Association of alveolar rhabdomyosarcoma with the Beckwith-Wiedemann syndrome

Rhabdomyosarcoma (RMS) is a soft tissue tumor of childhood frequently diagn osed between the first and fifth year of life. Children with the Beckwith-W iedemann syndrome (BWS), a congenital overgrowth syndrome characterized by exomphalos, macroglossia, and macrosomia, have an increased risk of develop ing 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 report ed as embryonal RMS. Based on these data, an association between BWS and em bryonal 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 alve olar 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 demonstra ted. 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 develo pment of alveolar RMS tumors in BWS may occur without the chromosomal rearr angement producing the PAX-FKHR fusion protein. In summary, we present thre e new cases of RMS demonstrating a new association between BWS and an uncom mon subtype of alveolar RMS. The absence of the translocations commonly ass ociated with alveolar rhabdomyosarcoma. suggests a common 11p15 pathway for alveolar RMS and BWS.