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

Abstract

SUMMARY:

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.

• Authors: Ryan C DeCoster, Mark W Clemens, Arianna Di Napoli, Evan B Lynch, Alisha R Bonaroti, Brian D Rinker, Timothy A Butterfield, Henry C Vasconez
• Journal: Plastic and reconstructive surgery (Plast Reconstr Surg) Vol. 147 Issue 1 Pg. 30e-41e (01 01 2021) ISSN: 1529-4242 [Electronic] United States
• PMID: 33370049 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2020 by the American Society of Plastic Surgeons.

Chemical References

• Lipopolysaccharides
• STAT3 Transcription Factor
• STAT3 protein, human
• Janus Kinases

Topics

• Biofilms
• Breast Implantation (adverse effects, instrumentation)
• Breast Implants (adverse effects)
• Breast Neoplasms (surgery)
• Carcinogenesis (genetics, immunology)
• Disease Progression
• Female
• Genetic Predisposition to Disease
• Gram-Negative Bacterial Infections (complications, immunology, microbiology)
• Humans
• Inflammation (drug therapy, etiology, pathology)
• Janus Kinases (antagonists & inhibitors, genetics, metabolism)
• Lipopolysaccharides (immunology)
• Lymphoma, Large-Cell, Anaplastic (drug therapy, etiology, pathology)
• Mastectomy (adverse effects)
• Mutation
• Postoperative Complications (drug therapy, etiology, pathology)
• Prognosis
• STAT3 Transcription Factor (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction (drug effects, genetics, immunology)
• Surface Properties
• T-Lymphocytes (immunology)
• Tumor Microenvironment (immunology)