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Rhabdoid tumor (RT) is an aggressive pediatric soft tissue sarcoma that arises in the kidney, the liver, the peripheral nerves and all miscellaneous soft-parts throughout the body. RT involving the central nervous system (CNS) is called atypical teratoid rhabdoid tumor (ATRT; see this term).
ORPHA:69077Classification level: Disorder
The United Kingdom registry estimated that the age-standardized annual incidence of extra-CNS RT is about 1/2,000,000 children, which might be underestimated. Altogether, in infants less than one year, RT may account for 20% of renal cancers, and 15% of soft-part tumors. In the same age range, ATRT may be the most frequent malignant tumor of the posterior fossa.
RT usually occurs in infancy or childhood (mostly affecting patients < 2 years, with a median of 20 months).In most cases, the first symptoms are linked to the compressive effects of a bulky tumor (such as respiratory distress, abdomen mass, peripheral nerve palsy). Subcutaneous nodular metastases are specifically seen in patients with neonatal tumors. Exceptional cases can occur in adolescents and adults. RT arises in the kidney, liver, peripheral nerve and miscellaneous soft parts. Hypercalcemia may be seen at diagnosis (<1/3 of cases). RT affecting the CNS is called ATRT and constitutes about half of all RTs.
90% of RT cases have biallelic inactivation of SMARCB1 (22q11.23), a tumor suppressor gene encoding a member of SWI/SNF chromatin remodeling complex which broadly regulates the expression of the genome. Rare cases are associated with a biallelic mutation of SMARCA4 (19p13.3) (encoding another SWI/SNF chromatin-remodeling complex member).
Once a tumor is evidenced by imaging scans (magnetic resonance and computed tomography), the diagnosis relies on tumor biopsy. The tumor is composed of a diffuse proliferation of rounded or polygonal cells with eccentric nuclei, prominent nucleoli and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies, arranged in sheets and nests (rhabdoid cells). Tumor cells are usually positive to glypican-3 (50% of cases), vimentin, epithelial markers (keratins, epithelial membrane antigen) and mesenchymal markers (smooth muscle actin, muscle-specific actin, S100 protein). Diagnosis is confirmed by loss of nuclear staining of SMARCB1 (or SMARCA4, exceptionally) protein by immunohistochemistry.
Differential diagnosis includes all undifferentiated sarcomas, peripheral primitive neuroectodermal tumor in children, epithelioid sarcoma (especially the proximal type) in older patients, extraskeletal myxoid chondrosarcoma, and undifferentiated chordomas (see these terms) in cases with clivus involvement.
In 25% of cases, RT is associated with a germline mutation of SMARCB1. Rarely, germline mutations are inherited from asymptomatic parents, either because of gonadal mosaicism or incomplete penetrant mutations (familial RT; see this term). Adult carriers may develop multiple schwannomas or meningiomas (see these terms).
Management and treatment
No standard care exists for RT although several prospective trials are now running throughout the world. Treatment includes resection of the tumor mass (as complete as possible), multimodal aggressive chemotherapy and radiotherapy whenever feasible. However, the young age of patients may limit use of radiotherapy.
The survival rate is low with a 5 year survival rate of 20%. Prognostic factors include metastases, young age at diagnosis (< 2years), and incomplete resection.
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