All About Rhabdomyosarcoma
What is a sarcoma?
Sarcoma is a general medical term that refers to any cancer of the bone, muscle, or other connective tissue, such as cartilage and tendons. Sarcomas can occur in both children and adults, both males and females. In fact, there are many different types of sarcomas, depending on where the cancer cells grow and how they appear under a microscope. These different types are in turn associated with different clinical behavior, which naturally influences how they are treated. Some sarcomas arise from stem cells within the connective tissues, and these are more common in children than adults.
What is a rhabdomyosarcoma?
Rhabdomyosarcoma is the most common type of soft tissue sarcoma found in children. It is still a rare cancer overall, accounting for about 3.5% of all childhood cancers. About 250 new cases of rhabdomyosarcoma are diagnosed in the United States every year.
The name itself comes from a combination of 3 smaller words: rhabdo means "rod-shaped", myo is muscle, and sarcoma is the type of cancer, as described above. Rhabdomysarcoma cells tend to look rod-shaped under a microscope, and they have several features of muscle cells. During normal fetal development, cells called rhabdomyoblasts "grow up" to become the skeletal muscles of the body. When these cells multiply abnormally within a child’s body, a rhabdomyosarcoma results. Rhabdomyosarcomas can occur essentially anywhere in the body, but usually occur in the head, neck, bladder, vagina, extremities and the trunk.
Who gets rhabdomyosarcomas, and why?
Over 85% of all rhabdomyosarcomas occur in infants, children, and teenagers. There is no specific geographic location or racial background that has been associated with higher rates of rhabdomyosarcoma, although, Asian and black children have a lower annual incidence than do white children. There also appears to be a male predominance, as boys are about 1.5 times more likely than girls to get rhabdomyosarcoma.
It is known that rhabdomyosarcomas are associated with specific chromosomal abnormalities that can be seen within rhabdomyosarcoma tumors, but these tumors are not inherited from parents. The exact cause of these mutations is not known. Some children who develop rhabdomyosarcomas also have congenital anomalies of various organ systems (abnormal development of heart, gut, brain, etc). The risk of rhabdomyosarcoma may be elevated for children who also have certain rare genetic disorders, such as neurofibromatosis type 1. Unlike many adult cancers, there are no known definitive environmental conditions that increase the chance of a person developing rhabdomyosarcoma. No connection has ever been found between rhabdomyosarcoma and exposure to toxic substances, environmental pollution, radiation (eg: x-rays during pregnancy), or physical injury (trauma). Not even tobacco smoke has been linked with development of this or any other childhood cancers,.
Are all rhabdomyosarcomas the same?
No. Just as there are different types of sarcomas, there are different types of rhabdomyosarcomas, as well. The 2 major types of rhabdomyosarcomas are described below. The classification is based on unique microscopic appearance, genetic mutations, and clinical behavior.
Embryonal, or "translocation negative" rhabdomyosarcoma
This is the most common type of rhabdomyosarcoma. It tends to occur in the head and neck, bladder, vagina in girls, and around the prostate and testes in boys. This type usually affects infants and young children. As the name implies, the cells have an immature appearance, meaning they resemble developing muscle cells. Embryonal rhabdomyosarcomas have a relatively good to intermediate prognosis, depending on other individual aspects of the disease.
Alveolar, or "translocation positive" rhabdomyosarcoma
This type of rhabdomyosarcoma is found more often in large muscles of the trunk, arms, and legs, and typically affects older children or teenagers. It is called alveolar because the cancer cells form little hollow spaces, or "alveoli" (Latin for small hollow spaces). Although alveolar rhabdomyosarcomas were originally named this way because of their appearance under the microscope, researchers have now found that nearly all of them bear specific genetic mutations, most commonly one called a 2;13 translocation. Alveolar rhabdomyosarcomas may be more aggressive than embryonal tumors, and their treatment may be longer and more intense. Again, this depends on individual disease aspects, as well as the tumor diagnosis.
How are rhabdomyosarcomas detected?
The answer to this question really depends on the location of the tumor. As mentioned earlier, rhabdomyosarcomas can arise from any region in the body, but the most common sites are the head and neck region, the genitourinary organs (GU), and the extremities. Tumors in the head and/or neck region can cause headaches, nausea, vomiting, visual problems (double vision), facial drooping, and airway obstruction, among other things. Tumors in the GU area can cause blockage of the bladder or bowels, which can be a medical emergency depending on the degree of obstruction. Growths on the extremities can be painful and limit the use and motion of the affected arm or leg. Sometimes, the rhabdomyosarcoma is not diagnosed until after the tumor cells have spread to other parts of the body. The most common areas they spread to are the lungs, bones, bone marrow, and lymph nodes.
How are rhabdomyosarcomas evaluated?
The workup of these tumors typically includes the following studies:
- CT and MRI scans of affected region(s)
- Chest x-ray or CT scan of chest
- Bone scan
- Bone marrow biopsy
- For genitourinary location:
- Cystoscopy (scope to look inside the bladder)
- Barium enema and rectal ultrasound
How are rhabdomyosarcomas staged?
The staging system for rhabdomyosarcoma is very complicated. All rhabdomyosarcomas are assigned a group, a stage, and a risk category. In order for stage to be assigned, the disease must be determined to be in either a "favorable" or an "unfavorable" site.
Favorable sites include:
- Non-parameningeal head & neck: This includes all sites within the head and neck that do not touch the meninges, or the tissue that surrounds the brain and spinal cord.
- Biliary tract
- Paratesticular region
All other sites of disease are classified as "unfavorable."
Group assignments are made based on the amount of tumor, if any, that is removed surgically.
- Group I = Localized disease, completely resected (removed surgically)
- Group II = The tumor is removed surgically, but there are either microscopic cells left behind (2a) or microscopic cells seen in the lymph nodes (2b)
- Group III = The tumor is localized and has been biopsied, but has not been removed surgically.
- Group IV = Distant metastatic disease present
The staging uses the classic TNM system, defined as follows:
- T1 - Confined to site of origin
- a < 5 cm
- b > 5 cm
- T2 - Extension beyond site of origin
- a < 5 cm
- b > 5 cm
- N0 – no clinically involved lymph nodes
- N1 – clinically involved lymph nodes
- M0 – no distant disease
- M1 – distant disease
The group, stage and risk category are then combined to determine a numerical stage:
Stage I = Favorable sites, any size, any nodal status
Stage II = Unfavorable site, but small AND negative lymph nodes
Stage III = Unfavorable sites, small or large, BUT positive lymph nodes
Stage IV = Distant metastatic disease, regardless of site, size, or nodes
After a patient is assigned group and stage, he or she may also be classified as "low," "intermediate," or "high" risk. For the most part, stage I patients are low risk, stage II and III are intermediate risk, and stage IV are high risk.
How are rhabdomyosarcomas treated?
Treatment of these tumors truly requires a multidisciplinary approach, with important contributions from all 3 major fields of cancer therapy: surgery, chemotherapy, and radiation therapy. However, general clinical guidelines that apply to the majority of cases are very difficult to make because rhabdomyosarcomas behave extremely differently, depending on the type and location of involvement.
Chemotherapy has been studied extensively in rhabdomyosarcoma patients. Some of the most active and studied chemotherapy agents include: vincristine, actinomycin, cyclophosphamide, and doxorubicin. We know that, even when a rhabdomyosarcoma is completely removed, the child remains at high risk for development of metastatic disease. For this reason, chemotherapy is used for all patients to treat any microscopic cells that may be present in lymph nodes or the bloodstream. With use of aggressive chemotherapy, the risk of metastatic disease is reduced dramatically.
In addition to chemotherapy, patients require surgery, radiation, or a combination of these two for a phase of treatment called "local control." Although all rhabdomyosarcomas are biopsied surgically at the time of diagnosis, some are then completely removed surgically. Others are mostly or partly removed. Still others can't be removed safely. If the tumor can be removed completely, often only surgery and chemotherapy are employed. If the surgeon or pathologist are concerned that microscopic cells may have been left behind after surgery, either at the tumor margin or in the lymph nodes, post-operative radiation will likely be recommended. If the tumor cannot be removed at all, higher-dose radiation is utilized.
Delivery of radiation may be done with x-rays, often using a technique called intensity modulated radiation treatment (IMRT), or with proton therapy. Proton therapy is available at some specialized centers around the world, and may offer advantages during treatment of rhabdomyosarcomas through reduction of radiation to normal, growing tissues.
Follow-up Care and Survivorship
After treatment for childhood cancer, the patient will be followed closely to monitor for the cancer coming back, to help them heal from ongoing side effects, and to help them to transition to survivorship. Initially they will be seen often and have ongoing tests to monitor their health. As time goes on, these visits and testing will become less frequent. The oncology team will discuss each patient’s individual follow up plan with them.
Survivors often wonder what steps they can take to live healthier after cancer. There is no supplement or specific food you can eat to assure good health, but there are things you can do to live healthier, prevent other diseases, detect any subsequent cancers early and work with the social and emotional issues, including insurance, employment, relationships, sexual functioning, and fertility, that a prior cancer diagnosis sometimes brings with it. Your oncology team is there to support you and can help you find support resources.
It is important to have a plan for who will provide your cancer-focused follow up care (an oncologist, survivorship doctor or primary care doctor). Talk with your oncology team about developing a survivorship care plan. If you would like to find a survivorship doctor to review your history and provide recommendations, you can contact cancer centers in your area to see if they have a survivor's clinic or search for a clinic on OncoLink's survivorship clinic list.
Appendix: Site Specific Treatment Information
Finally, here are some general facts and treatment guidelines on specific disease sites.
- Usually develops as a pedunculated mass which may extend laterally and, in boys, deeply into the prostate, making origin difficult to determine
- Accounts for 50% of pelvic rhabdomyosarcomas
- Painful urination and blood in the urine are early signs
- Ultrasound and cystoscopy are used to diagnose
- 90% are embryonal, including botryoid ("cluster of grapes") subtype
- Induction chemo followed by limited resection if bladder preservation is possible
- Alternatively, induction chemo followed by radiation, then biopsy to document pathologic complete response (pCR = no more microscopic tumor seen). If no pCR, then limited surgery
- Tend to disseminate early and be more locally invasive
- Similar presentation to that of bladder
- Local measures should be pursued aggressively upfront
- Painless unilateral scrotal swelling
- Frequently spreads through lymphatics to para-aortic lymph nodes
- Retroperitoneal lymph node dissection is common
Vagina and Vulva
- Very young children
- Usually botryoid subtype of embryonal
- Treatment requires anterior exenteration with urinary diversion and chemotherapy
Uterus and Cervix
- Bleeding is common presentation
- Presents around puberty
- Polypectomy then chemo is highly curative
- High incidence of alveolar subtype
- Often locally lymph node positive
- Often metastatic at presentation
- Regional lymph node involvement may occur ~15%
- Chemo for all
- RT unless small, node negative, and completely excised
- Embryonal > alveolar (4:1)
- Successful surgery is nearly always impossible, so surgery is typically for diagnosis only (biopsy)
- Neck dissection is morbid and not warranted
- RT delivered at beginning of treatment course if clear meningeal involvement or intra cranial extension
- Otherwise, chemo first, with RT following. Proton therapy may offer significant advantage for these patients through sparing of normal tissues, including the brain.
- Often diagnosed early
- Eye swelling and displacement
- RT is the local modality of choice. Proton therapy may offer significant advantage for these patients through sparing of normal tissues, including the brain and the healthy eye.
- Chest wall and paraspinal area
- Treat with as wide an excision as safely possible
- Then follow with chemotherapy and radiation
- Proton therapy may offer significant advantage for these patients through sparing of normal tissues.
- Usually large and difficult to resect
- Lymph node involvement is common
- Radiation is often needed, and proton therapy may offer significant advantage for these patients through sparing of normal tissues.