ALK-positive large B-cell lymphoma (ALK+ LBCL) involving cervical lymph nodes in a 38 y/o male (same case as the previous two images). The tumor focally had highly anaplastic giant cells with bizarre nuclei. Multinucleated forms resembling Reed-Sternberg cells were also seen. Mitotic activity was brisk. By definition, this tumor overexpresses the ALK gene. This is due to t(2;17)(p23;q23) translocation which fuses CLTC (clathrin) gene on 17q23 with the ALK gene on 2p23. CLTC encodes the clathrin heavy polypeptide which is the main structural protein of coated vesicles. ALK codes for anaplastic lymphoma kinase which is a receptor tyrosine kinase. Rare cases show the t(2;5)(p23;q35) translocation (seen in ALK+ anaplastic large cell lymphoma of T/null phenotype) which fuses NPM and ALK genes leading to the nuclear as well as cytoplasmic expression of ALK protein. The differential diagnosis includes ALK+ anaplastic large cell lymphoma (of T/null phenotype), plasmablastic lymphoma, and diffuse large B-cell lymphoma with a sinusoidal pattern. The prognosis is poor; most patients die within a year of diagnosis despite multiagent chemotherapy. As these tumors are usually CD20-negative, they don't respond to rituximab.