Epidemiology

The most common pediatric soft tissue sarcoma, rhabdomyosarcoma, accounts for approximately 3.5% of childhood cancers. These tumors may occur at virtually any anatomic site but are usually found in the head and neck (25%), orbit (9%), genitourinary tract (24%), and extremities (19%); retroperitoneal and other sites account for the remainder of primary sites. The incidence at each anatomic site is related to both patient age and tumor type. Extremity lesions are more likely to occur in older children and to have alveolar histology. Rhabdomyosarcoma occurs with increased frequency in patients with neurofibromatosis and has been associated with maternal breast cancer in the Li-Fraumeni syndrome, suggesting a genetic influence.

Pathogenesis

Rhabdomyosarcoma is thought to arise from the same embryonic mesenchyme as striated skeletal muscle. On the basis of light microscopic appearance, it belongs to the general category of small round cell tumors that includes Ewing sarcoma, neuroblastoma, and non-Hodgkin lymphoma. Definitive diagnosis of a pathologic specimen requires immunohistochemical studies using antibodies to skeletal muscle (desmin, muscle-specific actin, myogenin) and reverse transcription polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH) for PAX-FKHR (PAX-FOX01A) transcript in the case of alveolar tumors.

Determination of the specific histologic subtype is important in treatment planning and assessment of prognosis. There are four recognized histologic subtypes. The embryonal type accounts for about 60% of all cases and has an intermediate prognosis. The botryoid type, a variant of the embryonal form in which tumor cells and an edematous stroma project into a body cavity like a bunch of grapes, is found most often in the vagina, uterus, bladder, nasopharynx, and middle ear. The alveolar type accounts for about 25-40% of cases and often is characterized by 2;13 or 1;13 chromosomal translocations. The tumor cells tend to grow in nests that often have cleftlike spaces resembling alveoli. Alveolar tumors occur most often in the trunk and extremities and carry the poorest prognosis. The pleomorphic type (adult form) is rare in childhood, accounting for <1% of cases.

Clinical Manifestations

The most common presenting feature of rhabdomyosarcoma is a mass that may or may not be painful. Symptoms are caused by displacement or obstruction of normal structures (Table 494-1). Origin in the nasopharynx may be associated with nasal congestion, mouth breathing, epistaxis, and difficulty with swallowing and chewing. Regional extension into the cranium can produce cranial nerve paralysis, blindness, and signs of increased intracranial pressure with headache and vomiting. When the tumor develops in the face or cheek, there may be swelling, pain, trismus, and, as extension occurs, paralysis of cranial nerves. Tumors in the neck can produce progressive swelling with neurologic symptoms after regional extension. Orbital primary tumors are usually diagnosed early in their course because of associated proptosis, periorbital edema, ptosis, change in visual acuity, and local pain. When the tumor arises in the middle ear, the most common early signs are pain, hearing loss, chronic otorrhea, or a mass in the ear canal; extensions of tumor produce cranial nerve paralysis and signs of an intracranial mass on the involved side. An unremitting croupy cough and progressive stridor can accompany rhabdomyosarcoma of the larynx. Because most of these signs and symptoms also are associated with common childhood conditions, clinicians must be alert to the possibility of tumor.

Table 494-1 COMMON CLINICAL SYMPTOMS OF RHABDOMYOSARCOMA

From McDowell HP: Update on childhood rhabdomyosarcoma, Arch Dis Child 88:354–357, 2003.