Marshall E Kadin1, John Morgan, Nick Kouttab, Haiying Xu2, William P Adams3, Caroline Glicksman4, Patricia McGuire, David Sieber, Alan L Epstein5, Roberto N Miranda6, Mark W Clemens7. 1. Dr Kadin is a Professor of Dermatology, Boston University and Roger Williams Medical Center, Providence RI. 2. Ms Xu is a Research Assistant, Roger Williams Medical Center, Providence, RI. 3. Dr Adams is an Associate Professor, Department of Plastic Surgery, University of Texas Southwestern Medical School, Dallas TX. 4. Dr Glicksman is a Clinical Assistant Professor, Hackensack Meridian School of Medicine at Seton Hall, Nutley, NJ. 5. Dr Epstein is a Professor of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA. 6. Dr Miranda is a Professor of Pathology, Department of Hematopathology, MD Anderson Cancer Center, Houston TX. 7. Dr Clemens is an Associate Professor, Department of Plastic Surgery, MD Anderson Cancer Center, Houston TX; and is Breast Surgery Section Co-editor for Aesthetic Surgery Journal.
Abstract
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Marshall E Kadin; John Morgan; Haiying Xu; Caroline Glicksman; David Sieber; William P Adams; Pat McGuire; Mark W Clemens; Archana Thakur; Lawrence G Lum Journal: Aesthet Surg J Date: 2021-11-12 Impact factor: 4.283
Authors: Anand K Deva; Suzanne D Turner; Marshall E Kadin; Mark R Magnusson; H Miles Prince; Roberto N Miranda; Giorgio G Inghirami; William P Adams Journal: Cancers (Basel) Date: 2020-12-21 Impact factor: 6.639