Pleomorphic variant as an independent predictor of axillary lymph node metastasis in invasive lobular carcinoma

Invasive lobular carcinoma (ILC) comprises distinct histological variants with diverse biological behaviors; however, data characterizing these variants in the Vietnamese population remain limited. This study aimed to evaluate the clinicopathological and molecular heterogeneity of ILC variants and identify predictors of axillary lymph node metastasis. A retrospective cohort study was conducted on 167 primary ILC patients treated at K Hospital, Vietnam (2019-2023). Tumours were classified into Classic, Pleomorphic, Solid, and composite "Others" group variants according to the 2019 WHO classification. Immunohistochemistry was performed for ER, PR, HER2, and Ki67 to determine molecular subtypes. The Classic variant was the most prevalent (53.9%), followed by Pleomorphic (22.8%), Others (15.0%), and Solid (8.4%). The Pleomorphic variant exhibited aggressive features, including high histological grade (71.1% Grade 3) and a significant enrichment of HER2-positive and Triple-negative phenotypes (p < 0.001). Conversely, the Solid variant predominantly displayed a Luminal A profile and the lowest rate of nodal involvement (42.9%). In multivariate analysis, the Pleomorphic subtype emerged as an independent predictor of axillary lymph node metastasis (p = 0.036), maintaining its prognostic value even after adjusting for tumor size (p < 0.001) and histological grade (p > 0.05). In conclusion, ILC variants in Vietnamese patients demonstrate significant prognostic heterogeneity. The Pleomorphic variant is an independent high-risk indicator, while the Solid variant in this cohort presented with an indolent clinical course. Routine pathological subtyping may provide incremental value beyond histological grading alone for risk stratification in ILC.