Cell of Origin and Immunologic Events in the Pathogenesis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma

Am J Pathol. 2020 Jan;190(1):2-10. doi: 10.1016/j.ajpath.2019.09.005. Epub 2019 Oct 11.

Abstract

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoma. Nearly all cases have been associated with textured implants. Most cases are of effusion-limited, indolent disease, with an excellent prognosis after implant and capsule removal. However, capsular invasion and tumor mass have a more aggressive course and a fatal outcome risk. This review summarizes the current knowledge on BIA-ALCL cell of origin and immunologic factors underlying its pathogenesis. Cytokine expression profiling of BIA-ALCL cell lines and clinical specimens reveals a predominantly type 17 helper T-cell (Th17)/Th1 signature, implicating this as its cell of origin. However, a Th2 allergic inflammatory response is suggested by the presence of IL-13, with infiltration of eosinophils and IgE-coated mast cells in clinical specimens of BIA-ALCL. The microenvironment-induced T-cell plasticity, a factor increasingly appreciated, may partially explain these divergent results. Mutations resulting in constitutive Janus kinase (JAK)-STAT activation have been detected and associated with BIA-ALCL pathogenesis in a small number of cases. One possible scenario is that an inflammatory microenvironment stimulates an immune response, followed by polyclonal expansion of Th17/Th1 cell subsets with release of inflammatory cytokines and chemokines and accumulation of seroma. JAK-STAT3 gain-of-function mutations within this pathway and others may subsequently lead to monoclonal T-cell proliferation and clinical BIA-ALCL. Current research suggests that therapies targeting JAK proteins warrant investigation in BIA-ALCL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Breast Implants / adverse effects*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery*
  • Cell Lineage*
  • Female
  • Humans
  • Lymphoma, Large-Cell, Anaplastic / etiology
  • Lymphoma, Large-Cell, Anaplastic / pathology*