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

• Authors: Carlie S. Sigel, Memorial Sloan Kettering Cancer Center; Vitor Werneck Krauss Silva, Memorial Sloan Kettering Cancer Center; Michelle Dian Reid, Emory University; David Chhieng, University of Washington; Olca Basturk, Memorial Sloan Kettering Cancer Center; Keith M. Sigel, Icahn School of Medicine; Tanisha D. Daniel, Memorial Sloan Kettering Cancer Center; David S. Klimstra, Memorial Sloan Kettering Cancer Center; Laura H. Tang, Memorial Sloan Kettering Cancer Center; Hunter Reid Moyer, Emory University
• Journal Title: Cancer
• Volume: Volume 126, Number 5
• Publisher: Wiley: 12 months | 2018-05-01, Pages 326-335
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/cncy.21982
• Subjects: Health Sciences, Oncology; Health Sciences, Pathology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Pathology; fine-needle aspiration (FNA); neuroendocrine carcinoma (NEC); neuroendocrine differentiation; pancreas fine-needle aspiration; pancreas; pancreatic neuroendocrine carcinoma; pancreatic neuroendocrine tumor (PanNET); CARCINOMAS; CYTOLOGY

Abstract

BACKGROUND: Pancreatic 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. METHODS: Fine-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. RESULTS: The 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. CONCLUSIONS: The 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.