Morphologic patterns and diagnostic criteria of VIP-producing endocrine tumors. A histologic, histochemical, ultrastructural, and biochemical study of 32 cases

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Abstract
Thirty‐two tumors (31 pancreatic and one jejunal) all associated with severe watery diarrhea, increased VIP levels in blood and most with hypokalemia, were investigated. The VIP content of tumor tissue ranged from 23 to 15,000 pmol/g. VIP immunoreactive cells were detected histochemically in 24 of 28 tumors investigated, PP immunoreactive cells in 11 of 28 tumors, hCG (α chain) immunoreactive cells in 12 of 25 tumors, and neuron specific enolase (NSE) immunoreactive cells in 24 of 26 tumors (the 2 negative results were due to inadequate fixation). All cases showed light microscopic features of epithelial endocrine tumors. Electron microscopy demonstrated a prevalence of agranular, poorly granulated and a minority of well granulated cells. Most secretory granules were round, small (150 ± 30 nm diameter) and of moderate electron density, resembling those of the so‐called D1 cells. By electron immunocyto‐chemistry, PP was directly localized in a subpopulation of relatively larger granules (154 ± 22 nm core diameter) showing closely applied membranes. VIP‐storing granules, directly identified only in the jejunal tumor, appear to correspond to a subpopulation of slightly smaller P‐type granules (126 ± 37 nm core diameter) showing a narrow, clear halo. The origin, behavior, and diagnostic criteria of VIPomas are discussed.