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Case ReportsAbstract
Mycosis fungoides, the most common form of cutaneous T-cell lymphoma (CTCL), typically follows an indolent course. The histopathology classically is characterized by monoclonal, epidermotropic small to medium T-cells with a mature immunophenotype of CD3+, CD4+, and CD8-. There is often aberrant loss of CD2, CD5, and CD7. Large cell transformation can occur, described as 25% or more large cells typically with retained CD4 positivity with or without CD30. There may be a cytotoxic shift with expression of TIA-1, perforin, and granzyme B. We present a 68-year-old female with longstanding mycosis fungoides, who developed a nodule concerning for large cell transformation. Skin biopsy revealed a lymphoma of uncertain lineage with cytotoxic phenotype. The infiltrate was characterized by atypical medium to large mononuclear cells positive for CD43, TIA-1, PRAME, and partially for perforin. The infiltrate was negative for CD2, CD3, CD4, CD5, CD7, CD30, CD56, CD34, ALK, CD20, CD68, Cd79a, CD117, CD138, T-BETA, TCRBF1, TCRdelta, CK(AE1/AE3), BOB1, GATA3, MART1, MPX, PAX5, SOX10, EBER, and largely negative for CD8. The Ki67 proliferation index was 90%. T-cell clonality study was negative, precluding comparison to her patch stage lesions. Whole exome sequencing (WES) detected MTAP and CDKN2A deletions, with pathogenic mutations in ARID1A (exon 3 pQ594*), NTHL1 and TP53. Chromosome 9p21 loss is a frequent occurrence in advanced CTCL, with possible prognostic implication. This locus encodes CDKN2A, and MTAP lies 110 kb telomeric to CDKN2A. The WES results, in conjunction with immunophenotype, suggested unusual transformation of mycosis fungoides, rather than a distinct primary lymphoma.