title: Pediatric renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions and clinicopathologic associations.
abstract: Renal cell carcinomas (RCCs) are rare in children and studies of their subtypes and clinicopathologic associations are limited to small series. We identified 8 patients with RCC treated at our institution between 1981 and 2003, reviewed their clinicopathologic features, cytogenetics findings, and evaluated the status of TFE3 expression by immunohistochemistry and numerical chromosomal alterations by interphase fluorescent in situ hybridization on paraffin-embedded tissue. These 8 patients (5 female and 3 male) had diploidy, and 5 had morphologic features compatible with the recently described RCC associated with Xp11.2 translocations/TFE3 gene fusions and demonstrated nuclear labeling for TFE3 protein by immunohistochemistry. The translocation was confirmed in 2 of these 5 patients by conventional cytogenetics. One case was a high-grade nonpapillary RCC and the other was compatible with type 2 papillary RCC. Four patients showed at least 1 chromosomal gain including trisomy 7 and/or trisomy 17. None of the tumors from male patients showed evidence of loss of the Y chromosome, but 2 patients showed numerical abnormalities of X chromosome +add(X). Two patients had sickle cell disease, and 1 of these also had stage IV-S neuroblastoma. This study suggests that many cases of RCC in children reported under the terms "papillary" and "clear cell" likely represent Xp11.2 translocation/TFE3 gene fusion-associated RCC. It also emphasizes the unusual associations of RCC with neuroblastoma and sickle cell hemoglobinopathy, which need further study.
authors.affiliation: Department of Pathology, Children's Hospital of Michigan and Wayne State University, Detroit, MI, USA.
authors.forename: G
authors.initials: G
authors.lastname: Altinok
authors.forename: M M
authors.initials: MM
authors.lastname: Kattar
authors.forename: A
authors.initials: A
authors.lastname: Mohamed
authors.forename: J
authors.initials: J
authors.lastname: Poulik
authors.forename: D
authors.initials: D
authors.lastname: Grignon
authors.forename: R
authors.initials: R
authors.lastname: Rabah
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications / Q000235:genetics / Q000473:pathology; D019677:Artificial Gene Fusion; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D020223:Chromosome Painting; D002880:Chromosomes, Human, Pair 11; D041321:Chromosomes, Human, X; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D009378:Neoplasms, Multiple Primary; D011003:Ploidies; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000235:genetics / Q000473:pathology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C069203:TFE3 protein, human; D014157:Transcription Factors