Rhabdomyosarcoma

ANATOMY

Rhabdomyosarcoma is a highly malignant soft tissue sarcoma that arises from unsegmented, undifferentiated mesoderm, or myotome-derived skeletal muscle.
It may occur in any site in the body The most frequently involved sites are the orbit (9%); head and neck (excluding parameningeal tumors) (7%); parameningeal (25%); genitourinary (31%); extremity (13%); trunk (5%); retroperitoneum (7%); and other miscellaneous sites (3%) (2, 4).

NATURAL HISTORY AND PATTERNS OF SPREAD

Rhabdomyosarcoma is heterogeneous and arises in multiple sites (3).
Tumors of the head and neck area occur throughout childhood and are commonly embryonal.
Tumors arising in the trunk and extremity occur in adolescents and are usually alveolar or undifferentiated.
Tumors arising in the urinary bladder and vagina occur primarily in infants and often are embryonal or botryoid. This locally invasive tumor spreads along fascial or muscle planes and by lymphatic extension, and may have hematogenous dissemination.
Lymph node metastases are rare in orbital tumors but occur in approximately 15% of tumors at other head and neck sites (most commonly the nasopharynx), 25% of paratesticular tumors, and 20% of extremity and truncal tumors (2).
Hematogenous metastases are detected at the time of presentation in approximately 15% of patients. The most common sites of hematogenous dissemination are lungs, bone marrow, and bone (2).

PROGNOSTIC FACTORS

• Poor prognostic factors include age less than 1 and more than 10 years, alveolar histology, unfavorable primary site, size greater than 5 cm, and higher clinical group (22).

CLINICAL PRESENTATION

Rhabdomyosarcoma usually presents as an asymptomatic mass. When symptoms are present, they relate to mass effect on associated organs.
Tumors of the orbit may cause proptosis and ophthalmoplegia.
Parameningeal tumors often present with cranial nerve palsy; headache; and nasal, aural, or sinus obstruction.
Genitourinary tumors may cause hematuria, urinary obstruction, or constipation (7).

DIAGNOSTIC WORKUP

The extent of the primary tumor is best determined with a multidisciplinary, expeditious workup by a radiation oncologist, pediatric oncologist, and appropriate subspecialty surgeon.
Recommended baseline evaluations are shown in Table 48-1 (7).

STAGING

• The clinical grouping classification used extensively by the Intergroup Rhabdomyosarcoma Study (IRS) is somewhat of a misnomer because it actually requires surgical-pathologic evaluation (Table 48-2).

TABLE 48-1 Recommended Workup for Tumors at Various Sites

All Patients		Optional
All sites
History
Physical examination by several observers		Examination under anesthesia for infants and youngsters
Laboratory studies
	Complete blood cell count
	Liver function tests
	Renal function tests
	Urinalysis
Imaging studies		Plain films of bones abnormal on scan
	Chest x-ray	Abdomen-pelvis CT, MRI, or ultrasound
	Thoracic CT scan
	Bone scan
	MRI or CT of primary tumor
Bone marrow biopsy and aspirate
Head and neck
	MRI or CT of primary tumor (with contrast)	Plain films of area
		Dental films
		Paranasal sinus and skull films
	Lumbar puncture with cytologic examination of fluid in parameningeal primary tumors	MRI of spine if cerebrospinal fluid is positive or patient is symptomatic
Genitourinary
	CT or MRI of abdomen-pelvis (with contrast)	Ultrasound of pelvis
	Pelvic examination under anesthesia	Cystoscopy
Extremity and truncal lesions
	MRI or CT of primary lesion (with contrast)	Plain films of primary site
		Ultrasound
		Barium gastrointestinal contrast studies
Source: From Breneman JC, Donaldson, SS. Rhabdomyosarcoma. In: Halperin EC, Perez CA, Brady LW, eds. Principles and practice of radiation oncology, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2008:1872-1885, with permission.

TABLE 48-2 IRS Clinical Grouping Classification

Group		Localized disease, completely resected
	A	Confined to organ or muscle of origin
	B	Infiltration outside organ or muscle of origin; regional nodes not involved
Group II		Compromised or regional resection
	A	Grossly resected tumor with microscopic residual disease
	B	Regional disease, completely resected, in which nodes may be involved or extension of tumor into adjacent organ may exist
	C	Regional disease with involved nodes, grossly resected, but with evidence of microscopic residual disease
Group III		Incomplete resection or biopsy with gross residual disease
Group IV		Distant metastases at diagnosis
Source: Adapted from Mauer HM. The Intergroup Rhabdomyosarcoma Study: objectives and clinical staging classification J Pediatr Surg 1975;10:977.

Pretreatment staging uses a tumor-node-metastasis system, which emphasizes characteristics of the primary tumor, size and invasiveness, nodal status, and systemic spread.
In the IRS-IV study, disease is designated as stage I if the tumor is without hematogenous metastases and is in a favorable site, such as orbit, genitourinary non-bladder-prostate (paratesticular, vagina, vulva, uterus), or head and neck nonparameningeal.
Stage II tumors are in an unfavorable primary site such as bladder-prostate, extremity, parameningeal, and other sites and are smaller than 5 cm with negative regional lymph nodes.
Stage III tumors are in an unfavorable primary site, are larger than 5 cm and node negative, or are in any unfavorable site and node positive.

PATHOLOGIC CLASSIFICATION

The classic classification of rhabdomyosarcoma, used by the IRS investigators, consists of four histologic subtypes: embryonal, botryoid subtype of embryonal, alveolar, and pleomorphic.
More recently, investigators have observed a subset of patients with a “solid” alveolar pattern, considered a subtype of alveolar rhabdomyosarcoma (31).
A lack of agreement among pediatric pathologists has led to the new International Classification of Rhabdomyosarcoma, based on a review of IRS-II data, which divides subgroups into distinct prognostic groups (Table 48-3).
The botryoid subtype, a polypoid variant of embryonal rhabdomyosarcoma, has a grapelike appearance; it is usually noninvasive and localized, and presents in mucosal-lined organs such as the vagina, urinary bladder, middle ear, biliary tree, and nasopharynx.
The spindle cell subtype of embryonal rhabdomyosarcoma has a spindled appearance and is frequently found in paratesticular sites.
Patients with embryonal rhabdomyosarcoma have intermediate outcome; the mesenchymal cells tend to differentiate into cross-striated muscle cells. Immunohistochemistry may demonstrate actin- or desmin-positive reactions. Ultrastructural studies exhibit evidence of myogenesis. The presence of cross-striations confirms the diagnosis.
Embryonal histology occurs in 60% of cases and is found most commonly in the orbit, head and neck, and genitourinary sites.

TABLE 48-3 International Classification of Rhabdomyosarcoma

I	Superior prognosis
		Botryoid rhabdomyosarcoma
		Spindle cell rhabdomyosarcoma
II	Intermediate prognosis
		Embryonal rhabdomyosarcoma
III	Poor prognosis
		Alveolar rhabdomyosarcoma
		Undifferentiated sarcoma
		Anaplastic rhabdomyosarcoma
IV	Subtypes whose prognosis is not presently evaluable
		Rhabdomyosarcoma with rhabdoid features
Source: From Breneman JC, Donaldson, SS. Rhabdomyosarcoma. In: Halperin EC, Perez CA, Brady LW, eds. Principles and practice of radiation oncology, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2008:1872-1885, with permission.

The poor-prognosis group includes alveolar and undifferentiated sarcomas.
Approximately 20% of rhabdomyosarcomas are the alveolar subtype, most commonly found in adolescents with truncal, retroperitoneal, and extremity tumors. The projected outcome for this group is 54% at 5 years (24).
The pleomorphic type is extremely rare; many cases formerly classified as pleomorphic are currently considered to be malignant fibrous histiocytoma.
Cases previously classified as extraosseous Ewing’s sarcoma are now more appropriately included in the Ewing’s family of tumors and are managed as such.

GENERAL MANAGEMENT

A multidisciplinary approach using surgery, irradiation, and chemotherapy is critical in the management of rhabdomyosarcoma; the optimal sequence and specific application of each modality are under investigation.
In general, stage I tumors resected with an adequate margin require chemotherapy but not adjuvant irradiation (34). Patients with more advanced stages benefit from irradiation and multiagent chemotherapy.

Orbit