Four Neuroendocrine Tumor Types and Neuroendocrine Carcinoma of the Duodenum: Analysis of 203 Cases

Abstract

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 nonfunctioning 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 (n = 23) were significantly associated with larger size, higher proliferative grade, lymphovascular invasion, deep invasion and local lymph node metastasis. Conclusion: Our careful analysis of a large series of duodenal NENs identified five histologically and prognostically different histotypes of potential clinical relevance.

The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter

“…However, the WHO 2010 classification did not regard this as a prognostic factor possibly because of enormous inter-observer differences among pathologists in identifying the presence of LVI [1,26]. However, the recent study showed that LVI is one of the risk factors for LN metastasis in D-NET [21]. This study firstly demonstrates LVI as a risk factor for metastasis in NAD-NET measuring ≤20 mm in diameter.…”

“…NAD-NETs >20 mm in diameter were known as a risk factor for metastasis [7,10,12,21]. However, in NAD-NETs ≤20 mm in diameter, the therapeutic approach of individual patients still remains in dispute [7,12,13,14].…”

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up

“…Grozinsky-Glasberg et al [36] found primary tumor size of ≥1 cm in all of the 20 (locally or distantly) metastatic cases they collected (out of 254 patients scrutinized, 7.9%) with, however, a Ki67 index of between 3 and 20% (i.e., G2) in only 6 out of the 17 metastatic cases investigated. In our type I NETs, G2 failed to be associated with gastric wall invasion or metastases, despite the fact that an association of grade with tumor behavior as well as patient outcome was ascertained for type III gastric NETs, as well as for pancreatic and duodenal NETs [39-41]. These results bring the attention to previous type I NET series where G2 failed to predict tumor behavior [27, 42] or showed no apparent impact on tumor behavior and patient survival despite a high G2 type I NET percentage (71% reported by Lee et al [29] and 34% by Campana et al [43]).…”

S2k-Leitlinie Neuroendokrine Tumore

“…Da selbst kleine Gastrinome < 1 cm häufig metastasieren, ist eine endoskopische Behandlung nicht adäquat [233], s. auch Erläuterungstext zu Empfehlung 3.10.…”