CLINICAL, PATHOLOGICAL, AND MOLECULAR-SPECTRUM OF TUMORS ASSOCIATED WITH T(11-22)(P13-Q12) - DESMOPLASTIC SMALL ROUND-CELL TUMOR AND ITS VARIANTS

Purpose: Intense investigation has reshaped concepts about undifferent iated tumors occurring in young people (small round-cell tumors). Tumo rs associated with t(11;22)(p13;q12) and descriptively designated desm oplastic small round-cell tumor (DSRCT) are a distinctive, ra re, poor ly understood member of this family We reviewed 109 eases of DSRCT to further characterize this entity better.Methods: Clinical information and histology were reviewed. Immunohistochemistry and immunoblotting w ere performed using standard techniques. Chimeric EWS-WT1 RNA and DNA were detected by polymerase chain reaction (PCR) and genomic transloca tion breakpoints mapped in a subset of cases. Results: There were 90 m ales and 19 females from 6 to 49 years of age (mean, 22 years). A tota l of 103 held tumor in the abdominal cavity, four in the thoracic regi on, one in the posterior cranial fossa, and one in the hand. Typical h istologic and immunohistochemical features were usually evident in wel l-sampled tumors, but variations in cellularity, stromal components, c ytology, architecture, and immunoreactivity occurred. Tumor cells were usually reactive with antibodies to keratin (67 of 78 cases, 86%), ep ithelial membrane antigen (50 of 54, 93%), vimentin (64 of 66, 97%), d esmin (70 of 78, 90%), neuron-specific enolase (60 of 74, 81%), and th e EWS-WT1 chimeric protein (25 of 27, 93%); typically nonreactive for muscle common actin (one of 58, 2%), myogenin (zero of eight 0%), and chromogranin (one of 46, 2%); and variably reactive for MIC2 (nine of 47, 20%) and p53 (five of 17 with >20% tumor cells reactive). Function al EWS-WT1 gene fusion was evident in 25 of 26 cases with genomic brea kpoints in WT1 intron 7, and EWS introns 7, 8, and 9. Prognosis in gen eral is poor, but tumors are responsive to aggressive therapy. Conclus ion: This large review identifies a greater degree of clinical, pathol ogic, and molecular variation than originally appreciated for tumors a ssociated with t(11;22)(p13;q12). Translocation and functional fusion of the EWS and WT1 genes appears to be a consistent feature of this un ique tumor. J Clin Oncol 16:3028-3036. (C) 1998 by American Society of Clinical Oncology.