title: Malignant rhabdoid tumor of the bladder and ganglioglioma in a 14 year-old male with a germline 22q11.2 deletion.
abstract: Malignant rhabdoid tumors (MRTs) are rare pediatric malignancies characterized by clinically aggressive lesions that typically show loss of SMARCB1 expression. We herein describe a case of a malignant rhabdoid tumor of the bladder in a 14-year-old male with an autism spectrum disorder and a de novo 3 Mb germline deletion in chromosome band 22q11.2 that included the SMARCB1 gene. The malignancy developed in the setting of chronic hematuria (>2 years) following the occurrence of two other lesions: a central nervous system ganglioglioma and an intraoral dermoid cyst. MRTs of the bladder are exceedingly rare, and this patient is the oldest child reported with this tumor to date. This case adds to the growing body of literature regarding the recently described, phenotypically diverse, distal 22q11.2 syndrome. Furthermore, this is the first reported case in which an MRT of the bladder appears to have developed from a pre-existing bladder lesion. Finally, this case further supports a rhabdoid tumorigenesis model in which heterozygous loss of SMARCB1 predisposes to initial tumor formation with intact SMARCB1 expression, with subsequent inactivation of the other SMARCB1 allele, which results in transformation into more malignant lesions.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Kristopher R
authors.initials: KR
authors.lastname: Bosse
authors.affiliation: Division of Urology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Aseem R
authors.initials: AR
authors.lastname: Shukla
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Pawel
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Kudakwashe R
authors.initials: KR
authors.lastname: Chikwava
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Santi
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Laura
authors.initials: L
authors.lastname: Tooke
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Castagna
authors.affiliation: Department of Pathology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Electronic address: bagatellr@email.chop.edu.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Bagatell
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D020817:Asperger Syndrome / Q000150:complications; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018303:Ganglioglioma / Q000235:genetics* / Q000473:pathology; D018095:Germ-Line Mutation; D006417:Hematuria / Q000150:complications; D006801:Humans; D008297:Male; D018335:Rhabdoid Tumor / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
keywords: Rhabdoid; SMARCB1; distal 22q11.2 syndrome