Rhabdomyosarcomas

ALSO KNOWN AS: Embryonal rhabdomyosarcomas, alveolar rhabdomyosarcomas, botryoid rhabdomyosarcomas, soft-tissue sarcomas

RELATED CONDITIONS: Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, Costello syndrome

DEFINITION: Rhabdomyosarcomas are soft-tissue, malignant tumors that develop from cells called rhabdomyoblasts. These cells normally develop into skeletal, cardiac, and smooth muscles. This cancer develops from embryonal cells and is more common in children than in adults.

Risk factors: There are no known environmental factors that increase the risk of rhabdomyosarcoma. Some evidence suggests that an increased risk of rhabdomyosarcoma occurs with certain related, inherited conditions. These syndromes are rare, but children may inherit an increased risk of the tumor when these diseases are present. There is no evidence that lifestyle-related risk factors, including the use of drugs or X-rays during pregnancy, impact rhabdomyosarcoma.

Etiology and the disease process: There is no known cause for most cases of rhabdomyosarcoma, but it is assumed that there is a genetic component. With embryonal rhabdomyosarcomas, research has demonstrated that a small piece of deoxyribonucleic acid (DNA) on chromosome 11 may be missing. Further, researchers believe that chromosomal translocations, in which two chromosomes exchange small pieces of each other, may play a role. 

Incidence: The annual incidence of rhabdomyosarcoma is about 350 to 500 new cases, or 4.58 cases per one million, in patients under the age of twenty. These cases represent between 3 and 5 percent of all malignancies in children. Boys are slightly more likely to develop rhabdomyosarcoma.

Symptoms: The symptoms of rhabdomyosarcoma depend on the initial site of the tumor. Tumors on the trunk, groin, arms, or legs may be first noticed as swelling that causes little or no pain. Tumors that grow inside the abdomen or pelvis may cause nausea, vomiting, difficulties with bowel and bladder function, such as constipation or frequent urination, and pain. These symptoms are caused by pressure on internal organs. Masses that grow in the bladder or vagina may cause bleeding. Tumors in the ear or the sinuses have symptoms similar to ear infections or sinus infections and cause pain in the area affected. A rhabdomyosarcoma of the eye, or orbital area, may cause the eye to bulge, or the child may appear cross-eyed.

If the tumor goes undetected for a period of time, the child may develop symptoms of fatigue, cough, weight loss, enlarged lymph nodes, and generalized muscle weakness. This may indicate that the rhabdomyosarcoma has already metastasized (spread) to other parts of the body.

Screening, diagnosis, and staging: There is no screening test for rhabdomyosarcoma. If a family has a history of cancer, particularly childhood cancer, it is important to tell the pediatrician at the first visit. Parents should note of any unusual lumps, swellings, or blood in the stool or urine, as many tumors are picked up by parents bathing the child or changing a diaper. Children should be taken to the doctor if they complain of persistent pain in any area or if a bump or swelling does not go away.

Diagnosis begins with imaging (X-ray) studies, as tumors may be hidden or hard to see. Tests may include ordinary X-rays, computed tomography (CT) scans, a magnetic resonance imaging (MRI) scan, a bone scan, and a positron emission tomography (PET) scan. These scans can detect the location of the tumor, reveal any spread to other areas, and, in the case of the PET scan, determine whether the tumor may be cancer. A biopsy, the removal of a small piece of the tumor for review under the microscope by a pathologist, usually follows imaging studies. A bone marrow biopsy is done once the diagnosis of rhabdomyosarcoma is made to determine if the tumor has spread.

Staging rhabdomyosarcoma is important to determine the treatment needed to best effect cure. Generally, staging begins with the pathology review and initial biopsy or surgery. Staging is done in two ways: clinical groups I-IV and TNM (tumor/lymph node/metastasis) stages I-IV. Clinical group staging is based on how much of the tumor is removed during the initial surgery and knowledge of the extent of the disease. The TNM stage is determined by the size and type of the tumor (T), spread to lymph nodes (N) and distant organs, and metastases (M). Once the clinical group and TNM stage are determined, patients are categorized as low, intermediate, or high risk.

Treatment and therapy: Surgery is the initial treatment to remove as much of the rhabdomyosarcoma as possible. If surgery may be disfiguring or damaging, only partial tumor removal is possible. Chemotherapy is used to kill any cells remaining after surgery or to attack cells that may have spread elsewhere in the body. Radiation therapy may be used, especially if part of the tumor has been left behind after surgery or the tumor has metastasized. A team will make the best treatment decisions for the child based on staging, location of the tumor, and other factors.

Prognosis, prevention, and outcomes: The prognosis for rhabdomyosarcoma depends on the stage at diagnosis, the site and the size of the tumor, the success of surgical removal, and whether the tumor has spread. Patients who are low-risk have a between 70 and 90 percent five-year survival rate. Intermediate-risk patients have a 50 to 70 percent five-year survival rate, and high-risk patients have a 20 to 30 percent five-year survival rate. However, advances in treating rhabdomyosarcomas, including combining treatments into a multimodal treatment plan and novel therapies, such as ganitumab, trametinib, and KDM4-blocking drugs, have increased survival rates in the twenty-first century. Depending on the site of surgery, there may be residual damage to the patient, such as loss of an eye or other body part or organ. There is no way to prevent rhabdomyosarcoma.

Bibliography

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