Cell of Origin and Immunologic Events in the Pathogenesis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.
Miranda, Roberto N
Kadin, Marshall E
The American journal of pathology
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Turner, S., Inghirami, G., Miranda, R. N., & Kadin, M. E. (2020). Cell of Origin and Immunologic Events in the Pathogenesis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.. The American journal of pathology, 190 (1), 2-10. https://doi.org/10.1016/j.ajpath.2019.09.005
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 following implant and capsule removal. However, capsular invasion and tumor mass has a more aggressive course, and a fatal outcome risk. This review summarizes the current knowledge on BIA-ALCL cell of origin and immunological factors underlying its pathogenesis. Cytokine expression profiling of BIA- ALCL cell lines and clinical specimens reveal a predominantly 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 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.
Humans, Breast Neoplasms, Breast Implants, Cell Lineage, Female, Lymphoma, Large-Cell, Anaplastic
Writing and editorial assistance was provided to the authors by Robert Rydzewski, MS, CMPP, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and was funded by Allergan plc, Dublin, Ireland.
External DOI: https://doi.org/10.1016/j.ajpath.2019.09.005
This record's URL: https://www.repository.cam.ac.uk/handle/1810/296971
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Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/