ATRT (Atypical Teratoid Rhabdoid Tumor)
ATRT (atypical teratoid rhabdoid tumor) is an extremely rare and aggressive embryonal brain tumor of infants and young children. It is characterized by loss of the SMARCB1 (rarely SMARCA4) gene and is classified as grade 4 in the World Health Organization (WHO) classification.
Última actualización: 2026-06-06
Definition
ATRT, first described in 1987, is an embryonal central nervous system tumor. It is named after the characteristic 'rhabdoid' cells seen microscopically. Classified as grade 4 in the WHO scheme, it grows rapidly and tends to spread early.
Epidemiology
ATRT accounts for about 1-2% of all pediatric brain tumors; however, in infants under 3 years this proportion rises markedly, representing a significant share of malignant brain tumors in this age group. It is most common in infants aged 18-24 months, with a slight male predominance. About 60% of cases are infratentorial (posterior fossa) and 40% supratentorial.
Genetic and Molecular Basis
About 95% of cases show inactivation of the SMARCB1 (INI1) gene and roughly 5% the SMARCA4 gene; both are critical components of the SWI/SNF chromatin-remodeling complex. In about one-quarter of cases the mutation is germline (inherited), defining rhabdoid tumor predisposition syndrome (RTPS). DNA methylation profiling separates ATRT into three molecular subtypes — ATRT-TYR, ATRT-SHH and ATRT-MYC — which follow different courses.
Symptoms
Symptoms vary with tumor location and the child's age and usually progress rapidly. Infratentorial tumors cause signs of raised intracranial pressure: irritability in infants, projectile vomiting, rapid head growth (macrocephaly) and a bulging fontanelle. Imbalance and incoordination (ataxia) are common. Supratentorial tumors may cause seizures, weakness and personality changes. ATRT can spread early via the cerebrospinal fluid; leptomeningeal involvement is present at diagnosis in a substantial proportion of cases.
Diagnosis
Contrast-enhanced brain MRI is the first-line study; the tumor typically appears as a heterogeneous, avidly enhancing mass with solid and cystic components and often shows diffusion restriction. Imaging of the entire spine is mandatory to assess spread. Definitive diagnosis is made on tissue analysis; the key marker is loss of INI1 (SMARCB1) expression on immunohistochemistry. Demonstrating SMARCB1 or SMARCA4 mutations by molecular testing confirms the diagnosis, and germline testing is recommended to assess for an inherited mutation.
Treatment
Treatment requires a multidisciplinary approach and relies on intensive protocols combining surgery, chemotherapy and radiotherapy. Surgery aims for the widest safe resection (gross total resection is the most important prognostic factor). Intensive multi-agent chemotherapy is used, and in selected cases high-dose chemotherapy with autologous stem-cell rescue. Radiotherapy is part of standard care in children over 3 years; below this age it is deferred where possible because of its effects on the developing brain. The EZH2 inhibitor tazemetostat has received accelerated approval for SMARCB1-deficient tumors and is being studied in selected cases.
Prognosis
The overall prognosis of ATRT is poor; median survival is reported as 12-18 months in the literature. However, long-term survival is possible in selected patients who achieve gross total resection and receive intensive multimodal therapy. Molecular subtype affects outcome: ATRT-SHH is relatively more favorable and ATRT-MYC less favorable. Recurrence rates are high. Outcomes are individual and none can be guaranteed; comprehensive support and, where appropriate, genetic counseling should be offered to families.
Referencias
- Greenberg MS. Greenberg's Handbook of Neurosurgery. 10th ed. Thieme; 2023:755.
- Osborn AG, Hedlund GL, Salzman KL. Osborn's Brain: Imaging, Pathology, and Anatomy. 2nd ed. Elsevier; 2018:652.
- Louis DN, et al. The 2021 WHO Classification of Tumors of the Central Nervous System. Neuro Oncol. 2021.
Este artículo es informativo y no sustituye un examen médico. Las decisiones de diagnóstico y tratamiento son individuales.