Comparative Analysis of Cytokines of Tumor Cell Lines, Malignant and Benign Effusions Around Breast Implants

More than 700 women have developed an anaplastic large T cell lymphoma (ALCL) surrounding textured surface breast implants, termed breast implant-associated ALCL (BIA-ALCL). Most patients with BIA-ALCL present with an accumulation of fluid (delayed seroma) around the implant. However, benign seromas without malignant cells complicating scar contracture, implant rupture, trauma, infection, and other causes are more common. For proper patient management and to avoid unnecessary surgery, a simple diagnostic test to identify malignant seromas is desirable.

The aim of this study was to develop an ancillary test for the diagnosis of malignant seromas and to gain insight into the nature of the malignant cells and their microenvironment.

We employed an immunologic assay on only 50 µL of aspirated seroma fluid. The assay measures 13 cytokines simultaneously by flow cytometry. To establish a baseline for clinical studies we measured cytokines secreted by BIA-ALCL and cutaneous ALCL lines.

Our study of cell line culture supernatants, and 8 malignant compared with 9 benign seromas indicates that interleukin 9 (IL-9), IL-10, IL-13, IL-22, and/or interferon γ concentrations >1000 pg/mL distinguish malignant seromas from benign seromas. IL-6, known to be a driver of malignant cells, is also elevated in benign seromas and does not distinguish them from malignant seromas.

The cytokine assay introduced in this study can be used together with levels of soluble CD30 to identify malignant seromas. Validation of these findings in a larger prospective patient cohort is warranted. The unique pattern of cytokine expression in malignant effusions surrounding breast implants gives further insight into the pathogenesis and cells of origin of BIA-ALCL.

Level of Evidence: 5.