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Histopathologic Characterization of Mogamulizumab-associated Rash.
- Source :
-
The American journal of surgical pathology [Am J Surg Pathol] 2020 Dec; Vol. 44 (12), pp. 1666-1676. - Publication Year :
- 2020
-
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.
- Subjects :
- 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
Antibodies, Monoclonal, Humanized adverse effects
Antineoplastic Agents adverse effects
Drug Eruptions etiology
Exanthema chemically induced
Skin drug effects
T-Lymphocytes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1532-0979
- Volume :
- 44
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The American journal of surgical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 32976123
- Full Text :
- https://doi.org/10.1097/PAS.0000000000001587