Prevalence and clinical impact of anaplasia in childhood rhabdomyosarcoma : a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.
ABSTRACT Anapalsia is rare in childhood rhabdomyosarcoma and has not been included in the International Classification of Rhabdomyosarcoma (ICR). A recent review of cases from the Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG) suggests that anaplasia might be more common than previously reported and may impact clinical outcome.
The prevalence of anaplasia (focal or diffuse) was prospectively assessed in 546 eligible cases who were registered in an Intergroup Rhabdomyosarcoma Study Group (IRSG) or COG therapeutic trial from 1995 through 1998. The incidence of anaplasia in tumor samples and its impact in predicting clinical outcome was assessed.
Overall, 71 (13%) of all samples analyzed had anaplasia. Anaplasia was more common in patients with tumors in favorable sites and was less commonly observed in younger patients and in those with stage II, III, or clinical group III disease. Regardless of its distribution (focal or diffuse), on univariate analysis the presence of anaplasia negatively influenced the failure-free survival rate (63% vs 77% at 5 years) and overall survival (68% vs 82% at 5 years) rates in patients with embryonal rhabdomyosarcoma. This effect was most pronounced in children with intermediate-risk tumors. Anaplasia did not affect outcome in patients with alveolar tumors.
The incidence of anaplasia in patients with rhabdomyosarcoma is higher than previously described and may be of prognostic significance in children with intermediate-risk embryonal rhabdomyosarcoma.
Full-textDOI: · Available from: David Parham, Jun 22, 2015
- SourceAvailable from: Zhongxin Yu[Show abstract] [Hide abstract]
ABSTRACT: Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin, we demonstrate that eRMS and undifferentiated pleomorphic sarcoma (UPS) lie in a continuum, with satellite cells predisposed to giving rise to UPS. Conversely, p53 loss in maturing myoblasts gives rise to eRMS, which have the highest myodifferentiation potential. Regardless of origin, Rb1 loss modifies tumor phenotype to mimic UPS. In human sarcomas that lack pathognomic chromosomal translocations, p53 loss of function is prevalent, whereas Shh or Rb1 alterations likely act primarily as modifiers. Thus, sarcoma phenotype is strongly influenced by cell of origin and mutational profile.Cancer cell 02/2011; 19(2):177-91. DOI:10.1016/j.ccr.2010.12.023 · 23.89 Impact Factor
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ABSTRACT: BACKGROUND 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 TP53 mutations correlates with certain RMS histologies. METHODS The histology of RMS tumors diagnosed in 8 consecutive children with TP53 germline mutations was reviewed retrospectively. In addition, germline TP53 mutation analysis was performed in 7 children with anaplastic RMS (anRMS) and previously unknown TP53 status. RESULTSRMS tumors diagnosed in 11 TP53 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 TP53 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 TP53 germline mutations was 73% (11 of 15 children) in pediatric patients with anRMS. The frequency of TP53 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. CONCLUSIONS Individuals harboring germline TP53 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. Cancer 2013;. © 2013 American Cancer Society.Cancer 04/2014; 120(7). DOI:10.1002/cncr.28507 · 4.90 Impact Factor
Article: Pediatric genitourinary tumors.[Show abstract] [Hide abstract]
ABSTRACT: Childhood genitourinary tumors are rare and continue to demand collaborative protocols to accumulate adequate numbers of patients for studies, and a multidisciplinary approach for treatment. This paper reviews all the 1990 literature on the most common of these tumors--Wilms' and testicular tumors and rhabdomyosarcoma. The molecular and cellular biology and pathology of Wilms' tumor, as well as treatment advances, are discussed, emphasizing attempts to minimize treatment morbidity and mortality while maintaining optimal quality and quantity of life.Current Opinion in Oncology 07/1991; 3(3):545-52. · 3.76 Impact Factor