The pathologic and clinical spectrum of anaplastic large cell lymphoma and correlation with ALK gene dysregulation

Anaplastic large cell lymphoma (ALCL) is clinically and pathologically heterogeneous, leading to some difficulty in its diagnosis and acceptance as a specific entity. ALCL can be subdivided into different groups according to histologic features (pleomorphic, monomorphic, small cell predominant, Hodgkin's disease-related, and other less common variants), immunophenotype (T, null, B, and rarely B and T), and clinical features (systemic, primary cutaneous type, ALCL arising in HIV-positive patients, and ALCL occurring after another lymphoproliferative process, such as lymphomatoid papulosis, mycosis fungoides, and Hodgkin's disease. Cytogenetic studies and subsequent cloning of the translocation t(2;5) have shown a high degree of association with Ki-1-positive lymphoma but have revealed that this genetic abnormality is not specific for anaplastic morphologic features, is more common in the monomorphic and small cell variants, and is rare in primary cutaneous ALCL. It is likely that this t(2;5)-positive group is pathogenetically related. The purpose of this article is to review the pathologic and clinical spectrum of ALCL, including the borderline with Hodgkin's disease and lymphomatoid papulosis and to discuss the use of the t(2;5) in better defining a more specific molecular pathologic entity within this group of diseases with CD30 expression.