Rhabdomyosarcoma

Supplemental Studies

Desmin is an effective screening stain as nearly all cases of all types are positive
- Smooth muscle neoplasms are also desmin positive
More specific and virtually diagnostic are myogenin and MyoD1
- The only sensitivity exception is the sclerosing type, which may show only dot like desmin and may be only variably positive for myogenin
- The only specificity exception is rare expression by melanotic neuroectodermal tumor of infancy
  - Composite tumors must be ruled out
- MyoD1 reagents may produce nonspecific cytoplasmic staining
  - Myogenin is preferred by many for this reason

PAX-FOXO1 fusion transcripts are specific for alveolar rhabdomyosarcoma.
- PAX3-FOXO1 t(2;13)(q35;q14) – 60%
- PAX7-FOXO1 t(1;13)(p36;q14) – 20% (better prognosis)
- Nonspecific minor translocations and fusion negative cases may occur
  - Fusion negative ~ 15%
  - Amplifications of genes: MYCN, MDM2, CDK4, IGF-R1
  - FGFR1-FOXO1 t(8;13;9)(p11.2;q14;9q32)
  - PAX3-NCOA1 t(2;2)(p23;q53)
  - PAX3-NCOA2 t(2;8)(q35;q13)
There is no specific genetic abnormality specific for embryonal or other subtypes of rhabdomyosarcoma.
- A number of nonspecific genetic abnormalities have been described
  - LOH at 11p15.5
  - Gains of chromosomes 2,7,8,11,12,13,17,19 and 20
  - Amplifications of genes: MYCN, MDM2, CDK4, IGF-R1
We test all cases of pediatric rhabdomyosarcoma for FOXO1 abnormalities with FISH on paraffin sections
- Classical cytogenetic study is then necessary in positive cases to determine the specific fusion partner
- All pediatric specimens considered suspicious for soft tissue sarcomas should have a portion of unfixed tissue set aside for cytogenetic study
No specific genetic abnormalities associated with anaplasia