Episode 70 An integrated approach to differentiate Grade 3 PanNET from PanNEC
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- čas přidán 8. 01. 2024
- Distinguishing grade 3 pancreatic neuroendocrine tumor (G3 PanNET) from neuroendocrine carcinoma (PanNEC) is a known diagnostic challenge, and accurate classification is critical because clinical behavior and therapies differ.
Dr. Nancy Joseph from the University of California San Francisco discusses her group’s recent study on high-grade neoplasms originally diagnosed as pancreatic neuroendocrine neoplasms. In addition to the currently recommended stains (p53, Rb, ATRX, and DAXX), 500 NGS panel and immunohistochemistry for p16 and trypsin or chymotrypsin were also performed. The authors were able to classify 89% of cases as either G3 PanNET, PanNEC or mixed acinar-NEC.
G3 PanNETs demonstrated frequent alterations in MEN1 (71%), DAXX (47%), ATRX (24%), TSC2 (35%), SETD2 (42%), and CDKN2A (41%). Contrary to prior reports, TP53 alterations were also common in G3 PanNETs (35%) but were always mutually exclusive with CDKN2A alterations in this group.
PanNECs demonstrated frequent alterations in TP53 (88%), cell cycle genes RB1 (47%), CCNE1/CCND1 (12%), CDKN2A (29%), and in KRAS (53%) and SMAD4 (41%); TP53 was co-altered with a cell cycle gene in 76% of PanNECs. Diffuse strong p16 staining was observed in 69% of PanNECs in contrast to 0% of G3 PanNETs. Acinar-NECs had recurrent alterations in ATM (25%), APC (25%), and STK11 (25%).
Molecular profiling and immunohistochemistry for p16 greatly improve the diagnostic accuracy of high-grade pancreatic neuroendocrine neoplasms and identify a subset of rare cases with overlapping features of both PanNET and PanNEC.
DOI: 10.1016/j.modpat.2022.100065