An Unusual Case of Primary Mucocutaneous Cytotoxic T-Cell Lymphoma With Epidermotropism and Phenotype Switch: Diagnostic and Molecular Insights.

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (PCAECTCL) is a rare, rapidly progressive cutaneous T-cell lymphoma that poses significant diagnostic challenges, particularly in mucocutaneous variants. We report a case in a 49-year-old man who presented with upper lip swelling initially misdiagnosed as angioedema and cheilitis granulomatosa. A lip biopsy revealed atypical CD4/CD8 double-negative T cells with marked epidermotropism, initially interpreted as pagetoid mycosis fungoides. Subsequent immunophenotyping demonstrated a cytotoxic profile (CD3+, CD2+, CD7+, CD5-, CD4-, CD8+, CD20+, perforin+, granzyme B+, TCRBF1+, CD56-, and TCRδ-). Imaging later identified tongue involvement with a similar phenotype, though CD8 expression was weak and CD20 expression was absent. The disease progressed to lymph nodes, oropharynx, and stomach, with an eventual phenotypic switch to CD8+. Molecular testing confirmed similar clonal T-cell rearrangements across all sites. Sequencing identified JAK3 and TP53 mutations, while chromosomal microarray revealed recurrent losses (1p, 2q, 3p, 4p, 11q, 13q, and 17q) and gains (7q, 17p), without JAK2 fusion. Despite aggressive therapy, the patient died 21 months after diagnosis. This case delineates the importance of early biopsy, integration of molecular studies, and the urgent need for therapies to improve outcomes in this aggressive lymphoma.