Abstract
Simple SummaryInvasive lobular breast cancer (ILC) is a special type of breast cancer (BC) that was first described in 1941. The diagnosis of ILC is made by microscopy of tumor specimens, which reveals a distinct morphology. This review recapitulates the developments in the microscopic assessment of ILC from 1941 until today. We discuss different concepts of ILC, provide an overview on ILC variants, and highlight advances which have contributed to a better understanding of ILC as a special histologic spectrum of tumors.Invasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triple-negative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research.
Highlights
Modern tumor classifications are based on histomorphology enriched with molecular analyses that confirmed the taxonomic network of tumor entities established by histomorphology [1,2]
invasive lobular breast cancer (ILC) has been one of the first tumor types associated with a specific tumor suppressor gene, namely, CDH1/E-cadherin [11]
The spectrum of tumors collectively classified as ILC deserves greater attention as a special tumor entity in patient care and cancer research
Summary
Modern tumor classifications are based on histomorphology enriched with molecular analyses that confirmed the taxonomic network of tumor entities established by histomorphology [1,2]. The term “lobular carcinoma” was eventually coined by Stewart and Foote in 1941 [7] They were the first to emphasize the loss of cell cohesion as the key histological feature of lobular carcinoma in situ (LCIS) and invasive lobular breast cancer (ILC) [7]. Foote and Stewart asserted a “high probability” of a lobular origin for BCs growing in loose, isolated cells, even if LCIS could not be proven by microscopy [7]. This seemed relevant for ILC in atrophic breast tissue with few lobules in elderly patients. ILC might be slightly over-diagnosed in current practice and according to the concept of a special growth pattern
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