Rhabdomyosarcoma is the most common type of cancer – an aggressive, highly malignant soft tissue tumor, usually affecting children and adolescents.
Cancer is a group of various diseases characterized by an abnormal uncontrolled cell proliferation. There are known more than 100 types of cancer.
Malignant tumors derived from the mesenchymal tissues are called sarcomas. These tumors include fibrosarcomas, liposarcomas, leiomyosarcomas for smooth muscle cancers and rhabdomyosarcoma for striated muscle tumors.
Rhabdomyosarcomas most often occur in children and adolescents, rarely – in adults over 40. Common sites for rhabdomyoma include:
- head and neck (40%),
- genitourinary tract (20%),
- retroperitoneal cavity,
- the limbs. .
There are several types of rhabdomyosarcoma – alveolar, embryonal (60% of cases), and anaplastic rhabdomyosarcoma.
- Mutations in the RAS and FGFR4 genes, 11p15 are associated with embryonal rhabdomyosarcoma.
- In alveolar rhabdomyosarcoma the translocation between the FKHR/FOXO1 transcription factor gene (on chromosome 13) and either PAX3 transcription factor gene (on chromosome 2) or PAX7 gene (on chromosome 1) may be identified, mutations of N‐MYC, ALK and MET genes may also be present.
- Alveolar and embryonal subtypes are characterized by the over‐expression of insulin growth factor 2 (IGF‐2).
See also: Kaposis sarcoma
The tumor may be associated with other congenital disorders such as
- Neurofibromatosis type 1 – a disorder characterized by the development of the tumors along the nerves, skin pigmentation and is caused by the mutations in the NF1 gene;
- Li–Fraumeni syndrome – an autosomal dominant disease characterized by an early onset of cancer and development of various tumors;
- Noonan syndrome – a congenital disorder characterized by multiple lesions in different organs due to genetic mutations;
- Pleuropulmonary blastoma – a rare type of childhood cancer;
- Costello syndrome – multisymptomatic disorder caused by the mutation in the HRAS gene.
Possible link to parental use of cocaine and marijuana was reported.
Common symptoms of rhabdomyosarcoma include:
- the swelling/painful palpable mass at the site of origin;
- local symptoms – displacement of the eye, vaginal bleeding, dysuria, etc.
Rhabdomyosarcoma of the head and neck may be suspected when the following symptoms are present:
- diplopia (doubled vision),
- exophtalmos (bulging of the eyeball),
- congestion, nasal discharge,
- cranial nerve palsy,
- hearing or vision loss.
Genitourinary rhabdomyosarcoma may cause urinary tract obstruction or constipation. Abdominal or pelvic manifestations include abdominal pain and abdominal mass, ascites, haematuria.
Cancer commonly disseminates to lungs, bones, bone marrow and brain.
According to the estimated risk and possible outcomes the following risk groups are distinguished:
- Low-risk – embryonal rhabdomyosarcoma without dissemination, which locates in the orbit, vagina and paratesticularly;
- Intermediate-risk – alveolar rhabdomyosarcoma without metastases, parameningeal tumors or extremities tumors;
Based on the size of the tumor, its location and dissemination there are 4 stages of rhabdomyosarcoma:
- Stage 1 – a tumor of any size, which grows in the favorable area (the orbit, the head and neck, genitourinary tract and bile ducts). It hasn’t spread to a distant areas of the body;
- Stage 2 – a tumor about 5 cm in size originates from an unfavorable area (the bladder and prostate, limb, a parameningeal area). Lymph nodes or other body parts are unaffected;
- Stage 3 – a tumor originates from an unfavorable area (the bladder and prostate, limb, a parameningeal area). This tumor may be 5 cm in size or even smaller with no signs of dissemination. If the neoplasm is bigger than 5 cm it may have disseminated or may not.
- Stage 4 – a tumor has disseminated to the distant parts of the body;
The diagnosis is made based on:
- Radiographic imaging of the site of origin, chest X-ray;
- CT of the chest, tumor site;
- MRI of the tumor site;
- Total body bone scan;
- Bone marrow biopsy;
- Lumbar puncture (only for parameningeal RMS);
- Biopsy of the lesion and lymph nodes;
Treatment depends on the size of the tumor, its location and spread. Surgery solely is used when the tumor is localized. The combination of surgery, chemotherapy, radiotherapy and immunotherapy is usually used. Adjuvant radiotherapy is used for local control of the tumor.
Chemotherapy agents which are used in the treatment of rhabdomyosarcoma include vincristine, actinomycin D, doxorubicin, cyclophosphamide, ifosfamide, etoposide, melphalan and cisplatin.
In peadiatrics commonly a combination vincristine + actinomycin + cyclophosphamide is administered.
In general the survival rate is 70-75%. The five-year survival rate for low-risk is 95%, intermediate-risk – 65% and high risk – 15%.