STAT3 pathway is activated in ALK-positive large B-cell lymphoma carrying SQSTM1-ALK rearrangement and provides a possible therapeutic target.

ALK-positive large B-cell lymphomas usually harbor clathrin (CLTC)-ALK rearrangement or, more rarely, nucleophosmin (NPM)-ALK fusion gene. Here we report a large B-cell lymphoma with a peculiar pattern of diffuse and cytoplasmic immunohistochemical staining and carrying sequestosome 1 (SQSTM1)-ALK rearrangement, identified by reverse transcription polymerase chain reaction analysis and Rapid Amplification of cDNA Ends analysis and confirmed by fluorescence in situ hybridization with specific dual-color fusion probes. The gene fusion product and the transcription factor STAT3 are both phosphorylated, and thereby the pathogenetic mechanism of this case shows important analogies with that of NPM-ALK and CLTC-ALK lymphomas, in which STAT3 plays a central role in the lymphomagenesis. Consequently, STAT3 inhibition provides a possible therapeutic target also for lymphomas with SQSTM1-ALK variant translocation.