Assessment of cytologic differentiation in high-grade pancreatic neuroendocrine neoplasms: A multi-institutional study Journal Article


Authors: Sigel, C. S.; Werneck Krauss Silva, V.; Reid, M. D.; Chhieng, D.; Basturk, O.; Sigel, K. M.; Daniel, T. D.; Klimstra, D. S.; Tang, L. H.
Article Title: Assessment of cytologic differentiation in high-grade pancreatic neuroendocrine neoplasms: A multi-institutional study
Abstract: BACKGROUND: Well-differentiated (WD) and poorly differentiated (PD) pancreatic neuroendocrine neoplasms are biologically distinct entities with different therapies and prognoses. WD neoplasms with elevated proliferation (Ki-67 > 20%) have been shown to have an overlapping histology with PD neuroendocrine carcinomas. This study compared expert cytomorphologic assessments of differentiation in pancreatic neuroendocrine neoplasms in a multi-institutional study. METHODS: Fine-needle aspiration specimens from pancreatic neuroendocrine neoplasms (grade 2 [G2] and grade 3 [G3] according to the 2017 World Health Organization classification; n = 72) were diagnosed independently by 3 cytopathologists as WD or PD (poorly differentiated large cell type [PD-L] or poorly differentiated small cell type [PD-S]) purely on the basis of cytomorphology. Their diagnoses were compared with a final classification supported by immunohistochemistry (retinoblastoma (RB), death domain- associated protein (DAXX), and α thalassemia/mental retardation syndrome X-linked (ATRX) protein expression), targeted mutation analysis (Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets), prior history of G1/G2 histology, and consensus. RESULTS: The rate of agreement on differentiation was 38% (15 WD cases and 12 PD cases) for the 70 cases included (55 WD cases [n = 19 G2, n = 31 G3, and n = 5 could not be graded] and 15 PD cases [n = 6 PD-S, n = 6 PD-L, and n = 3 PD, not otherwise specified). Two cases could not be classified by the employed methods. PD carcinomas had a higher rate of agreement (10 of 15 [67%]) than WD neoplasms (15 of 55 [27%]). Round nuclei and plasmacytoid cells were associated with agreement for WD cases, whereas apoptosis and angulated nuclei were associated with disagreement. Necrosis was associated with agreement for PD cases. CONCLUSIONS: A purely morphologic approach to the distinction between G2 and G3 pancreatic neuroendocrine neoplasms based on cytology can be challenging, with disagreement found among experienced cytopathologists. Cancer Cytopathol 2018;126:44-53. © 2017 American Cancer Society. © 2017 American Cancer Society
Keywords: immunohistochemistry; controlled study; human tissue; protein expression; major clinical study; cancer grading; pancreas; cell death; apoptosis; tumor differentiation; mutational analysis; retrospective study; cell nucleus; retinoblastoma protein; tumor classification; pancreas islet cell tumor; daxx protein; fine needle aspiration biopsy; neuroendocrine differentiation; human; priority journal; article; brain histology; fine-needle aspiration (fna); pancreas fine-needle aspiration; pancreatic neuroendocrine carcinoma (pannec); pancreatic neuroendocrine tumor (pannet); transcriptional regulator atrx
Journal Title: Cancer Cytopathology
Volume: 126
Issue: 1
ISSN: 1934-662X
Publisher: John Wiley & Sons  
Date Published: 2018-01-01
Start Page: 44
End Page: 53
Language: English
DOI: 10.1002/cncy.21934
PROVIDER: scopus
PMCID: PMC5766365
PUBMED: 29044913
DOI/URL:
Notes: Article -- Export Date: 6 February 2018 -- Source: Scopus
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MSK Authors
  1. Olca Basturk
    352 Basturk
  2. David S Klimstra
    978 Klimstra
  3. Laura Hong Tang
    447 Tang
  4. Carlie Selbo Sigel
    115 Sigel
  5. Tanisha Dee Daniel
    8 Daniel