Dr Vincent-Salomon on Persisting Gaps in Clinical Interpretation of Invasive Lobular Carcinoma

“In literature, several studies have been done that have shown that the use of immunohistochemistry helps to improve the reproducibility of the diagnosis of invasive lobular carcinoma.”

Anne Vincent-Salomon, PR, MD, PhD, HDR, head of the Department of Pathology at Institut Curie, outlined contemporary updates in the diagnostic classification of invasive lobular carcinoma and highlighted persistent gaps that continue to challenge reproducibility and clinical interpretation.

In the fifth edition of the WHO Classification of Breast Tumours, invasive lobular carcinoma is no longer subdivided into distinct histologic subtypes, Vincent-Salomon began; instead, the WHO now conceptualizes these variants as patterns within the broader category of invasive lobular carcinoma. This shift reflects the evolving understanding of invasive lobular carcinoma biology but also underscores the limitations of morphology alone in capturing clinically meaningful heterogeneity.

Vincent-Salomon reiterated that classic invasive lobular carcinoma is defined by discohesive tumor cells infiltrating fibrous stroma or adipose tissue in single-file or dispersed patterns. These cells typically display small size, ovoid or notched nuclei, and low proliferative indices. The WHO classification also emphasizes minimal stromal reaction as a characteristic feature, she said. Importantly, precursor lesions—atypical lobular hyperplasia and lobular carcinoma in situ—are present in more than 78% of invasive lobular carcinoma cases, Vincent-Salomon added.

Despite these defined morphologic criteria, Vincent-Salomon noted that reproducibility across expert breast pathologists. This highlights an ongoing gap in the current classification system: histologic ambiguity persists, particularly in tumors with mixed features or borderline morphologic presentations.

One controversial aspect of the WHO update concerns the role of immunohistochemistry (IHC), specifically E-cadherin staining. Although loss of E-cadherin expression is a hallmark molecular alteration in lobular neoplasia, the WHO does not consider E-cadherin IHC an essential diagnostic criterion for invasive lobular carcinoma. Vincent-Salomon noted, however, that multiple studies have demonstrated that incorporating E-cadherin and related adhesion markers improves diagnostic consistency, particularly in challenging cases where morphology alone is insufficient. The exclusion of IHC from the essential criteria represents a meaningful gap between current evidence and formal classification guidelines.

Vincent-Salomon emphasized that advancing the diagnostic framework for invasive lobular carcinoma will require integrating morphology with molecular and immunophenotypic features to enhance accuracy, reproducibility, and alignment with emerging biological insights. Continued refinement of diagnostic tools and criteria remains critical as invasive lobular carcinoma–specific therapeutic strategies evolve.