Well-differentiated neuroendocrine tumors with a morphologically apparent high-grade component: A pathway distinct from poorly differentiated neuroendocrine carcinomas Journal Article


Authors: Tang, L. H.; Untch, B. R.; Reidy, D. L.; O'Reilly, E.; Dhall, D.; Jih, L.; Basturk, O.; Allen, P. J.; Klimstra, D. S.
Article Title: Well-differentiated neuroendocrine tumors with a morphologically apparent high-grade component: A pathway distinct from poorly differentiated neuroendocrine carcinomas
Abstract: Purpose:Mostwell-differentiated neuroendocrine tumors(WDNET) of the enteropancreatic system are low-intermediate grade (G1, G2). 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 (G3) 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 G1-G2 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 currentWHOG3 category contains both WDNETs as well as PD-NECs. © 2015 AACR.
Journal Title: Clinical Cancer Research
Volume: 22
Issue: 4
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2016-02-15
Start Page: 1011
End Page: 1017
Language: English
DOI: 10.1158/1078-0432.ccr-15-0548
PROVIDER: scopus
PUBMED: 26482044
PMCID: PMC4988130
DOI/URL:
Notes: Article -- Previously presented at the United States and Canadian Academy of Pathology (USCAP) Annual Meeting, March 20-26 2010, Washington D.C. -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Olca Basturk
    203 Basturk
  2. Diane Lauren Reidy
    146 Reidy
  3. David S Klimstra
    843 Klimstra
  4. Peter Allen
    436 Allen
  5. Laura Hong Tang
    320 Tang
  6. Eileen O'Reilly
    316 O'Reilly
  7. Brian Untch
    23 Untch