Year : 2008 | Volume
: 51 | Issue : 3 | Page : 389--391
Atypical teratoid/rhabdoid tumor of the central nervous system associated with congenital cataract
Avninder Singh1, Zeeba Jairajpuri1, Vikas Gupta2, Shruti Sharma1, Karam Chand2,
1 Institute of Pathology, ICMR, Safdarjung Hospital Campus, New Delhi - 110 029, India
2 Department of Neurosurgery, ICMR, Safdarjung Hospital Campus, New Delhi - 110 029, India
Institute of Pathology, ICMR, Safdarjung Hospital Campus, New Delhi - 110 029
Atypical teratoid /rhabdoid tumor (AT/RT) of the central nervous system is a rare but highly aggressive neoplasm that usually affects young children and infants and follows a rapidly fatal course. We report a case of AT/RT in a 3-month-old male infant who also had coincidental unilateral congenital cataract even though there was no associated congenital infectious disease.
|How to cite this article:|
AvninderS, ZeebaJ, VikasG, ShrutiS, KaramC. Atypical teratoid/rhabdoid tumor of the central nervous system associated with congenital cataract.Indian J Pathol Microbiol 2008;51:389-391
|How to cite this URL:|
AvninderS, ZeebaJ, VikasG, ShrutiS, KaramC. Atypical teratoid/rhabdoid tumor of the central nervous system associated with congenital cataract. Indian J Pathol Microbiol [serial online] 2008 [cited 2021 Nov 27 ];51:389-391
Available from: https://www.ijpmonline.org/text.asp?2008/51/3/389/42521
Atypical teratoid/rhabdoid tumor is a rare and highly malignant and now increasingly recognized central nervous system (CNS) tumor that primarily occurs in children below 2 years of age. We report a case of AT/ RT in a 3-month-old male infant who incidentally also had congenital cataract and corneal opacity.
A 3-month-old male infant presented with a history of gradually enlarging head, frequent vomiting and decreasing intake of feeds since birth. He had two episodes of seizures since the last 1 day. Physical examination revealed corneal opacity in the left eye and congenital cataract in the right eye. There was no family history of cataract or viral infections like rubella, herpes, or cytomegalovirus. All other laboratory investigations were unremarkable. CT scan of the brain showed a large contrast-enhancing hyperdense mass in the posterior fossa along the fourth ventricle and causing hydrocephalus and dilatation of the third and both lateral ventricles. Clinical differential diagnosis of medulloblastoma and primitive neuroectodermal (PNET) tumor were kept and suboccipital craniectomy was done and partial excision of the tumor achieved. The child died 1 week after the surgery.
The biopsy showed a tumor consisting of sheets of round-to-oval cells with abundant eosinophilic cytoplasm, with some cells showing intracytoplasmic vacuolation and round nucleus with prominent nucleolus and high mitotic rate [Figure 1]. The intracytoplasmic hyaline masses were not seen, but in some cells large artifactual cytoplasmic vacuolation was seen, giving it a somewhat spongy appearance. In addition to these classic rhabdoid areas, there were focal PNET-like areas with small round blue cells forming pseudorosettes and foci of necrosis [Figure 2]. MIB-1 labeling was not done as the tumor showed high proliferation demonstrated by frequent mitoses of 1-2/hpf. Immunohistochemistry showed positive labeling of tumor cells with epithelial membrane antigen (EMA) and vimentin [Figure 3] and focally for smooth muscle actin. Desmin and GFAP were negative, but focal neurofilament protein positivity was seen in the PNET-like areas. A histopathological diagnosis of AT/RT was given.
Within the past decade, a series of reports have described an aggressive CNS neoplasm that resembles the Rhabdoid tumors of the kidneys. Rorke et al  first described AT/ RT of the CNS as an entity in 1996. Prior to its recognition as a separate entity, it was often misdiagnosed and classified as a medulloblastoma or a primitive neuroectodermal (PNET) tumor.  Because they histologically resemble rhabdoid tumor of the kidney, they were sometimes referred to as malignant rhabdoid tumor of the CNS. 
AT/RT is an extremely rare tumor so that its exact incidence is difficult to determine. It is primarily a disease of young children, usually less than 2 years of age. Approximately half of the AT/ RT arises in the posterior fossa, though they have been described throughout the CNS.  They present with signs and symptoms that reflect the location of the tumor. In posterior fossa, they present with symptoms related to hydrocephalus or with ataxia. Infants have open sutures and very pliable skulls and so they may present with rapidly enlarging head circumference. Radiologically, they present as hyperdense on CT and hypertense on T1W MRI and are heterogeneously contrast-enhancing and may contain area of necrosis and hemorrhage. They are indistinguishable from other malignant brain tumors based on clinical history and radiology.
Microscopically, they are distinct, as they show sheets of polygonal cells with abundant eosinophilic cytoplasm, high nucleus-to-cytoplasm ratio, plenty of mitosis and areas of extensive cytoplasmic vacoulation giving a spongy appearance. There may be intermixed areas of small undifferentiated embryonal cells, true or pseudo, with or without rosettes or PNET. Large areas of necrosis are usually present. Some tumors show predominantly rhabdoid cells, while others show a combination of rhabdoid cells and areas resembling or PNET or medulloblastoma.  Another differential diagnosis is choroid plexus carcinoma that has to be excluded by the absence of entrapped choroids plexus. Immunohistochemical profile of AT/RT is characteristic in that the tumor cells show diverse immunophenotype with positivity for EMA and also vimentin and SMA, suggesting a mesenchymal component. The PNET-like areas may show positivity for NF, GFAP, or rarely keratin. It was due to this diverse immunophenotype that they were conjointly called AT/RT. Their aggressive nature is demonstrated by a very high MIB-1 labeling index of 50-100%. 
More recently, molecular genetics has demonstrated deletions of chromosomes 22q11.2 in AT/RT and other rhabdoid tumors. Biegel et al have identified a tumor suppressor gene INI1, which is abnormal in the majority of CNS, renal and extra-renal rhabdoid tumors. It has been demonstrated that 76% of all AT/RT had a deletion or mutation in INI1 gene. It is believed that the presence of INI1 mutation in a tumor with histological features suggestive of PNET without a clear rhabdoid component is considered sufficient to establish a diagnosis of AT/ RT. In addition to somatic mutations, germline mutations in INI1 have been reported in some patients with rhabdoid tumors at multiple sites.  This may be an important predictor of risk to develop multiple primary rhabdoid tumors. An immunohistochemical staining to INI product has been developed and may be a useful tool in distinguishing from their differential diagnoses.
The initial treatment of choice is surgical excision and patients with gross total resection have better survival, but that is possible only in half.  Chemotherapy has been the main form of post-surgical adjuvant therapy, but the majority of AT/RT patients respond poorly to chemotherapy. To conclude, AT/RT are rare biologically aggressive tumors affecting young children, which can be confused with medulloblastoma and PNET. Histology and IHC are useful for the correct diagnosis and molecular genetics may in future help in directing targeted therapy. The association of congenital cataract seems to be coincidental.
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