Hodak Emmilia, David Michael, Maron Leah, Aviram Adina, Kaganovsky Ella, Feinmesser Meora
Department of Dermatology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel.
J Am Acad Dermatol. 2006 Aug;55(2):276-84. doi: 10.1016/j.jaad.2006.01.020.
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 alpha/beta 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 betaF1(+)/delta(-) phenotype, indicating a TCR of the alpha/beta heterodimer, was found in 8 of 16; betaF1(-)/delta(+) phenotype, indicating a TCR of the gamma/delta heterodimer, in 1 of 16; betaF1(-)/ delta(-) in 5 of 16; and no determinable phenotype in 2 of 16. The TCR gamma 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 alpha/beta 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.
蕈样肉芽肿（MF）是一种亲表皮性皮肤T细胞淋巴瘤，其中肿瘤细胞表达成熟的辅助性T记忆表型，即CD3(+)、CD4(+)、CD8(-)、CD45RO(+)，具有α/β异二聚体的T细胞受体（TCR）。少数患者具有不寻常的免疫组化特征，表现为CD4(-)、CD8(+)成熟T细胞表型。早期MF患者中异常的CD4/CD8双阴性（DN）免疫表型鲜有报道。
我们试图评估早期MF患者中CD4/CD8 DN免疫表型的频率，并研究其临床、组织病理学和免疫组化特征以及疾病进程。
在我们科室的档案中查找早期MF且具有CD4/CD8 DN免疫表型的患者。
在我们实验室进行免疫表型分析的140例早期MF患者中，18例（12%）在新鲜冷冻和石蜡包埋样本的表皮内T细胞中，CD4和CD8表达均低于10%。该组包括13例男性和5例女性患者；14例成人和4例儿童；15例犹太人和3例阿拉伯人。其中，8例为经典MF，10例具有不寻常的临床变异型（5例色素减退型、3例局限性、1例鱼鳞病样、1例紫癜型）。所有患者均接受了针对皮肤的治疗，病程均呈惰性（平均随访3.5年）。组织病理学显示为早期MF。表皮内淋巴细胞的免疫组化分析结果如下：所有患者CD3(+)、CD4(-)、CD8(-)；17例患者均为CD7(-)；16例中有15例CD45RO(+)；15例中有11例T细胞限制性细胞内抗原-1(+)；16例中有2例CD30(+)；16例中有2例CD56(+)。16例中有8例表现为βF1(+)/δ(-)表型，提示α/β异二聚体的TCR；16例中有1例表现为βF1(-)/δ(+)表型，提示γ/δ异二聚体的TCR；16例中有5例表现为βF1(-)/δ(-)；16例中有2例无法确定表型。16例患者中有10例TCRγ基因发生克隆性重排。
这是一个单中心病例系列。
有一部分早期MF患者表现出CD4/CD8 DN免疫表型。在我们地区，这种异常免疫表型并不像文献中所反映的那样罕见，在MF的不寻常临床变异型中占比过高，且似乎没有预后意义。与CD4(+) MF一样，肿瘤细胞代表记忆T细胞，且在许多情况下表达α/β TCR，但与CD4(+) MF不同的是，它们大多具有细胞毒性表型。我们建议将CD4/CD8 DN MF识别为这种淋巴瘤的另一种免疫组化变异型。
