Does Breast Implant Associated ALCL begin as a Lymphoproliferative Disorder?

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) has been included as a provisional entity in the revised version of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissue. To increase opportunities to intervene with early diagnosis, treatment and possible prevention, it is important to consider that BIA-ALCL may evolve from a pre-existing lymphoproliferative disorder (LPD) characterized by (1) an indolent localized (in situ) disease in about 80% of reported cases; (2) a requirement for external cytokine stimulation for cell survival; (3) CD30+ cells in some clinically benign seromas/capsules; (4) undetected T-cell clonality in some cases; (5) JAK/STAT mutations in only a minority of cases (6) cure by capsulectomy and implant removal in most cases. BIA-ALCL resembles CD30+ cutaneous LPD: ALK-, CD30+ anaplastic cells with an aberrant T cell phenotype; overexpression of oncogenes (JUNB, SATB1, pSTAT3, SOCS3) in lymphomatoid papulosis (LyP); frequent apoptosis; complete spontaneous regression in LyP and partial spontaneous regression in cutaneous ALCL. Unlike CD30+ cutaneous LPD, BIA-ALCL cannot be readily observed over time to study the different steps in progression to ALCL. BIA-ALCL also shares features of lymphomas of mucosa associated lymphoid tissue (MALT lymphomas) which are clinically indolent, initially localized, antigen driven, and caused by gram negative bacteria. Further studies of cytokines, clonality, mutations and other biomarkers are needed to identify possible premalignant steps in the evolution of benign late seromas to BIA-ALCL.