Definition:

Anaplastic large cell lymphoma (ALCL) is a lymphoid neoplasm characterized by a proliferation of large lymphoid cells, referred to as hallmark cells, with strong expression of CD30. The World Health Organization recognizes 3 entities: primary cutaneous ALCL (pcALCL), anaplastic lymphoma kinase (ALK)-positive ALCL, and, provisionally, ALK-negative ALCL. pcALCL presents in the skin and, while it may involve locoregional lymph nodes, rarely disseminates. ALK-positive ALCL, by definition overexpresses an ALK-fusion gene, typically via t(2;5)(p23;35) which fuses the ALK gene on chromosome 2 with the nucleophosmin (NPM) gene on chromosome 5, resulting in a NPM-ALK chimeric protein with constitutive tyrosine kinase activity. ALK-negative ALCLs lack ALK rearrangements and their genetic and clinical features are more variable. A subset of ALK-negative ALCLs has rearrangements at 6p25.3 involving DUSP22, a gene encoding a dual-specificity phosphatase that inhibits T-cell receptor signaling. DUSP22 rearrangements also are seen in a subset of pcALCLs.