Diagnosis: Well-differentiated pancreatic neuroendocrine tumor, serotonin-secreting

Histology: This pancreatic resection specimen displays areas of unremarkable pancreatic parenchyma, with separate regions displaying chronic pancreatitis, suggestive of ductal obstruction. Within the pancreas is a fibrotic tumor characterized by cells arranged in nests, trabeculae, single file, and single cell patterns. The cells have amphophilic granular cytoplasm and oval to rounded nuclei with finely dispersed “salt and pepper chromatin,” occasionally prominent nucleoli, and scattered degenerative-type atypia. Mitotic figures are inconspicuous. Perinerual invasion is readily identified, and metastatic foci are present within a peripancreatic lymph node. Immunotains show the lesional cells to be immunoreactive for synaptophysin and serotonin, and negative for BCL10, with a Ki67 proliferation index of <2%.

Discussion: This lesion exhibits the morphologic and immunophenotypic features of a well-differentiated, pancreatic neuroendocrine tumor (PanNET), which are further subdivided on the basis of tumor grade and (to an extent) tumor functionality. PanNETs are graded on the basis of the mitotic count per high power field (HPF) or the Ki67 proliferation index (measured as a percentage of cells with nuclear Ki67 labeling), and the higher of the two measures is used to determine the grade. Well-differentiated PanNETs display bland morphologic features (i.e., lack necrosis, lack features of small cell or large cell neuroendocrine carcinoma) and are classified as Grade 1 (mitoses <2/10 HPF or Ki67 <2%), Grade 2 (mitoses 2-20/10 HPF or Ki67 3-20%), or Grade 3 (mitoses >20/10 HPF or Ki67 >20%). Poorly differentiated pancreatic neuroendocrine carcinoma is also Grade 3 (mitoses >20/10 HPF or Ki67 >20%) but in addition displays histologic features of small cell carcinoma or large cell neuroendocrine carcinoma. The differential diagnosis of a solid cellular neoplasm in the pancreas includes acinar cell carcinoma, solid pseudopapillary neoplasms, metastases to the pancreas, and possibly ductal adenocarcinoma. In this particular tumor, there is abundant fibrosis, which can mimic the desmoplasia seen in ductal adenocarcinoma. However, the presence of the fibrosis as well as the trabecular growth pattern is a clue to the functional status of this tumor: it is a serotonin-secreting, well-differentiated grade 1 PanNET. Serotonin-secreting PanNETs characteristically show fibrosis, calcification, large duct involvement, and trabecular growth. Not all PanNETs are functional, but all should display some degree of labeling for neuroendocrine markers (synaptophysin, chromogranin, CD56)

References:
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