Pitfalls in the histological diagnosis of morphologic variants of invasive lobular carcinoma of the breast Review


Authors: Floris, G.; Djerroudi, L.; Zels, G.; De Schepper, M.; Richard, F.; Brahimaj, R.; Derksen, P. W. B.; Christgen, M.; Lakhani, S. R.; Van Diest, P. J.; Brogi, E.; Desmedt, C.; Schnitt, S. J.; Vincent-Salomon, A.; on behalf of the European Lobular Breast Cancer Consortium
Review Title: Pitfalls in the histological diagnosis of morphologic variants of invasive lobular carcinoma of the breast
Abstract: Invasive lobular carcinoma (ILC) is the second most frequent histological type of breast cancer and the most frequent special type. Disruption of cell-to-cell adhesion, caused most often by E-cadherin loss of function, results in the distinctive histomorphology of ILC, which is characterized by single threads of monotonous, dyscohesive neoplastic epithelial cells infiltrating the breast parenchyma with little or no stromal reaction, referred to as classic ILC. In the past 4 decades, ILC variants that differ from classic ILC with regard to architectural, cytological, and/or nuclear features have been described. The recognition and correct characterization of ILC, including its variant forms, is essential to avoid misdiagnosis and its possible treatment implications. Some ILC variants may be associated with more aggressive clinical behavior compared with classic ILC, independent of standard predictive and prognostic parameters. Additionally, the distinctive biological and clinical features of ILC are increasingly being investigated as therapeutic targets in ILC-tailored clinical trials. In this manuscript, we have undertaken an in-depth review of the current state of knowledge about ILC variants. Evidence gained from molecular analysis of ILC and its microenvironment suggests that ILC variants are biologically distinct from classic ILC. However, this conclusion is undermined by the imprecise histopathological identification of ILC variants. In the absence of standardized and simplified criteria for the diagnosis of ILC, underrecognition of ILC variants may translate into missed opportunities for tailored treatment of ILC patients. Therefore, we propose steps toward the development of a roadmap that will ultimately lead to a more reproducible classification of ILC variants and improve our knowledge of these challenging tumors. © 2025 Elsevier B.V., All rights reserved.
Keywords: clinical article; controlled study; human cell; clinical feature; histopathology; review; biological marker; breast cancer; uvomorulin; histology; diagnosis; diagnostic error; epithelium cell; drug therapy; beta catenin; cell adhesion; epithelium tumor; e-cadherin; aggression; beta-catenin; parenchyma; invasive lobular carcinoma; p120; human; invasive lobular breast carcinoma; classic invasive lobular carcinoma; non-classic invasive lobular carcinoma
Journal Title: Modern Pathology
Volume: 38
Issue: 9
ISSN: 15300285
Publisher: Elsevier B.V.  
Date Published: 2025-09-01
Start Page: 100837
Language: English
DOI: 10.1016/j.modpat.2025.100837
PUBMED: 40617531
PROVIDER: scopus
PMCID: PMC12311960
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Giuseppe Floris -- Source: Scopus
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    522 Brogi