The tumors grow in a trabecular, microglandular, or mixture of both pattern, a clue to the diagnosis even on low power. At this power, however, more pleomorphism than the usual low grade neuroendocrine tumor is already apparent.
The architecture of this tumor, with is distinct ribbon-like growth, serves to help recognize the neuroendocrine nature of the lesion.
Extensive geographic necrosis isolates the tumor cells into irregular islands of viable cells, with limited supporting stroma.
Features of high grade neuroendocrine carcinoma include extensive tumor necrosis, numerous mitoses, and more pleomorphism than the usual neuroendocrine tumor.
Irregular outlines to the architecture is evident, in contrast to low grade tumors which are more obviously nested and have rounded architectural contours.
Strong and consistent immunoreactivity for neuroendocrine markers defines these tumors. Synaptophysin, as well as chromogranin, neuron-specific enolase and keratin are almost invariably positive.
Chromogranin is also typically positive although more variable in intensity.
Gastric neuroendocrine tumors arise from the various endocrine cells scattered among gastric epithelial cells. Endocrine cells that produce serotonin are called enterochromaffin cells (ECC) and ones that produce gastrin and are called “G-cells”; proliferation of these cells are form a minority of gastric neuroendocrine tumors.
The majority of GNETs (70%) derive from “enterochromaffin-like” (ECL) cells that produce histamine (Odze, pg 495). These neoplasms are associated with atrophic (type A autoimmune) gastritis, MEN1 and/or Zollinger-Ellison syndrome. The underlying mechanism of pathogenesis is posited to be hypergastrinemia, leading to ECL cell hyperplasia which is considered a preneoplastic condition (Robbins, 827). Gastrin has a trophic influence on ECL cells (Odze).
Gastric neuroendocrine tumors used to be all grouped under the broad heading “carcinoids”, however, the 2000 WHO classification scheme has separated benign neuroendocrine tumors (still called carcinoids) from ones with known metastatic potential, now called neuroendocrine tumors or neuroendocrine carcinomas (well-differentiated or poorly differentiated) (ACS).