Rhabdomyosarcoma

Rhabdomyosarcomas are a malignancy of connective tissue in which abnormal cells are thought to arise from skeletal muscle progenitors. They account for more than half of all tissue sarcomas (i.e. cancer of the connective tissue) in children. Other types of sarcomas are liposarcomas, fibrosarcomas and mesenchymomas.

Rhabdomyosarcomas can occur anywhere in the body but occur more commonly near muscular structures. Examples of locations include around the intestines, around the ocular muscles and in the cardiac muscle in tuberous sclerosis.¹

Rhabdomyosarcomas are highly malignant and grow rapidly - but are now potentially curable.

Rhabdomyosarcomas account for 7-8% of all childhood malignant solid cancers with less than 60 children diagnosed per year (mostly under 10 years of age).^2,3 It is actually the commonest soft tissue sarcoma in children. It has a slightly higher preponderance in males than females.

Rhabdomyosarcomas can occur at any age but the two commonest peaks of presentation are 1-5 years (approximately two thirds of cases) and 15-19 years, although the presence in the latter group is very rare.³

Rhabdomyosarcomas arise from rhabdomyoblasts - a primitive muscle cell. There are four types:

• Embryonal rhabdomyosarcoma - the cells have a similar appearance to embryo cells aged 6-8 weeks. This is the commonest type and has a predilection for the head, neck and the genitourinary tract.
• Alveolar rhabdomyosarcoma - the cells have a similar appearance to embryo cells aged 10-12 weeks. This tends to affect older children and teenagers and has a more aggressive nature. It is associated with muscles of the trunk and limbs.
• Botryoid type - this is a variant of the embryonal type and presents as grape-like lesions in the vagina and bladder. Almost all cases are in infants.³
• Pleomorphic rhabdomyosarcoma - this entity is more common in adults and has a tendency to affect muscles of the extremities.

Most cases are sporadic in nature. The aetiology of rhabdomyosarcomas is most probably related to germline mutations e.g. p53 mutations.³ This is supported by an increased risk in patients with certain genetic disorders e.g. Li-Fraumeni syndrome, neurofibromatosis, fetal alcohol syndrome and nevoid basal cell carcinoma.

Explosives have also been associated with rhabdomyosarcomas, namely Dense Inert Metal Explosives (DIME) - but this may just relate to acquired genetic defects.

Rhabdomyosarcomas usually present as a lump or swelling. Other features depend upon the area of the body affected. Examples include:

• Nose - nasal obstruction and discharge
• Eyes - protrusion of the eyeball
• Abdomen - pain and change in bowel habit
• Bladder - haematuria

Non-resolving lumps in children should be investigated by a centre recognised by the United Kingdom Children's Cancer Study Group as they will have better expertise in these rare tumours.

• Blood tests - FBC may show anaemia; LFT's raised ALT; raised LDH.
• Bone marrow studies may be required (to look for infiltration).
• Radiological imaging - this may include CXR, ultrasonography and may proceed to CT or MRI scanning. More recently FDG-PET ((18)F-fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography (PET)) scanning looks promising especially in staging of the neoplasia.⁴
• Bone scan to look for metastases.
• MyoD1 is an immature protein found in developing skeletal muscle which disappears once the muscle matures and can be used as an immunohistochemical marker.⁵

Initially staging was identified by the Intergroup Rhabdomyosarcoma Study Group (IRSG) into the following groups(surgicopathologic clinical grouping system).^3,6

• Surgery - this is recommended for all lesions provided it is feasible and as much of the tumour should be removed as possible. Surgery is only occasionally possible as the tumour is usually deeply embedded in surrounding tissue. If the rhabdomyosarcoma is in an extremity then amputation is required. Surgery may also be the only way to obtain a tissue biopsy.⁷
• Chemotherapy - this is given postoperatively and preoperatively to shrink tumour size. Vincristine, actinomycin D and cyclophosphamide (VAC) have been considered the gold standard.⁸ Dose intensification has been used to try and improve outcomes in children with rhabdomyosarcomas. However, one trial looking at dose intensification of cyclophosphamide failed to find an improved outcome.⁸ There has also been good results with the use of etoposide and ifosfamide.^3,7
• Radiotherapy - this is given postoperatively and occasionally preoperatively to shrink tumour size and commonly in head, neck and pelvic tumours.

The prognosis has improved over the last two to three decades. The 5-year overall survival rate is 72% with two thirds of children being cured.² The embryonal type is the most treatable. However, presence of metastases in any type is associated with a very poor prognosis. Location of the tumour also affects the prognosis, with orbital and genitourinary tract rhabdomyosarcomas having a better outcome compared with head and neck tumours.