IL-13 is produced by tumor cells in breast implant–associated anaplastic large cell lymphoma: implications for pathogenesis

Marshall E. Kadin, John Morgan, Haiying Xu, Alan L. Epstein, David Sieber, Bradley A. Hubbard, William P. Adams, Carlos E. Bacchi, Joao C.S. Goes, Mark W. Clemens, L. J. Medeiros, Roberto N. Miranda

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

More than 500 women worldwide have developed a CD30+ T-cell lymphoma around breast implants, strongly suggesting a cause-and-effect relationship, and designated as breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). The mechanism of lymphomagenesis is unknown. Recently, a bacterial biofilm containing gram-negative bacilli was discovered on the surface of breast implants associated with ALCL. We and others have described overexpression of the proto-oncogene JUNB and mutations of JAK1/2, TP53 and STAT3 in BIA-ALCL. Here we report that BIA-ALCL cell lines and anaplastic lymphoma cells in clinical specimens produce IL-13, the signature cytokine of allergic inflammation. Supporting the link of BIA-ALCL to allergic inflammation, lymphoma cells were often surrounded by eosinophils and mast cells, features typically absent in systemic ALCL. Because of the link of IL-13 to allergy, we looked for IgE and found it decorating the surface of mast cells and antigen-presenting follicular dendritic cells in capsules and lymph nodes infiltrated by anaplastic lymphoma cells, but not uninvolved capsules. Plasma cells within capsules and regional lymph nodes were identified as a possible source of IgE. Together, these findings suggest the hypothesis that an amplified immune response with features of a chronic allergic reaction in a susceptible patient underlies the pathogenesis of BIA-ALCL.

Original languageEnglish (US)
Pages (from-to)54-62
Number of pages9
JournalHuman Pathology
Volume78
DOIs
StatePublished - Aug 1 2018

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Keywords

  • BIA-ALCL
  • Breast implants
  • Breast implant–associated anaplastic large cell lymphoma
  • IL-13
  • Lymphomagenesis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kadin, M. E., Morgan, J., Xu, H., Epstein, A. L., Sieber, D., Hubbard, B. A., Adams, W. P., Bacchi, C. E., Goes, J. C. S., Clemens, M. W., Medeiros, L. J., & Miranda, R. N. (2018). IL-13 is produced by tumor cells in breast implant–associated anaplastic large cell lymphoma: implications for pathogenesis. Human Pathology, 78, 54-62. https://doi.org/10.1016/j.humpath.2018.04.007