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 origins of BIA-ALCL, future research should focus on prevention and treatment strategies, recognizing susceptible populations, and whether decreasing the risk of BIA-ALCL is possible.

Boston University School of Medicine Boston MA 02908 USA

Department of Dermatology Roger Williams Medical Center Providence RI 02908 USA

Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Department of Pathology Weill Cornell Medicine New York NY 10065 USA

Department of Plastic and Reconstructive Surgery Macquarie University and the Integrated Specialist Healthcare Education and Research Foundation Sydney NSW 2109 Australia

Department of Plastic Surgery School of Medicine Griffith University Southport QLD 4222 Australia

Department of Plastic Surgery University of Texas Southwestern Medical Center Dallas TX 75390 USA

Division of Cellular and Molecular Pathology Department of Pathology University of Cambridge Cambridge CB2 1TN UK

Epworth Healthcare East Melbourne Richmond VIC 3121 Australia

Senior Researcher Šárka Pospíšilová Research Group CEITEC Masaryk University 601 77 Brno Czech Republic

Sir Peter MacCallum Department of Oncology University of Melbourne Parkville VIC 3000 Australia

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