CD4- CD8- 'double-negative' cutaneous T-cell lymphomas share common histologic features and an aggressive clinical course

We report 15 patients with CD4-CD8- "double-negative" T-cell lymphoma arising in skin. There were seven women and eight men with a mean age at diagnosis of 53 years (range 19-77 years). All but two patients presented with solitary or multiple cutaneous nodule(s). Initial and recurrent biopsy specimens showed a dense infiltrate centered in the mid-dermis (extending into subcutis when sampled) of small to intermediate-sized lymphocytes with indistinct nucleoli and frequently irregular nuclear contours. Periadnexal infiltration and epidermal ulceration were present in five cases with the intraepidermal cells being primarily reactive CD4+ T cells. All cases were negative for CD30 and terminal deoxynucleotidyl-transferase; one showed expression of CD56, and six of eight tested cases were positive for T-cell receptor-8 expression. Despite systemic chemotherapy, all 12 patients with clinical follow-up showed recurrent or progressive disease with wide-spread cutaneous dissemination in 10 of 12. Eventual dissemination to lymph nodes or bone marrow occurred in two patients each, with at least nine patients dead of disease or treatment complications. Only two patients achieved lasting clinical remission (with 2′-deoxycoformycin/pentostatin and nelarabine, respectively). CD4-CD8- "double-negative" CTCL has distinctive histologic features and cytomorphology with a marked propensity for rapid multifocal cutaneous dissemination.