Rhabdomyosarcoma is a malignant tumor that originates from rhabdomyosarcoma cells or mesenchymal cells that differentiate into rhabdomyosarcoma cells, and is the most common type of soft tissue sarcoma in children. The incidence of rhabdomyosarcoma is the third most common soft tissue sarcoma after malignant fibrous histiocytoma and liposarcoma. It is less common in adults and more common in males than females. Embryonal rhabdomyosarcoma is most common in children before the age of 8 years (mean age 6 years); adenoid rhabdomyosarcoma is seen in adolescent males (mean age 12 years); rhabdomyosarcoma with multiple types is common in adults, but also seen in children.
1.Etiology
The cause of rhabdomyosarcoma is unclear. It is a malignant tumor of soft tissue composed of rhabdomyoblasts of various degrees of differentiation. The disease may be related to genetic factors, chromosomal abnormalities, gene fusion and other factors.
2.Clinical manifestations
Embryonal rhabdomyosarcoma accounts for about 2/3 of rhabdomyosarcoma, and it occurs in children and adolescents with two peaks in age distribution, i.e., after birth and in late adolescence, with an average age of 5 years. It occurs in the head, neck, genitourinary tract and retroperitoneum. The main symptoms are painful or painless masses, red and swollen skin surface, and high skin temperature. The tumors vary in size and hardness, and most of the masses are fixed at the time of consultation. Most of the masses are fixed at the time of consultation. The tumor is fast growing and may have skin rupture and bleeding. Pain may occur when the tumor compresses the nerve.
Head and neck masses may have protruding eyes, bloody discharge, nasal bleeding, swallowing and breathing disorders. Genitourinary system tumor manifests as bloody vaginal discharge, hematuria and urinary retention, and pelvic mass can be palpated by anal finger. This type mostly metastasizes to retroperitoneal lymph nodes and the regional lymph nodes to which it belongs, and late stage is often accompanied by hematogenous metastasis.
Adenoid rhabdomyosarcoma is more common in adolescents, and is more common in males than females. It occurs in the extremities, head and neck, trunk and perineum, and also in the orbit. The main symptom is painful or painless masses. Tumor compression of peripheral nerves and invasion of surrounding tissues and organs may cause pain, compression symptoms and sensory disturbance. Lymph node metastasis and hematogenous dissemination to the lung can occur at an early stage.
Rhabdomyosarcoma multiforme mainly occurs in adults, mostly between 40 and 70 years old. It occurs in the extremities and trunk, and is located in muscle hypertrophy, such as the quadriceps, the adductors of the thighs, and the biceps. The tumor often infiltrates to the outer envelope and forms multiple nodules in distant parts of the muscle interval. The duration of disease varies, with some reaching more than 20 years. The main symptom is painful or painless lump, which is located in the muscle with unclear boundary.
When the tumor invades the skin surface, there may be high skin temperature, rupture and bleeding. This type of tumor is characterized by large size, mostly 5-10 cm, but there are some cases up to 40 cm. The mass is hard and cystic in nature. Polymorphic rhabdomyosarcoma may show lymph node metastasis.
3.Examination
HE staining of rhabdomyosarcoma cells observed under light microscope may sometimes be difficult to confirm the diagnosis due to low cell differentiation and unformed transverse lines, etc. Immunohistochemical staining method is a reliable method to confirm the diagnosis of rhabdomyosarcoma. In this case, the tumor cells were observed under light microscope in a bundle arrangement and were shuttle-shaped, similar to fibrosarcoma, and a few tumor cells were seen with obvious eosinophils in the cytoplasm, i.e., rhabdomyoblasts.
There are no typical radiological features and no calcification. The tumor may invade and destroy adjacent bones, especially in the skull, forearm, hand and foot. CT and MRI with contrast can better show the location, volume, margin and its relationship with surrounding tissues. Intravenous pyelogram can reveal irregular filling defects in the bladder and hydronephrosis. Other examination methods include bone scan (suspected bone metastasis) and lymphangiography (suspected lymph node metastasis).
4. Diagnosis
1. Head
Rhabdomyosarcoma of the head and neck is mostly embryonal in pediatric patients and chylous sarcoma in the ear, nose and sinuses. All children present with masses, and their symptoms include protruding eyes, voice changes, dysphagia, respiratory obstruction, cough and discharge from the external ear canal. If the nerve is invaded, acid reflux pain occurs; swelling and infiltrative growth of the tumor can worsen the symptoms and develop brain symptoms. If metastasis occurs, corresponding symptoms will be produced.
2. Eye orbit
Transverse myosarcoma can come from the eye muscle or lacrimal gland, mostly seen in boys aged 7 to 8 years old, causing unilateral proptosis. The disease progresses rapidly, with ptosis occurring in 1/3 of children, headache in 10% of children, and bone destruction on x-ray. In children with unilateral proptosis, a neurological examination, including carotid radiography and brain scan, is indicated. The differential diagnosis should include leukemia and neuroblastoma. Leukemia is easily differentiated by peripheral blood and bone marrow smears. When neuroblastoma invades the orbit, the lesions in other parts of the body are more obvious and can be differentiated.
3. Ear
Tumors can occur in the external auditory canal, middle ear, mastoid process or paranasal sinuses, often invading only one ear and the opposite side is normal. It is often diagnosed as a polyp-like mass in the external auditory canal and a bloody discharge in the ear, which can be easily mistaken for an inflammatory polyp, so it is especially important to consider this disease in young children with inflammation in the ear that has not been treated with antibiotics. Less commonly, the mass is a fast-growing lateral mass behind the ear, which may be inconspicuously raised and soft at the time of initial diagnosis, but may increase to an alarming size at the time of follow-up, and is often advanced when diagnosed because it is not painful. Occasionally, facial nerve palsy is the main complaint, and vertigo is a fairly advanced symptom. The tumor spreads from the middle ear to the mastoid process and invades the posterior cranial fossa through the internal plate.
4.Mouth and neck
Rhabdomyosarcoma is a common malignant tumor in childhood, accounting for 50% of all soft tissue sarcomas in children, 45% of which occur in the head and neck, and 25%-35% of rhabdomyosarcomas in the head and neck originate in the orbit. Rhabdomyosarcomas are classified as embryonal, glandular and pleomorphic. 80% of rhabdomyosarcomas occurring in the orbit are embryonal in nature. Embryonal rhabdomyosarcomas include spindle cell, chylomicron and mesenchymal rhabdomyosarcomas, which are easily confused with tumors such as non-Hodgkin’s lymphoma and fibrosarcoma.
Embryonal rhabdomyosarcoma originates from the floor of the mouth, tongue, uvula, soft palate, nasopharynx, larynx, lips, nose, gums, temporal, cheek, mandibular muscles, parotid glands, and neck muscles. Superficial ones present as simple painless masses and can be misdiagnosed as benign tumors in early stages. In young children, laryngeal tumor may cause hoarseness and acute respiratory obstruction.
5.Treatment
1. Surgical treatment
The main treatment for rhabdomyosarcoma is surgical resection, which includes all the muscles where the tumor is located. For embryonic rhabdomyosarcoma, in addition to resection, chemotherapy and radiotherapy should be combined to relieve symptoms; pleomorphic rhabdomyosarcoma is not effective for chemotherapy and radiotherapy.
Biopsy of the tumor showed good results after complete surgical resection of rhabdomyosarcoma. Only 10% of patients with rhabdomyosarcoma are completely resected. Even in patients with complete resection, chemotherapy and radiotherapy are necessary because rhabdomyosarcoma is highly susceptible to metastasis.
At the time of surgery, a biopsy of the lymph nodes in the area of the tumor is required. Complete surgical resection of rhabdomyosarcoma of the head and neck requires consultation with an otolaryngologist, plastic surgeon, maxillofacial surgeon and neurosurgeon. If complete excision affects the appearance of the face and its function, then surgery is delayed until the course of chemotherapy and radiation is completed. The decision to perform a second facial surgery depends on the surgical site and the results of chemotherapy and radiation therapy.
The basic requirement for surgical removal of rhabdomyosarcoma is a biopsy. The form of biopsy is based on medical imaging results, the site and size of the tumor, the patient’s age and health status, and the experience of the surgeon. The purpose of complete removal of the tumor at the time of surgery is to avoid secondary surgery.
2. Chemotherapy
Chemotherapy is required for patients who cannot have complete resection of rhabdomyosarcoma. Chemotherapy can completely destroy the remaining tumor. Even if the tumor seems to be completely removed, chemotherapy is still necessary.
There are many cytotoxic chemotherapeutic agents, most of which are administered intravenously. The main agents used for completely resected embryonal rhabdomyosarcoma are vincristine and rennet, and cyclophosphamide is also commonly used for class II and III tumors.
Isocyclophosphamide kills rhabdomyosarcoma cells and is expected to improve survival in class IV patients. Chemotherapy drugs can also kill some normal cells and can cause side effects. Side effects include hair loss, nausea, vomiting, loss of appetite, fatigue, anemia, and susceptibility to infection. Most side effects go away when you stop taking the drug. Some drugs can permanently damage cells in the ovaries and testicles, making it difficult or even impossible to have children. The damage to the kidneys and bladder from cyclophosphamide or isocyclophosphamide is also permanent.
3. Radiation therapy
For rhabdomyosarcoma, radiotherapy is a very effective means of treatment and can be used as an adjunct to surgery. The radiation dose is selected according to age and site, and the radiation field should include the tumor bed and the surrounding 2-5 cm of normal tissue with an effective radiation dose of not less than 40Gy.
4. Magnetic induction therapy
Magnetic induction therapy uses the principle of heat generation of ferromagnetic material under alternating magnetic field to warm up tumor tissues to effective temperature so as to achieve treatment purpose. Magnetic induction therapy is characterized by targeting, conformability, self-control of temperature, internal heating, repeatability, and large temperature difference between normal tissue and tumor, etc. It is expected to overcome the shortcomings of previous local heat therapy methods for tumor and become a new effective means to treat tumor.
6.Prognosis
The location of transverse myosarcoma will affect the prognosis. The prognosis is better if it occurs in the head and neck and genitourinary area, and worse if it occurs in the limbs and trunk. Currently, the 5-year survival rate is close to 80% when combined with surgical radiotherapy and chemotherapy for those without metastases before starting treatment. Two-thirds of children with rhabdomyosarcoma survive.
Of greatest importance is the resection of the tumor.
Children with class I rhabdomyosarcoma have a good outcome, with more than 90% not recurring; 80% of class II and 70% of class III will survive long term; children with class IV have a poor outlook, with a 5-year survival rate of less than 30%. The prognosis for children with alveolar rhabdomyosarcoma is not as good as for children with embryonal rhabdomyosarcoma, who require more intensive chemotherapy.