Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is a cancerous tumor that originates in the soft tissues of the body, including the muscles, tendons, and connective tissues. The most common sites for this tumor to be found include the head, neck, bladder, vagina, arms, legs, and trunk. Rhabdomyosarcoma can also be found in places where skeletal muscles are absent or very small, such as in the prostate, middle ear, and bile duct system. The cancer cells associated with this disease can spread (metastasize) to other areas of the body.

Embryonal rhabdomyosarcoma, the most common type, usually occurs in children under 6 years of age. Alveolar rhabdomyosarcoma occurs in older children and is less common.

Rhabdomyosarcoma accounts for about 3 percent of childhood cancers. In the U.S., about 350 children are diagnosed with rhabdomyosarcoma each year. This disease mostly affects children under the age of 10, but can occur at any age. For unknown reasons, males are affected slightly more often than females.

What causes rhabdomyosarcoma?

It is believed that some rhabdomyosarcoma tumors begin developing in the fetus. Rhabdomyoblasts are the cells that will mature and develop into muscles. There has been much research into the gene structure of these rhabdomyoblasts and possible detection of a gene error that can produce the disease later in development.

Rhabdomyosarcomas usually have some type of chromosome abnormality in the cells of the tumor, which are responsible for the tumor formation.  In children with an embryonal rhabdomyosarcoma (ERMS), there are usually extra chromosome copies, known as hyperdiploidy, which can be seen with other pediatric cancers. For alveolar rhabdomyosarcoma (ARMS), a rearrangement in the chromosome material between chromosomes 1 or 2 and chromosome 13 is usually present. This rearrangement changes the position and function of genes, causing a fusion of genes referred to as a fusion transcript. Patients have an abnormal fusion transcript involving two genes known as PAX7 or PAX3 and FKHR. This important discovery has led to improvements in diagnosing rhabdomyosarcoma.

Rhabdomyosarcomas are also more common in children with neurofibromatosis or Li-Fraumeni syndrome, which are genetic disorders. Li-Fraumeni syndrome is a clustering of soft tissue and other cancers in a family caused by mutations in a tumor suppressor gene called p53, which results in uncontrolled cell growth.

There has been no association between rhabdomyosarcoma and environmental exposures.

What are the symptoms of rhabdomyosarcoma?

The following are the most common symptoms of rhabdomyosarcoma. However, each child may experience symptoms differently. Many symptoms depend on the size and the location of the tumor. Symptoms may not be present until the tumor is very large, especially if it is located deep in the muscle or in the stomach. Symptoms may include:

• A tumor or mass that can be seen or felt (may or may not be painful)
• Bleeding from the nose, vagina, rectum, or throat (may occur if the location of the tumor is in these areas)
• Tingling, numbness, pain, and movement may be affected if the tumor compresses nerves in the area
• Protrusion of the eye or a drooping eyelid (may indicate a tumor behind the eye)

The symptoms of rhabdomyosarcoma may resemble other conditions or medical problems. Always consult your child's doctor for a diagnosis.

How is rhabdomyosarcoma diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for rhabdomyosarcoma may include:

• Biopsy of the tumor. When a sample of tissue is removed from the tumor and examined under a microscope. This can be done during surgery or by using a needle to get to the area that may be cancer. The type of biopsy done depends on where the mass is located, the age of the child, and the expertise and experience of the doctor doing the biopsy. A biopsy is the only way to know for sure if the tumor is cancer.
• Blood and urine tests
• Multiple imaging studies:
  • Computed tomography scan (also called a CT or CAT scan). A diagnostic imaging procedure that uses a combination of X-rays and computer technology to produce horizontal, or axial, images (often called slices) of the body. A CT scan shows detailed images of any part of the body, including the bones, muscles, fat, and organs. CT scans are more detailed than general X-rays.
  • Magnetic resonance imaging (MRI). A diagnostic procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.
  • X-ray. A diagnostic test that uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film.
  • Ultrasound (also called sonography). A diagnostic imaging technique that uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs as they function, and to assess blood flow through various vessels.
  • Positron emission tomography (PET) scan. Radioactive-labeled glucose (sugar) is injected into the bloodstream. Tissues, such as tumors that use the labeled glucose more than normal tissues can be detected by a scanning machine. PET scans can be used to find small tumors or to check if treatment for a known tumor is working.
  • Bone scans. Pictures or X-rays taken of the bone after a dye has been injected that is absorbed by bone tissue. These are used to detect tumors and bone abnormalities.
• Bone marrow aspiration and/or biopsy. A procedure that involves taking a small amount of bone marrow fluid (aspiration) and/or solid bone marrow tissue (called a core biopsy), usually from the hip bones, to be examined for the number, size, and maturity of blood cells and/or abnormal cells.
• Lumbar puncture (also called spinal tap). A special needle is placed between the bones of the lower back, into the spinal canal. This is the area around the spinal cord. The pressure in the spinal canal and brain can then be measured. A small amount of cerebral spinal fluid (CSF) can be removed and sent for testing to determine if there is an infection or other problems. CSF is the fluid that bathes your child's brain and spinal cord.  This procedure may be needed if child presents with tumor in the head.

Unlike most other cancers, comprehensive staging for children diagnosed with rhabdomyosarcoma is more complicated as it takes into account the extent of the disease (TNM stage) and its clinical features (clinical group), which are important in determining treatment options. 

TNM Stage

Tumor staging is the process of finding out whether cancer has spread, and, if so, how far. There are various staging systems that are used for rhabdomyosarcoma. Always consult your child's doctor for more information on staging. One method of staging is the TNM staging system. This system uses tumor (T), nodes (N), and metastases (M) to differentiate the disease by stages. This system evaluates the disease before surgery and classifies it by one of the four following stages:

• Stage I. Tumors involving the area near the eye, the head, neck, genitourinary tract (except the prostate and bladder), or biliary tract. The tumor is localized, meaning the tumor has not spread to distant areas of the body.
• Stage II. Small, localized tumors less than 5 cm in any site not in stage I. There are no tumor cells in the surrounding lymph nodes and it has not spread to distant sites.
• Stage III. Localized tumor at any site not included in stage I that is smaller than 5 cm and has spread to surrounding lymph nodes or is larger than 5 cm and may or may not have spread to surrounding lymph nodes. There is no spread to distant sites.
• Stage IV. Disease that has spread to other areas of the body at the time of diagnosis, such as the liver, lung, bones, or bone marrow.

Clinical Group

• Group I. Group includes children with localized RMS that is completely removed by surgery. About 10% to 15% of RMS patients are in group I.
• Group II. All of the visible cancer was removed by surgery, but cancer cells have been found at the edges of the specimen by the pathologist.  This can mean that there may be a small amount of cancer left behind, in the nearby lymph nodes, or in both places.  About 20% of RMS patients are in group II.
• Group III. Tumors that could not be removed completely. Some tumor was left behind that could be seen but do to the location and overall safety of the child it could not be removed. The cancer may have spread to nearby lymph nodes, but there is no sign that it has spread to distant organs. About 50% of RMS patients are in group III.
• Group IV. At the time of diagnosis there is evidence of distant cancer spread to places such as the lungs, liver, bones, bone marrow, or to distant muscles or lymph nodes. About 15% to 20% of RMS patients are in group IV.

Risk groups

Based upon the type of RMS, the TNM stage, and the clinical group, doctors classify patients into 3 risk groups. This will help guide the treatment regimens for the child.

• Low-risk group. About 1 in 3 children with RMS falls into the low-risk group. It includes:
  • Children with TNM stage 1 embryonal rhabdomyosarcomas (ERMS) that fall into clinical groups I, II, or III
  • Children with stage 2 or 3 ERMS who are in clinical groups I or II
• Intermediate-risk group. About half of children of RMS fall into the intermediate-risk group. It includes:
  • Children with stage 2 or 3 ERMS who are in clinical group III
  • Children with alveolar rhabdomyosarcoma (ARMS) that has not spread to distant parts of the body (stage 1, 2, or 3)
• High-risk group. This group includes:
  • Children with widespread (stage 4) RMS (ERMS or ARMS)

What is the treatment for rhabdomyosarcoma?

• Specific treatment for rhabdomyosarcoma will be determined by your child's doctor based on:
• Your child's age, overall health, and medical history
• Extent of the disease
• Your child's tolerance for specific medications, procedures, or therapies
• Expectations for the course of the disease
• Your opinion or preference

Treatment may include (alone or in combination):

• Surgical resection (removal) of tumor and/or metastases
• Chemotherapy
• Radiation therapy
• Lumbar puncture (to administer medication and treat cancer cells if found in this cerebrospinal fluid)
• Supportive care (for the side effects of treatment)
• Antibiotics (to prevent or treat infections)
• Bone marrow or stem cell transplantation
• Continuous follow-up care (to manage disease and detect any recurrence of the tumor)

What is the long-term outlook for a child with rhabdomyosarcoma?

Prognosis greatly depends on:

• the extent of the disease,
• the size and location of the tumor,
• presence or absence of metastasis,
• the tumor's response to therapy,
• the age and overall health of your child,
• your child's tolerance of specific medications, procedures, or therapies, and
• new developments in treatment.

As with any cancer, prognosis and long-term survival can vary greatly from child to child. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential if your child is diagnosed with rhabdomyosarcoma. Side effects of radiation and chemotherapy, as well as second malignancies, can occur in survivors of rhabdomyosarcoma.