title: Association of alveolar rhabdomyosarcoma with the Beckwith-Wiedemann syndrome.
abstract: Rhabdomyosarcoma (RMS) is a soft tissue tumor of childhood frequently diagnosed between the first and fifth year of life. Children with the Beckwith-Wiedemann syndrome (BWS), a congenital overgrowth syndrome characterized by exomphalos, macroglossia, and macrosomia, have an increased risk of developing childhood tumors including Wilms tumor, hepatoblastoma, neuroblastoma, and RMS. Although an association between RMS and the BWS is well accepted, only four cases have been reported to date, and of these, three were reported as embryonal RMS. Based on these data, an association between BWS and embryonal RMS has been proposed. We report three additional cases of BWS with RMS and review the clinical data for each patient as well as the pathology of their tumors. All three cases of BWS had histology consistent with alveolar RMS and were diagnosed at 6 weeks and 5 and 13 years of age. In two of these BWS cases, constitutional defects of 11p15 imprinting were demonstrated. Furthermore, cytogenetic analysis of the tumors did not detect the t(2;13) or t(1;13) translocations that generate the PAX3- or PAX7-FKHR fusion proteins common to alveolar RMS. These observations suggest that the development of alveolar RMS tumors in BWS may occur without the chromosomal rearrangement producing the PAX-FKHR fusion protein. In summary, we present three new cases of RMS demonstrating a new association between BWS and an uncommon subtype of alveolar RMS. The absence of the translocations commonly associated with alveolar rhabdomyosarcoma suggests a common 11p15 pathway for alveolar RMS and BWS.
authors.affiliation: Institute of Medical Sciences, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
authors.forename: A C
authors.initials: AC
authors.lastname: Smith
authors.forename: J A
authors.initials: JA
authors.lastname: Squire
authors.forename: P
authors.initials: P
authors.lastname: Thorner
authors.forename: M
authors.initials: M
authors.lastname: Zielenska
authors.forename: C
authors.initials: C
authors.lastname: Shuman
authors.forename: R
authors.initials: R
authors.lastname: Grant
authors.forename: D
authors.initials: D
authors.lastname: Chitayat
authors.forename: J L
authors.initials: JL
authors.lastname: Nishikawa
authors.forename: R
authors.initials: R
authors.lastname: Weksberg
mesh_terms: D000293:Adolescent; D001506:Beckwith-Wiedemann Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018232:Rhabdomyosarcoma, Alveolar / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm