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  • Updated 03.21.2024
  • Released 04.29.2003
  • Expires For CME 03.21.2027

Atypical teratoid/rhabdoid tumors



Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor that typically affects young children. Once considered uniformly fatal, intensive multimodal treatment regimens have resulted in improved survival for some patients. The Children’s Oncology Group (COG) published the largest series of prospectively treated patients with atypical teratoid/rhabdoid tumor, demonstrating significantly improved survival for patients younger than 3 years of age compared to historical cohorts. Atypical teratoid/rhabdoid tumor is the first pediatric brain tumor for which a candidate tumor suppressor gene, SMARCB1, was identified. Gene expression profiling analysis suggests that there are three to four distinct molecular subtypes of atypical teratoid/rhabdoid tumors, each with distinct clinic-pathological characteristics.

Key points

• Intensive multimodal therapy has improved the outcomes of patients with atypical teratoid/rhabdoid tumors.

• A somatic mutation of the SMARCB1 or SMARCA4 gene is found in nearly all atypical teratoid/rhabdoid tumors, and an immune-histochemical stain for the gene product can help pathologists readily identify the tumor.

• Patients with germline mutations for the SMARCB/SMARCA4 gene may have synchronous tumors, and their disease may behave more aggressively.

• ATRT appears to contain three to four subgroups with distinct epigenomic, transcriptional, and clinic-pathologic features.

• Studies that incorporated targeted biological therapies to treat atypical teratoid/rhabdoid tumors are underway.

Historical note and terminology

Atypical teratoid/rhabdoid tumor of the central nervous system is a rare, highly malignant disease that occurs primarily in young children. The disease is often simply referred to as ATRT. It was first identified by Rorke and colleagues as a unique tumor type in 1987. Before that time, patients with atypical teratoid/rhabdoid tumor were often misdiagnosed as having medulloblastoma or other embryonal tumor. This is understandable as approximately two thirds of atypical teratoid/rhabdoid tumors have components that resemble medulloblastoma or other embryonal tumors (42). In addition to rhabdoid cells, atypical teratoid/rhabdoid tumors often contain malignant epithelial and mesenchymal components that further distinguish them from medulloblastoma or other embryonal tumors. Because it histologically resembles the rhabdoid tumor of the kidney, atypical teratoid/rhabdoid tumor was sometimes referred to as malignant rhabdoid tumor of the brain or central nervous system (17) before it was recognized as a distinct entity. The World Health Organization began classifying atypical teratoid/rhabdoid tumor as embryonal grade IV neoplasm in 1993 (32).

Work by Biegel and colleagues identified recurrent deletions/translocations of chromosome 22 as characteristic cytogenetic abnormality in the majority of atypical teratoid rhabdoid tumors (05). The deletions target the SMARCB1 gene in chromosome band 22q11.2, which demonstrates biallelic mutations, deletions, or intragenic duplications in up to 98% of atypical teratoid rhabdoid tumors (06).

Several names are given to the mutated gene in atypical teratoid rhabdoid tumor. It is referred to here as SMARCB1, as this is now its official Human Genome Organization (HUGO) name (31). Other names used for this gene are SNF5, INI-1, and BAF47; they all refer to the same gene or encoding protein.

In 2014, Hasselblatt and colleagues demonstrated that biallelic inactivation of SMARCA4 (or it’s protein BRG-1) was associated with somatic and germline alterations in patients with atypical teratoid/rhabdoid tumor and rhabdoid tumor predisposition syndrome (RTPS), further expanding the diagnostic criteria for atypical teratoid/rhabdoid tumor (23).

Since the description of BAF47/INI1 protein expression using immunostaining (30; 29), atypical teratoid/rhabdoid tumors have been increasingly recognized and frequently diagnosed (52).

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