Breast Implant Associated ALCL Tumor Expresses Prostaglandin D2 Receptor: An Allergic Inflammation Pathogenesis
Marshall E. Kadin, MD1, John Morgan, PhD2, Haiying Xu, BS2, Alan Epstein, MD, PhD3, Roberto N. Miranda, MD4, David Sieber, MD5, Mark W. Clemens, MD4.
1Roger Williams Medical Center Department of Dermatology, Providence, RI, USA, 2Roger Williams Medical Center, Providence, RI, USA, 3USC-Keck School of Medicine, Los Angeles, CA, USA, 4MD Anderson Cancer Center, University of Texas, Houston, TX, USA, 5Sieber Plastic Surgery, San Francisco, CA, USA.
PURPOSE: Breast implant associated ALCL (BIA-ALCL) is a T cell lymphoma surrounding textured breast implants in over 400 women worldwide. This study was undertaken to understand the pathogenesis of BIA-ALCL. METHODS: 15 patients with BIA-ALCL diagnosed in capsules or fluid from breast implants and three cell lines were evaluated. Histology and immunohistochemistry was performed for CRTH2, GATA3, IL-13, IL-4 and IgE. RESULTS: Malignant cells were frequently surrounded by eosinophils characteristic of allergic inflammation. IgE coated mast cells, known to release prostaglandin D2 upon IgE activation, were detected. BIA-ALCL cells expressed Th2 transcription factor GATA3 and Th2 cytokines IL-13 and IL-4 and displayed CRTH2, a mediator of Th2 and eosinophil chemotaxis. TNM solid tumor staging was a spectrum of disease from stage IA in five patients (35.7%), IC in two patients (14.3%), 2A in four patients (28.6%), 2B in one patient (7.1%), and stage III in two patients (14.3%). CONCLUSION: CRTH2 initiates the respiratory burst and degranulation of eosinophils which are frequent in BIA-ALCL. CRTH2 also induces production of proinflammatory cytokines by Th2 cells, and enhances the release of histamine from basophils and mast cells. Histamine promotes microvascular permeability and thereby could contribute to seroma formation. CRTH2 antagonists are being considered as a potentially useful approach for the treatment of asthma and other allergic diseases. Because BIA-ALCL appears to arise in the context of chronic allergic inflammation, we suggest that CRTH2 antagonists may be useful in the treatment of delayed seromas and warrant further investigation as a prevention measure for BIA-ALCL.
Back to 2018 Program