Hematolymphoid Neoplasms of the Breast: Clinicopathological Features of a 42-Case Single- Center Series With Emphasis on Bilateral Primary Breast Lymphoma

Abstract Background Hematolymphoid neoplasms involving the breast are rare and encompass a broad pathological spectrum, with mature B-cell lymphomas predominating. Primary breast diffuse large B-cell lymphoma (DLBCL) frequently shows a non-GCB/ABC phenotype. Purpose We aimed to characterize breast hematolymphoid neoplasms, compare primary and secondary breast involvement, and examine bilateral primary breast lymphoma (PBL). Methods We retrospectively reviewed 42 breast hematolymphoid neoplasms diagnosed between 2014 and 2026 and classified them according to 2022 WHO and International Consensus Classification criteria. Cases were categorized as PBL, secondary breast lymphoma/hematopoietic neoplasia (SBL/HN), or unspecified. Clinicopathological, radiological, staging, outcome, and molecular data were analyzed. Results Twelve cases (28.6%) were PBL, 24 (57.1%) SBL, and six (14.3%) unspecified. B-cell neoplasms comprised 85.7% of cases; DLBCL/ABC (45.2%) and marginal zone lymphoma (19.0%) were most frequent. Stage I–II disease was more frequent in PBL than SBL (72.7% vs. 18.2%; p = 0.005), whereas stage IV disease was less frequent (27.3% vs. 77.3%; p = 0.009). Mortality at last follow-up was 8.3% in PBL and 62.5% in SBL (p = 0.004). All three bilateral PBLs were ABC-DLBCL, classified as stage IV, and alive at last follow-up. BCL6 rearrangement was detected in 5/11 tested cases. Conclusions Breast hematolymphoid neoplasms are heterogeneous, with ABC/non-GCB DLBCL predominating. PBL more often presented with localized disease and lower mortality at last follow-up than SBL. Bilateral PBL presents a staging challenge and may not have the same clinical implications as disseminated stage IV lymphoma.