The morphology and neuroendocrine profile of pancreatic epithelial VIPomas and extrapancreatic, VIP-producing, neurogenic tumors.

The histology, histochemistry, and ultrastructure of 43 VIP-producing tumors (34 from the pancreas, one jejunal, six retroperitoneal and two mediastinic), 37 of which were associated with the WDHA syndrome, have been investigated on paraffin sections of primary or metastatic tumor tissue. The pancreatic and jejunal tumors showed all structural and secretory patterns of epithelial endocrine tumors, including expression of cytokeratin, neuroendocrine markers like neuron-specific enolase, chromogranins and synaptophysin, peptides like VIP, PHM, GRH, PP, insulin, neurotensin, glucagon, somatostatin and enkephalin, secretory granules, small clear vesicles, peculiar osmiophilic bodies, and occasional formation of tubules or microacini with specialized luminal surfaces. All the remaining tumors were neurogenic, showing either neurons and nerve fibers together with Schwann cells (ganglioneuromas and ganglioneuroblastomas) or endocrine cells (pheochromocytomas) reacting with VIP, PHM, NPY, enkephalin, somatostatin, neuron-specific enolase, synaptophysin, and MAP2 (but not cytokeratin, PP, or GRH) antibodies. A possible origin of pancreatic VIPomas from transformed pancreatic PP cells or ductular stem cells partially committed to differentiation along the PP cell line is suggested.