Received: Tue 01, Apr 2025
Accepted: Thu 08, May 2025
Abstract
Granulomatous lobular mastitis (GLM) is a rare, chronic inflammatory breast condition often mistaken for malignancy, with an unclear etiology involving potential autoimmune, infectious, or hormonal triggers. This study aimed to characterize the immune microenvironment of GLM using multiplex immunofluorescence (mIF) analysis, focusing on immune cell phenotypes, spatial distribution, and prolactin (PRL) expression. Tissue microarrays from GLM patients and normal breast controls were stained with two mIF panels targeting T cells (CD3, CD4, CD8) and macrophages (CD68, CD163, HLA-DR) alongside PRL. We found no significant changes in T-cell infiltration in GLM compared to controls, but a marked increase in CD68+ macrophages, with balanced HLA-DR+ (M1-like) and CD163+ (M2-like) subtypes. Spatially, HLA-DR+ macrophages clustered around residual glandular spaces, while CD163+ macrophages dominated stromal regions, suggesting distinct roles in inflammation and tissue remodeling. PRL expression was significantly elevated in GLM (mean intensity: 82.02 vs. 46.02, P < 0.001), particularly surrounding HLA-DR+ macrophages, indicating a potential immunomodulatory role. These findings portray GLM as a macrophage-driven process with minimal adaptive immunity, modulated by PRL in a spatially dependent manner. This immune profile enhances understanding of GLM’s pathogenesis and suggests macrophage- or PRL-targeted therapies as future directions. Our study underscores mIF’s utility in dissecting complex inflammatory microenvironments and lays a foundation for precision approaches to GLM management.
Keywords
Granulomatous lobular mastitis, immune microenvironment, multiplex immunofluorescence, prolactin, T cells, macrophage polarization
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