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Rhabdomyosarcoma


Description

Rhabdomyosarcoma (also referred to as rhabdosarcoma) is a highly malignant tumor of straited muscle. There are 3 forms - pleomorphic, alveolar, and embryonal. The pleomorphic form affects predominantly the extremities of adults. The alveolar form, occurring primarily in adolescents and young adults affects muscles of extremities, trunk, and orbital region. The embryonal form, occurring mainly in infants and children, affects the head and neck, lower genitourinary tract, pelvis and extremities. Sarcomas are one of the most common solid tumors of childhood and are the fifth most common cause of cancer deaths in children.

Causes

Rhabdomyosarcoma is a consequence of fetal alcohol syndrome. Alveolar rhabdomyosarcoma is associated with translocation of gene 2; 13.

Trauma or previous injury is rarely involved, but sarcomas can arise in scar tissue resulting from a prior operation, burn, fracture, or foreign body implantation. Chemical carcinogens such as polycyclic hydrocarbons, asbestos, and dioxin may be involved in the pathogenesis.

Sarcomas in bone or soft tissues occur in cancer patients who are treated with radiation and survive at least 5 years. The tumor nearly always arises in the irradiated field. The risk increases with time.

The association of Kaposi's sarcoma (KS) with human immunodeficiency virus (HIV) type 1 has led to studies of the role of viruses in the pathogenesis of KS. Herpesvirus-like DNA sequences have been documented in AIDS-associated KS, classic KS, and KS in HIV-negative homosexual men, leading to the hypothesis that this new herpes virus [human herpes virus (HHV8)] may be the common etiologic factor for all three variants of KS.

Congenital or acquired immunodeficiency, including therapeutic immunosuppression, is associated with or influences sarcoma development.

Li-Fraumeni syndrome is a familial cancer syndrome in which affected individuals have germ-line abnormalities of the tumor suppressor gene p53 and an increased incidence of soft tissue sarcomas and other malignancies, including breast cancer, osteosarcoma, brain tumors, leukemia, and adrenal carcinoma. Neurofibromatosis-1, the peripheral form of von Recklinghausen's disease, is characterized by multiple neurofibromas and cafe au lait spots. Neurofibromas occasionally undergo malignant degeneration to become malignant peripheral nerve sheath tumors. The gene for NF-1 is located in the pericentromeric region of chromosome 17 and encodes neurofibromin, a tumor suppressor protein with GTPase-activating activity that inhibits Ras function (Chap. 375). Germ-line mutation of the Rb-1 locus (chromosome 13q14) in patients with inherited retinoblastoma is associated with the development of osteosarcoma in those who survive the retinoblastoma and of soft tissue sarcomas unrelated to radiation therapy. Other soft tissue tumors, including desmoid tumors, lipomas, leiomyomas, neuroblastomas, and paragangliomas, occasionally show a familial predisposition.

Insulin-like growth factor (IGF) type 2 is produced by some sarcomas and is thought to act both as an autocrine growth factor and as a motility factor that promotes metastatic spread. Antibodies to IGF-1 receptors block the stimulation of growth by IGF-2 in vitro but do not affect IGF-2-induced motility. If secreted in large amounts, IGF-2 may produce hypoglycemia.

Several studies have shown that nickel toxicity can cause sarcoma.

Many patients with sarcoma also present with thyroid disorders. Oncogene erbA activity is related to thyroid receptors to T3 and to the development of sarcoma.

Rhabdomyosarcoma has occurred after commencement of hormone replacement therapy with estrogen and progesterone. One study concluded that the steroid hormones might be closely related to tumor cell infiltration of some malignant soft tissue tumors.

One study showed a relationship between tumor growth and homocysteine. Homocysteine is a toxic compound that is reduced with vitamin B6, B12, folic acid and methyl donors (betain, TMG, SAMe). Another study also showed that methionine (a methyl donor) inhibited tumorigenesis.

 

 

 

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