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

Ryan C. Decoster, Mark W. Clemens, Arianna Di Napoli, Evan B. Lynch, Alisha R. Bonaroti, Brian D. Rinker, Timothy A. Butterfield, Henry C. Vasconez

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)30E-41E
JournalPlastic and reconstructive surgery
Volume147
Issue number1
DOIs
StatePublished - Jan 1 2021
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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