IL-13 is produced by tumor cells in breast implant-associated anaplastic large cell lymphoma: implications for pathogenesis

More than 500 women worldwide have developed a CD30+ T-cell lymphoma around breast implants, strongly suggesting a cause-and-effect relationship, and designated as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The mechanism of lymphomagenesis is unknown. Recently, a bacterial biofilm containing gram-negative bacilli was discovered on the surface of breast implants associated with ALCL. We and others have described overexpression of the proto-oncogene JUNB and mutations of JAK1/2, TP53 and STAT3 in BIA-ALCL. Here we report that BIA-ALCL cell lines and anaplastic lymphoma cells in clinical specimens produce IL-13, the signature cytokine of allergic inflammation. Supporting the link of BIA-ALCL to allergic inflammation, lymphoma cells were often surrounded by eosinophils and mast cells, features typically absent in systemic ALCL. Because of the link of IL-13 to allergy, we looked for IgE and found it decorating the surface of mast cells and antigen-presenting follicular dendritic cells in capsules and lymph nodes infiltrated by anaplastic lymphoma cells, but not uninvolved capsules. Plasma cells within capsules and regional lymph nodes were identified as a possible source of IgE. Together, these findings suggest the hypothesis that an amplified immune response with features of a chronic allergic reaction in a susceptible patient underlies the pathogenesis of BIA-ALCL.