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Clin Cancer Res. 2016 Feb 15;22(4):1011-7. doi: 10.1158/1078-0432.CCR-15-0548. Epub 2015 Oct 19.

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

Author information

1
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. tangl@mskcc.org.
2
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
3
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
4
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California.
5
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.

Abstract

PURPOSE:

Most well-differentiated neuroendocrine tumors (WD-NET) 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 current WHO G3 category contains both WD-NETs as well as PD-NECs.

PMID:
26482044
PMCID:
PMC4988130
DOI:
10.1158/1078-0432.CCR-15-0548
[Indexed for MEDLINE]
Free PMC Article

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