Immunophenotypic shift from CD4⁺to CD8⁺in mycosis fungoides

Abstract

DEAR EDITOR, A 46-year-old Japanese man had experienced multiple slightly scaly erythematous patches on his flanks, hips and thighs for about 20 years, and had received no medical treatment. The patient noticed a small red nodule on the posterior aspect of his right thigh, which increased in size and ulcerated rapidly over the course of 1 year. The tumour was 4 cm in diameter, forming a central ulcer with yellow and black necrotic tissue ( Fig. 1a,b). A biopsy specimen taken from an erythematous patch showed atypical T-cell infiltration with epidermotropism and multiple Pautrier microabscesses ( Fig. 2a). These cells were positive for CD3 and CD4, but not for CD8 or CD30 ( Fig. 2b-d, and data not shown). The condition was diagnosed as mycosis fungoides (MF).A biopsy specimen taken from the tumour revealed dense infiltration of highly atypical medium-sized lymphocytes in the dermis (Fig. 2e). Pleomorphism and mitotic figures were observed (Fig. 2f). Immunohistochemically, atypical lymphocytes were positive for CD3, CD8 and granzyme B, but not for CD4 or CD30 (Fig. 2g,h, and data not shown). T-cell receptor (TCR) gene rearrangement analysis using polymerase chain reaction (PCR) revealed monoclonal peaks of the same size for the b and c chains of TCR in both lesions (Fig. 2i, j). The tumour was removed surgically. Erythematous lesions were treated with a topical steroid and narrowband ultraviolet B phototherapy. No new nodules or tumours developed for 31 months after the initial diagnosis.

Double CD4/CD8-Positive, Nonpoikilodermic Mycosis Fungoides Expressing CD56 in a Young Man

“…7 Moreover, cases have been described with a shift in phenotype from CD4 to CD8 (and vice versa) before or after having received treatment. 8,9 Furthermore, hyperpigmented MF is frequently CD8 positive. 10 Nevertheless, CD56 expression has classically correlated with the poikilodermatous variant of MF.…”

Immunophenotypic switch in cutaneous T‐cell lymphoma: A series of three cases and review of the literature

“…Many cases with IS were treated with multiple agents before the switch was documented on relapse. The most common IS reported in MF (13/15 cases) is a switch from a CD4‐positive/CD8‐negative profile without cytotoxic proteins to a CD4‐negative/CD8‐positive or CD4‐negative/CD8‐negative profile with expression of the cytotoxic markers TIA‐1 and granzyme B 1,3‐13 . Eighteen of 28 patients expired.…”

“…Eighteen of 28 patients expired. The average progression time from diagnosis of IS to death is 22 months with a range of (1‐76 months) 1,3‐14 . Notably, Merrill et al described 20 patients with a gamma delta phenotype and noted that CD8 expression appeared to change over time in two patients and CD30 changed over time in four patients, but detailed clinicopathologic information is not available for these cases 14 .…”

“…Immunophenotypic switch (IS) is defined as an alteration in the immunophenotypic expression of a tumor while retaining its genotypic signature and occurs during lymphoma progression 1 . It is a known phenomenon in hematologic malignancies, 2 but has rarely been reported in cutaneous T‐cell lymphoma (CTCL) 1,3‐14 and its clinical and biological significance is not well studied. IS poses a diagnostic challenge and may be associated with a worse prognosis 1,3‐14 .…”

Spatially Guided and Single Cell Tools to Map the Microenvironment in Cutaneous T-Cell Lymphoma

“…IS is defined as a change in the immunophenotype of tumor cells while maintaining their genetic expression profile. The most common IS reported particularly in MF patients comprises the change from a CD4+ phenotype to a cytotoxic CD8+ phenotype, especially after treatment [ 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. IS has been more recently documented in a series of three cases of CTCL patients presenting disease relapse post-treatment [ 60 ].…”