Atypical teratoid rhabdoid tumor
As atypical teratoid / rhabdoid tumor, often abbreviated as ATRT or AT / RT, is a rare brain tumor from the group of embryonic tumors is called. The highly malignant tumor is classified as grade IV according to the WHO classification of tumors of the central nervous system and occurs predominantly on in young children.
Epidemiology
Atypical teratoid / rhabdoid tumors account for about 2% of all brain tumors in children, which predominantly affects children in the first years of life. In adults, the incidence is described only in isolated cases.
Sporadic cases where there is no connection with a hereditary disease can be seen predominate. A familial aggregation occurs at the so-called Rhabdoid - predisposition syndrome.
Symptoms
Atypical teratoid / rhabdoid tumors can be localized in the posterior fossa, but also occur in the cerebral hemispheres. The clinical presentation depends on the tumor location and the age of the child and is usually characterized by rapid tumor growth. Drowsiness, nausea and vomiting are common, but nonspecific symptoms.
Neuropathology
Typical name for the factor and histological ( histological ) characteristics are relatively large tumor cells, the marginal, prominent nucleolus ( nucleoli ) and have inclusions in their cell bodies, so-called rhabdoid tumor cells. You remember in her cell image to a malignant soft tissue tumor, rhabdomyosarcoma. Mitotic activity, cell density and nuclear pleomorphism are increased. Tumor necrosis are common. The tumor grows in unstructured or papillary structures, which can make differentiation from Plexuskarzinomen difficult. On the other hand, come next sections rhaboiden tumor cells often small cell before minority whose histology similar to that of other embryonic tumors such as medulloblastoma and the integrated SPNet.
Pathogenesis
Genetic changes that affect the SMARCB1 gene on chromosome 22q11.2 and its gene product, the INI1 protein lead to decreased expression, are characteristic. Approximately one third of patients have a germline mutation of the SMARCB1 gene is detectable. This finding is associated with younger age of onset and an even poorer prognosis.
The immunohistochemical detection of a lack of INI1 protein expression can be used diagnostically to differentiation from other tumors in the majority of cases. However, since ATRT can rarely occur in the context of genetic alterations of SMARCA4 ( BRG1 ), a gene chromatin remodeling complex encoding another subunit of the SWI / SNF, the evidence of a preserved INI1 expression makes the diagnosis of ATRT However, although unlikely, it excludes any circumstances.
Treatment and Prognosis
A complete surgical removal is often not achieved. As part of further treatment, which usually takes place in the context of clinical trials, therefore adjuvant chemotherapy and ( under an individual treatment regimen depending on the age of the child) may also be a radiation follows.
Even after surgical removal and initial good response to chemotherapy, the further course is often marked by a renewed tumor growth. Two years after diagnosis, 83 % of affected infants had died during a clinical study, despite intensive therapeutic efforts. Children with an age of about three years, have a slightly better prognosis, possibly due to (due to the side effects only in this age group can be carried out ) irradiation.
Through an intensive and aggressive combination treatment, a two -year survival rate of 70 % was achieved in the context of a study conducted at American clinics clinical trial.