Orbital Rhabdomyosarcoma

The commonest primary orbital malignancy in children and the most common orbital sarcoma. Median age about 7 to 8 years (range 2 months to 20 years), slight male predominance.

• Histology: embryonal (about 70 percent; best prognosis), alveolar (about 15 percent; PAX3-FOXO1 or PAX7-FOXO1 fusion, aggressive), pleomorphic (rare, adults) and botryoid (conjunctival, rare).
• Arises from primitive mesenchymal cells (not necessarily from extraocular muscle), and usually from the superonasal orbit.
• Orbital disease has a relatively favourable prognosis compared with other sites because of early presentation and low rate of metastasis (about 5 percent at diagnosis).

• Rapidly progressive unilateral proptosis over days to weeks, with globe displacement (down and out), eyelid swelling and ptosis, conjunctival chemosis and a palpable subcutaneous mass in the upper lid, and a pink or salmon coloured conjunctival mass.
• Often mistaken for orbital cellulitis, chalazion, or haemangioma; pain is mild or absent; fever absent.
• Restricted motility, diplopia, reduced vision, optic disc swelling or choroidal folds.
• Haemorrhage into the tumour can precipitate sudden proptosis.
• Regional extension to the sinuses or intracranial space, and metastases to lung, bone and bone marrow, with weight loss.

• Urgent biopsy (incisional) within days of presentation; fine needle aspiration is not adequate; send fresh tissue for immunohistochemistry (desmin, myogenin, MyoD1) and molecular testing for fusion genes.
• MRI orbits and brain with gadolinium (isointense to muscle on T1, hyperintense on T2, homogeneously enhancing mass), CT for bone destruction.
• Staging: chest CT, bone marrow aspirate and trephine, bone scan or PET-CT, cerebrospinal fluid cytology if parameningeal extension, lymph node assessment.
• Risk group assignment by stage, histology and extent of residual disease after surgery: low risk (embryonal, localised, completely resected or microscopic residual), intermediate (alveolar, or embryonal with gross residual), high (metastatic disease).

• Multimodal therapy at a paediatric oncology centre; complete exenteration is no longer first line.
• Chemotherapy: vincristine, dactinomycin and cyclophosphamide (VAC). Doses: vincristine 1.5 mg/m2 (maximum 2 mg) weekly in induction then every 3 weeks, dactinomycin 0.045 mg/kg (1.5 mg/m2) every 3 weeks, cyclophosphamide 1.2 g/m2 every 3 weeks; alternating VAC with vincristine and irinotecan (irinotecan 50 mg/m2 on days 1 to 5) in intermediate risk disease; total duration 24 to 48 weeks. Monitor for peripheral neuropathy, haemorrhagic cystitis (give mesna and hydration), and veno occlusive disease.
• Radiotherapy to the orbit: 36 Gy for low risk with complete response, 45 to 50.4 Gy for residual disease, begun at week 4 to 13 (earlier for parameningeal extension); proton beam preferred to reduce late effects (cataract, orbital hypoplasia, dry eye, retinopathy, secondary tumours, endocrine deficiency).
• Surgery: biopsy and reserved for residual or recurrent disease; exenteration for persistent or recurrent tumour.
• Survival: 5-year overall survival above 90 percent for orbital embryonal disease and 65 to 80 percent for alveolar; poor for metastatic or relapsed.
• Late follow up: ophthalmic care for cataract, dry eye, orbital growth impairment, visual rehabilitation, and screening for second tumours.