Primary brain tumors, including atypical teratoid/rhabdoid tumors, are a diverse group of diseases that together constitute the most common solid tumor of childhood. The PDQ childhood brain tumor treatment summaries are primarily organized according to the World Health Organization classification of nervous system tumors.[
CNS atypical teratoid/rhabdoid tumor (AT/RT) is a rare, clinically aggressive tumor that most often affects children aged 3 years and younger but can occur in older children and adults. Approximately one-half of AT/RTs arise in the posterior fossa.[
Based on present biological understanding, AT/RT is part of a larger family of rhabdoid tumors. In this summary, the term AT/RT refers to CNS tumors only and the term rhabdoid tumor reflects the possibility of both CNS and non-CNS tumors. Unless specifically noted in the text, this summary is referring to CNS AT/RT.
Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.
The exact incidence of childhood CNS AT/RT is difficult to determine because the tumor is rare and has only been recognized since 1996.[
The incidence in older patients is unknown. However, in the Central Nervous System Atypical Teratoid/Rhabdoid Tumor Registry (AT/RT Registry), 12 of the 42 patients (29%) were older than 36 months at the time of diagnosis.[
Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain. The tentorium separates the cerebrum from the cerebellum. The infratentorium (posterior fossa) is the region below the tentorium that contains the brain stem, cerebellum, and fourth ventricle. The supratentorium is the region above the tentorium and denotes the region that contains the cerebrum.
Childhood AT/RT is a clinically aggressive tumor that primarily occurs in children younger than 3 years, but it also can occur in older children and adults.[
Approximately one-half of all AT/RTs arise in the posterior fossa, although it can occur anywhere in the CNS.[
Because AT/RT grows rapidly, patients typically have a fairly short history of progressive symptoms, measured in days to weeks. Signs and symptoms depend on tumor location. Young patients with posterior fossa tumors usually present with symptoms related to hydrocephalus, which include the following:
They may also develop ataxia or regression of motor skills.
Registry data suggest that up to 30% of patients present with disseminated disease.[
All patients with suspected childhood AT/RT should undergo MRI of the brain and spine. Unless medically contraindicated, the lumbar cerebrospinal fluid should be inspected for evidence of tumor. Patients may also undergo renal ultrasonography to detect synchronous tumors.
AT/RTs cannot be reliably distinguished from other malignant brain tumors on the basis of clinical history or radiographic evaluation alone. Surgery is necessary to obtain tissue and confirm the diagnosis. Immunohistochemical staining for loss of SMARCB1 protein expression is also used to confirm the diagnosis.[
Prognostic factors that affect survival for patients with AT/RTs are not fully delineated.
Known factors associated with a poor outcome include the following:
Most published data on outcomes of patients with AT/RT are from small series and are retrospective in nature. Initial retrospective studies reported an average survival from diagnosis of only about 12 months.[
There are reports of long-term survivors.[
Childhood central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT) was first described as a discrete clinical entity in 1987 [
Histologically, AT/RT is morphologically heterogeneous, typically containing sheets of large epithelioid cells with abundant eosinophilic cytoplasm and scattered rhabdoid cells, most often with accompanying components of primitive neuroectodermal cells (small round blue cells), mesenchymal cells, and/or glial cells.[
Immunohistochemical staining for epithelial markers (cytokeratin or epithelial membrane antigen), glial fibrillary acidic protein, synaptophysin (or neurofilament), and smooth muscle (desmin) may help to identify the heterogeneity of differentiation, but will vary depending on the cellular composition.[
Immunohistochemical staining for the SMARCB1 protein is useful in establishing the diagnosis of AT/RT. A loss of SMARCB1 staining is noted in neoplastic cells, but staining is retained in non-neoplastic cells (e.g., vascular endothelial cells).[
AT/RT is a rapidly growing tumor that can have an MIB-1 labeling index of 50% to 100%.[
Genomics of CNS Atypical Teratoid/Rhabdoid Tumor (AT/RT)
AT/RT was the first primary pediatric brain tumor in which a candidate tumor suppressor gene, SMARCB1 (previously known as INI1 and hSNF5), was identified.[
Rare cases of rhabdoid tumors expressing SMARCB1 and lacking SMARCB1 mutations have also been associated with somatic or germline mutations of SMARCA4/BRG1, another member of the SWI/SNF chromatin-remodeling complex.[
Less commonly, SMARCA4-negative (with retained SMARCB1) tumors have been described.[
The 2016 WHO classification defines AT/RT by the presence of either SMARCB1 or SMARCA4 alterations. Tumors with histological features of AT/RT that lack these genomic alterations are termed CNS embryonal tumor with rhabdoid features.[
Despite the absence of recurring genomic alterations beyond SMARCB1 and SMARCA4,[
Cribriform neuroepithelial tumor is a brain cancer that also presents in young children and has genomic and epigenomic characteristics that are very similar to AT/RT TYR.[
In addition to somatic mutations, germline mutations in SMARCB1 have been reported in a substantial subset of patients with AT/RT.[
Gonadal mosaicism has also been observed, as evidenced by families in which multiple siblings are affected by AT/RT and have identical SMARCB1 alterations, but both parents lack a SMARCB1 mutation/deletion.[
Loss of SMARCB1 or SMARCA4 protein expression has therapeutic significance, because this loss creates a dependence of the cancer cells on EZH2 activity.[
Rhabdoid Tumor Predisposition Syndrome (RTPS)
RTPS, which is primarily related to germline SMARCB1 alterations (and less commonly to germline SMARCA4 alterations), has been clearly defined.[
This syndrome is manifested by a marked predisposition to the development of malignant rhabdoid tumors in infancy and early childhood. Up to one-third of AT/RTs are thought to arise in the setting of RTPS, and most of these occur within the first year of life. The most common non-CNS malignancy of RTPS is malignant rhabdoid tumor of the kidney, which is also noted in infancy.
For more information about RTPS, see the Genetic Testing and Surveillance of Rhabdoid Tumors of the Kidney section in Wilms Tumor and Other Childhood Kidney Tumors Treatment.
Cribriform Neuroepithelial Tumor
Cribriform neuroepithelial tumor is histologically and clinically distinct from AT/RT, but it has genomic and epigenomic characteristics that are very similar to AT/RT TYR.[
There is no defined staging system for childhood central nervous system atypical teratoid/rhabdoid tumor. For treatment purposes, patients are classified as having newly diagnosed or recurrent disease with or without neuraxis dissemination.
A standard treatment for children with newly diagnosed central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT) has not yet been defined. Given the highly aggressive nature of the tumor, most patients have been treated with intensive multimodality therapy. However, the extent of treatment, particularly for radiation therapy, is limited because of the young age of most patients.
Treatment options for newly diagnosed CNS AT/RT include the following:
Surgery, Chemotherapy, and Radiation Therapy (Multimodality Therapy)
The extent of the surgical resection may affect survival. Data from the Central Nervous System Atypical Teratoid/Rhabdoid Tumor Registry (AT/RT Registry) suggest that patients who have had a complete resection may have a longer median survival, although complete surgical resection is often difficult because of the invasive nature of the tumor.[
Chemotherapy has been the main adjuvant therapy for very young children with AT/RT. Cooperative group studies that included children younger than 36 months demonstrated poor survival when treated with standard chemotherapeutic regimens alone.[
Intensive regimens that use varying combinations of high-dose chemotherapy,[
Thirteen patients in the AT/RT Registry were treated with high-dose chemotherapy with hematopoietic stem cell rescue as part of initial therapy.[
Radiation therapy appears to have a positive impact on survival for patients with AT/RT.
Evidence (radiation therapy):
Evidence (multimodality therapy):
On the basis of the two prospective studies summarized above, multimodality therapy with surgery, radiation therapy, and chemotherapy seems to be the best treatment to optimize the survival of children with AT/RT. However, toxicities can be significant, and the most effective regimen and the optimal sequencing of therapies still need to be determined.
Treatment Options Under Clinical Evaluation
Early-phase therapeutic trials may be available for selected patients. These trials may be available via the Children's Oncology Group, the Pediatric Brain Tumor Consortium, or other entities. Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.
There is no standard treatment for children with recurrent central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT).
Trials of molecularly targeted therapy are ongoing. In a study of the EZH2 inhibitor tazemetostat in adult patients with epithelioid sarcoma and non-CNS malignant rhabdoid tumors with SMARCB1 or SMARCA4 loss, prolonged stable disease and objective responses were observed.[
Stereotactic radiation therapy/radiosurgery or focal radiation therapy can also be considered for the treatment of children with recurrent disease.[
Patients or families who desire additional disease-directed therapy should consider entering trials of novel therapeutic approaches because no standard agents have demonstrated clinically significant activity.
Regardless of whether a decision is made to pursue disease-directed therapy at the time of progression, palliative care remains a central focus of management. This ensures that quality of life is maximized while attempting to reduce symptoms and stress related to the terminal illness.
Treatment Options Under Clinical Evaluation
Early-phase therapeutic trials may be available for selected patients. These trials may be available via the Children's Oncology Group (COG), the Pediatric Brain Tumor Consortium, or other entities. Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website.
The following are examples of national and/or institutional clinical trials that are currently being conducted:
Patients with tumors that have molecular variants addressed by open treatment arms in the trial may be enrolled in treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment of Recurrent Childhood CNS Atypical Teratoid/Rhabdoid Tumor (AT/RT)
Added text about the PEPN2121 clinical trial as a treatment option under clinical evaluation for children with recurrent AT/RTs.
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood central nervous system atypical teratoid and rhabdoid tumor. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment are:
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Levels of Evidence
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PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Central Nervous System Atypical Teratoid/Rhabdoid Tumor Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/brain/hp/child-cns-atrt-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389426]
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Last Revised: 2022-12-07
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