Soft Tissues: Rhabdomyosarcoma

2009-01-01   Jennifer Reichek  , Frederic G Barr  

1.Department of Pathology, Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

Summary

Note

Rhabdomyosarcoma (RMS) refers to a family of mesenchymal tumours related to the skeletal muscle lineage.

Classification

Classification

The two main histopathologic subtypes of rhabdomyosarcoma are :
  • Embryonal rhabdomyosarcoma (ERMS)
  • Alveolar rhabdomyosarcoma (ARMS)

    • Clinics and Pathology

    Embryonic origin

    RMS is postulated to be derived from mesodermal tissues.

    Epidemiology

    RMS is the most common pediatric soft tissue sarcoma, representing ~5% of all malignancies among children and adolescents. The annual incidence is 4-5 per million. ERMS accounts for 70-80% of all RMS, and usually occurs in young children (median age of 6.5 years). ARMS accounts for the remaining 20-30% of RMS, and more often occurs in older children and young adults (median age of 12 years).

    Clinics

    RMS often presents as a painless mass. In other cases, the tumor may be discovered from symptoms produced by compression of structures at the primary site, such as diplopia (double vision) caused by RMS in the orbital region. The two histopathologic subtypes tend to occur at different sites. ERMS often occurs in the head and neck region, genitourinary tract, and retroperitoneum whereas ARMS often occurs in the extremities. All types of RMS are treated with a combination of surgery, radiation therapy, and intensive chemotherapy.

    Pathology

  • In ERMS, the tumor cells range from small round cells to large elongated cells, and exhibit varying degrees of myogenic differentiation. There is often varying cell density with highly cellular areas alternating with low cellular areas in a loose myxoid stroma.
  • In ARMS, tumor cells are small with a round nucleus and scant cytoplasm. Aggregates of these tumors cells often become discohesive and produce spaces, reminiscent of lung alveoli.
  • An anaplastic RMS subset is recognized by large, lobated hyperchromatic nuclei and atypical mitoses. Anaplasia is more prevalent in ERMS and can be found as a focal or diffuse feature in the tumor.
  • The tumor cells of both subtypes of RMS variably express muscle specific proteins (such as desmin, myoglobin, muscle-specific actin, or the myogenic transcription factors MyoD and myogenin) that can be detected by immunohistochemistry.
    • Atlas Image
    Histopathology of rhabdomyosarcoma subtypes. A. Embryonal subtype. B. Alveolar subtype. (hematoxylin-eosin, original magnification: 100X; courtesy of Dr. Linda Ernst)

    Prognosis

    Factors that influence the selection of therapy and the outcome of patients include primary site (orbit, superficial head and neck, biliary tree, vagina, and paratestis are considered favorable), size of primary tumor, extent of local spread, presence of nodal and distal metastases, and histologic subtype. Of the two histologic subtypes, ARMS has a poorer prognosis than ERMS.

    Cytogenetics

    Cytogenetics morphological

    Studies of cytogenetics and other acquired genetic changes in ERMS and ARMS have revealed significant genetic differences between these two subtypes.

  • Most ARMS cases are distinguished from ERMS and other solid tumors by the presence of one of two recurrent chromosomal translocations, which generate related fusion genes.
    - t(2;13)(q35;q14) generates PAX3 - FOXO1 in ~60% of ARMS cases
    - t(1;13)(p36;q14) generates PAX7 - FOXO1 in ~20% of ARMS cases

  • ERMS does not have recurrent structural chromosome rearrangements, but rather has frequent chromosome gains and losses. In addition, ERMS has a much higher frequency of loss of one of the two alleles of many chromosome 11 loci, particularly in the 11p15.5 region.

    • Genetics

    Note

    Most cases of RMS occur sporadically without an apparent genetic predisposition. However, a small subset of RMS is associated with the following known genetic syndromes:
  • Hereditary retinoblastoma syndrome (RB1)
  • Li-Fraumeni syndrome (TP53)
  • Neurofibromatosis type I (NF1)
  • Costello syndrome (HRAS)
  • Beckwith-Wiedemann syndrome (11p15 genes)
  • Nevoid basal cell carcinoma syndrome (PTCH)
  • Rubinstein-Taybi syndrome (CREBBP).

    • Article Bibliography

    Pubmed IDLast YearTitleAuthors
    161703162005Germline mutations in HRAS proto-oncogene cause Costello syndrome.Aoki Y et al
    80989851993Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma.Barr FG et al
    116078232001Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma.Barr FG et al
    125061742003Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study IV.Breneman JC et al
    114085062001Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease.Crist WM et al
    81870701994Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma.Davis RJ et al
    77126371995Nevoid basal cell carcinoma syndrome.Gorlin RJ et al
    160106792005Tumor predisposition in Costello syndrome.Gripp KW et al
    98081271998Second primary rhabdomyosarcomas in patients with bilateral retinoblastoma: a clinicopathologic and immunohistochemical study.Hasegawa T et al
    53602871969Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome?Li FP et al
    97819041998Molecular genetics of Wiedemann-Beckwith syndrome.Li M et al
    19787571990Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.Malkin D et al
    1027561978Rhabdomyosarcoma complicating multiple neurofibromatosis.McKeen EA et al
    77477731995Tumors in Rubinstein-Taybi syndrome.Miller RW et al
    170901872006Rhabdomyosarcomas in adults and children: an update.Parham DM et al
    76304031995Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.Petrij F et al
    189856762008Prevalence and clinical impact of anaplasia in childhood rhabdomyosarcoma : a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.Qualman S et al
    36579881987Chromosomal localization of the human rhabdomyosarcoma locus by mitotic recombination mapping.Scrable HJ et al
    127839652003Myogenin and MyoD1 expression in paediatric rhabdomyosarcomas.Sebire NJ et al
    151270102004Neurofibromatosis in children with Rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma study IV.Sung L et al
    39430531986Consistent chromosomal translocation in alveolar rhabdomyosarcoma.Turc-Carel C et al
    93150991997Allelotype of pediatric rhabdomyosarcoma.Visser M et al
    33380901988Chromosomal analysis of sixteen human rhabdomyosarcomas.Wang-Wuu S et al
    121707812002Molecular pathogenesis of rhabdomyosarcoma.Xia SJ et al

    Citation

    Jennifer Reichek ; Frederic G Barr

    Soft Tissues: Rhabdomyosarcoma

    Atlas Genet Cytogenet Oncol Haematol. 2009-01-01

    Online version: http://atlasgeneticsoncology.org/solid-tumor/5004/tumors-explorer/gene-explorer/

    Historical Card

    1998-03-01 Soft Tissues: Rhabdomyosarcoma by  Jérôme Couturier