Cellular and Molecular Mechanisms of Breast Implant-Associated Anaplastic Large Cell Lymphoma

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging and highly treatable cancer of the immune system that can form around textured-surface breast implants. Although the underlying cause has yet to be elucidated, an emerging theme - linking pathogenesis to a chronic inflammatory state - continues to dominate the current literature. Specifically, the combination of increasing mutation burden and chronic inflammation leads to aberrant T-cell clonal expansion. However, the impetus remains largely unknown. Proposed mechanisms include a lipopolysaccharide endotoxin response, oncogenic transformation related to viral infection, associated trauma to the breast pocket, particulate matter digestion by capsular macrophages, chronic allergic inflammation, and genetic susceptibility. The Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway is a major signaling pathway that regulates a variety of intracellular growth and survival processes. Constitutive activation of JAK-STAT3 has been implicated in several malignancies, including lymphomas, and has recently been identified as a potential key mediator in BIA-ALCL. The purpose of this article is to review the cellular and molecular mechanisms of BIA-ALCL with a focus on the role of oncogenic JAK-STAT3 signaling in BIA-ALCL tumorigenesis and progression. Selected experimental work from the authors' group on aberrant JAK-STAT3 signaling in BIA-ALCL is also included. The authors discuss how an inflammatory microenvironment may facilitate malignant transformation through the JAK-STAT3 pathway - highlighting its potential mechanistic role. The authors' hope is that further investigation of this signaling pathway will reveal avenues for using JAK-STAT3 signaling as a prognostic indicator and novel therapeutic target in the case of advanced disease.