Well differentiated grade 3 pancreatic neuroendocrine tumors compared with related neoplasms: A morphologic study

BACKGROUNDPancreatic neuroendocrine neoplasms with a Ki‐67 labeling index greater than 20% were reclassified in 2017 by the World Health Organization into well differentiated (WD) and poorly differentiated grade 3 neuroendocrine carcinoma (NEC). The authors describe the cytologic features of grade 3 WD pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NEC.METHODSFine‐needle aspirates from 65 pancreatic neuroendocrine neoplasms were reviewed, and their cytomorphologic features were compared across grade 2, WD grade 3, and PD small cell type (PD‐S), large cell type (PD‐L), and type not otherwise specified (PD‐NOS) neoplasms.RESULTSThe 65 aspirates consisted of 19 grade 2 neoplasms, 32 WD grade 3 neoplasms, and 14 NECs (6 PD‐S, 5 PD‐L, and 3 PD‐NOS). The medians Ki‐67 proliferation index was 11% (range, 3.2%‐17%) in grade 2 neoplasms, 40% (range, 21%‐89%) in WD grade 3 neoplasms, 80% (range, 63%‐95%) in PD‐S neoplasms, 39% (range, 25%‐61%) in PD‐L neoplasms, and 70% (range, 30%‐80%) in PD‐NOS neoplasms. Both grade 2 and WD grade 3 neoplasms were associated with plasmacytoid morphology and smooth nuclear contours, but WD grade 3 neoplasms had significant increases in abundant cytoplasm (72% vs 17%; P = .007), nuclear tangles (75% vs 42%; P = .006), and apoptosis (86% vs 58%; P = .005). Compared with NECs, WD grade 3 neoplasms had increased plasmacytoid morphology (75% vs 7%; P < .001), smooth nuclear contours (94% vs 64%; P = .02), round nuclei (59% vs 21%; P = .01), and less pleomorphism (13% vs 50%; P = .004), molding (9% vs 79%; P < .001), and necrosis (13% vs 43%; P = .003). WD grade 3 neoplasms had less pleomorphism (13% vs 50%; P = .04), less necrosis (13% vs 60%; P = .04), and more plasmacytoid morphology (75% vs 20%; P = .03) than PD‐L.CONCLUSIONSThe prevalence of cytologic features differs in WD grade 3 pancreatic neuroendocrine neoplasms compared with grade 2 neoplasms and NECs, and these differences assist in the recognition of this newly classified entity. Cancer Cytopathol 2018;126:326‐35. © 2018 American Cancer Society.