Etiology of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Current Directions in Research

Simple Summary The first report of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) was in 1997. Although BIA-ALCL develops around breast implants, it is considered a cancer of the immune system and not a cancer of the breast ducts or lobules. Nearly all confirmed cases to date have been associated with textured surface (versus smooth surface) breast implants. As physicians have become more aware of BIA-ALCL, so has the number of reported cases, although the number of cases remains low. In most instances, patients have an excellent prognosis following removal of the breast implant and its surrounding fibrous capsule. Many theories on factors that trigger the development of BIA-ALCL, such as the presence of bacteria, have been proposed. However, the sequence(s) of events that follow the initial triggering event(s) have not been fully determined. This article summarizes the current scientific knowledge on the development of BIA-ALCL. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoma. Where implant history is known, all confirmed cases to date have occurred in patients with exposure to textured implants. There is a spectrum of disease presentation, with the most common occurring as a seroma with an indolent course. A less common presentation occurs as locally advanced or, rarely, as metastatic disease. Here we review the immunological characteristics of BIA-ALCL and potential triggers leading to its development. BIA-ALCL occurs in an inflammatory microenvironment with significant lymphocyte and plasma cell infiltration and a prominent Th1/Th17 phenotype in advanced disease. Genetic lesions affecting the JAK/STAT signaling pathway are commonly present. Proposed triggers for the development of malignancy include mechanical friction, silicone implant shell particulates, silicone leachables, and bacteria. Of these, the bacterial hypothesis has received significant attention, supported by a plausible biologic model. In this model, bacteria form an adherent biofilm in the favorable environment of the textured implant surface, producing a bacterial load that elicits a chronic inflammatory response. Bacterial antigens, primarily of Gram-negative origin, may trigger innate immunity and induce T-cell proliferation with subsequent malignant transformation in genetically susceptible individuals. Although much remains to be elucidated regarding the multifactorial o