Mycosis fungoides (MF) is an epidermotropic cutaneous T-cell lymphoma in which the tumor cells express a mature T-helper memory phenotype, ie, CD3⁺, CD4⁺, CD8⁻, CD45RO⁺, with a T-cell receptor (TCR) of the ⍺/β heterodimer. A minority of patients have an unusual immunohistochemical profile consisting of a CD4⁻, CD8⁺ mature T-cell phenotype. An aberrant CD4/CD8 double-negative (DN) immunophenotype in patients with early MF has rarely been reported.

We sought to evaluate the frequency of CD4/CD8 DN immunophenotype in patients with early MF, and to study their clinical, histopathologic, and immunohistochemical features, and the course of their disease.

Our departmental archives were searched for patients with early-stage MF and CD4/CD8 DN immunophenotpye.

Of the 140 patients with early MF immunophenotyped in our laboratory, 18 (12%) showed CD4 and CD8 expression in less than 10% of their intraepidermal T cells on fresh-frozen and paraffin-embedded samples. The group included 13 male and 5 female patients; 14 adults and 4 children; and 15 Jews and 3 Arabs. In all, 8 had classic MF and 10 had unusual clinical variants (5 hypopigmented, 3 localized, 1 ichthyosiform, 1 purpuric). All received skin-targeted therapies and all had an indolent course (mean follow-up 3.5 years). Histopathology revealed early MF. Results of immunohistochemical analysis of the intraepidermal lymphocytes were as follows: CD3⁺, CD4⁻, CD8⁻ in all patients; CD7⁻ in all of 17; CD45RO⁺ in 15 of 16; T-cell–restricted intracellular antigen-1⁺ in 11 of 15; CD30⁺ in 2 of 16; and CD56⁺ in 2 of 16. A βF1⁺/δ⁻ phenotype, indicating a TCR of the ⍺/β heterodimer, was found in 8 of 16; βF1⁻/δ⁺ phenotype, indicating a TCR of the γ/δ heterodimer, in 1 of 16; βF1⁻/ δ⁻ in 5 of 16; and no determinable phenotype in 2 of 16. The TCR γ gene was clonally rearranged in 10 of 16 patients.

This was a single-center case series.

There is a subgroup of patients with early MF that exhibit a CD4/CD8 DN immunophenotype. In our region, this aberrant immunophenotype is not as rare as reflected in the literature, is overrepresented in the unusual clinical variants of MF, and does not seem to have prognostic significance. Like CD4⁺ MF, the tumor cells represent memory T cells and in many cases express ⍺/β TCR, but unlike CD4⁺ MF, they have a mostly cytotoxic phenotype. We suggest that CD4/CD8 DN MF should be recognized as another immunohistochemical variant of this lymphoma.