The malignant cells overexpress ALK1 (anaplastic large cell kinase), as demonstrated by immunohistochemistry. Aside from ALCL, ALK1 expression is limited to rare cells in the brain and a rare subpopulation of diffuse large B-cell lymphomas and is therefore rather specific for ALCL. The ALK1 tyrosine kinase receptor is involved in chromosomal translocations in 60-85% of ALCL cases, resulting in overexpressed aberrantly functioning fusion proteins that presumably mediate transforming growth signals. The most common of these translocations is t(2;5)(p23;q35) involving the nucleophosmin gene, which results in cytoplasmic, nuclear, and nucleolar ALK1 localization. ALK1 positivity is the most important prognostic factor for ALCL, associated with ∼80% average survival rates compared to ∼40% for ALK1-negative tumors.