Description
Orbital rhabdomyosarcoma is a malignant soft tissue tumour, originating from undifferentiated mesenchymal cells destined to form striated skeletal muscle. It is the most common soft tissue sarcoma of childhood and adolescence and the most common primary orbital malignancy in the paediatric population. It has a predilection for the superonasal quadrant.
Pathogenesis
The pathogenesis of orbital rhabdomyosarcoma is poorly understood. However, genetic mutations such as those involving the PAX3, PAX7, and FOXO1 genes have been implicated, leading to the uncontrolled proliferation of skeletal muscle precursor cells. Loss of tumour suppressor genes like Rb and p53 can also contribute to the tumour’s development.
Subtype
- Embryonal Rhabdomyosarcoma: The most common subtype, frequently seen in the head and neck region and urogenital tract, and less commonly in the orbit. It primarily affects children younger than 10 years and is marked by the presence of round, spindle-shaped, or tadpole-shaped cells, typically organised in a loose myxoid stroma.
- Alveolar Rhabdomyosarcoma: This subtype tends to be more aggressive and occurs in older children and adolescents. It is characterised histologically by a dense cellular pattern of round cells and a distinctive alveolar architecture.
- Pleomorphic Rhabdomyosarcoma: This is an extremely rare subtype usually seen in adults. The tumour cells vary greatly in size and shape, with both spindle and giant cells.
- Spindle cell/sclerosing Rhabdomyosarcoma: This is a rare subtype that usually affects adults. It is composed of elongated, spindle-shaped cells and demonstrates an abundance of hyalinised collagen.
Epidemiology, Risk Factors & Associations
- Represents the most common primary malignant orbital tumour in children (80% of orbital malignancies in patients younger than 15 years).
- There is a slight male predominance.
- Majority of cases occur sporadically, though there is an association with genetic syndromes such as Li-Fraumeni syndrome and Neurofibromatosis type 1.
Clinical Features
- Proptosis is the most common clinical presentation, followed by lid swelling and mass.
- Decreased visual acuity, strabismus, and globe displacement may also be seen.
- The presence of systemic symptoms like fever, weight loss may suggest metastatic disease.
Complications
- Visual loss.
- Metastatic spread to the regional lymph nodes, lungs, bone marrow, and brain.
- Recurrence is common especially in higher-grade tumours.
Pathological Features
Histopathology
- Macroscopic: Tumours are usually firm, lobulated masses with a whitish-grey appearance.
- Microscopic: Tumours demonstrate undifferentiated mesenchymal cells, with rhabdomyoblasts showing eosinophilic cytoplasm and cross-striations. Findings vary depending on the subtype; spindle cells and myxoid stroma in embryonal, dense cellular pattern in alveolar, pleomorphic cells in pleomorphic, and hyalinised collagen in sclerosing/spindle cell subtype.
Serology
- Elevated lactate dehydrogenase levels are often seen.
Biochemistry
- No specific biochemical markers.
Radiological Features
General Features
- Characteristically demonstrates a unilateral, poorly defined soft-tissue mass in the orbit leading to proptosis.
- Typically demonstrates homogenous enhancement, with irregular shape and ill-defined margins.
- Calcifications are rare.
- Ring and Arc sign can be seen, indicating haemorrhagic and mineralised components.
- Calcifications are rare, seen in less than 5% of cases.
- Ring and Arc sign may be present – haemorrhagic (ring) and mineralised (arc) components, reflecting intra-tumoural blood flow.
CT
- Non-contrast: Soft-tissue density mass with bone destruction in aggressive forms.
- Contrast-enhanced: Homogeneous enhancement of the tumour.
MRI
- T1WI: Isointense to hypointense compared to muscle.
- T2WI: Hyperintense with areas of heterogeneity representing haemorrhage or necrosis.
- T1 C+: Demonstrates strong enhancement.
- DWI/ADC: Restricted diffusion can be seen indicating high cellularity.
US
- Usually hypoechoic with high internal reflectivity.
NM
- PET FDG: Show increased uptake.
Grading and Staging
The Intergroup Rhabdomyosarcoma Study (IRS) grouping system is used for staging.
Diagnosis
Diagnosis is made on the basis of clinical features, imaging findings and confirmed by histopathological analysis after biopsy.
Differential Diagnosis
- Orbital cellulitis: Typically presents in a patient with a recent history of sinusitis or upper respiratory tract infection. CT demonstrates inflammatory changes and possibly an abscess.
- Orbital pseudotumour: An idiopathic inflammatory condition commonly presents with pain, diplopia, and vision changes. MRI reveals a poorly defined mass with uniform enhancement.
- Neuroblastoma metastasis: Often presents in a child with a known primary neuroblastoma. Imaging shows a solid mass with calcifications.
Management
Management usually involves multi-modal therapy with surgery, chemotherapy, and radiotherapy. Consultation with an ophthalmologist, radiologist, and oncologist is essential. The next step in management is usually a tissue biopsy for histopathological analysis.