Histopathologic Characterization of Mogamulizumab-associated Rash. (December 2020)

• Record Type: Journal Article
• Authors: Wang, Jennifer Y.; Hirotsu, Kelsey E.; Neal, Tatiana M.; Raghavan, Shyam S.; Kwong, Bernice Y.; Khodadoust, Michael S.; Brown, Ryanne A.; Novoa, Roberto A.; Kim, Youn H.; Rieger, Kerri E.
• Is Part Of: American journal of surgical pathology. Volume 44:Number 12(2020)
• Publication Date: 2020-12
• Subjects: mogamulizumab -- rash -- mycosis fungoides -- histopathology -- high-throughput sequencing; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001587
• Languages: English
• ISSNs: 0147-5185

Abstract

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.