Update in lobular breast lesions: Pathological diagnosis in the molecular era.

IF 2.7 2区 医学 Q2 PATHOLOGY
Lixia Bai, Megan L Troxell
{"title":"Update in lobular breast lesions: Pathological diagnosis in the molecular era.","authors":"Lixia Bai, Megan L Troxell","doi":"10.1016/j.humpath.2025.105857","DOIUrl":null,"url":null,"abstract":"<p><p>Lobular breast carcinoma has been recognized as a distinct entity for over 80 years, and the clinicopathologic features of classic cases are familiar. However, the repertoire of morphologic variants, intersection of contemporary immunophenotyping (E-cadherin, catenins), and genomic studies (CDH1, loss of heterozygosity, alterations in other cell adhesion pathway genes), provides opportunity to critically revisit diagnostic challenges and update criteria. Judicious application of well validated E-cadherin immunostaining with careful interpretation to distinguish strong membrane pattern from aberrant staining (discontinuous or weak membrane, granular, cytoplasmic, dot-like) can aid in diagnostic reproducibility; p120 and β-catenin immunohistochemistry provides further confirmation, with similar caveats. Nevertheless, with increasing application of immunohistochemistry, 'lobular' cancers with intact E-cadherin expression are increasingly encountered. CDH1, encoding E-cadherin, harbors pathogenic mutations in 65-70 % of lobular carcinomas, as one facet of biallelic inactivation. As with immunohistochemistry, CDH1 mutations are not universal, such that lobular carcinoma defies classification as a purely molecular entity at present. In addition to solidifying contemporary criteria for lobular carcinoma, there is a need to reset the terminology used for 'mixed' or 'uncertain' ductal-lobular carcinomas, as prior studies in the literature have been inconsistent in nomenclature and definitions. Recent studies provide insight into invasive lobular carcinoma with tubular elements associated with cadherin switching (P-cadherin upregulation) in tubular areas. Lobular-like invasive mammary carcinoma is another term recently applied to morphologically lobular carcinomas with membranous E-cadherin and p120 expression. These studies further understanding of the biologic spectrum of lobular carcinoma, yet salient morphologic, immunophenotypic, and molecular questions remain.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"105857"},"PeriodicalIF":2.7000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.humpath.2025.105857","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Lobular breast carcinoma has been recognized as a distinct entity for over 80 years, and the clinicopathologic features of classic cases are familiar. However, the repertoire of morphologic variants, intersection of contemporary immunophenotyping (E-cadherin, catenins), and genomic studies (CDH1, loss of heterozygosity, alterations in other cell adhesion pathway genes), provides opportunity to critically revisit diagnostic challenges and update criteria. Judicious application of well validated E-cadherin immunostaining with careful interpretation to distinguish strong membrane pattern from aberrant staining (discontinuous or weak membrane, granular, cytoplasmic, dot-like) can aid in diagnostic reproducibility; p120 and β-catenin immunohistochemistry provides further confirmation, with similar caveats. Nevertheless, with increasing application of immunohistochemistry, 'lobular' cancers with intact E-cadherin expression are increasingly encountered. CDH1, encoding E-cadherin, harbors pathogenic mutations in 65-70 % of lobular carcinomas, as one facet of biallelic inactivation. As with immunohistochemistry, CDH1 mutations are not universal, such that lobular carcinoma defies classification as a purely molecular entity at present. In addition to solidifying contemporary criteria for lobular carcinoma, there is a need to reset the terminology used for 'mixed' or 'uncertain' ductal-lobular carcinomas, as prior studies in the literature have been inconsistent in nomenclature and definitions. Recent studies provide insight into invasive lobular carcinoma with tubular elements associated with cadherin switching (P-cadherin upregulation) in tubular areas. Lobular-like invasive mammary carcinoma is another term recently applied to morphologically lobular carcinomas with membranous E-cadherin and p120 expression. These studies further understanding of the biologic spectrum of lobular carcinoma, yet salient morphologic, immunophenotypic, and molecular questions remain.

乳腺小叶病变的最新进展:分子时代的病理诊断。
80多年来,小叶乳腺癌一直被认为是一种独特的疾病,其典型病例的临床病理特征是熟悉的。然而,形态学变异、当代免疫表型(E-cadherin, catenins)和基因组研究(CDH1,杂合性缺失,其他细胞粘附途径基因的改变)的交叉,为批判性地重新审视诊断挑战和更新标准提供了机会。明智地应用验证良好的e -钙粘蛋白免疫染色,仔细解释,以区分强膜模式和异常染色(不连续或弱膜,颗粒状,细胞质,点状),有助于诊断的重复性;P120和β-连环蛋白免疫组化提供了进一步的证实,并有类似的警告。然而,随着免疫组织化学应用的增加,越来越多地遇到完整e -钙粘蛋白表达的“小叶”癌。编码e -钙粘蛋白的CDH1在65-70%的小叶癌中携带致病性突变,这是双等位基因失活的一个方面。与免疫组织化学一样,CDH1突变并不是普遍存在的,因此小叶癌目前无法被归类为纯粹的分子实体。除了巩固小叶癌的当代标准外,还需要重新定义“混合型”或“不确定型”导管小叶癌的术语,因为先前的文献研究在命名和定义上不一致。最近的研究揭示了浸润性小叶癌与小管区钙粘蛋白转换(p -钙粘蛋白上调)相关的小管元件。小叶样浸润性乳腺癌是最近用于描述膜性E-cadherin和p120表达的形态学小叶癌的另一个术语。这些研究进一步了解了小叶癌的生物学谱,但仍存在显著的形态学、免疫表型和分子问题。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Human pathology
Human pathology 医学-病理学
CiteScore
5.30
自引率
6.10%
发文量
206
审稿时长
21 days
期刊介绍: Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信