Search

CD30 lymphocyte activation antigen and phosphorylated STAT3 (pSTAT3) are consistent markers of tumor cells in breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). We present a case of BIA-ALCL in a breast implant capsule containing clustered tumor cells expressing CD30, pSTAT3, pSTAT6, interleukin 9, and granzyme B tumor cell biomarkers. Remarkably, the contralateral breast contained many scattered large, atypical CD30+ cells surrounded by inflammatory cells, raising a suspicion of bilateral BIA-ALCL, known to occur in some patients. To clarify the diagnosis, immunohistochemistry and multilabel immunofluorescence were performed. Unlike the tumor cells, the atypical CD30+ cells of the contralateral breast lacked pSTAT3, pSTAT6, interleukin 9, and granzyme B, eliminating a diagnosis of bilateral BIA-ALCL. This case highlights the importance of interpreting CD30 staining in the context of other tumor cell biomarkers and histopathology to avoid an incorrect diagnosis of BIA-ALCL. We believe the findings also suggest the possibility of CD30 expression as an early event in the multistep pathogenesis of BIA-ALCL.Level Of Evidence:5: [ABSTRACT FROM AUTHOR]

Background: Granzyme B (GrB) is a serine protease secreted, along with pore-forming perforin, by cytotoxic lymphocytes to mediate apoptosis in target cells. GrB has been detected in tumor cells associated with systemic and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) but its potential use for detection of early BIA-ALCL has not been fully investigated.Objectives: Prompted by the increased incidence of BIA-ALCL, the aim of this study was to assess GrB as a new biomarker to detect early disease in malignant seromas and to better understand the nature of the neoplastic cell.Methods: A Human XL Cytokine Discovery Magnetic Luminex 45-plex Fixed Panel Performance Assay was used to compare cytokine levels in cell culture supernatants of BIA-ALCL and other T-cell lymphomas, as well as malignant and benign seromas surrounding breast implants. Immunohistochemistry was employed to localize GrB to cells in seromas and capsular infiltrates.Results: Differences in GrB concentrations between malignant and benign seromas were significant (P < 0.001). GrB was found in and around apoptotic tumor cells, suggesting that the protease may be involved in tumor cell death.Conclusions: GrB is a useful marker for early detection of malignant seromas and to identify tumor cells in seromas and capsular infiltrates. Because there is an overlap between the lowest concentrations of soluble GrB in malignant seromas and the highest concentrations of GrB in benign seromas, it is recommended that GrB be used only as part of a panel of biomarkers for the screening and early detection of BIA-ALCL.Level Of Evidence:5: [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]