Original ArticlesHistopathologic Characterization of Mogamulizumab-associated RashWang, Jennifer Y. MD*,†; Hirotsu, Kelsey E. MD*; Neal, Tatiana M. BA*; Raghavan, Shyam S. MD‡; Kwong, Bernice Y. MD*; Khodadoust, Michael S. MD, PhD*,§; Brown, Ryanne A. MD, MBA*,†; Novoa, Roberto A. MD*,†; Kim, Youn H. MD*,§; Rieger, Kerri E. MD, PhD*,†Author Information *Department of Dermatology, Stanford University School of Medicine, Redwood City †Department of Pathology §Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA ‡Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA Conflicts of Interest and Source of Funding: B.Y.K., M.S.K., Y.H.K., and K.E.R. received honorariums from Kyowa Kirin for participation in a drug advisory board for mogamulizumab. For the remaining authors none were declared. Correspondence: Kerri E. Rieger, MD, PhD, Department of Dermatology, Stanford University School of Medicine, 450 Broadway Street, Pavilion B, Floor 4, Redwood City, CA 94061 (e-mail: [email protected]). The American Journal of Surgical Pathology: December 2020 - Volume 44 - Issue 12 - p 1666-1676 doi: 10.1097/PAS.0000000000001587 Buy Metrics Abstract Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient’s previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient’s MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.