Genetics of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a newly included provisional entity in the 2016 revision of the World Health Organization classification, is a distinct form of CD30-positive T-cell non-Hodgkin lymphoma that arises in association with a breast implant after reconstructive or cosmetic surgery. In addition to its characteristic clinical presentation, recent studies using next-generation sequencing have revealed that BIA-ALCL has a unique pattern of genetic alterations. BIA-ALCL is consistently negative for ALCL-related gene rearrangements involving ALK, DUSP22, and TP63. However, the JAK-STAT3 pathway is constitutively activated in BIA-ALCL, which in some cases is associated with recurrent somatic mutations of JAK1 and/or STAT3. These activating mutations, which may be concurrent, are identified in 13% (3/23) and 26% (6/23) of BIA-ALCLs, respectively. Other genetic alterations include point mutations of DNMT3A and TP53. Although the number of examined cases has been limited, these findings suggest that BIA-ALCL shows more uniform molecular features than systemic and primary cutaneous ALCLs, which show considerable genetic heterogeneity. Targeted therapies inhibiting JAK-STAT signaling are being developed and may offer novel therapeutic options for patients with BIA-ALCL, especially those with advanced disease.