Pediatric sclerosing rhabdomyosarcoma

Harvard University, Cambridge, Massachusetts, United States
International Journal of Surgical Pathology (Impact Factor: 0.96). 08/2006; 14(3):193-9. DOI: 10.1177/1066896906290558
Source: PubMed

ABSTRACT Sclerosing rhabdomyosarcoma, a particular phenotypic variant of rhabdomyosarcoma initially described in the adult population, has emerged as a potential pitfall in the evaluation of pediatric sarcomas. Because of its densely hyalinized collagenous matrix and its occasional expression of a pseudovascular pattern of growth, sclerosing rhabdomyosarcoma has been at times misdiagnosed as chondrosarcoma, osteosarcoma, or angiosarcoma. We describe 3 pediatric patients with sclerosing rhabdomyosarcoma and provide a detailed description of its distinguishing pathologic features. Awareness about this rhabdomyosarcoma variant and careful immunophenotypical evaluation are necessary to establish the correct diagnosis. Although no specific genetic aberrations have been recognized, yet the cytogenetic findings in 2 tumors of this series suggest a link with embryonal rhabdomyosarcoma. It is likely that further genotyping will result in better nosologic delineation of sclerosing rhabdomyosarcoma and that it will uncover pathogenetically and prognostically relevant genes.

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    ABSTRACT: Sclerosing and spindle cell rhabdomyosarcoma (RMS) are rare types of RMS recently reclassified as a stand-alone pathologic entity, separate from embryonal RMS (ERMS). Although sclerosing and spindle cell RMS share clinical and morphologic features, a pathogenetic link based on shared molecular alterations has not been established. Spindle cell RMS in children have been associated with a less aggressive clinical course compared to adults. Recently, recurrent MYOD1 mutations were described in 44% of adult spindle cell RMS, but no pediatric tumors or sclerosing RMS were studied for comparison. Thus, we investigated 16 RMS (5 sclerosing and 11 spindle cell) in children and adults for the presence of MYOD1 mutations by targeted Polymerase Chain Reaction (PCR). Remarkably, all 5 sclerosing RMS and 4 of 11 spindle cell RMS showed the MYOD1 p.L122R hot-spot mutation. Of the five pediatric tumors, 2/2 sclerosing RMS and 2/3 spindle cell RMS showed MYOD1 mutations. Three of nine MYOD1-mutant RMS showed coexistent PIK3CA mutations, while no MDM2 amplifications were identified. All four pediatric MYOD1-mutated RMS patients died of the disease at 12–35 months following diagnosis. In conclusion, spindle cell and sclerosing RMS show recurrent MYOD1 mutations, in keeping with a single pathologic entity, regardless of age at presentation. This group however, is distinct from the infantile RMS associated with NCOA2 fusions. Although our study suggests that pediatric MYOD1-mutant RMS follow an aggressive behavior with high mortality, further studies are required to confirm this finding. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 09/2014; 53(9). DOI:10.1002/gcc.22187 · 3.84 Impact Factor
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    ABSTRACT: Sclerosing RMS (SRMS) is a recently described subtype of RMS that has not yet been included in any of the classification systems for RMSs. We did pubmed search using keywords "sclerosing, and rhabdomyosarcomas" and included all pediatric cases (age ≤ 18 years) of SRMSs in this review. We also included our case of an eleven-year-old male child with skull base SRMS and discuss the clinical, histopathological, immunohistochemical, and genetic characteristics of these patients. Till now, only 20 pediatric cases of SRMSs have been described in the literature. Pediatric SRMS more commonly affects males at a mean age of 9 years. Extremeties and head/neck regions were most commonly affected. Follow-up details were available for 16 patients with mean follow-up of 25.3 months. Treatment failure rate was 43.75%. Overall amongst these 16 patients, 10 were alive without disease, 4 were alive with disease, and two died. Thus, overall and disease-free survival amongst these 16 patients were 87.5% and 62.5%, respectively. The literature regarding clinical behaviour and outcome of pediatric patients with SRMSs is patchy. Detailed molecular/genetic analysis and clinicopathological characterization with longer follow-ups of more cases may throw some light on this possibly new subtype of RMS.
    03/2014; 2014:640195. DOI:10.1155/2014/640195
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    ABSTRACT: Recently, spindle cell/sclerosing rhabdomyosarcoma (RMS) has been recognized as another distinct variant of a RMS. We evaluated clinicopathological features of 21 cases of spindle cell and sclerosing RMS and performed fluorescent in situ hybridization (FISH) testing in 10 (47.6%) tumours. Twenty-one tumours occurred in 16 males and 5 females (mean age, 19.7 years); commonly in the head and neck region (8) (38%) and extremities (7) (33.3%), followed by paratesticular region (2) (9.5%), chest wall (1), abdomen (1), pelvis (1) and paraspinal region (1). Average tumour size was 7.9 cm. Histopathologically, tumours that were spindle cell type (8) (38%) mostly occurred in the head and neck region, while sclerosing type (10) (47.6%) mostly occurred in the extremities. Remaining three (14.2%) tumours were mixed (sclerosing with spindle cell type). Tumour areas resembling embryonal RMS (ERMS) and alveolar RMS (ARMS) were noted in eight and three tumours respectively. Immunohistochemically, tumour cells were positive for desmin (21/21) (100%), MyoD1 (19/19) (100%), myogenin (13/15) (86.6%), SMA (2/3) and MIC2 (1/8) (12.5%). On FISH testing, none of the 10 tumours exhibited RMS1 (PAX3-FOXO1) or RMS 2 (PAX7-FOXO1) fusion. Eighteen patients underwent surgical resection and were offered adjuvant chemotherapy (CT) (4 cases), adjuvant CT + radiotherapy (RT) (4 cases) and adjuvant RT (1 case). Two patients underwent CT and a single patient received CT + RT. On follow-up (16 cases) (2–36 months), six tumours recurred and nine metastasized. Spindle/sclerosing RMSs are aggressive tumours and occur commonly in the head and neck and extremity sites. These tumours are histopathologically interrelated. Their immunohistochemical and cytogenetic profile is closer to ERMS than ARMS.
    Apmis 04/2014; 122(11). DOI:10.1111/apm.12272 · 1.92 Impact Factor