Histopathologic Characterization of Mogamulizumab-associated Rash.
Wang JY; Department of Dermatology, Stanford University School of Medicine, Redwood City.; Department of Pathology.
Hirotsu KE; Department of Dermatology, Stanford University School of Medicine, Redwood City.
Neal TM; Department of Dermatology, Stanford University School of Medicine, Redwood City.
Raghavan SS; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA.
Kwong BY; Department of Dermatology, Stanford University School of Medicine, Redwood City.
Khodadoust MS; Department of Dermatology, Stanford University School of Medicine, Redwood City.; Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA.
Brown RA; Department of Dermatology, Stanford University School of Medicine, Redwood City.; Department of Pathology.
Novoa RA; Department of Dermatology, Stanford University School of Medicine, Redwood City.; Department of Pathology.
Kim YH; Department of Dermatology, Stanford University School of Medicine, Redwood City.; Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA.
Rieger KE; Department of Dermatology, Stanford University School of Medicine, Redwood City.; Department of Pathology.
The American journal of surgical pathology [Am J Surg Pathol] 2020 Dec; Vol. 44 (12), pp. 1666-1676.
Typ publikacji :
Imprint Name(s) :
Publication: <2015- > : Philadelphia, PA : Wolters Kluwer Health, Inc.
Original Publication: New York, Masson.
MeSH Terms :
Antibodies, Monoclonal, Humanized/*adverse effects
Antineoplastic Agents/*adverse effects
CD4-CD8 Ratio ; Drug Eruptions/genetics ; Drug Eruptions/immunology ; Drug Eruptions/pathology ; Exanthema/genetics ; Exanthema/immunology ; Exanthema/pathology ; Female ; Genes, T-Cell Receptor ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Skin/immunology ; Skin/pathology ; T-Lymphocytes/immunology
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Substance Nomenclature :
0 (Antibodies, Monoclonal, Humanized)
0 (Antineoplastic Agents)
Entry Date(s) :
Date Created: 20200925 Date Completed: 20210111 Latest Revision: 20210131
Update Code :
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.