ALK-POSITIVE LYMPHOMA - A SINGLE DISEASE WITH A BROAD-SPECTRUM OF MORPHOLOGY

The t(2;5)(p23;q35) translocation, associated with anaplastic large-ce ll lymphoma (ALCL), results in the expression of a chimeric NPM-ALK pr otein that can be detected by the ALK1 monoclonal antibody. This repor t describes the morphologic and phenotypic spectrum of 123 cases of ly mphoma that all express ALK protein. The results provide strong eviden ce that the morphologic patterns of ALCL described in previous reports as representing possible subtypes of ALCL, eg, common type, lymphohis tiocytic, or small cell patterns, are morphologic variants of the same disease entity. All of these morphologic patterns could be found with in this series, and in some patients different subtypes coexisted in a single biopsy or were found in successive biopsies from a single pati ent. The link between these morphologic subtypes is further reinforced by the presence in all cases of a highly characteristic large cell, w ith an eccentric nucleus and an eosinophilic paranuclear region. We su ggest that this cell can be considered as a major distinguishing featu re of ALK-positive lymphomas. Another characteristic of these tumors w as the perivascular pattern of neoplastic cell infiltration seen in a significant number of cases. In addition to ALK protein, all tumors ex pressed epithelial membrane antigen and lacked CD15, features that may be of value in differentiating ALCL from Hodgkin's disease. In the ma jority of cases (84%), malignant cells showed both a cytoplasmic and n uclear staining for ALK1 and thus presumably carried the 2;5 transloca tion, but staining was restricted to the cytoplasm in a few cases, sug gesting that translocations other than t(2;5) may induce expression of ALK protein. We conclude from this study that ALK-positive neoplasms represent a distinct entity. Because their morphology is often neither anaplastic nor large cell, we suggest that they should henceforward h e referred to as ALK lymphomas. (C) 1998 by The American Society of He matology.