Molecular pathology of pediatric rhabdomyosarcoma

Abstract

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and adolescents. It is classified into embryonal, botryoid, spindle cell and alveolar subtypes in the International Classification of Rhabdomyosarcoma (ICR), but the spindle cell/sclerosing rhabdomyosarcoma is listed as an independent category in the WHO classification (4^th edition) published in 2013. Most alveolar rhabdomyosarcomas harbor fusion genes involving either PAX3 or PAX7 and FOXO1. Recent studies showed that the fusion-positive alveolar rhabdomyosarcoma has the poorest prognosis. In tumors of spindle cell rhabdomyosarcoma of infants, fusion genes involving VGLL2, TEAD and SRF were reported, and these tumors showed favorable outcomes. In a subset of spindle cell/sclerosing rhabdomyosarcoma, tumors with a hot-spot mutation of MYOD1 were reported, and the same type of mutation was observed in a small number of cases with the embryonal type. These tumors with the MYOD1 mutation were reportedly aggressive. In this paper, the pathological classification and molecular genetic alterations of rhabdomyosarcoma are reviewed and their clinical implications are discussed.