Fibrin associated large B-cell lymphoma accidentally identified in a breast implant capsule: a molecular report of a rare entity

Breast implant-associated (BIA) lymphoma is a rare malignancy, typically originating from T-cells; however, few cases of diffuse large B-cell lymphoma (LBCL) have been recently described. These cases share major features: Epstein-Barr virus positivity and a favorable prognosis with surgical intervention alone, hinting at a potential link to fibrin-associated LBCL (FA-LBCL). This study presents the first case of BIA-FA-LBCL in Italy and one of the few assessed from a molecular standpoint so far. We identified two pathogenic mutations in DNMT3A and a variant of uncertain significance (VUS) in JAK2. These findings suggest that dysfunctional epigenetic mechanisms and constitutive activation of the JAK-STAT pathway may underpin BIA-FA-LBCL lymphomagenesis. Finally, we summarized all the previously reported cases in alignment with the updated WHO-HAEM5 classification, shedding further light on the nature of this new entity. This report highlights the rarity of BIA-FA-LBCL and underscores the importance of comprehensive capsule sampling and reporting to national databases for accurate characterization and management of these lymphomas. The study supports the classification of BIA-FA-LBCL within the spectrum of FA-LBCL, emphasizing the need for further research to elucidate its molecular underpinnings and improve clinical outcomes.