Well-Differentiated Neuroendocrine Tumors with a Morphologically Apparent High-Grade Component: A Pathway Distinct from Poorly Differentiated Neuroendocrine Carcinomas

作者：Tang, Laura H.^*; Untch, Brian R.; Reidy, Diane L.; O'Reilly, Eileen; Dhall, Deepti; Jih, Lily; Basturk, Olca; Allen, Peter J.; Klimstra, David S.

来源：Clinical Cancer Research, 2016, 22(4): 1011-1017.

DOI：10.1158/1078-0432.CCR-15-0548

• PANCREATIC ENDOCRINE NEOPLASMS
• KI67 PROLIFERATIVE INDEX
• GASTROINTESTINAL-TRACT
• PROGNOSTIC-FACTORS
• SMALL-CELL
• SYSTEM
• CLASSIFICATION
• G3
• QUANTIFICATION
• PROPOSAL

Purpose: Mostwell-differentiated neuroendocrine tumors(WDNET) of the enteropancreatic system are low-intermediate grade (G(1), G(2)). Elevated proliferation demonstrated by either a brisk mitotic rate (> 20/10 high power fields) or high Ki-67 index (> 20%) defines a group of aggressive neoplasms designated as high-grade (G(3)) neuroendocrine carcinoma (NEC). High-grade NEC is equated with poorly differentiated NEC (PD-NEC) and is associated with a dismal outcome. Progression of WD-NETs to a high-grade neuroendocrine neoplasm very rarely occurs and their clinicopathologic and molecular features need to be characterized. @@@ Experimental Design: We investigated 31 cases of WD-NETs with evidence of a component of a high-grade neoplasm. The primary sites included pancreas, small bowel, bile duct, and rectum. Histopathology of the cases was retrospectively reviewed and selected IHC and gene mutation analyses performed. @@@ Results: The high-grade component occurred either within the primary tumor (48%) or at metastatic sites (52%). The clinical presentation, radiographic features, biomarkers, and the genotype of these WD-NETs with high-grade component remained akin to those of G(1)-G(2) WD-NETs. The median disease-specific survival (DSS) was 55 months (16-119 months), and 2-year and 5-year DSS was 88% and 49%, respectively-significantly better than that of a comparison group of true PD-NEC (DSS 11 months). @@@ Conclusions: Mixed grades can occur in WD-NETs, which are distinguished from PD-NECs by their unique phenotype, proliferative indices, and the genotype. This phenomenon of mixed grade in WD-NET provides additional evidence to the growing recognition that the current WHOG3 category contains both WDNETs as well as PD-NECs.

• 出版日期2016-2-15