Rhabdomyosarcoma

What is rhabdomyosarcoma?

Rhabdomyosarcoma is a cancerous tumor that originates in the soft tissues of the body, including the muscles, tendons and connective tissues – a sarcoma. 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.

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood. In the US, about 350 children are diagnosed with rhabdomyosarcoma each year. This disease most commonly affects children between the ages of 0 to 20 years of age, but can occur at any age. For unknown reasons, males are affected slightly more often than females.

Embryonal rhabdomyosarcoma, the most common histology type, usually occurs in children under 6 years of age. Alveolar rhabdomyosarcoma occurs in older children and accounts for about 20 percent of all cases. The use of molecular characterization is gradually replacing histology. FOXO1 gene fusions are frequently found in alveolar rhabdomyosarcoma.

What causes rhabdomyosarcoma?

The majority of children with rhabdomyosarcoma do not have an identified risk factor. However, rhabdomyosarcomas are more common in children with some rare genetic disorders. These include Neurofibromatosis Type 1, DICER1 syndrome, Costello Syndrome, Noonan Syndrome, Beckwith-Wiedemann syndrome and  Li-Frameni cancer susceptibility syndrome (germline variants of TP53).

Rhabdomyosarcomas usually have some type of chromosome or gene abnormality in the cells of the tumor, which are responsible for the cancer formation. In children with an embryonal rhabdomyosarcoma, an abnormality of chromosome 11 or the genes of the RAS pathway is most common. In alveolar rhabdomyosarcoma, a rearrangement in the chromosome material between chromosomes 2 and 13 or chromosomes 1 and 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 PAX3 and FOXO1 or PAX7 and FOXO1. This important discovery has led to improvements in classifying rhabdomyosarcoma.

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 pelvis. 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 area)
• Trouble having bowel movements or urinating (if the tumor compresses this area)

The symptoms of rhabdomyosarcoma may resemble other conditions or medical problems. Always consult your child's physician 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 a open biopsy where tissue is collected by a cut in the skin or a core needle biopsy where a needle is used to collect the tumor tissue. A needle biopsy can be guided by an imaging technique such as ultrasound, CT scan or MRI.
• Sentinel lymph node biopsy – removal of a sample of a lymph node during surgery for rhabdomyosarcoma, most commonly when the rhabdomyosarcoma arises in the arms/legs or the trunk. This is guided by injection of a radioactive tracer or a dye near the tumor to ensure sample collection from the optimal lymph node.
• Blood and urine tests – these tests are commonly looking to see side effects from the tumor on systems of the body.
• Multiple imaging studies, including:

• X-ray - a diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones and organs onto film.
• Computed tomography scan (CT or CAT scan) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, 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 imaging procedure that uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body.
• Positron Emission Tomography scan (PET scan) – a diagnostic imaging procedure that injects a radioactive tracer that is taken up with metabolic activity. The scanner then takes a full body picture to see where the tracer is accumulating. Cancer cells show up brighter because they are more active and take up more tracer than normal cells.
• Ultrasound (Also called sonography) - a diagnostic imaging technique which 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.

• Bone marrow aspiration/biopsy - a procedure that involves a small amount of bone marrow fluid and tissue to be taken, usually from the hip bones, to further examine the number, size and maturity of blood cells and look under a microscope for cancer cells.
• Lumbar puncture/spinal tap - cerebral spinal fluid (CSF) is the fluid that bathes your child's brain and spinal cord. A special needle is placed into the lower back, into the spinal canal. The pressure in the spinal canal and brain can then be measured. A small amount of CSF is then removed and examined under a microscope for evidence of cancer cells. .

Diagnosis involves staging and classifying the tumor, which is important in determining the risk group and treatment options. Advances in the molecular changes in the tumor are becoming more important in this process.

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 physician for more information on staging.

One method of staging is the TNM clinical 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 1 - tumors involving the area near the eye, the head and neck (except around the lining of the brain), and genitourinary tract (except the prostate and bladder). The tumor is localized, meaning the tumor has not spread to other areas of the body. Local lymph nodes can in some cases still be Stage 1.
• Stage 2 - small, localized tumors less than 5 cm in any site not in Stage 1. There are no tumor cells in the surrounding lymph nodes.
• Stage 3 - localized tumor at any site not included in Stage 1 that is larger than 5 cm and/or has spread to surrounding lymph nodes.
• Stage 4 - disease that has spread to other areas of the body at the time of diagnosis.

  The next method of staging is the surgical-pathological Group assignment. For this method the different Groups are differentiated by the extent of the disease and how complete of an initial surgery or biopsy was performed.

• Group I – localized tumors that have been completely resected.
• Group II - localized tumors resected with microscopic residual disease or tumors with regional disease, commonly lymph nodes, that has been completely resected or with only microscopic residual disease.
• Group III – localized or regional tumor that was biopsied only or gross disease remains after resection
• Group IV - disease that has spread to distant areas of the body at the time of diagnosis. This can include the CSF, bone marrow, distant bones or tissues, pleural, abdominal or peritoneal fluids.

Using the Staging classification and the Group assignment along with the molecular or histology information patients are then assigned to a Risk Group Classification. Different organizations such as the Children’s Oncology Group or the European equivalent organization have different terminology for these Risk Group Classifications.

Treatment for rhabdomyosarcoma

Specific treatment for rhabdomyosarcoma will be determined by your child's physician based on:

• Your child's age, overall health and medical history
• Extent of the disease – specifically the combination of the Stage, Group, and histology/molecular changes which determine the Risk Classification
• 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):

• Surgery
• Resection of tumor and metastases
• Chemotherapy
• Radiation therapy
• Lumbar punctures (to assess response to treatment - if present initially)
• Bone marrow aspiration/biopsy (to assess response to treatment – if present initially)
• Supportive care (for the side effects of treatment)
• Antibiotics (to prevent/treat infections)
• Continuous follow-up care (to manage disease and detect any recurrence of the tumor)

Long-term outlook for a child with rhabdomyosarcoma

Prognosis greatly depends on:

• The extent of the disease
• The size and location of the tumor
• The molecular findings 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
• 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. Short and long-term side effects of surgery, radiation and chemotherapy, as well as second malignancies, can occur in survivors of rhabdomyosarcoma. New methods are continually being discovered to improve treatment and to decrease side effects.