Atypical teratoid rhabdoid tumor (ORPHA:99966)
A rare, highly malignant central nervous system (CNS) rhabdoid tumor (RT) found almost exclusively in children.
Epidemiology
The prevalence of ATRT is estimated to be 1- 2% among all pediatric CNS tumors and 10-20% of CNS tumors in patients less than 3 years. The age-standardized incidence rate is estimated to be 1/72,500 persons/year in Austria.
Clinical description
Onset of primary ATRT occurs from birth to adulthood, with the highest incidence in the first 2 years of life. Only single cases have been reported in adults. Manifestations of ATRT include macrocephaly, vomiting, irritability, headache, apathy/lethargy, ataxia, neck stiffness, and seizures. ATRT can occur in the posterior fossa, fourth ventricle, cerebellar vermis (with intraventricular extension), cerebellum (alone or in combination with a supratentorial tumor), cerebral hemisphere, pineal region, frontal lobe, brainstem, spinal cord or result from metastases of renal RT. ATRT can involve the cerebellopontine angle (CPA), resulting in acute cranial nerve deficits (such as acute facial nerve palsy) as the presenting sign.
Etiology
The vast majority of ATRT tumors show biallelic somatic inactivation of SMARCB1, a gene suppressor which encodes a core member of the adenosine triphosphate (ATP)-dependent SWI/SNF chromatin remodeling complex and which is a key regulator of cell proliferation and differentiation. In rare cases, mutations in the SMARCA4 gene, which encode another SWI/SNF chromatin-remodeling complex member, are observed.
Diagnostic methods
Diagnosis is based on imaging findings (magnetic resonance and computed tomography scan) showing large and hyperdense solid tumors with marked tumor necrosis, intratumoral hemorrhage, patchy pattern of enhancement and association with moderate to marked adjacent parenchymal edema. Intratumoral calcification may be observed. Histological examination of the tumor shows a diffuse growth pattern of predominantly polygonal cells, vesicular nuclei with prominent nucleoli, high mitotic index, multiple necrosis or cystic foci and scattered cells that contain a cytoplasmic hyaline globular inclusion adjacent to the nucleus (rhabdoid cells). ATRT may be composed only of rhabdoid cells or, more commonly, may contain areas of rhabdoid cells juxtaposed to areas of primitive neuroepithelial cells and/or mesenchymal tissue and/or epithelial tissue. Tumor cells are immunopositive for vimentin, epithelial markers (cytokeratin, epithelial membrane antigen), rarely positive for the mesenchymal marker S-100 and immunonegative for desmin, GFAP, synaptophysin and neurofilaments. Diagnosis is confirmed by loss of nuclear staining of SMARCB1 (or SMARCA4) protein by immunohistochemistry.
Differential diagnosis
Differential diagnosis includes medulloblastoma, ependymoblastoma, primitive neuroectodermal tumor, choroid plexus carcinoma, Ewing sarcoma (see these terms), undifferentiated chordoma, anaplastic meningioma and small cell sarcoma.
Genetic counseling
ATRT can occur sporadically or as part of a RT predisposition syndrome (familial RT; see this term).
Management and treatment
No standard of care exists for ATRT. Treatment includes the maximal resection of the tumor mass and postoperatively, chemotherapy with radiotherapy as long as it is compatible with the age of the patient.
Prognosis
ATRT is highly aggressive and the prognosis is exceedingly dismal compared with other malignant brain tumors. Reported survival times have ranged from 0.5 to 11 months, with a particularly poor outcome for infants.

                            Last update: 
                            February 2014


                            - Expert reviewer(s): 
                            Dr Franck BOURDEAUT