Lymphomas expressing ALK fusion protein(s) other than NPM-ALK

The tumor cells in ALK-positive lymphoma ("ALKoma") usually express the pro duct of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal tran slocation. However, 10% to 20% of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunoh istologic and clinicopathologic features of 15 such cases. The absence of t he NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase ch ain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. In each case, ALK staining was restri cted to the cytoplasm and the hi-terminus of NPM to the nucleus (contrastin g with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). However, in the course of screening 53 ALK-positive lym phomas, 2 biopsies were found that had a "cytoplasm-only" ALK staining patt ern but that nevertheless were shown to carry the (2;5) (by NPM staining an d RT-PCR). The 15 cases resembled typical NPM-ALK-positive lymphomas in tha t all were of T or null phenotype, usually occurred in young male patients, and frequently presented with advanced disease associated with systemic sy mptoms and extranodal involvement: Moreover, their prognosis was excellent and indistinguishable from that of classical t(2;5)positive tumors, but was clearly different from that of ALK-negative anaplastic large-cell lymphoma s. These results suggest that lymphomas carrying variants of the NPM-ALK fu sion protein can be detected by immunostaining for ALK and NPM and also tha t they can be grouped with classical t(2;5)-positive tumors as a single ent ity (ALK-positive lymphoma or "ALKoma") that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma. (C) 1999 by The American Socie ty of Hematology.