> Table of Contents > Rhabdomyosarcoma
Rhabdomyosarcoma
Olusola Fasusi, MD
E. James Kruse, DO
image BASICS
DESCRIPTION
  • Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children <20 years of age. (It is exceedingly rare in adults, representing 3% of all soft tissue sarcomas.)
    • 50% occur in the 1st decade of life.
  • Overall, it is an uncommon malignancy that arises from myoblasts.
  • Common anatomic sites
    • Head and neck (most common primary site in children)
    • Genitourinary
    • Musculoskeletal (Extremities are the most common primary sites in adults.)
  • Subtypes
    • Alveolar (ARMS): 23% of cases
      • More common in the trunk and extremities; clinically more aggressive
    • Embryonal (ERMS): early onset; 57% of cases (most common subtype in children)
      • More likely to occur in the head, neck, and genitourinary areas
        • Classic: comprises 50% of cases
        • Botryoid: Sarcoma botryoids is typically seen in girls <4 years of age, 6% of cases.
        • Spindle cell: 3% of cases pleomorphic: usually occurs in adults, 1% of cases
  • Sarcoma (not otherwise specified): comprises 11% of all cases of RMS (most common subtype in adults, reflects inability for pathologists to characterize tumor)
  • Undifferentiated: comprises 8% of all cases of RMS
  • Associated term(s): soft tissue sarcoma

Stage

Site

T

Tumor diameter

N

M

1

Orbit; head and neck (excluding parameningeal); genitourinary—nonbladder and nonprostate; biliary tract

T1 or T2

a or b

N0 or N1 or NX

M0

2

Bladder or prostate; extremity; cranial parameningeal; other (includes trunk, retroperitoneum, etc.)

T1 or T2

a

N0 or NX

M0

3

Bladder or prostate; extremity; cranial parameningeal; other (includes trunk, retroperitoneum, etc.)

T1 or T2

a

N1

M0

0 or N1 or NX

M0

4

All sites

T1 or T2

a or b

N0 or N1

M1

Note: a, ≤5 cm in diameter; b, >5 cm in diameter; T1, confined to site of origin; T2, extension and/or fixation to surrounding tissue; N0, regional nodes not clinically involved; N1, regional nodes clinically involved by neoplasm; Nx, clinical status of regional nodes unknown; M0, no distant metastasis present; M1, metastasis present.

EPIDEMIOLOGY
Incidence
  • 4.5 cases of RMS per 1 million patients <20 years old per year − 50% occur within 1st decade of life.
  • In adults, RMS represents 3% of all soft tissue sarcomas in adults.
Prevalence
  • RMS comprises 3% of all childhood cancers.
  • Predominant sex: male > female (1.37:1)
Genetics
  • Alveolar: PAX3-FOXO1 or PAX7-FOXO1 fusion genes as a result of t(2;13) and t(1;13), respectively; found in 75% of ARMS
  • Embryonal: Loss of alleles on chromosome 11 may be seen.
RISK FACTORS
Smoking, advanced maternal age, in utero x-ray exposure, maternal recreational drug use, and history of stillbirths
COMMONLY ASSOCIATED CONDITIONS
  • Neurofibromatosis (NF1) 1: 20-fold increased risk of RMS in patients with NF1
  • Li-Fraumeni syndrome: p53 mutations predispose to multiple tumors, including RMS.
image DIAGNOSIS
PHYSICAL EXAM
  • Painless, enlarging mass
  • Polypoid mass protruding from vagina (botryoid)
  • Exophthalmos and chemosis (orbital involvement)
  • Abdominal pain
  • Compression symptoms (i.e., seizures, visual field defects, nerve palsy, headaches)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Ultrasound: used for differentiation of cystic versus solid mass
  • MRI/CT: used to evaluate tumor
  • Staging tests: chest x-ray, CT thorax, fluorodeoxyglucose (FDG)-PET
    • Most common site of metastasis is lung; evaluated by CT
    • FDG-PET scans may be useful to detect lymph node or distant metastases; not readily evident on CT or MRI scans
Diagnostic Procedures/Other
  • Core needle biopsy, incisional biopsy, or excisional biopsy (based on size of mass)
    • The presence of rhabdomyoblast indicates the diagnosis.
  • Immunohistochemical markers
    • Myogenin: commonly expressed in ARMS
    • Desmin: associated with multiple subtypes of RMS
  • Pathology
    • Alveolar: rhabdomyoblasts arranged in what grossly appears to mimic pulmonary alveoli
    • Embryonal
    • Classic: rhabdomyoblasts configured in sheets without alveolar pattern
    • Botryoid: “grape-like” appearance of rhabdomyoblasts with notable clustering in the subepithelium forming the cambium layer
    • Spindle cell: rhabdomyoblasts with a spindle-like appearance
  • Undifferentiated: rhabdomyoblast arrangement that cannot be classified as any other subtype
  • Staging
    • Based on site, size, regional nodal involvement, and distance spread
    • See table.
P.923

image TREATMENT
The three tenets of treatment for adults and children are composed of surgical resection, radiation therapy, and chemotherapy. Patients should be referred to a multidisciplinary treatment team with expertise in oncology for definitive treatment.
SURGERY/OTHER PROCEDURES
  • Wide local resection of tumor. If possible, resect metastasis as well.
  • However, wide resection may not be feasible in cases where grossly impaired functionality results.
    • All children receive chemotherapy (1)[B].
    • In North America, the three-drug combination of vincristine, dactinomycin, and cyclophosphamide (VAC) is the standard regimen:
      • Vincristine
        • Adverse reactions: alopecia, constipation, peripheral neuropathy
      • Actinomycin-D
        • Adverse reactions: pancytopenia, hepatotoxicity
      • Cyclophosphamide
        • Adverse reactions: hemorrhagic cystitis (mesna for prophylaxis), sterility, transitional cell carcinoma
  • In addition, ifosfamide, topotecan, doxorubicin, etoposide, and irinotecan may also be used.
  • Duration of chemotherapy depends on risk stratification and ranges from 6 to 12 months.
  • Chemotherapy has been less commonly used in adults, who generally undergo treatment with resection and radiation therapy.
  • Radiotherapy is currently used for those whose tumor cannot be completely resected.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patients should follow up with their multidisciplinary treatment team. Long-term follow-up is necessary for detection of recurrence, metastatic disease, and development of secondary malignancies. Follow-up is composed of physical exam, chest x-ray, and imaging of the primary tumor site every 3 to 6 months for the first 3 years.
PROGNOSIS
  • RMS (all cases): 62% 5-year survival
  • ARMS: 48% 5-year survival
  • ERMS: 73% 5-year survival
  • Prognosis in adults is worse; it is unclear whether this is related to subtype of tumor or lack of clear guidelines for adults; this is a rare presentation in adults.
REFERENCES
1. Ray A, Huh WW. Current state-of-the-art systemic therapy for pediatric soft tissue sarcomas. Curr Oncol Rep. 2012;14(4):311-319.
Additional Reading
&NA;
  • Arndt CA, Rose PS, Folpe AL, et al. Common musculoskeletal tumors of childhood and adolescence. Mayo Clin Proc. 2012;87(5):475-487.
  • Hawkins DS, Spunt SL, Skapek SX. Children’s Oncology Group’s 2013 blueprint for research: soft tissue sarcomas. Pediatr Blood Cancer. 2013;60(6): 1001-1008.
  • Kapoor G, Das K. Soft tissue sarcomas in children. Indian J Pediatr. 2012;79(7):936-942.
  • Klem ML, Grewal RK, Wexler LH, et al. PET for staging in rhabdomyosarcoma: an evaluation of PET as an adjunct to current staging tools. J Pediatr Hematol Oncol. 2007;29(1):9-14.
  • Malempati S, Hawkins DS. Rhabdomyosarcoma: review of the Children’s Oncology Group (COG) Soft-Tissue Sarcoma Committee experience and rationale for current COG studies. Pediatr Blood Cancer. 2012;59(1):5-10.
  • Ognjanovic S, Linabery AM, Charbonneau B, et al. Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005. Cancer. 2009;115(18):4218-4226.
  • Parham DM, Ellison DA. Rhabdomyosarcomas in adults and children: an update. Arch Pathol Lab Med. 2006;130(10):1454-1465.
  • Sultan I, Qaddoumi I, Yaser S, et al. Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol. 2009;27(20):3391-3397.
Codes
&NA;
ICD10
  • C49.9 Malignant neoplasm of connective and soft tissue, unsp
  • C49.0 Malignant neoplasm of connective and soft tissue of head, face and neck
  • C49.5 Malignant neoplasm of connective and soft tissue of pelvis
Clinical Pearls
&NA;
  • RMS is the most common soft tissue sarcoma in children.
  • They can arise at any site and in any tissue except bone.
  • All persistent soft tissue masses should be evaluated with imaging (ultrasound to rule out cystic vs. solid, then MRI/CT).
  • Fine-needle aspiration may be helpful but core needle versus incisional/excisional biopsy for confirmation.