Rhabdomyosarcoma (RMS)

BASICS

Definition: Malignant soft tissue tumor of presumed mesenchymal origin with striated muscle differentiation.
Subtypes (WHO):
Embryonal RMS (ERMS): 60% (classic, botryoid, spindle cell); common in head/neck and genitourinary tract of children; botryoid and spindle cell = better prognosis.
Alveolar RMS (ARMS): 20%; aggressive, often trunk/extremities.
Spindle/Sclerosing RMS: ~10%; mainly paratesticular.
Anaplastic/Pleomorphic: <10%; adults, associated with Li-Fraumeni, poor prognosis.
Common Primary Sites: Head/neck (25%), genitourinary (31%), extremities/musculoskeletal (13%).

Most common soft tissue sarcoma in children.
Incidence: 4.5/million children/year; 50% of cases <10 years (often <6).
Prevalence: 3% of pediatric, 1% of adult tumors. Slight male > female (1.3:1). More common in African-American population.
Metastasis: Bone marrow, lung, lymph nodes.

Origin: Rhabdomyoblast cell.
Tumor: >5 cm, poorly circumscribed, white, infiltrative.
Genetics:
Alveolar: FOXO1 fusions (PAX7-FOXO1, PAX3-FOXO1).
Embryonal: Complex genetic aberrations, e.g., MYOD1, IGF-2, H19, 11p15.5.
Spindle/Sclerosing: SRF-NCOA2, TEAD1-NCOA2.
Risk Factors: Largely unknown, but increased with in utero growth/radiation, low socioeconomic status, maternal recreational drug use.
Syndromic Associations: Beckwith-Wiedemann, Costello, Li-Fraumeni, NF1, Noonan.

Symptoms vary by site: progressive/palpable mass, diplopia, sinusitis, nasal discharge (head/neck), urinary symptoms (GU), vaginal bleeding (botryoid), exophthalmos, mass effect symptoms.

Painless enlarging mass (head/neck); can be painful (extremities, with erythema).
Polypoid vaginal mass (botryoid), exophthalmos/chemosis (orbit), abdominal mass, or neurological symptoms if compressing structures.

Osteosarcoma, Ewing sarcoma, liposarcoma, Wilms tumor, lymphoproliferative disorders, NF1, lipoma.

Labs: CBC, chemistry, LFTs, coagulation profile.
Imaging: MRI (or CT) of primary, CT chest/abdomen/pelvis, bone scan.
Staging: Lymph node biopsy, bone marrow aspirate/biopsy.
Biopsy: Core/incisional/excisional (for definitive diagnosis).
Histology:
Embryonal: Myxoid matrix.
Alveolar: Rhabdomyoblasts in alveolar-like spaces.
Botryoid: “Grape-like,” cambium layer.
Spindle: Spindle-shaped cells.
Anaplastic: Hyperchromatic, bizarre nuclei.
Immunohistochemistry: Positive for desmin, sarcomeric actin, myogenin, myoglobin; negative for CD99, CK, S100.
Molecular testing: PAX/FOXO1 fusion (PCR, FISH).
Staging: Site, size, lymph node involvement, metastasis (see TNM).

Multimodal: Surgery, radiation, chemotherapy; managed by interdisciplinary team.
Surgery: Local resection ± lymph node sampling (to guide adjuvant therapy).
Radiation: Enhances local control, especially high-risk/higher stage tumors.
Chemotherapy: Based on risk stratification:
“VAC” (vincristine, actinomycin D, cyclophosphamide)
“IVA” (ifosfamide, vincristine, actinomycin D)
Other agents: topotecan, doxorubicin, etoposide, irinotecan
Adverse effects: vincristine—neuropathy; dactinomycin—myelosuppression/hepatotoxicity; cyclophosphamide—hemorrhagic cystitis (use mesna), infertility, leukopenia
Duration: 12–24 months, up to 15 cycles.
Emergent therapy: Considered for compression symptoms.

Surveillance: Physical and imaging every 3 months (year 1), every 4 months (years 2–3), every 6 months (years 4–5).
After 5 years: No further imaging unless symptoms develop.

RMS is the most common pediatric soft tissue sarcoma; more aggressive in adults.
Syndromic/genetic disorders (e.g., Li-Fraumeni, Beckwith-Wiedemann, NF1) increase risk.
Most common metastasis: lung > bone marrow/bone > peritoneum.
Lymph node involvement warrants aggressive therapy.