Atypical teratoid rhabdoid tumor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Atypical teratoid rhabdoid tumor (AT/RT) is a rare tumor usually diagnosed in childhood. Although usually a brain tumor, AT/RT can occur anywhere in the central nervous system (CNS) including the spinal cord. About 60% will be in the posterior cranial fossa (particularly the cerebellum). One review estimated 52% posterior fossa (PF), 39% sPNET (supratentorial primitive neuroectodermal tumors), 5% pineal, 2% spinal, and 2% multi-focal.

Diagnosis

The standard work-up for AT/RT includes:

• MRI Magnetic resonance imaging of the brain and spine
• LP (Lumbar puncture) to look for M1 disease
• CT (Computed tomography) of chest and abdomen to check for a tumor
• BMA (Bone Marrow Asperant) to check for bone tumors. Often a doctor will want perform a stem cell transplant
• BX Bone marrow biopsy
• Bone scan

The initial diagnosis of a tumor is made with a radiographic study (MRI or CT-). If CT was performed first, a MRI is usually performed as the images are often more detailed and may reveal previously undetected metastatic tumors in other locations of the brain. In addition, an MRI of the spine is usually performed. The AT/RT tumor often spreads to the spine. It is difficult to diagnosis AT/RT only from radiographic study; usually a pathologist must perform a cytological or genetic analysis.

Examination of the cerebrospinal fluid is important as one-third of patients will have intracranial dissemination with involvement of the cerebrospinal fluid (CSF). Large tumor cells, eccentricity of the nuclei and prominent nucleoli are consistent findings. Usually only a minority of AT/RT biopsies have Rhabdoid cells, making diagnosis more difficult. Increasingly it is recommended that a genetic analysis be performed on the brain tumor, especially to find if a deletion in the INI1/hSNF5 gene is involved (appears to account for over 80% of the cases). The correct diagnosis of the tumor is critical to any protocol. Studies have shown that 8% to over 50% of AT/RT tumors are diagnosed incorrectly.

Appearance on radiologic exam

AT/RTs can occur at any sites within the CNS, however, approximately 60% are located in the posterior fossa or cerebellar area. The ASCO study showed 52% posterior fossa (PF); 39% sPNET (supratentorial primitive neuroectodermal tumors); 5% pineal; 2% spinal, and 2% multi-focal.

The tumors' appearance on CT and MRI are nonspecific, tending towards large size, calcifications, necrosis (tissue death),and hemorrhage (bleeding). Radiological studies alone cannot identify AT/RT; a pathologist almost always has to evaluate a brain tissue sample.

The increased cellularity of the tumor may make the appearance on an uncontrasted CT to have increased attenuation. Solid parts of the tumor often enhance with contrast MRI finding on T1 and T2 weighted images are variable. Pre-contrast T2 weighted images may show an iso-signal or slightly hyper-signal. Solid components of the tumor may enhance with contrast but do not always. MRI studies appear to be more able to pick up metastatic foci in other intracranial locations as well as intraspinal locations.

Preoperative and followup studies are needed to detect metastatic disease.

Prognosis

The prognosis for AT/RT is very poor, although there are some indications that an IRSIII-based therapy can produce long-term survival (60 to 72 months). Two-year survival is less than 20%, average survival postoperatively is 11 months, and doctors recommend palliative care, especially with younger children because of the poor outcomes.

Patients with metastasis (disseminated tumor), larger tumors, tumors that could not be fully removed, tumor reoccurrence, and were younger than 36 months had the worse outcomes (i.e., shorter survival times).

A retrospective survey from 36 AT/RT St. Jude Children's Hospital patients from 1984 to 2004 found a less than 10% survival rate in children under three, but a 70% survival rate in older children. A retrospective register at the Cleveland Children's hospital on 42 AT/RT patients found median survival time is 16.25 months and a survival rate around 33%. One-quarter of these cases did not show the mutation in the INI1/hSNF5 gene.

The longest term survivals reported in the literature are:

• (a) Hilden and associates reported a child who was still free from disease at 46 months from diagnosis.
• (b) Olson and associates reported a child who was disease free at five years from diagnosis based on the IRS III protocol.
• (c) In 2003 Hirth reported a case who had been disease free for over six years.
• (d) Zimmerman in 2005 reported 50-to-72 month survival rates on four patients using an IRS III-based protocol. Two of these LT survivors had been treated after an AT/RT reoccurrence.
• (e) A NYU study (Gardner 2004) has 4 of 12 longer term AT/RT survivors; the oldest was alive at 46 months after diagnosis.
• (f) Aurélie Fabre, 2004, reported a 16-year survivor of a soft-tissue rhabdoid tumor.

Cancer treatments in long-term survivors who are children usually cause a series of negative effects on physical well being, fertility, cognition, and learning.

Metastasis

Metastatic spread is noted in approximately one-third of the AT/RT cases at the time of diagnosis and tumors can occur anywhere throughout the CNS. The ASCO study of the 188 documented AT/RT cases prior to 2004 found 30% of the cases had metastasis at diagnosis. Metastatic spread to the meninges (leptomenigeal spread sometimes referred to as sugar coating) is common both initially and with relapse. Average survival times decline with the presence of metastasis. Primary CNS tumors metastasize only within the CNS.

One case of metastatic disease to the abdomen via ventriculoperitoneal shunt has been reported with AT/RT . Metastatic dissemination via this mechanism has been reported with other brain tumors including germinomas, medulloblastomas, astrocytomas, glioblastomas, ependymomas and endodermal sinus tumors. Guler and Sugita separately reported cases of lung metastasis without a shunt.

History

Atypical teratoid/rhabdoid tumor was first described as a distinct entity in 1987. In some early subsequent reports the tumor was known also as malignant rhabdoid tumor (MRT) of the CNS. Between 1978 and 1987, AT/RT likely was misdiagnosed as rhabdoid tumor. Before 1978, when rhabdoid tumor was described, AT/RT likely was misdiagnosed as medulloblastoma. However, both AT/RT and non-CNS MRT have a worse prognosis than medulloblastoma and are resistant to the standard treatment protocols for medulloblastoma.

By 1995, AT/RT had become regarded as a newly-defined aggressive, biologically unique class of primarily brain and spinal tumors, usually affecting infants and young children. In January 2001, the U.S. National Cancer Institute and Office of Rare Diseases hosted a Workshop on Childhood Atypical Teratoid/Rhabdoid Tumors of the Central Nervous System. Twenty-two participants from 14 institutions came together to discuss the biology, treatments and new strategies for these tumors. The consensus paper on the biology of the tumor was published in Clinical Research. The workshop's recognition that CNS atypical teratoid/rhabdoid tumors (AT/RT) have deletions of the INI1 gene indicates that rhabdoid tumors of the kidney and brain are identical or closely related entities. This observation is not surprising because rhabdoid tumors at both locations possess similar histologic, clinical, and demographic features.

External links

• The Rhabdoid Registry
• Hilden JM, Meerbaum S, Burger P et al. (2004-07-15). "Central Nervous System Atypical Teratoid/Rhabdoid Tumor: Results of Therapy in Children Enrolled in a Registry". Journal of Clinical Oncology. 22 (14): 2877–84. doi:10.1200/JCO.2004.07.073. Retrieved 2007-05-23. CS1 maint: Uses authors parameter (link) CS1 maint: Explicit use of et al. (link)
• Beigel J, Kalpana G, Knudsen E et al. (2002). "The role of INI and the SWI/SNF complex in the development of rhabdoid tumors: Meeting Summary from the workshop on childhood atypical teratoid rhabdoid tumors". Cancer Research 2002 (63:): 323–28.CS1 maint: Uses authors parameter (link) CS1 maint: Explicit use of et al. (link)
• Huret J, Sevenet N (2002). "Rhabdoid predisposition syndrome". Atlas of Genetics and Cytogenetics in Oncology and Haematology.