Comprehensive characterization of invasive mammary carcinoma with lobular features: integrating morphology and E-cadherin immunohistochemistry patterns.

Background

Breast cancer treatment prioritizes molecular subtypes over histologic types. However, considering the unique biological behavior of invasive lobular carcinoma (ILC), its diagnosis is crucial for patient management. Therefore, this study aimed to review breast cancer cases, focusing on the E-cadherin patterns and lobular morphology of cases misclassified in the original reports.

Methods

A comprehensive review was conducted on 481 breast cancer biopsy cases diagnosed as invasive breast carcinoma of no special type (IBC-NST) or ILC with E-cadherin staining. These cases were categorized into six groups based on tumor morphology (ductal/lobular) and E-cadherin expression pattern (membranous/loss/aberrant): (1) ductal/membranous, (2) lobular/loss, (3) lobular/aberrant, (4) mixed, (5) ductal/loss or aberrant, and (6) lobular/membranous.

Results

In 211 cases (43.8%), an E-cadherin pattern indicating ILC (loss and aberrant) was observed alongside lobular morphology, representing 5.52% of all breast cancer biopsies during the relevant period. Moreover, 181 cases (37.6%) showed a membranous pattern with ductal morphology, 4 (0.8%) were mixed IBC-NST and ILC, and 85 (17.7%) exhibited discordance between morphology and E-cadherin expression. Notably, only 25.9% (15/58) of cases in group 3, characterized by aberrant E-cadherin patterns, were initially diagnosed as ILC, highlighting a significant diagnostic discrepancy. In group 6, where membranous E-cadherin pattern was present with lobular morphology, only 3.4% (2/58) were diagnosed as ILC in the original reports, indicating diagnostic challenges in morphology and immunohistochemistry discordance. Similarly, in group 5, which had ductal morphology with loss or aberrant E-cadherin expression, the initial diagnosis rate of IBC-NST was 33.3% (9/27), reflecting the complexities in interpreting discordant cases.

Conclusions

In real-world practice, diagnosing ILC often heavily depends on E-cadherin results. This study emphasizes the need for diagnostic clarification in cases with discordance between morphology and E-cadherin patterns.

References:

• McCart Reed AE, Kalinowski L, Simpson PT, Lakhani SR. Invasive lobular carcinoma of the breast: the increasing importance of this special subtype. Breast Cancer Res. 2021;23:6.
• Lee JH, Park S, Park HS, Park BW. Clinicopathological features of infiltrating lobular carcinomas comparing with infiltrating ductal carcinomas: a case control study. World J Surg Oncol. 2010;8:34.
• Jung YS, Na KY, Kim KS, Ahn SH, Lee SJ, Park HK, et al. Nation-wide Korean breast cancer data from 2008 using the breast cancer registration program. J Breast Cancer. 2011;14:229–36.
• Taha SR, Boulos F. E-cadherin staining in the diagnosis of lobular versus ductal neoplasms of the breast: the emperor has no clothes. Histopathology. 2024. https://doi.org/10.1111/his.15295 .
• Lobo J, Petronilho S, Newell AH, Coach J, Harlow G, Cruz A, et al. E-cadherin clone 36 nuclear staining dictates adverse disease outcome in lobular breast cancer patients. Mod Pathol. 2019;32:1574–86.