title: Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants.
abstract: OBJECTIVE
  Intense investigation has reshaped concepts about undifferentiated tumors occurring in young people (small round-cell tumors). Tumors associated with t(11;22)(p13;q12) and descriptively designated desmoplastic small round-cell tumor (DSRCT) are a distinctive, rare, poorly understood member of this family. We reviewed 109 cases of DSRCT to further characterize this entity better.
  
  
  METHODS
  Clinical information and histology were reviewed. Immunohistochemistry and immunoblotting were performed using standard techniques. Chimeric EWS-WT1 RNA and DNA were detected by polymerase chain reaction (PCR) and genomic translocation breakpoints mapped in a subset of cases.
  
  
  RESULTS
  There were 90 males and 19 females from 6 to 49 years of age (mean, 22 years). A total of 103 had tumor in the abdominal cavity, four in the thoracic region, one in the posterior cranial fossa, and one in the hand. Typical histologic and immunohistochemical features were usually evident in well-sampled tumors, but variations in cellularity, stromal components, cytology, architecture, and immunoreactivity occurred. Tumor cells were usually reactive with antibodies to keratin (67 of 78 cases, 86%), epithelial membrane antigen (50 of 54, 93%), vimentin (64 of 66, 97%), desmin (70 of 78, 90%), neuron-specific enolase (60 of 74, 81%), and the 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). Functional EWS-WT1 gene fusion was evident in 25 of 26 cases with genomic breakpoints in WT1 intron 7, and EWS introns 7, 8, and 9. Prognosis in general is poor, but tumors are responsive to aggressive therapy.
  
  
  CONCLUSIONS
  This large review identifies a greater degree of clinical, pathologic, and molecular variation than originally appreciated for tumors associated with t(11;22)(p13;q12). Translocation and functional fusion of the EWS and WT1 genes appears to be a consistent feature of this unique tumor.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. geraldw@mskcc.org
authors.forename: W L
authors.initials: WL
authors.lastname: Gerald
authors.forename: M
authors.initials: M
authors.lastname: Ladanyi
authors.forename: E
authors.initials: E
authors.lastname: de Alava
authors.forename: M
authors.initials: M
authors.lastname: Cuatrecasas
authors.forename: B H
authors.initials: BH
authors.lastname: Kushner
authors.forename: M P
authors.initials: MP
authors.lastname: LaQuaglia
authors.forename: J
authors.initials: J
authors.lastname: Rosai
mesh_terms: D000008:Abdominal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002880:Chromosomes, Human, Pair 11; D002892:Chromosomes, Human, Pair 22; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D034802:RNA-Binding Protein EWS; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014178:Translocation, Genetic; D025721:WT1 Proteins
chemical_list: D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009363:Neoplasm Proteins; D034802:RNA-Binding Protein EWS; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; D025721:WT1 Proteins