General
- Rhabdomyosarcomas are a family of malignant primitive neoplasms that demonstrate at least focal, predominantly skeletal muscle differentiation.
- These tumours are rarely identified as primary tumours within the central nervous system.
Diagnostic criteria
- Essential criteria
- Malignant primitive tumour with at least focal immunohistochemical demonstration of skeletal muscle lineage.
- Absence of non-rhabdomyosarcomatous components.
- Desirable criterion
- Confirmation of a FOXO1 gene fusion in cases that are diagnostically difficult, though this is considered essential for the diagnosis of the alveolar type.
Numbers
- The majority of rhabdomyosarcomas develop in children, though adults may also be affected.
WHO grade
- While a specific CNS WHO grade is not explicitly assigned to the whole category in the sources, these tumours are defined as malignant primitive neoplasms that almost always demonstrate clinically aggressive behaviour.
- They are listed as malignant tumours with a primary site behaviour code of /3.
Histopathology
Macroscopic
- Gross specimens are usually described as being firm and moderately vascular.
- These characteristics can make complete neurosurgical removal difficult to achieve without complications.
Microscopic
- These tumours manifest varying proportions of strap cells with cross-striations and undifferentiated small cells.
- Mitotic activity is often brisk.
- Embryonal rhabdomyosarcomas are composed of variably differentiated rhabdomyoblasts within a loose, myxoid mesenchyme, often showing alternating areas of dense and loose cellularity.
- Alveolar rhabdomyosarcomas are highly cellular and composed of primitive round cells with scant cytoplasm and hyperchromatic nuclei.
- These cells are typically arranged in nests separated by fibrovascular septa, and the alveolar type often contains scattered multinucleated, wreath-like giant tumour cells.
- Spindle cell or sclerosing rhabdomyosarcoma is heterogeneous, showing fascicular, whorling, or herringbone architecture with uniform spindled cells, or round to spindled cells within a hyalinized/collagenized stroma.
- Pleomorphic rhabdomyosarcoma shows sheets of large, pleomorphic rhabdoid, spindled, or polygonal cells that are often multinucleated.
- The Ki-67 labelling index is usually high.
Immunophenotype
- All rhabdomyosarcomas should show cytoplasmic immunoreactivity for desmin, though the extent is variable.
- The skeletal muscle-specific nuclear regulatory proteins MYOD1 and myogenin (MYF4) are positive in essentially all cases.
- Myogenin is usually diffusely positive in the alveolar type, but the embryonal and spindle cell types may show only scattered positive cells.
- MSA and SMA immunoreactivity is frequently present.
- Primary intracranial alveolar rhabdomyosarcoma may express OLIG2, which should not be misinterpreted as evidence of a glial component.
Pathogenesis
- Sporadic cases of embryonal rhabdomyosarcoma are often aneuploid, frequently showing whole-chromosome gains, particularly of chromosome 8.
- Most embryonal types show a loss of heterozygosity at chromosome 11p15, which contains genes encoding growth factors and growth suppressors.
- The majority of alveolar rhabdomyosarcomas harbour a t(2;13)(q36;q14) translocation, resulting in a PAX3::FOXO1 fusion, or a t(1;13)(p36;q14) translocation resulting in a PAX7::FOXO1 fusion.
- Spindle cell or sclerosing rhabdomyosarcomas arising in older children and adults often show mutations in MYOD1, while congenital or infantile forms typically involve NCOA2 and VGLL2 rearrangements.
Localisation
- There is no stereotypical location for primary intracranial rhabdomyosarcoma;
- Infratentorial and skull base sites (66%)
- Supratentorial locations (34%)
- Examples have occurred in meningeal, pineal, sellar, and cerebellopontine angle locations.
Clinical features
- Symptoms depend on the location of the tumour.
- Many patients present with headache and mass effects such as nausea and vomiting.
- Supratentorial examples may cause hemiparesis or extremity weakness.
- Infratentorial or skull base examples are often associated with cranial nerve palsies.
- Intrasellar examples have been reported to mimic the symptoms of pituitary adenomas, such as bitemporal hemianopsia.
Radiological features
- Imaging studies are required to define the site of origin, the extent of local disease, and metastatic spread, but they do not otherwise provide specific diagnostic findings.
- Tumours may appear as bulky masses with heterogeneous signal features and inhomogeneous enhancement.
- Ref: Nair 2017
Management
- Complete neurosurgical removal is often difficult due to the firm and vascular nature of the tumours.
- Management typically involves chemotherapy, as evidenced by descriptions of tumour cytodifferentiation and necrosis in post-chemotherapy specimens.
Prognosis
- The prognosis is usually poor due to local recurrence.
- The 1-year survival rate is estimated at 44 per cent, and long-term survival beyond 24 months is considered exceptional.
- Metastasis occurs in fewer than 20 per cent of primary intracranial examples.
- A worse prognosis is associated with alveolar rhabdomyosarcomas that lack characteristic gene fusions.
Differential diagnosis
- Diifferentiate from other tumours with some component of skeletal muscle differentiation
- Medullomyoblastomas
- Gliosarcomas
- MPNSTs
- Germ cell tumours
- Meningiomas
- Malignant ectomesenchymoma
- Mixed tumour composed of ganglion cells or neuroblasts and one or more mesenchymal elements (usually rhabdomyosarcoma) may also occur in the brain
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