Atypical teratoid rhabdoid tumor overview

# Overview
Atypical teratoid rhabdoid tumor is an uncommon WHO Grade IV tumor, which in the vast majority of cases occurs in young children less than two years of age. It most frequently presents as a posterior fossa mass. Atypical teratoid rhabdoid tumor is comprised of rhabdoid tumor cells and varying amounts of small undifferentiated primitive neuroectodermal tumor (PNET)-like, mesenchymally, and/or epithelially differentiated tumor cells. Gene involved in the pathogenesis of atypical teratoid rhomboid tumor include SMARCB1 (hSNF5/INI-1), a tumor suppressor gene. Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome. On gross pathology, atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately vascular. On microscopic histopathological analysis, atypical teratoid rhabdoid tumor is characterized by round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures. Atypical teratoid rhabdoid tumor is demonstrated by positivity to tumor markers such as epithelial membrane antigen, vimentin, and smooth muscle actin. Atypical teratoid rhabdoid tumor must be differentiated from medulloblastoma, pineoblastoma, spinal primitive neuroectodermal tumors, and other pineal gland masses. Atypical teratoid rhabdoid tumor comprises approximately 12% of all pediatric brain tumors; however, in patients less than 3 years of age, this tumor accounts for up to 20% of cases. The incidence of atypical teratoid rhabdoid tumor is approximately 0.3 per 100,000 individuals in the United States. Males are more commonly affected with atypical teratoid rhabdoid tumor than females. The male to female ratio is approximately 1.9 to 1. If left untreated, patients with atypical teratoid rhabdoid tumor may progress to develop obstructive hydrocephalus, leptomeningeal dissemination, and ultimately death. Common complications of atypical teratoid rhabdoid tumor include obstructive hydrocephalus, leptomeningeal dissemination, and recurrence. Prognosis is generally poor, and the 5-year overall survival rate of patients with atypical teratoid rhabdoid tumor is 29  9%. Symptoms of atypical teratoid rhabdoid tumor include headache, vomiting, increased head size in infant, trouble with balance and coordination, and weight loss. Common physical examination findings of atypical teratoid rhabdoid tumor include papilledema, ataxia, upper motor neuron lesion, and hemiparesis. On MRI, atypical teratoid rhabdoid tumor is characterized by iso- to slight hyperintensity on T1-weighted imaging and hyperintensity on T2-weighted imaging. There is heterogenous enhancement on contrast administration. The predominant therapy for atypical teratoid rhabdoid tumor is surgical resection. Adjunctive chemotherapy and radiation is required.

# Historical Perspective
Atypical teratoid rhabdoid tumor was first reported by Bonnin et al., in 1984. It was incorporated as a separate entity into the WHO classification of tumors of the nervous system, in 1993.

# Classification
There is no classification system established for atypical teratoid rhabdoid tumor.

# Pathophysiology
Atypical teratoid rhabdoid tumor is comprised of rhabdoid tumor cells and varying amounts of small undifferentiated primitive neuroectodermal tumor (PNET)-like, mesenchymally, and/or epithelially differentiated tumor cells. Gene involved in the pathogenesis of atypical teratoid rhomboid tumor include SMARCB1 (hSNF5/INI-1), a tumor suppressor gene. Atypical teratoid rhabdoid tumor may be associated with rhabdoid predisposition syndrome. On gross pathology, atypical teratoid rhabdoid tumor is characterized by an encapsulated, grayish, friable mass which is moderately vascular. On microscopic histopathological analysis, atypical teratoid rhabdoid tumor is characterized by round blue tumor cells of high cellularity composed of atypical cells with eccentric nuclei, small nucleoli, and abundant amounts of eosinophilic cytoplasm with frequent mitotic figures. Atypical teratoid rhabdoid tumor is demonstrated by positivity to tumor markers such as epithelial membrane antigen, vimentin, and smooth muscle actin.

# Causes
There are no established direct causes for atypical teratoid rhabdoid tumor. The development of atypical teratoid rhabdoid tumor is the result of multiple genetic mutations. Common genetic mutations involved in the development of atypical teratoid rhabdoid tumor can be found here.

# Differentiating Atypical Teratoid Rhabdoid Tumor from other Diseases
Atypical teratoid rhabdoid tumor must be differentiated from medulloblastoma, pineoblastoma, spinal primitive neuroectodermal tumors, and other pineal gland masses.

# Epidemiology and Demographics
Atypical teratoid rhabdoid tumor comprises approximately 12% of all pediatric brain tumors; however, in patients less than 3 years of age, this tumor accounts for up to 20% of cases. The incidence of atypical teratoid rhabdoid tumor is approximately 0.3 per 100,000 individuals in the United States. Atypical teratoid rhabdoid tumor is a rare disease that tends to affect the children population. The median age at diagnosis is approximately 24-30 months. Males are more commonly affected with atypical teratoid rhabdoid tumor than females. The male to female ratio is approximately 1.9 to 1.

# Risk Factors
There are no established risk factors for atypical teratoid rhabdoid tumor.

# Screening
There is insufficient evidence to recommend routine screening for atypical teratoid rhabdoid tumor.

# Natural History, Complications and Prognosis
If left untreated, patients with atypical teratoid rhabdoid tumor may progress to develop obstructive hydrocephalus, leptomeningeal dissemination, and ultimately death. Common complications of atypical teratoid rhabdoid tumor include obstructive hydrocephalus, leptomeningeal dissemination, and recurrence. Prognosis is generally poor, and the 5-year overall survival rate of patients with atypical teratoid rhabdoid tumor is 29  9%.

# Diagnosis

## Diagnostic Criteria
The diagnosis of atypical teratoid rhabdoid tumor is based on the current WHO classification of tumors of the central nervous system criteria, which include presence of rhabdoid tumor cells and/or divergent differentiation along epithelial, mesenchymal, neuronal, or glial lines in addition to the complete loss of SMARCB1 protein expression in tumor cell nuclei, but the expression retained in preexisting cells (e.g., endothelial cells).

## Staging
There is no established system for the staging of atypical teratoid rhabdoid tumor.

## History and Symptoms
When evaluating a patient for atypical teratoid rhabdoid tumor, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus when obtaining the history include the review of associated conditions such as rhabdoid predisposition syndrome. Symptoms of atypical teratoid rhabdoid tumor include headache, vomiting, increased head size in infant, trouble with balance and coordination, and weight loss.

## Physical Examination
Common physical examination findings of atypical teratoid rhabdoid tumor include papilledema, ataxia, upper motor neuron lesion, and hemiparesis.

## Laboratory Findings
CSF analysis is done to detect any leptomeningeal dissemination with involvement of the cerebrospinal fluid.  Large tumor cells, eccentricity of the nuclei, and prominent nucleoli are consistent findings.

## CT
Head CT scan is helpful in the diagnosis of atypical teratoid rhabdoid tumor. On head CT scan, atypical teratoid rhabdoid tumor is characterized by an isodense, calcified mass with heterogenous enhancement. There may be associated findings of obstructive hydrocephalus.

## MRI
Brain MRI is helpful in the diagnosis of atypical teratoid rhabdoid tumor. On MRI, atypical teratoid rhabdoid tumor is characterized by iso- to slight hyperintensity on T1-weighted imaging and hyperintensity on T2-weighted imaging. There is heterogenous enhancement on contrast administration.

## Ultrasound
Ultrasound may be performed to detect atypical teratoid rhabdoid tumor in other parts of the body, especially the kidneys.

## Other Imaging Findings
Other imaging studies for atypical teratoid rhabdoid tumor include magnetic resonance spectroscopy, which demonstrates elevated choline and N-Acetylaspartate.

## Other Diagnostic Studies
Other diagnostic studies for atypical teratoid rhabdoid tumor include biopsy (definitive diagnostic test), fluorescence in situ hybridization (abnormalities of chromosome 22q11.2), and immunohistochemistry (loss of INI-1 staining in the neoplastic cells).

# Treatment

## Medical Therapy
The predominant therapy for atypical teratoid rhabdoid tumor is surgical resection. Adjunctive chemotherapy and radiation is required.

## Surgery
Surgery is the mainstay of treatment for atypical teratoid rhabdoid tumor. Surgery plays a critical role in obtaining tissue to make an accurate diagnosis. Stem cell transplantation is indicated in very aggressive atypical teratoid rhabdoid tumors, to receive high doses of chemotherapy.

## Primary Prevention
There are no primary preventive measures available for atypical teratoid rhabdoid tumor.