Rhabdomyosarcoma: Causes, Symptoms, Treatment and Prognosis — Overview, Diagnosis & Treatment Options | MyMedicPlus

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents, accounting for approximately 3% of childhood cancers. It arises from primitive mesenchymal cells. Key subtypes: embryonal RMS (~60%, better prognosis), alveolar RMS (~20%, FOXO1 fusion, worse prognosis), and pleomorphic RMS (adults only).

Most cases are sporadic. Hereditary associations include Li-Fraumeni syndrome (TP53), neurofibromatosis type 1 (NF1), Beckwith-Wiedemann syndrome, Costello syndrome (HRAS), and DICER1 syndrome. Alveolar RMS is characterized by PAX3-FOXO1 or PAX7-FOXO1 gene fusions, conferring worse prognosis and treatment resistance.

Symptoms depend on primary site. Head/neck (most common): facial swelling, proptosis, nasal obstruction, cranial nerve palsies. Genitourinary: urinary obstruction, scrotal mass, hematuria, vaginal mass or bleeding. Extremity: painless enlarging soft tissue mass. Parameningeal tumors: headache, cranial nerve deficits, meningeal symptoms.

MRI of primary site is the imaging of choice. CT chest plus whole-body PET/CT or bone scan for staging. Bone marrow biopsy. Core needle biopsy with immunohistochemistry (desmin+, myogenin+, MyoD1+), FOXO1 FISH, and comprehensive molecular profiling. CSF cytology for parameningeal tumors. COG IRS grouping and TNM staging guide therapy intensity.

Multiagent chemotherapy with the VAC backbone (vincristine, actinomycin D, cyclophosphamide) is given for all risk groups. Local control: surgery (wide excision when feasible) and/or radiotherapy (IMRT or proton therapy) based on site and resectability. High-risk/metastatic protocols use intensified regimens (VDC/IE: vincristine-doxorubicin-cyclophosphamide alternating with ifosfamide-etoposide). Vinorelbine plus metronomic cyclophosphamide for maintenance in some protocols.

Low-risk embryonal RMS (localized, Group I/II): 5-year OS exceeds 90%. Intermediate-risk: approximately 65-80%. Metastatic alveolar RMS (highest risk): 5-year OS approximately 20-30%. FOXO1-fusion positive and metastatic presentations have the worst outcomes. New genomic-targeted therapies and immunotherapy approaches are in clinical trials.