Final Diagnosis
Invasive mammary carcinoma, predominantly ductal with focal lobular features
Discussion
This case presents with features overlapping between Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC). The characteristic finding of discohesive growth (lobular features) occurring alongside generally retained E-cadherin/p120 membranous staining places this tumor within the category of Lobular-Like Invasive Mammary Carcinoma (LLIMCa) (Yu).
LLIMCa is defined as an invasive mammary carcinoma characterized by uniform discohesive cells with low- to intermediate-grade nuclei and a dispersed, lobular-like growth pattern. These tumors typically present as individual cells in single-files and cords within the fibrous stroma. They are often morphologically difficult or impossible to definitively classify as either lobular or ductal based on H&E staining alone.
The crucial feature distinguishing LLIMCa from classical ILC is the integrity of the adherens junction (AJ) complex. While ILC is defined by disruption of cell-to-cell adhesion—most often due to E-cadherin loss of function (LOF) mutations in CDH1 (Floris)—LLIMCa typically shows moderate to strong circumferential membranous reactivity for both E-cadherin and p120 catenin throughout the tumor. Indeed, LLIMCa cases usually lack pathogenic CDH1 mutations and instead may harbor epigenetic alterations, such as CDH1 promoter methylation (identified in 4 of 7 cases) that could contribute to the single-cell infiltrative morphology sometimes observed (Yu). Supporting this distinction, Yu et al. found that all LLIMCa cases demonstrated membranous expression of E-cadherin, p120 catenin, and beta-catenin, including intact staining with an antibody against the E-cadherin N-terminus—a result not seen in ILC. Taken together, these findings indicate that the discohesive, diffuse growth pattern of LLIMCa arises despite preservation of an intact E-cadherin/p120 junctional complex (Yu).
However, recent reviews caution against overreliance on E-cadherin immunohistochemistry in distinguishing ductal from lobular carcinomas. Taha et al. emphasizes that E-cadherin expression often shows aberrant, attenuated, or fragmented patterns, and concordance between morphology and staining is far from perfect. For example, classic lobular tumors may retain E-cadherin expression, while some ductal tumors can lack it entirely. They stress that the definition of lobular carcinoma should remain fundamentally morphologic, and that immunostains (E-cadherin, p120, β-catenin) should be interpreted descriptively rather than categorically (Taha). This reinforces the ambiguity surrounding tumors such as LLIMCa, where discohesive lobular-like morphology coexists with intact E-cadherin staining.
The strong Hormone Receptor positivity in this case (ER/PR positive) aligns with LLIMCa characteristics, as 98% of LLIMCas were ER positive (Yu). However, the extremely high Ki-67 proliferation index (80%) is unusual for LLIMCa as Yu et al showed a mean Ki-67 index of 21%.
The recognition of LLIMCa carries important clinical implications, particularly concerning surgical management. Similar to ILC, LLIMCas often exhibit pathologic tumor size that is significantly larger than the size estimated by imaging. This underestimation on imaging frequently translates to higher rates of positive or close margins (37% in LLIMCa) during the initial surgery compared to IDC (19%). Given this propensity for inaccurate sizing and frequent margin issues, distinguishing LLIMCas from usual IDCs in the biopsy report and considering preoperative MRI is suggested to guide subsequent surgical management.
Sources
- Yu J, da Silva EM, La H-S, et al. Clinicopathologic and genomic features of lobular like invasive mammary carcinoma: is it a distinct entity? npj Breast Cancer. 2023;9:60.
- Floris G, Djerroudi L, Zels G, et al. Pitfalls in the Histological Diagnosis of Morphologic Variants of Invasive Lobular Carcinoma of the Breast. Mod Pathol. 2025;38:100837.
- Taha SR, Boulos F. E-cadherin staining in the diagnosis of lobular versus ductal neoplasms of the breast: the emperor has no clothes. Histopathology. 2025;86:327-340.