Anaplastic Large Cell Lymphomas: ALK Positive, ALK Negative, and Primary Cutaneous

Anaplastic large cell lymphomas (ALCLs) comprise a group of CD30-positive non-Hodgkin lymphomas that generally are of T-cell origin and share common morphologic and phenotypic characteristics. The World Health Organization recognizes 3 entities: primary cutaneous ALCL (pcALCL), anaplastic lymphoma kinase (ALK)-positive ALCL, and, provisionally, ALK-negative ALCL. Despite overlapping pathologic features, these tumors differ in clinical behavior and genetics. pcALCL presents in the skin and, while it may involve locoregional lymph nodes, rarely disseminates. Outcomes typically are excellent. ALK-positive ALCL and ALK-negative ALCL are systemic diseases. ALK-positive ALCLs consistently have chromosomal rearrangements involving the ALK gene with varied gene partners, and generally have a favorable prognosis. ALK-negative ALCLs lack ALK rearrangements and their genetic and clinical features are more variable. A subset of ALK-negative ALCLs has rearrangements in or near the DUSP22 gene and has a favorable prognosis similar to that of ALK-positive ALCL. DUSP22 rearrangements also are seen in a subset of pcALCLs. In this review, we discuss the clinical, morphologic, phenotypic, genetic, and biological features of ALCLs.