Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pathology, Emory University Hospital, Atlanta, Georgia.
Cancer Cytopathol. 2018 Jan;126(1):44-53. doi: 10.1002/cncy.21934. Epub 2017 Oct 17.
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.
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.
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.
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.
高分化（WD）和低分化（PD）胰腺神经内分泌肿瘤是具有不同治疗方法和预后的生物学实体。Ki-67 增殖指数>20%的 WD 肿瘤已被证明与 PD 神经内分泌癌具有重叠的组织学特征。本研究比较了多机构研究中胰腺神经内分泌肿瘤的专家细胞形态学分化评估。
根据 2017 年世界卫生组织分类，对 72 例胰腺神经内分泌肿瘤（2 级[G2]和 3 级[G3]）的细针抽吸标本进行独立诊断，由 3 位细胞病理学家根据细胞形态学单纯诊断为 WD 或 PD（分化不良的大细胞型[PD-L]或分化不良的小细胞型[PD-S]）。他们的诊断与免疫组织化学（视网膜母细胞瘤（RB）、死亡结构域相关蛋白（DAXX）和α地中海贫血/智力迟钝综合征 X 连锁（ATRX）蛋白表达）、靶向突变分析（纪念斯隆凯特琳综合可操作癌症靶点突变分析）、先前的 G1/G2 组织学病史和共识支持的最终分类进行比较。
在纳入的 70 例病例中（55 例 WD 病例[包括 19 例 G2、31 例 G3 和 5 例无法分级]和 15 例 PD 病例[包括 6 例 PD-S、6 例 PD-L 和 3 例 PD，其他未指定]），分化的一致性率为 38%（15 例 WD 病例和 12 例 PD 病例）。有 2 例无法用所采用的方法进行分类。PD 癌的一致性率（15 例中的 10 例[67%]）高于 WD 肿瘤（55 例中的 15 例[27%]）。圆形核和浆细胞样细胞与 WD 病例的一致性有关，而凋亡和角状核与不一致性有关。坏死与 PD 病例的一致性有关。
根据细胞学，单纯采用形态学方法区分 G2 和 G3 胰腺神经内分泌肿瘤具有挑战性，经验丰富的细胞病理学家之间存在分歧。癌症细胞病理学 2018；126：44-53。© 2017 美国癌症协会。
