CD4/CD8 double-negative epidermotropic cutaneous T-cell lymphoma: An immunohistochemical variant of mycosis fungoides - 09/08/11

Doi : 10.1016/j.jaad.2006.01.020

Emmilia Hodak, MD ^a,^d,^⁎ , Michael David, MD ^a,^d, Leah Maron, MSc ^a, Adina Aviram, PhD ^b,^d, Ella Kaganovsky, PhD ^c, Meora Feinmesser, MD ^c,^d
^a From the Department of Dermatology
^b Laboratory of Molecular Hematology
^c Institute of Pathology
^d Rabin Medical Center, Beilinson Campus, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University

Reprint requests: Emmilia Hodak, MD, Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa 49 100 Israel.

Petah Tiqwa and Tel Aviv, Israel

Abstract

Background

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.

Objectives

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.

Methods

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

Results

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.

Limitation

This was a single-center case series.

Conclusions

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.

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Abbreviations used : CTCL, DN, EORTC, MF, TCR