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Morphologic Reproducibility, Genotyping, and Immunohistochemical Profiling Do Not Support a Category of Seromucinous Carcinoma of the Ovary.

形态学的可重复性、基因分型及免疫组化不支持卵巢浆粘液性癌的分类

Rambau PF,McIntyre JB,Taylor J,Lee S,Ogilvie T,Sienko A,Morris D,Duggan MA,McCluggage WG,Köbel M

Abstract

The 2014 World Health Organization Classification of Tumors of Female Reproductive Organs endorsed the new category of seromucinous carcinoma, a neoplasm that exhibits morphologic and immunophenotypic overlap with other histotypes of ovarian carcinoma. The goal of this study was to determine whether seromucinous carcinoma was a distinct histotype by assessing its diagnostic reproducibility and comparing its molecular composition to the 5 major histotypes of ovarian carcinoma. Thirty-two tumors diagnosed as seromucinous carcinomas from 2 centers were studied. Eighteen cases were randomly selected for a review set comprising a total of 50 ovarian carcinomas of various histotypes. Morphologic histotype was independently assessed by 4 pathologists. For the 32 seromucinous carcinomas, a histotype-specific immunophenotype was assigned using a diagnostic immunohistochemical panel. Histotype-specific genotype was assigned using a combination of immunohistochemistry and targeted next-generation sequencing for somatic mutations, including genes recurrently mutated in ovarian carcinomas. There was low to modest agreement between pathologists with the reference diagnosis of seromucinous carcinoma, ranging from 39% to 56% for the 4 observers. The immunophenotype was not unique but overlapped predominantly with endometrioid and to a lesser extent with mucinous and low-grade serous carcinoma. Genomic and immunohistochemical alterations were detected in a number of target genes, including KRAS (70%), PIK3CA (37%), PTEN (19%), and ARID1A (16%); no CTNNB1 mutations were identified. Nine cases (30%) harbored concurrent KRAS/PIK3CA mutations. An endometrioid genotype was assigned to 19 cases, a low-grade serous genotype to 9, and a mucinous genotype to 1 and 3 cases were uninformative. Integrating morphology, immunophenotype, and genotyping resulted in reclassifying the seromucinous carcinomas to endometrioid 23/32 (72%), low-grade serous 8/32 (25%), and mucinous 1/32 (3%). The morphologic diagnosis of seromucinous carcinomas is not very reliable and it does not exhibit a distinct immunophenotype or genotype. The molecular features overlap mostly with endometrioid and low-grade serous carcinomas. Our data suggest the category of seromucinous carcinoma be discontinued as ancillary molecular tests can assign cases to one of the major histotypes.

摘要

 2014版 WHO女性生殖器官肿瘤分类支持浆粘液性癌的新分类,该肿瘤表现出与其他组织学类型卵巢癌形态学上和免疫表型上的重叠。本研究目的是通过评估诊断的可重复性并与5种主要组织学类型的卵巢癌分子信息进行比较,确定浆粘液性癌是否为一种不同的组织学类型。对来自2个中心诊断的32例浆粘液性癌进行了研究。随机抽取18例多种组织类型卵巢癌构成50例进行研究。形态学分型由4个病理学家独立评估。对32例浆粘液性癌采用诊断性免疫组化套餐进行组织学类型的免疫评估。采用免疫组化和检测体细胞突变(包括卵巢癌中重复突变的基因)的靶向二代测序联合方法作为特定组织学类型的基因型评估。浆粘液性癌的诊断在病理学家之间有低到中度的一致性,4名观察者的一致率从39%到56%不等。免疫表型不是独特的,主要与宫内膜样癌重叠,与粘液性癌及低级别浆液性癌有较小程度的重叠。基因组和免疫组化的改变出现于多个靶基因,包括KRAS(70%)、PIK3CA(37%)、PTEN(19%)及ARID1A(16%); 没有CTNNB1突变。纳入的9个病例(30%)同时发生KRAS/PIK3CA突变。子宫内膜样基因型表现者有19个病例,低级别浆液性基因型表现者9个,黏液型基因型1个, 3例无相关信息。结合形态学、免疫表型和基因型,将浆粘液性癌重新分类为子宫内膜样癌(23/32,72%),低级别浆液性癌(8 / 32,25%)和粘液性癌(1 / 32,3%)。浆粘液性癌的形态学诊断是不可靠的,它并不表现出不同的免疫表型或基因型。分子特征大多与宫内膜样癌和低级别浆液性癌重叠。我们的数据表明,由于辅助分子检测能将这些病例归为某一个主要组织学类型,所以浆粘液性癌的分类应该弃用。

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