Lobular Breast Cancer: Histomorphology and Different Concepts of a Special Spectrum of Tumors

Abstract

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.

Loss of E-cadherin leads to Id2-dependent inhibition of cell cycle progression in metastatic lobular breast cancer

“…It is well established that loss of E-cadherin is sufficient to drive anchorage-independence in breast cancer cells in the context of oncogenic modulation of p53 [ 4 ] or activation of the PTEN/PI3K/AKT signaling axis [ 6 , 7 ]. Because of cell-cell adhesion deficiency, ILC cells invade as single non-adhesive cells that - due to physical restriction - appear as collective invasive strands (reviewed in: [ 8 ]). ILC is mostly estrogen receptor (ER) positive with indolent growth characteristics, reflected by its low to intermediated grade.…”

Aquaporin‐5 in breast cancer

“…Invasive lobular carcinomas are composed of dis‐cohesive tumor cell populations infiltrating the surroundings as single tumor cells or tumor cells in single filing. The diffuse growth pattern is promoted by the loss of E‐cadherin, which may be visualized by immunohistochemical staining [38]. Loss of E‐cadherin expression may, however, also be seen in IDC [39].…”

Management of HR+/HER2+ lobular breast cancer and trends do not mirror better outcomes

“…While the hallmark pathological characteristic of ILC remains the loss of E-cadherin (CDH1) protein expression [ 7 ], the unique genomic profile of these tumors also harbors mutations in various proteins related to impaired cell adhesion, such as α-catenin/CTNNA1 [ 9 ]. Consequently discohesive tumor cell growth in the stroma in a single-file pattern [ 10 ] is referred to as the “classical subtype”, but other subtypes have also been described based on tumor architecture (alveolar, solid, and trabecular) or cell cytonuclear characteristics (apocrine, histiocytoid, pleomorphic, and signet ring) [ 11 ].…”