Clinical, histopathological and prognostic features of primary cutaneous acral CD8+ T-cell lymphoma and other dermal CD8+ cutaneous lymphoproliferations - Results of an EORTC Cutaneous Lymphoma Group Workshop

Background: The differential diagnosis of atypical dermal non-epidermotropic CD8+lymphocytic infiltrates includes a heterogenous spectrum of lymphoproliferations with overlapping histological and phenotypic features, but divergent clinical manifestations and prognoses. As these neoplasms are rare, more data on their clinicopathological presentation and course are needed. Objectives: To assess the clinical, histological, immunophenotypic features, outcome of and differences between dermal CD8+ lymphoproliferations. Methods: Retrospective analysis of a series of 47 patients and biopsies by the international EORTC Cutaneous Lymphoma Group. Results: The dermal CD8+ lymphoproliferations (n=46) could be assigned to one of the following 3 groups: (1) cutaneous acral CD8+ T-cell lymphoma (n=31), characterized mostly by a solitary nodule arising at acral sites, a monotonous dermal infiltrate of small to medium-sized CD8+ lymphocytes with a characteristic dot-like pattern of CD68, a low proliferation rate and an excellent prognosis; (2) primary cutaneous CD8+ peripheral T-cell lymphoma, unspecified/NOS (n=11), presenting with one or multiple rapidly evolving tumors, mostly medium-sized pleomorphic CD8+ tumor cells with expression of several cytotoxic markers and high proliferative activity. After chemotherapy or radiotherapy relapses occurred in one third and 1 of 11 patients died due to lymphoma (9%); (3) The third group (n=4) comprised cutaneous CD8+ lymphoproliferations associated with congenital immunodeficiency syndromes in 2 patients with persisting localized or disseminated violaceous to brownish plaques on the extremities, a histiocyte-rich infiltrate of mostly small CD8+ lymphocytes with subtle atypia and a protracted course, and papular CD8+ eruptions in two patients with acquired immunosuppression (HIV-infection, solid organ transplantation). Conclusions: A constellation of distinct clinical, histopathologic and phenotypic features allows discrimination and assignment of dermal CD8+ infiltrates to distinct disease entities including cutaneous acral CD8+ T-cell lymphoma, primary cutaneous CD8+ peripheral T-cell lymphoma, unspecified/NOS and cutaneous CD8+ lymphoproliferations associated with congenital or acquired immunodeficiency syndromes. Primary cutaneous acral CD8+ lymphoma, assigned a provisional category in current lymphoma classifications, is a distinct and reproducible entity. A correct diagnosis is essential to avoid unnecessarily aggressive treatment for indolent CD8+ lymphoproliferations and to identify cases with underlying immunodeficiency or potential for dismal outcome.