of serous cystadenoma is the “solid serous adenoma” does not display contain any microcysts with central lumina but rather consists of nests of cells in small acini. This variant especially mimics neuroendocrine neoplasms due to the grossly solid appearance.

Serous cystadenomas may be seen in von Hippel Lindau syndrome (VHL gene mutations). A potential pitfall is that VHL patients also develop pancreatic neuroendocrine neoplasms with clear cell change and clear cell renal cell carcinomas (which can metastasize to the pancreas).

The differential diagnosis of solid and cystic pancreatic neoplasms include pancreatic neuroendocrine tumors and solid pseudopapillary neoplasms. Pancreatic neuroendocrine neoplasms are typically solid but may show cystic change, and they usually display typical neuroendocrine cytologic features and positivity for synaptophysin, chromogranin and CD56. Solid pseudopapillary neoplasms are comprised of loosely cohesive cells with nuclear grooves, the formation of pseudopapillae, the presence of foam cells and cholesterol clefts and positivity for nuclear beta-catenin, CD56 and CD10.

The malignant counterpart of serous cystadenoma is serous cystadenocarcinoma, which is defined by clinical behavior, that is, the presence of distant metastasis. They are histologically bland in appearance.

Reference(s):
- Singhi AD, Chu LC, Tatsas AD, Shi C, Ellison TA, Fishman EK, Kawamoto S, Schulick RD, Wolfgang CL, Hruban RH, Edil BH. Cystic pancreatic neuroendocrine tumors: a clinicopathologic study. Am J Surg Pathol. 2012 Nov;36(11):1666-73.