Bai Lixia, Troxell Megan L
Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, Department of Pathology, Cleveland, OH, USA.
Stanford University Medical Center, Department of Pathology, Stanford, CA, USA.
Hum Pathol. 2025 Aug;162:105857. doi: 10.1016/j.humpath.2025.105857. Epub 2025 Jun 23.
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.
小叶型乳腺癌作为一种独特的实体已被认识超过80年，经典病例的临床病理特征为人熟知。然而，形态学变异的种类、当代免疫表型分析（E-钙黏蛋白、连环蛋白）与基因组研究（CDH1、杂合性缺失、其他细胞黏附途径基因的改变）的交叉，为审慎地重新审视诊断挑战并更新标准提供了契机。明智地应用经过充分验证的E-钙黏蛋白免疫染色并仔细解读，以区分强膜性模式与异常染色（不连续或弱膜性、颗粒状、细胞质、点状），有助于提高诊断的可重复性；p120和β-连环蛋白免疫组化可提供进一步的确认，但也有类似的注意事项。尽管如此，随着免疫组化应用的增加，越来越多地遇到E-钙黏蛋白表达完整的“小叶型”癌。编码E-钙黏蛋白的CDH1在65% - 70%的小叶癌中存在致病性突变，这是双等位基因失活的一个方面。与免疫组化一样，CDH1突变并不普遍，因此目前小叶癌难以被归类为纯粹的分子实体。除了巩固小叶癌的当代诊断标准外，还需要重新设定用于“混合性”或“不确定”导管-小叶癌的术语，因为文献中的先前研究在命名和定义上并不一致。最近的研究深入了解了伴有管状成分的浸润性小叶癌，其在管状区域与钙黏蛋白转换（P-钙黏蛋白上调）相关。小叶样浸润性乳腺癌是最近应用于具有膜性E-钙黏蛋白和p12O表达且形态学为小叶型的癌的另一个术语。这些研究进一步加深了对小叶癌生物学谱的理解，但形态学、免疫表型和分子方面的突出问题仍然存在。
