Childhood rhabdomyosarcoma is a rare and aggressive cancer originating in soft tissues, developing from mesenchymal cells that would normally form skeletal muscle.
What is Childhood Rhabdomyosarcoma?
Rhabdomyosarcoma (RMS) is a malignant soft tissue sarcoma, meaning it arises from connective tissues rather than bone. RMS originates from primitive mesenchymal cells that fail to fully differentiate into skeletal muscle cells. Although RMS can occur anywhere in the body, it is often found in the head and neck, genitourinary tract, and extremities.
This cancer accounts for approximately 40% of all soft-tissue sarcomas and about 4.5% of all childhood cancers, with an incidence of about 4.5 cases per million children and adolescents annually. The majority of cases, roughly two-thirds, are diagnosed in children under 10 years old, and it is observed slightly more often in males than females. While the exact cause remains largely unknown, some cases are associated with familial syndromes, such as Li-Fraumeni syndrome, Neurofibromatosis, Beckwith-Wiedemann syndrome, and Costello syndrome.
RMS has two primary types: embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS). ERMS is the most common subtype, accounting for 60-70% of childhood cases, and presents in younger children, often in the head and neck region or genitourinary tract. ERMS cells resemble embryonic muscle and have a more favorable prognosis.
Alveolar rhabdomyosarcoma (ARMS) is the second most common type, accounting for 25-30% of cases, and is seen in older children, teenagers, and young adults. ARMS often develops in the arms, legs, or trunk and is more aggressive as it tends to spread quickly. This subtype is characterized by small, round cells arranged in a distinct alveolar (sac-like) pattern. Other rarer types include pleomorphic and spindle cell/sclerosing rhabdomyosarcoma, with spindle cell/sclerosing RMS often found in the paratesticular region, carrying an excellent prognosis.
Identifying the Signs and Diagnosis
Signs and symptoms vary by tumor location and can be subtle or mimic common childhood illnesses. A common initial sign is a growing lump or swelling, which may or may not be painful.
If a tumor is located near the eye, symptoms can include bulging of the eye (proptosis), crossed eyes, or changes in vision. Tumors in the head and neck region, particularly in the nasal sinuses, may cause headaches, ear pain, or nasal discharge. When rhabdomyosarcoma affects the urinary or reproductive organs, symptoms can include difficulty with urination or bowel movements, or blood in the urine or vaginal bleeding. Tumors in the abdomen might lead to pain, vomiting, or constipation.
The diagnostic process begins with a physical examination. If rhabdomyosarcoma is suspected, a variety of imaging tests are performed to determine the tumor’s size and exact location. These imaging studies include X-rays, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and bone scans. MRI is preferred for assessing tissues surrounding the tumor and planning subsequent treatments.
A definitive diagnosis requires a biopsy, where a tissue sample is examined by a pathologist. This pathological examination is important for identifying the specific type of rhabdomyosarcoma and assessing its characteristics. Genetic testing on the biopsy sample can also identify specific gene changes, like the PAX/FOXO1 fusion gene, found in alveolar rhabdomyosarcoma, influencing treatment. Further tests determine if the cancer has spread (staging), which may involve additional imaging or a bone marrow examination.
Treatment Strategies
Treating childhood rhabdomyosarcoma involves a multidisciplinary approach, combining treatments tailored to the patient. The treatment plan considers the tumor’s location, size, specific type, and whether it has spread, and is managed by a team of pediatric cancer specialists.
Surgery plays a role in removing the tumor, aiming to remove as much cancerous tissue as possible. If the tumor can be completely removed without significant disfigurement or loss of function, surgery may be performed before other treatments. However, for many tumors, complete surgical removal is not feasible, especially if they are located near vital organs. In these cases, a biopsy is performed, and other treatments may shrink the tumor before surgery.
Chemotherapy is a systemic treatment using drugs to kill cancer cells throughout the body. It is often a component of rhabdomyosarcoma treatment, even if the tumor appears to be localized, due to the likelihood of microscopic spread. Chemotherapy is often administered before surgery to shrink larger tumors (neoadjuvant chemotherapy), or after surgery to eliminate any remaining cancer cells. The specific chemotherapy drugs, dosage, and duration depend on the child’s age and the cancer’s risk group (low, intermediate, or high).
Radiation therapy uses high-energy beams to destroy cancer cells in a specific area. It is often used in combination with surgery and chemotherapy, particularly for intermediate and high-risk tumors, to improve local control of the disease. Radiation therapy can be delivered using techniques like intensity-modulated radiation therapy (IMRT), aiming beams from multiple angles to minimize damage to healthy tissues. Proton therapy may also be an option for tumors in sensitive areas like the eye or brain, as it delivers a precise dose that stops at the tumor, sparing healthy tissue. Clinical trials are continuously exploring new approaches, including targeted therapies that focus on specific molecular characteristics of the cancer cells, and immunotherapy, which harnesses the body’s immune system to fight the cancer.
Outlook and Family Support
The prognosis for children with rhabdomyosarcoma is influenced by several factors, including the tumor’s location, size at diagnosis, specific type (histology), spread (to lymph nodes or distant sites), and its response to initial therapy. Tumors originating in favorable locations such as around the eye or in non-parameningeal areas of the head and neck have a more favorable outlook. Conversely, tumors that have spread to distant parts of the body at diagnosis carry a poorer prognosis.
Significant advancements in treatment strategies over the past decades have improved outcomes for children with rhabdomyosarcoma. The 5-year overall survival rate for rhabdomyosarcoma has seen improvements, increasing from approximately 53% to 67% for children under 15 years old between 1975 and 2010. However, for patients with advanced or metastatic disease, improvements in cure rates have been more limited.
Ongoing follow-up care is important for survivors of childhood rhabdomyosarcoma, as long-term side effects from treatment can emerge after therapy. This monitoring helps address potential issues such as reduced bone growth, infertility, or changes in heart and kidney function.
Comprehensive support for children and their families is important. This includes psychosocial support services to help cope with the emotional challenges of a cancer diagnosis and treatment. Financial assistance programs can help families manage the costs associated with medical care, accommodations, and travel. Connecting with support groups or organizations dedicated to pediatric cancer provides a community where families can share experiences, information, and emotional support.