Rhabdoid tumour
Encyclopedia
Malignant rhabdoid tumour (MRT) is a very aggressive form of tumour
originally described as a variant of Wilms' tumour
, which is primarily a kidney
tumour that occurs mainly in children.
Malignant rhabdoid tumour was first described as a variant of Wilms' tumour
of the kidney in 1978. Malignant rhabdoid tumours (MRT) are a rare and highly malignant childhood neoplasm. Later rhabdoid tumours outside the kidney were reported in many tissues including the liver, soft tissue, and the central nervous system
. Several cases of primary intracranial MRT have been reported since its recognition as a separate entity in 1978. The term "rhabdoid" was used due to its similarity with rhabdomyosarcoma
under the light microscope. The exact pathogenesis of MRT is unknown.
The cerebellum
is the most common location for primary intracerebral MRT (i.e., AT/RT). Biggs et al. were first to report a primary intracranial MRT around 1987.
Although the cell of origin is not known, cytogenetic studies
have suggested a common genetic basis for rhabdoid tumours regardless of location with abnormalities in chromosome 22 commonly occurring.
In MRTs, the INI1 gene (SMARCB1)on chromosome 22q functions as a classic tumour suppressor gene. Inactivation of INI1 can occur via deletion, mutation, or acquired UPD.
In a recent study, SNP array karyotyping identified deletions or LOH of 22q in 49/51 rhabdoid tumours. Of these, 14 were copy neutral LOH (or acquired UPD), which is detectable by SNP array karyotyping, but not by FISH, cytogenetics, or arrayCGH. MLPA detected a single exon homozygous deletion in one sample that was below the resolution of the SNP array. SNP array karyotyping
can be used to distinguish, for example, a medulloblastoma with an isochromosome 17q from a primary rhabdoid tumour with loss of 22q11.2. When indicated, molecular analysis of INI1 using MLPA and direct sequencing may then be employed. Once the tumour-associated changes are found, an analysis of germline DNA from the patient and the parents can be done to rule out an inherited or de novo germline mutation or deletion of INI1, so that appropriate recurrence risk assessments can be made.
.
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
originally described as a variant of Wilms' tumour
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of tumor....
, which is primarily a kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
tumour that occurs mainly in children.
Malignant rhabdoid tumour was first described as a variant of Wilms' tumour
Wilms' tumor
Wilms' tumor or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults.Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon who first described this kind of tumor....
of the kidney in 1978. Malignant rhabdoid tumours (MRT) are a rare and highly malignant childhood neoplasm. Later rhabdoid tumours outside the kidney were reported in many tissues including the liver, soft tissue, and the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
. Several cases of primary intracranial MRT have been reported since its recognition as a separate entity in 1978. The term "rhabdoid" was used due to its similarity with rhabdomyosarcoma
Rhabdomyosarcoma
A rhabdomyosarcoma is a type of cancer, specifically a sarcoma , in which the cancer cells are thought to arise from skeletal muscle progenitors. It can also be found attached to muscle tissue, wrapped around intestines, or in any anatomic location...
under the light microscope. The exact pathogenesis of MRT is unknown.
The cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
is the most common location for primary intracerebral MRT (i.e., AT/RT). Biggs et al. were first to report a primary intracranial MRT around 1987.
Although the cell of origin is not known, cytogenetic studies
Cytogenetics
Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-Banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ...
have suggested a common genetic basis for rhabdoid tumours regardless of location with abnormalities in chromosome 22 commonly occurring.
Rhabdoid tumours in kidney and brain
Considerable debate has been focused on whether AT/RTs are the same as rhabdoid tumours of the kidney (i.e., just extra-renal MRTs (maligant rhabdoid tumours). The recent recognition that both CNS atypical teratoid/rhabdoid tumours (AT/RTs) and MRTs have deletions of the INI1 gene in chromosome 22 indicates that rhabdoid tumours of the kidney and brain are identical or closely related entities. Although, the CNS variant tends to have its mutations on Taxon 9 and MRTs elsewhere. This observation is not surprising because rhabdoid tumours at both locations possess similar histologic, clinical, and demographic features. Moreover, 10-15% of patients with MRTs have synchronous or metachronous brain tumours, many of which are second primary malignant rhabdoid tumours. This similarity excludes composite Rhabdoid tumours, which occur mainly in adults.Diagnosis
The histologic diagnosis of malignant rhabdoid tumour depends on identification of characteristic rhabdoid cells—large cells with eccentrically located nuclei and abundant, eosinophilic cytoplasm. However, the histology can be heterogenous and the diagnosis of MRT can often be difficult. Misclassifications can occur.In MRTs, the INI1 gene (SMARCB1)on chromosome 22q functions as a classic tumour suppressor gene. Inactivation of INI1 can occur via deletion, mutation, or acquired UPD.
In a recent study, SNP array karyotyping identified deletions or LOH of 22q in 49/51 rhabdoid tumours. Of these, 14 were copy neutral LOH (or acquired UPD), which is detectable by SNP array karyotyping, but not by FISH, cytogenetics, or arrayCGH. MLPA detected a single exon homozygous deletion in one sample that was below the resolution of the SNP array. SNP array karyotyping
Virtual Karyotype
Virtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...
can be used to distinguish, for example, a medulloblastoma with an isochromosome 17q from a primary rhabdoid tumour with loss of 22q11.2. When indicated, molecular analysis of INI1 using MLPA and direct sequencing may then be employed. Once the tumour-associated changes are found, an analysis of germline DNA from the patient and the parents can be done to rule out an inherited or de novo germline mutation or deletion of INI1, so that appropriate recurrence risk assessments can be made.
Prognosis
Regardless of location, all rhabdoid tumours are highly aggressive, have a poor prognosis, and tend to occur in children less than two years of age.Genetics
There have been reported cases of a child having both atypical teratoid rhaboid tumours in the brain as well as rhabdoid tumours of the kidney. Weeks and associates reported on 111 renal rhabdoid cases of which 13.5% also had a central nervous system malignancy. It has been hypothesized that a germline INI mutation may predispose a child to these tumours. There have been some references in the literature alluding to a new diagnosis called rhabdoid predispostion syndrome related to the gene hSNF5/INI1SWI/SNF
SWI/SNF is a yeast nucleosome remodeling complex composed of several proteins – products of the SWI and SNF genes as well as several other polypeptides...
.