Table of Contents

    1.    Introduction: What Is Atypical Teratoid/Rhabdoid Tumor (AT/RT)?
    2.    Epidemiology and Genetic Causes
    3.    Symptoms and Clinical Presentation
    4.    Diagnostic Evaluation and Genetic Testing
    5.    Staging and Risk Stratification
    6.    Multidisciplinary Treatment of AT/RT
    •    Neurosurgery
    •    Chemotherapy
    •    Radiotherapy
    •    Stem Cell Transplantation
    •    Targeted and Experimental Therapies
    7.    Personalized Medicine: The Role of Genetics (SMARCB1/INI1)
    8.    Prognosis and Survival Rates
    9.    Rehabilitation and Neurocognitive Support
    10.    AT/RT Care at RecMed: Advanced Pediatric Oncology in Türkiye
    11.    References

 1. Introduction: What Is Atypical Teratoid/Rhabdoid Tumor (AT/RT)?

Atypical Teratoid/Rhabdoid Tumor (AT/RT) is a rare and highly aggressive brain tumor that primarily affects infants and very young children, usually under 3 years of age.
It arises in the central nervous system (CNS) — most commonly in the posterior fossa (cerebellum) or cerebral hemispheres — and accounts for about 1–2 % of all pediatric brain tumors, but nearly 10 % of CNS tumors in children under 3.

AT/RT is classified as a WHO Grade IV embryonal tumor, characterized by inactivation of the SMARCB1 (INI1) or less commonly SMARCA4 tumor-suppressor gene, which disrupts chromatin regulation and leads to uncontrolled tumor growth.

 2. Epidemiology and Genetic Causes

    •    Median age at diagnosis: 11–18 months.
    •    Slight male predominance (1.5 : 1).
    •    May arise in the cerebellum, brainstem, or spinal cord; occasionally in extracranial sites (kidney, soft tissue).

Genetic drivers:
    •    SMARCB1 (INI1) gene inactivation on chromosome 22q11.2 is detected in ~95 % of cases.
    •    Germline mutations (rhabdoid tumor predisposition syndrome type 1 / 2) may occur.
    •    The tumor is part of the SWI/SNF chromatin-remodeling complex pathway disorder group.

Understanding these genetic alterations is essential for accurate diagnosis, risk assessment, and targeted therapy planning.

 3. Symptoms and Clinical Presentation

Symptoms depend on tumor location and rate of growth. Common features include:
    •    Persistent vomiting, irritability, or lethargy (signs of raised intracranial pressure).
    •    Rapidly increasing head circumference in infants (hydrocephalus).
    •    Ataxia, imbalance, or poor coordination (posterior fossa involvement).
    •    Seizures or focal neurological deficits (supratentorial tumors).
    •    Cranial nerve palsy, nystagmus, or visual disturbances.

AT/RT can progress rapidly — even over days or weeks — making early neuroimaging and referral critical.

 4. Diagnostic Evaluation and Genetic Testing

A precise diagnosis requires a combination of imaging, histology, and molecular testing.

Diagnostic steps:
    •    MRI of the brain and spine with contrast (gold standard for detection).
    •    Surgical biopsy or resection for histopathological confirmation.
    •    Immunohistochemistry: loss of INI1 (SMARCB1) nuclear expression is diagnostic.
    •    Cerebrospinal fluid (CSF) analysis to assess dissemination.
    •    Molecular genetic testing (germline and somatic SMARCB1/SMARCA4 sequencing).

Differential diagnoses include medulloblastoma, CNS PNET, and choroid plexus carcinoma — but the loss of INI1 expression is pathognomonic for AT/RT.

 5. Staging and Risk Stratification

AT/RT is staged according to:
    •    Extent of resection (gross total vs. subtotal).
    •    Presence of leptomeningeal dissemination on MRI/CSF cytology.
    •    Patient age (under 3 years = high-risk).

While no universal staging exists, classification into localized vs. disseminated disease helps guide intensity of therapy.

 6. Multidisciplinary Treatment of AT/RT

Treatment requires coordination among pediatric neurosurgeons, neuro-oncologists, radiation oncologists, and rehabilitation teams.
Because of the tumor’s aggressiveness and rarity, management in specialized pediatric oncology centers is essential.

Neurosurgery
    •    Aim: maximal safe resection without compromising vital neurological function.
    •    Complete removal improves survival but is often limited by tumor location.

Chemotherapy
    •    Used postoperatively to target residual microscopic disease.
    •    Common regimens include high-dose methotrexate, vincristine, cisplatin, cyclophosphamide, etoposide, carboplatin, and ifosfamide.
    •    Some protocols employ high-dose chemotherapy with autologous stem cell rescue.

Radiotherapy
    •    Radiotherapy is highly effective but limited in very young children due to neurotoxicity.
    •    For children ≥3 years, craniospinal irradiation with focal boost is standard; for younger patients, delayed or proton therapy may be used to minimize side effects.

Stem Cell Transplantation
    •    High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is increasingly used to consolidate remission.

Targeted and Experimental Therapies
    •    Investigational approaches include EZH2 inhibitors, immune checkpoint blockade, and molecular agents restoring SWI/SNF function.
    •    Enrollment in international AT/RT clinical trials (e.g., EU-RHAB, COG ACNS protocols) is encouraged.

 7. Personalized Medicine: The Role of Genetics (SMARCB1/INI1)

AT/RT is among the most genetically defined pediatric tumors.
Testing for SMARCB1/SMARCA4 mutations guides diagnosis, identifies hereditary syndromes, and may open access to novel therapies targeting epigenetic dysregulation.
Genetic counseling for families is recommended, as ~25 % of cases carry germline variants.

 8. Prognosis and Survival Rates

Despite progress, AT/RT remains a challenging diagnosis.
    •    Overall survival: 40–50 % in recent series (higher in children >3 years).
    •    Median survival: 18–24 months with intensive multimodal therapy.
    •    Prognostic factors: extent of surgical resection, age, dissemination, and molecular subgroup (AT/RT-TYR, MYC, SHH).

Survival rates continue to improve due to early molecular diagnosis, advanced surgery, and international treatment protocols.

 9. Rehabilitation and Neurocognitive Support

Comprehensive post-treatment care includes:
    •    Neurocognitive and psychomotor rehabilitation;
    •    Endocrine and hearing monitoring;
    •    Physiotherapy and speech therapy;
    •    Psychological and family support programs.

Long-term follow-up aims to preserve quality of life and detect late complications early.

 10. AT/RT Care at RecMed: Advanced Pediatric Oncology in Türkiye

RecMed Medical Travel (Istanbul, Türkiye) collaborates with leading pediatric neurosurgery and oncology centers to offer advanced multidisciplinary care for AT/RT:
    •    Expert diagnostics including MRI, molecular testing, and histopathology review.
    •    Complex neurosurgery performed by high-volume pediatric brain tumor surgeons.
    •    Tailored chemotherapy and radiotherapy based on international protocols (COG, EU-RHAB).
    •    Access to clinical trials and targeted agents.
    •    Dedicated patient coordination — visa, accommodation, translation, and family support.

RecMed’s mission is to combine world-class medical expertise and compassionate family-oriented care, giving every child access to cutting-edge treatment and hope for recovery.

 11. References

    1.    National Cancer Institute (NCI). Childhood Atypical Teratoid/Rhabdoid Tumor Treatment (PDQ®), 2025.
    2.    ESMO Clinical Practice Guidelines. CNS Embryonal Tumors Including AT/RT, 2024.
    3.    Children’s Oncology Group (COG) Protocol ACNS0333. AT/RT Treatment and Outcomes, 2025.
    4.    WHO Classification of CNS Tumors, 5th Edition (2024).
    5.    PubMed. Molecular Subgroups and Targeted Therapy in AT/RT, 2024.
    6.    EU-RHAB Registry (2025). International Prospective Study on Pediatric AT/RT.