Extensive Posttreatment Ganglioneuromatous Differentiation of Rhabdomyosarcoma: Malignant Ectomesenchymoma in an Infant

Sebire, Neil J.; Ramsay, Alan D.; Malone, M; Risdon, R. A.

doi:10.1007/s10024-002-0047-4

Cited by 12 publications

(12 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, HRAS mutations were detected in both naive and treated MEMs, suggesting an intrinsic event rather than a chemotherapy-induced process. As previously reported 37 and seen in 2 of our cases, a diagnosis of MEM was rendered only after the surgical specimen was examined, the biopsy material showing only ERMS areas.…”

Section: Discussionsupporting

confidence: 68%

Frequent HRAS Mutations in Malignant Ectomesenchymoma

Huang

Alaggio

Sung³

et al. 2016

American Journal of Surgical Pathology

View full text Add to dashboard Cite

Malignant ectomesenchymoma (MEM) is an exceedingly rare pediatric sarcoma, with predilection for infants and young children, composed of dual malignant mesenchymal and neuroectodermal components. Microscopically, MEM displays areas of rhabdomyosarcoma (RMS) with intermixed neuronal/neuroblastic foci. The molecular alterations MEM and its relationship with embryonal RMS (ERMS) and malignant peripheral nerve sheath tumor (MPNST) have not yet been elucidated. In this study we use whole transcriptome sequencing in 2 MEM index cases with available frozen tissue, followed by screening the identified genetic abnormalities in 5 additional cases. No candidate fusion genes were detected by FusionSeq analysis, however, the mutation detection algorithms revealed HRAS and PTPRD hot-spot mutations in both index cases, with one case harbouring an additional FBXW7 mutation. As these mutation profiles have been previously described in ERMS we have tested their incidence in a control group of 7 age-matched ERMS. Additionally, the gene signature of MEM was compared to that of RMS, MPNST and neuronal lineage. All 7 MEM patients were male, with a mean age of 7.5 months (range 0.6–17 mo). All except one occurred in the pelvis/urogenital region. Most cases showed ERMS elements, with occasional spindle or undifferentiated/round cell areas. The intermixed neuroectodermal components were mostly scattered ganglion cells, ganglioneuroma, or ganglioneuroblastoma. By Sanger sequencing, 6 of 7 (86%) MEMs had HRAS mutations, with no additional case harboring PTPRD or FBXW7 mutations. The only case lacking HRAS mutation showed neuroblastic micronodules without ganglion cells. The trimethylation at lysine 27 of histone H3 (H3K27me3) expression, typically lost in MPNST, was retained in all cases. In the control ERMS group, 5 of 7 (71%) showed RAS mutations, equally distributed among NRAS, KRAS, and HRAS genes. The expression profiling of MEM showed upregulation of skeletal muscle and neuronal genes, with no significant overlap with MPNST. Our results of common HRAS mutations and composite gene signature with RMS and neuronal/ neuroblastic elements, suggest a closer genetic link of MEM to RMS rather than MPNST.

show abstract

Section: Discussionsupporting

confidence: 68%

Frequent HRAS Mutations in Malignant Ectomesenchymoma

Huang

Alaggio

Sung³

et al. 2016

American Journal of Surgical Pathology

View full text Add to dashboard Cite

show abstract

“…6C-F, essentially all tumor cells were positive for myogenin and Pax7 expression while ϳ50% were positive for MyoD expression. The histology combined with widespread myogenic regulatory gene expression is most compatible with the alveolar form of human rhabdomyosarcoma (55)(56)(57)(58)(59).…”

Section: Incidence Of Tumoregenesismentioning

confidence: 97%

Dystrophin‐deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma

Metzger²,

et al. 2007

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is the most common, lethal genetic disorder of children. A number of animal models of muscular dystrophy exist, but the most effective model for characterizing the structural and functional properties of dystrophin and therapeutic interventions has been the mdx mouse. Despite the approximately 20 years of investigations of the mdx mouse, the impact of the disease on the life span of mdx mice and the cause of death remain unresolved. Consequently, a life span study of the mdx mouse was designed that included cohorts of male and female mdx and wild-type C57BL/10 mice housed under specific pathogen-free conditions with deaths restricted to natural causes and with examination of the carcasses for pathology. Compared with wild-type mice, both mdx male and female mice had reduced life spans and displayed a progressively dystrophic muscle histopathology. Surprisingly, old mdx mice were prone to develop muscle tumors that resembled the human form of alveolar rhabdomyosarcoma, a cancer associated with poor prognosis. Rhabdomyosarcomas have not been observed previously in nontransgenic mice. The results substantiate the mdx mouse as an important model system for studies of the pathogenesis of and potential remedies for DMD.

show abstract

“…However, other cytogenetic studies show features of embryonal rhabdomyosarcoma [93], and we have seen 1 case with a FOXO1 rearrangement typical of alveolar rhabdomyosarcoma. Of interest is that extensive ganglioneuromatous differentiation may be seen before or after therapy [94]. Regardless of nosologic considerations, ectomesenchymomas are currently treated as rhabdomyosarcomas by the Children's Oncology Group [90].…”

Section: Unusual Variants Of Rhabdomyosarcomamentioning

confidence: 99%

Myogenic Tumors in Children and Adolescents

2012

View full text Add to dashboard Cite

Neoplasms of striated and smooth muscle in children are a diverse group of neoplasms that have some unique aspects in contrast to these tumors in adults. Rhabdomyosarcoma is the most common soft tissue sarcoma of infancy and childhood and is relatively common in adolescents. In contrast, smooth muscle tumors are relatively rare, and the various types of rhabdomyoma and smooth and skeletal muscle hamartomas are very uncommon. In recent years, the understanding of the pathologic and genetic aspects of rhabdomyosarcoma has been enhanced by adjunct techniques, such as immunohistochemistry and cytogenetic or molecular genetic analysis. The current classification of rhabdomyosarcoma emphasizes the histologic-prognostic correlations. This article reviews the clinicopathologic features of striated and smooth muscle tumors with an emphasis on the unique aspects of these neoplasms in children and adolescents and the differential diagnosis.

show abstract

Extensive Posttreatment Ganglioneuromatous Differentiation of Rhabdomyosarcoma: Malignant Ectomesenchymoma in an Infant

Cited by 12 publications

References 9 publications

Frequent HRAS Mutations in Malignant Ectomesenchymoma

Frequent HRAS Mutations in Malignant Ectomesenchymoma

Dystrophin‐deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma

Myogenic Tumors in Children and Adolescents

Contact Info

Product

Resources

About