Anaplastic rhabdomyosarcoma in <i>TP53</i> germline mutation carriers

<jats:sec> <jats:title>BACKGROUND</jats:title> <jats:p> Rhabdomyosarcoma (RMS) represents a diverse category of myogenic malignancies with marked differences in molecular alterations and histology. This study examines the question if RMS predisposition due to germline <jats:italic>TP53</jats:italic> mutations correlates with certain RMS histologies. </jats:p> </jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p> The histology of RMS tumors diagnosed in 8 consecutive children with <jats:italic>TP53</jats:italic> germline mutations was reviewed retrospectively. In addition, germline <jats:italic>TP53</jats:italic> mutation analysis was performed in 7 children with anaplastic RMS (anRMS) and previously unknown <jats:italic>TP53</jats:italic> status. </jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p> RMS tumors diagnosed in 11 <jats:italic>TP53</jats:italic> germline mutation carriers all exhibited nonalveolar, anaplastic histology as evidenced by the presence of enlarged hyperchromatic nuclei with or without atypical mitotic figures. Anaplastic RMS was the first malignant diagnosis for all <jats:italic>TP53</jats:italic> germline mutation carriers in this cohort, and median age at diagnosis was 40 months (mean, 40 months ± 15 months; range, 19‐67 months). The overall frequency of <jats:italic>TP53</jats:italic> germline mutations was 73% (11 of 15 children) in pediatric patients with anRMS. The frequency of <jats:italic>TP53</jats:italic> germline mutations in children with anRMS was 100% (5 of 5 children) for those with a family cancer history consistent with Li‐Fraumeni syndrome (LFS), and 80% (4 of 5 children) for those without an LFS cancer phenotype. </jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p> Individuals harboring germline <jats:italic>TP53</jats:italic> mutations are predisposed to develop anRMS at a young age. If future studies in larger anRMS cohorts confirm the findings of this study, the current Chompret criteria for LFS should be extended to include children with anRMS irrespective of family history. <jats:bold> <jats:italic>Cancer</jats:italic> 2014;120:1068–1075 </jats:bold> . © <jats:italic>2013 American Cancer Society</jats:italic> . </jats:p> </jats:sec>