Neuroendocrine Tumors (NETs) of the Minor Papilla/Ampulla

Abstract

Neuroendocrine tumors (NETs) of the minor papilla/ampulla (MIPA) are rare and poorly studied. Only individual case reports and no comprehensive analysis are available from the literature. We collected 16 MIPA NETs and investigated their clinicopathologic and immunohistochemical features, including markers such as somatostatin, pancreatic polypeptide, gastrin, serotonin, MUC1, cytokeratin 7, and somatostatin receptors type 2A and 5. The median age at diagnosis was 57.5 years, and the female-to-male ratio was 2.2:1. The median NET size was 1.45 cm, and most (94%) were low-grade (G1) tumors. Similarly to what was observed in the major ampulla, 3 histotypes were found: (i) ampullary-type somatostatin-producing tumors (ASTs, 10 cases), characterized by somatostatin expression in most tumor cells, focal-to-extensive tubulo-acinar structures, often with psammoma bodies, MUC1 reactivity, and no or rare membranous reactivity for somatostatin receptor type 2A; (ii) gangliocytic paragangliomas (3 cases), characterized by the coexistence of 3 tumor cell types: epithelioid, often reactive for pancreatic polypeptide, ganglion-like cells, and S100 reactive sustentacular/stromal cells; and (iii) ordinary nonfunctioning NETs (3 cases), resembling those more commonly observed in the extra-ampullary duodenum. Comparable histotypes could also be recognized among the 30 MIPA NETs from the literature. No NET-related patient death among MIPA cases was observed during a median follow-up of 38 months; however, MIPA ASTs showed lymph node metastases and invasion of the duodenal muscularis propria or beyond in 44% and 40% of cases, respectively. In conclusion, MIPA NETs closely resemble tumors arising in the major ampulla, with predominance of ASTs.

Ampullary Large-Cell Neuroendocrine Carcinoma, a Diagnostic Challenge of a Rare Aggressive Neoplasm: A Case Report and Literature Review

“…Neuron-specific enolase (NSE) and CD56 marker are in many cases positive in GEP-NENs but have low specificity [ 51 ]. While periampullary adenocarcinomas commonly express MUC1 and cytokeratin 7, 2 markers, they are unusual among GEP-NENs [ 52 ].…”

Neuroendocrine neoplasms of the duodenum, ampullary region, jejunum and ileum

“…2 ). AS-NETs represent the most common histologic subtype among NETs of the major and minor papilla/ampulla regions 4 , 7 ; they can, however, be occasionally found in the extra-ampullary duodenum. A fraction of such neoplasms occur in patients with neurofibromatosis type 1 and they show a biallelic inactivation of NF1 gene 8 .…”

Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations

“…Duodenal neuroendocrine neoplasms represent a relatively uncommon, heterogeneous group of lesions, arising in the duodenum and in the major and minor ampullary regions [ 162 , 163 ]. The most recent WHO classification [ 164 ] recognizes three different entities, namely well-differentiated neuroendocrine tumors (NETs—grade 1, 2, or 3 according to proliferation), gangliocytic paragangliomas, and poorly differentiated neuroendocrine carcinomas (NECs).…”