An Atypical Teratoid Rhabdoid Tumor (ATRT) is a rare, highly aggressive cancer originating in the central nervous system (CNS). It is an embryonal tumor, developing from primitive cells that have not fully differentiated after birth. ATRT is classified as a Grade IV malignancy, indicating a fast-growing and highly malignant tumor requiring intensive medical intervention. This diagnosis overwhelmingly affects infants and very young children, and it is the most common malignant CNS tumor in infants under one year of age. The tumor most frequently develops in the cerebellum or brainstem, and its rapid growth causes symptoms like morning vomiting, headaches, or a bulging soft spot (fontanelle) in infants.
Defining Atypical Teratoid Rhabdoid Tumor (ATRT)
Atypical Teratoid Rhabdoid Tumor is classified by pathologists as a malignant rhabdoid tumor, distinguishing it from other brain cancers based on the specific appearance of the cells under a microscope. The term “rhabdoid” refers to the resemblance of some tumor cells to cells found in rhabdomyosarcoma, a type of soft tissue cancer. This classification links ATRT to a broader group of rhabdoid tumors that can occur outside the CNS. The tumor itself is often large and heterogeneous, meaning it contains a mixture of different cell types and tissues, which is why the term “teratoid” is used. These tumors can spread through the cerebrospinal fluid (CSF) to other areas of the brain and spinal cord, a process known as leptomeningeal spread.
The Genetic Basis of ATRT
The definitive identity of ATRT is rooted in a specific genetic alteration involving a tumor suppressor gene. Over 95% of ATRTs are characterized by the inactivation or deletion of both copies of the \(SMARCB1\) gene, also known as \(INI1\). This gene normally functions as a core subunit of the SWI/SNF chromatin remodeling complex, which regulates gene expression. When \(SMARCB1\) is inactivated, the resulting lack of the INI1 protein disrupts the cell’s ability to control growth and differentiation. This loss of protein is the defining molecular feature for diagnosis, and in a minority of patients, the mutation is present in all body cells, indicating a hereditary condition called Rhabdoid Tumor Predisposition Syndrome (RTPS).
Diagnostic Features and Confirmation
Initial detection of ATRT relies on advanced imaging techniques, such as magnetic resonance imaging (MRI) or computed tomography (CT) scans, which typically reveal a large, heterogeneous mass. However, a biopsy and pathological examination are required for a conclusive diagnosis, as ATRT can resemble other embryonal tumors. Confirmation focuses on two primary features: the presence of characteristic “rhabdoid cells” and the molecular signature. Rhabdoid cells are identifiable by their eccentric nucleus and abundant cytoplasm. The definitive diagnostic step involves immunohistochemical staining to check for the INI1 protein; in a true ATRT, genetic alterations cause a complete loss of this protein, leading to a negative nuclear stain in the tumor cells.
Current Treatment Approaches
Treatment for ATRT is aggressive and multimodal, involving a combination of therapies to combat the tumor’s fast-growing nature. The process usually begins with neurosurgery to achieve the maximum safe surgical resection, as the extent of removal influences the overall outcome. Following surgery, intensive chemotherapy is initiated, often including high-dose regimens and intrathecal chemotherapy, where drugs are delivered directly into the cerebrospinal fluid. Radiation therapy is also a component, but its use is often delayed or minimized in children under three years old due to neurotoxic effects on developing brains. To compensate, alternative approaches like high-dose chemotherapy with stem cell rescue are employed, and many patients are enrolled in clinical trials focused on targeted therapies.