Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a highly aggressive malignancy arising from mesenchymal cells that fail to differentiate into skeletal muscle myocytes. The tumour cells, known as rhabdomyoblasts, can be classified into four subtypes: embryonal, alveolar, pleomorphic, and spindle-cell/sclerosing. Embryonal and alveolar types are the most prevalent, particularly among children and adolescents, while pleomorphic RMS is more common in adults.

Non-contrast CT scan of head showing a large mass without any intracranial extension. The diagnosis was post-auricular congenital alveolar rhabdomyosarcoma.

Types

Embryonal

Embryonal rhabdomyosarcoma (ERMS) is the most frequent subtype, comprising 60–70% of childhood cases, typically affecting children under four years old. ERMS cells are spindle-shaped and resemble developing muscle cells of a 6- to 8-week-old embryo, often presenting in the head, neck, and genitourinary tract.

Embryonal Subtype

Botryoid rhabdomyosarcoma, a variant of ERMS, is commonly found in mucosal-lined organs such as the vagina, bladder, and nasopharynx. It often appears as a grape-like mass in infants and has a favourable prognosis.

Alveolar

Alveolar rhabdomyosarcoma (ARMS) is the second most common type, accounting for 20–25% of RMS cases. It affects all age groups and is characterised by densely packed cells arranged around spaces resembling pulmonary alveoli. ARMS predominantly occurs in the extremities, trunk, and peritoneum and is more aggressive than ERMS.

Pleomorphic

Pleomorphic rhabdomyosarcoma, also known as anaplastic rhabdomyosarcoma, is characterised by pleomorphic cells with large, hyperchromatic nuclei. This subtype exhibits high heterogeneity and poor differentiation, typically occurring in adults and presenting in the extremities.

Spindle-cell/sclerosing

Spindle-cell/sclerosing rhabdomyosarcoma is similar to leiomyosarcoma and is noted for its fascicular, spindled growth pattern with rhabdomyoblastic differentiation. Most commonly found in the paratesticular region, it has an excellent prognosis with a five-year survival rate of 95%.

Photomicrograph showing nodules of tumour cells separated by hyalinised fibrous septae (50×, HE stain). Inset: Discohesive large tumour cells with hyperchromatic nucleus and scant cytoplasm (200×, HE stain). The diagnosis was postauricular congenital alveolar rhabdomyosarcoma.

Signs and Symptoms

RMS can develop in any soft-tissue site, but common primary locations include the genitourinary tract, extremities, head, neck, and orbit. Symptoms vary based on the tumour site. For instance, genitourinary tumours may present with hematuria or urinary tract obstruction, while orbital tumours may cause swelling and proptosis. Extremity tumours generally manifest as a rapidly enlarging, firm mass.

Risk Factors

The exact risk factors for RMS are unclear, but certain inherited disorders like Li-Fraumeni syndrome, Neurofibromatosis type 1, and Beckwith-Wiedemann syndrome increase the likelihood of developing this cancer.

Genetic Factors

RMS subtypes can be distinguished by specific genetic markers. Alveolar RMS (ARMS) often involves translocations t(2;13)(q35, q14) or t(1;13)(p36, q15), resulting in fusion products like PAX3-FOXO1, which drive oncogene expression. Embryonal RMS typically presents with a loss of heterozygosity in chromosome 11 (p11,15.5), potentially implicating tumour suppressor genes.

Diagnosis

Diagnosing RMS involves histopathological analysis and immunohistochemical staining for muscle-specific proteins such as myogenin and desmin. Electron microscopy may reveal actin and myosin or Z bands, aiding diagnosis. Further classification into subtypes is achieved through cellular morphology and genetic sequencing.

Staging

Imaging techniques like MRI, ultrasound, and bone scans help determine local invasion and metastasis. The staging system for RMS uses a modified TNM system, considering tumour size, lymph node involvement, site, and metastasis presence.

Treatment

RMS treatment is multidisciplinary, involving surgery, chemotherapy, and radiation. Surgery aims for tumour resection, though complete removal is often challenging. Chemotherapy, typically using VAC (vincristine, actinomycin D, cyclophosphamide) or IVA (ifosfamide, vincristine, actinomycin D) regimens, is indicated for all patients. Radiation therapy is very important, especially for tumours in sensitive areas or those not fully resectable. Immunotherapy is a developing treatment modality, focusing on harnessing the patient's immune system to target cancer cells.

Prognostic Factors

Prognosis depends on factors like age, tumour site, resectability, size, lymph node involvement, and metastasis. Survival after recurrence is poor, highlighting the need for new salvage therapies.

Epidemiology

RMS is the most common soft-tissue sarcoma in children, with an incidence of approximately 4.5 cases per million children/adolescents. It occurs more frequently in males and slightly less in black and Asian children. RMS often arises sporadically, though familial cancer syndromes and congenital abnormalities are associated with increased risk.

History

Rhabdomyosarcoma was first described by Weber in 1845 and formally classified by Arthur Stout in 1946. The Intergroup Rhabdomyosarcoma Study Group (IRSG) has significantly contributed to the understanding and treatment of RMS.

Research

Research focuses on identifying cancer stem cells and looking at new treatments like epigenetic therapy and deacetylase inhibitors, showing promise for improving outcomes in aggressive RMS subtypes.

Self-assessment MCQs (single best answer)

Which subtype of rhabdomyosarcoma is most common in children under four years old?

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Botryoid rhabdomyosarcoma is a variant of which RMS subtype?

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Which genetic translocation is often associated with Alveolar rhabdomyosarcoma (ARMS)?

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What is the primary method used for diagnosing rhabdomyosarcoma?

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Which RMS subtype is characterised by pleomorphic cells with large, hyperchromatic nuclei?

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Which of the following is a common symptom of genitourinary rhabdomyosarcoma?

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What is the five-year survival rate for spindle-cell/sclerosing rhabdomyosarcoma?

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Which of the following is NOT a common primary location for rhabdomyosarcoma?

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Which treatment modality is essential for tumours in sensitive areas or those not fully resectable?

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Who first described rhabdomyosarcoma and in what year?

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