Four neuroendocrine tumor types and the neuroendocrine carcinoma of the duodenum: analysis of 203 cases

BACKGROUND: Several types of neuroendocrine neoplasms (NENs) have been described in the duodenal tract, from low grade tumors (NETs) to high grade neuroendocrine carcinomas (NECs). A comprehensive analysis of histology, hormonal profile and prognostic parameters of a sufficiently large duodenal NEN series to cover all main kinds of neoplasms is however lacking. METHODS: We collected a retrospective series of 203 duodenal wall and ampullary region NENs, from six specialized endocrine pathology centers. All were characterized histopathologically and histochemically and 190 were followed for a median of 9 years. RESULTS: Twenty seven poorly differentiated NECs, mostly from the ampullary region, were identified and shown to lead to patient demise in a median of 10 months. Among 176 NETs, four subtypes were characterized, including 20 gastrinomas, 37 ampullary-type somatostatin producing NETs (ASTs), 12 gangliocytic paragangliomas (GPs) and 106 non-functioning NETs (nfNETs). ASTs and GPs were mostly localized in the ampullary/periampullary region, while gastrinomas and nfNETs were mainly from the proximal duodenum. ASTs and gastrinomas showed high rates of local infiltration (especially lymphoinvasion and deep duodenal wall/pancreatic tissue invasion) and lymph node metastasis, while nfNETs had significantly lower, and more size-dependent, local invasive potential. Disease-specific survival differed significantly between NETs and NECs, though not among NET subtypes. NET cases with distant metastases (23) were significantly associated with larger size, higher proliferative grade, lymphovascular invasion, deep invasion and local lymph node metastasis. CONCLUSION: Careful analysis of a large series of duodenal NENs identifies five histologically and prognostically different histotypes, of potential clinical relevance