Atypical Teratoid/Rhabdoid Tumour of CNS

Atypical teratoid/rhabdoid tumor (ATRT) is a very rare and aggressive cancer of the brain or spinal cord that grows quickly and requires immediate medical attention.

Table of contents

• What is ATRT?
• Where do ATRT tumors occur?
• Who is affected by ATRT?
• What are the symptoms?
• What causes ATRT?
• How is ATRT diagnosed?
• How is ATRT classified?
• How is ATRT treated?
• What is the outlook?

What is ATRT?

An atypical teratoid/rhabdoid tumor (ATRT) is a very rare, aggressive tumor of the central nervous system (the brain and spinal cord)^[1]. ATRT is a type of cancer that begins in the tissues of the brain or spinal cord^[10].

ATRTs are classified as embryonal tumors, meaning that they develop from stem cells that helped the embryo to form in the womb, but have unfortunately remained active in the brain after birth. When these stem cells fail to stop dividing and developing after the child is born, they can form a cancerous tumor^[3].

These tumors are part of a larger group of malignant tumors called rhabdoid tumors, which also can occur outside the brain^[1]. They develop from several different very young cells called embryonal cells, including rhabdoid, neuroepithelial, epithelial, and mesenchymal cells^[2].

All ATRTs are classified as grade 4 tumors. This means they are malignant (cancerous) and fast-growing^[2]. ATRTs represent only 1 to 2 percent of childhood brain tumors^[1]. While only representing 3% of all pediatric central nervous system tumors, ATRT is the most common malignant central nervous system tumor in children less than one year of age and represents 20% of central nervous system tumors in children less than three years of age^[12].

• Brain
• Spinal cord
• Cerebellum
• Brain stem
• Cerebral hemispheres

Where do ATRT tumors occur?

ATRTs can form anywhere in the central nervous system. They can be found anywhere in the brain or spinal cord^[3]. About half of these tumors form in the cerebellum or brain stem^[10]. The cerebellum is the part of the brain that controls movement, balance, and posture. The brain stem controls breathing, heart rate, and the nerves and muscles used in seeing, hearing, walking, talking, and eating^[10].

ATRTs in the brain can arise in the cerebral hemispheres, ventricles, suprasellar region, pineal gland, or the cerebellum and brainstem. ATRTs can also begin in the spinal cord, but this is less common^[2]. They tend to begin in the brain and spread to the spinal cord rather than the other way around^[3].

ATRTs may be localized to one part of the brain, or they can spread to other locations in the brain, spine, or body^[1]. Because ATRTs are fast-growing, they often spread to other areas of the central nervous system through cerebrospinal fluid, the liquid that surrounds the brain and spinal cord^[2].

Who is affected by ATRT?

ATRT most often occurs in children age 3 and younger. It is the most common malignant central nervous system tumor in infants under 1 year old^[9]. ATRTs usually occur by age 3, but sometimes are found in older children^[1]. Although it can occur in older children and adults, this is rare^[5].

In the United States, an estimated 470 people are living with this tumor, and only 50 are adults^[2]. There are fewer than 100 new cases of ATRT in the United States each year^[9]. One study estimated that this equals about 73 people who receive this diagnosis each year, and only 4 people out of 73 are adults^[6].

Most patients are younger than two years of age at diagnosis^[2]. ATRTs occur slightly more often in males than females^[2].

What are the symptoms?

Atypical teratoid rhabdoid tumors can cause a variety of symptoms in children depending on their size and location^[1]. The symptoms of ATRT are not the same in every person^[10]. Symptoms depend on the child’s age and where the tumor has formed^[10].

ATRT symptoms can come on quickly, in a matter of days or weeks, due to the fast-growing nature of these tumors^[1]. Because ATRTs are fast growing, symptoms may develop quickly and get worse over a period of days or weeks^[10]. It may seem like your child has a common illness at first, but their symptoms don’t get better with time or traditional therapies^[6].

The following symptoms may happen suddenly and get worse quickly^[6]:

• Headache, generally upon awakening in the morning^[1]
• Hydrocephalus, where there is a buildup of fluid in the brain which can result in increased head size in infants or headaches and vomiting in older children^[1]
• Nausea and vomiting, often worse in the morning and improve throughout the day^[1]
• Lethargy and fatigue^[1]
• Trouble with balance and coordination^[1]
• Changes in activity levels^[2]
• Loss of balance^[2]
• Difficulty with walking^[6]

Parents or caregivers may notice that infants have a larger head size because of this tumor, but it may not be as noticeable in older children^[6].

Keep in mind, the symptoms may resemble other more common conditions or medical problems. It is important to consult your child’s physician if you have concerns^[1].

What causes ATRT?

As a parent, you undoubtedly want to know what may have caused your child’s tumor. It’s important to remember that nothing you could have done or avoided doing would have prevented the tumor from developing^[1].

Cancer is a genetic disease—that is, it is caused by certain changes to genes that control the way our cells function. Genes may be mutated (changed) in many types of cancer, which can increase the growth and spread of cancer cells^[2].

Most ATRTs are caused by changes in a gene known as SMARCB1 (also called INI1), and less frequently by mutations in a gene called SMARCA4^[2]. These are tumor suppressor genes. They make a protein that helps control how and when cells grow. A change to one of these genes can cause cells to grow uncontrollably, which leads to tumors^[6].

SMARCB1 normally signals proteins to stop tumor growth. But, in ATRTs, SMARCB1 doesn’t function properly and tumor growth is uncontrolled^[2]. More than 90 percent of cases of ATRT are associated with this mutation and are not inherited. However, the cause of this abnormality is not known^[1].

Yes, some cases of ATRT are genetic. You can inherit the gene change from your biological parents. But most cases aren’t inherited. Instead, the gene change happens randomly without a history in your biological family^[6]. The changes in the SMARCB1 or SMARCA4 genes may be inherited (passed on from parents to offspring). When this gene change is inherited, tumors may form in two parts of the body at the same time (for example, in the brain and the kidney)^[10].

Approximately one-third of patients with ATRT have an underlying germline SMARCB1 alteration resulting in rhabdoid tumor predisposition syndrome, carrying a risk of multiple central nervous system and non-central nervous system rhabdoid tumors^[12]. If this mutation has been inherited, your child may be at increased risk of developing other tumors^[1].

For children with ATRT, genetic counseling (a discussion with a trained professional about inherited diseases and a possible need for gene testing) may be recommended^[10].

In addition to occurring in the tumor’s DNA, SMARCB1 and SMARCA4 can also be found in a person’s own DNA. There are three groups of ATRTs based on their genetic alterations: AT/RT-TYR, AT/RT-SHH, and AT/RT-MYC. Each group tends to develop in a different location of the central nervous system and is more common in different age groups. AT/RT-MYC is the most frequent group in adults^[2].

How is ATRT diagnosed?

The first step in treating your child’s atypical teratoid rhabdoid tumor is forming an accurate and complete diagnosis. ATRT is most commonly diagnosed from imaging studies and biopsy^[1].

A healthcare provider will diagnose ATRT after a physical exam, a neurological exam and testing. During the exams, your child’s provider will learn more about their symptoms, medical history and family medical history^[6].

To get an accurate diagnosis, a piece of tumor tissue will be removed during surgery, if possible. A neuropathologist should then review the tumor tissue^[2]. Childhood ATRT is diagnosed using a biopsy, and the tumor may be removed in the same surgery^[10].

Although the morphologic appearance of ATRT varies significantly, the loss of INI1 (SMARCB1) or BRG1 (SMARCA4) by immunohistochemical staining allows for rapid histologic diagnosis^[12].

Tests used to diagnose ATRT may include^[6]:

• MRI (magnetic resonance imaging): ATRTs usually appear very large with fluid-filled areas that often brighten with contrast on an MRI scan. You can often see areas of bleeding or dead tissue^[2]
• Lumbar puncture (also called spinal tap): A procedure to collect cerebrospinal fluid to check if the tumor has spread
• Genetic testing: To check for gene changes in SMARCB1 or SMARCA4
• Biopsy: Removal and examination of tumor tissue

People diagnosed with ATRT need tests (called staging) to determine if the tumor has spread to other areas. These tests include MRI examinations of the brain and spinal cord, as well as a spinal tap^[2].

How is ATRT classified?

Successfully treating your child’s ATRT depends on where the tumor is located and whether the tumor has spread. For many tumors, we use a system of classification called “staging” to evaluate cancers. However, there is currently no standardized classification system for atypical teratoid rhabdoid tumors^[1].

An ATRT may be^[1]:

• Localized, occurring in only one location in the brain
• Disseminated, spread to multiple locations in the brain, spinal cord, or body

Primary central nervous system tumors are graded based on the tumor location, tumor type, extent of tumor spread, genetic findings, the patient’s age, and tumor remaining after surgery, if surgery is possible^[2].

Certain factors affect prognosis (chance of recovery) and treatment options. These include the child’s age, where the tumor has formed, whether the tumor has spread, the results of genetic testing, and how much of the tumor remains after surgery^[10].

How is ATRT treated?

Your child’s healthcare provider may recommend the following to treat ATRT^[6]:

Removal surgery: A neurosurgeon will surgically remove as much of the tumor as possible. Your child may need chemotherapy and radiation therapy after surgery to destroy any remaining cancer cells^[6].

Chemotherapy: Treatment generally involves surgery to remove the tumor followed by intensive chemotherapy^[7]. This uses medications to destroy cancer cells or stop them from growing.

Radiation therapy: Radiation is often utilized depending on the age of the patient and if the tumor has spread^[7]. This uses high-energy rays to destroy cancer cells.

Treatment decisions depend on several factors including the child’s age, tumor location, and whether the cancer has spread. The treatment approach must be carefully planned because many children with ATRT are very young, and some treatments can have lasting effects on development.

What is the outlook?

This type of tumor has a generally poor outcome. It spreads quickly and can be hard to remove. As a result, it may shorten your child’s life expectancy. However, not all cases have a poor outcome. Researchers are studying new treatment options every day to help improve your child’s chance of survival^[6].

While recent clinical trial results show that this tumor is curable, outcomes are still poor compared to other central nervous system embryonal tumors^[12].

Survival in ATRT is dependent on age at diagnosis, extent of surgery, therapy utilized, presence of rhabdoid tumor predisposition syndrome, and if the tumor has spread. The poorest survival is in young infants and patients with metastatic disease; in contrast, the highest survival is in children 3 years old or older at diagnosis without metastatic disease treated with aggressive surgical resection, chemotherapy, and radiation therapy^[7].

The 5-year relative survival rates for ATRT by age group are as follows^[7]:

• Children (ages 0-14): 47.8%
• Adolescents and Young Adults (ages 15-39): 41.5%
• Adults (ages 40+): 24.6%

There are a lot of uncertainties when you learn about a cancer diagnosis, especially a rare cancer like ATRT. Remember that your child’s care team will be with you throughout their journey. Support is available for families and caregivers as well^[6].