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Atypical teratoid/rhabdoid tumor (AT/RT), a highly aggressive primitive central nervous system (CNS) neoplasm of infancy. These tumors are often mistaken for medulloblastoma or central primitive neuroectodermal tumor (MB/PNET). It is important to distinguish these tumors from the latter since AT/RT is associated with a particularly poor prognosis and an unrelenting clinical course when conventional therapies for MB/PNET are used.


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Deletions of chromosome 22q

hSNF5/INI1 gene on 22q11.2 has been implicated as a tumor suppressor gene in RTs, including those occurring in the CNS

Site resides near the bcr locus

A role for fluorescence in situ hybridization detection of chromosome 22q dosage in distinguishing atypical teratoid/rhabdoid tumors from medulloblastoma (MB)/central primitive neuroectodermal tumors (PNET)

Hum Pathol 2001:32:156-162

Chromosome 22q11.2 deletions are common only in AT/RTs.

Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded biopsy tissue with commercially available probes to 22q11.2, the region associated with RTs

Studied 8 cases of AT/RT, 12 cases of MB/PNET, and 4 cases of primitive central nervous system (CNS) neoplasms, which were difficult to classify

22q Deletions were identified in 6 of 8 (75%) conventional AT/RTs and 0 of 12 (0%) children with classic MB/PNET
Of the 4 originally “difficult to classify” cases, 3 had deletions of 22q

Review of the morphology and immunophenotype resulted in 3 tumors being reclassified as AT/RTs and 1 as a large cell MB

These 4 cases highlight the potential diagnostic use of FISH for selected cases of primitive CNS malignancies in children and substantiate the notion that misdiagnosed AT/RTs may, in part account for the worse prognosis associated with “MB/PNET” in children younger than 2 years of age

Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system.

Kao CL, Chiou SH, Chen YJ, Singh S, Lin HT, Liu RS, Lo CW, Yang CC, Chi CW, Lee CH, Wong TT.

[1] 1Department of Physical Medicine & Rehabilitation, Taipei Veterans General Hospital, Taiwan, ROC [2] 7Institute of Clinical Medicine, National Yang-Ming University, Taiwan, ROC.

Mod Pathol. 2005 Jun;18(6):769-78. Abstract quote  

The atypical teratoid/rhabdoid tumor, primary to the central nervous system, is a highly malignant and aggressive neoplasm of infancy and childhood. Although having distinct biological features and clinical outcomes, it is frequently misdiagnosed as primitive neuroectodermal tumor/medulloblastoma.

To further distinguish the underlying pathogenesis and to identify biological markers for clinical use, an atypical teratoid/rhabdoid tumor-derived cell line was established and its gene expression pattern analyzed in comparison to the human astrocyte SVG12 cell line and the human DAOY medulloblastoma cell line using a complementary DNA microarray method. The osteopontin gene was found specifically upregulated in atypical teratoid/rhabdoid tumor cells. This specificity was confirmed by immunohistochemistry in pathological sections of tissues from atypical teratoid/rhabdoid tumor patients.

Even though the role of osteopontin in the cytopathogenesis of atypical teratoid/rhabdoid tumor still needs to be determined, our data support that overexpressed osteopontin is a potential diagnostic marker for atypical teratoid/rhabdoid tumor.


Atypical teratoid/rhabdoid tumor of the central nervous system in children: an atypical series and review.

Fenton LZ, Foreman NK.

Department of Radiology, The Children's Hospital, 1056 East 19th Avenue B125, Denver, CO 80218, USA.
Pediatr Radiol. 2003 Aug;33(8):554-8. Epub 2003 May 21. Abstract quote  

Primary atypical teratoid/rhabdoid tumor (AT/RhT) of the central nervous system is a recently described, highly malignant neoplasm in infants and young children. This tumor is an unusual combination of mixed cellular elements, similar but not typical of teratomas, and rhabdoid cells. This tumor is most common in the posterior fossa in children less than 2 years, and is radiologically similar to medulloblastoma.

No pathognomonic imaging features are present. The two tumors can be separated on histologic, molecular, and cytogenetic grounds. Separation of these two tumor types is crucial because the prognosis for AT/RhT is grim even with current multimodality treatment.

We present four consecutive cases of AT/RhT, three in locations other than the cerebellum, seen at our institution in a 14-month period, indicating that this tumor may be more common than previously thought.

Atypical teratoid/rhabdoid tumors.

Dang T, Vassilyadi M, Michaud J, Jimenez C, Ventureyra EC.

Division of Neurosurgery, Children's Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
Childs Nerv Syst. 2003 Apr;19(4):244-8. Epub 2003 Apr 02. Abstract quote  

CASE REPORTS: We describe three cases of atypical ATRT that were identified at the Children's Hospital of Eastern Ontario.

DISCUSSION: Over the past decade, atypical teratoid/rhabdoid tumors (ATRTs) of the central nervous system have emerged as a distinct entity. This tumor is typically misdiagnosed as a primitive neuroectodermal tumor (PNET)/medulloblastoma. The unique immunohistochemistry profile of an ATRT helps distinguish it from a PNET/medulloblastoma. This is of clinical importance because the prognosis of a patient with an ATRT is worse than that of a PNET/medulloblastoma despite aggressive surgical treatment with or without adjuvant chemotherapy and radiation therapy.


General Large pale cells with prominent nucleoli, eccentric eosinophilic cytoplasm, and paranuclear inclusions (rhabdoid cells) are pathognomonic but may be inconspicuous in some cases.

Atypical teratoid/rhabdoid tumor of the central nervous system: clinico-pathological study.

Lee MC, Park SK, Lim JS, Jung S, Kim JH, Woo YJ, Lee JS, Kim HI, Jeong MJ, Choi HY.

Department of Pathology, Chonnam National University Medical School and Research Institute of Medical Sciences, Kwangju, Korea
Neuropathology. 2002 Dec;22(4):252-60. Abstract quote  

Atypical teratoid/rhabdoid tumor (AT/RT) is a new entity among malignant pediatric brain tumors. This study was performed to investigate the clinicopathologic and cytogenetic features of the tumor. Five cases from a series of the brain tumors were studied. Clinical features of the patients were assessed with age, sex, location of the tumors, treatments and survival periods.

Histopathologic features were analyzed by routine HE stain and immunohistochemical stains for epithelial membrane antigen, cytokeratin, vimentin, smooth muscle actin, desmin, GFAP, S-100 protein, neurofilament protein, synaptophysin and alpha-feto protein.

Cytogenetic studies for karyotype analysis and fluorescent in situ hybridization were available in three cases. Mean age of patients was 5.6 years, and maximal survival periods were less than 13 months despite surgical and radiation therapy. The tumors were located in infratentorial and supratentorial areas.

Histopathologically, the tumors were chiefly composed of rhabdoid cells, modified rhabdoid cells and undifferentiated small cells, mixed with epithelial, mesenchymal, and neural tumor-like areas. These polyphenotypic features of the tumor cells were supported by diverse immunoreaction. Monosomy of chromosome 22 was demonstrated in two cases of the tumor.

These results suggest that AT/RT may be a unique clinicopathologic entity, and histopathologic diagnosis of it should be made judiciously by differentiating other polymorphous tumors of the brain.


Special stains  
Immunoperoxidase A polyphenotypic pattern of immunoreactivity:
Epithelial membrane antigen (EMA)
Smooth muscle actin (SMA)
Double immunolabeling of central nervous system atypical teratoid/rhabdoid tumors.

Bouffard JP, Sandberg GD, Golden JA, Rorke LB.

1Department of Neuropathology & Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
Mod Pathol. 2004 Jun;17(6):679-83. Abstract quote  

The central nervous system atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant tumor with a heterogeneous immunohistochemical profile and with some morphologic similarity to central nervous system primitive neuroectodermal tumors (PNET).

Although several studies have investigated double immunolabeling in PNET, we are aware of no studies of double labeling of ATRT. A total of 10 ATRT from surgical and consultation materials at the Children's Hospital of Philadelphia were selected and stained for a variety of antigens using indirect immunofluorescence to detect single and double labeling. Most tumor cells showed only single labeling; rare cells showed double labeling as follows: 70% of tumors coexpressed (VIM) and glial fibrillary acidic protein (GFAP), 30% smooth muscle actin and GFAP, 20% epithelial membrane antigen (EMA) and VIM, 20% EMA/GFAP, and 20% EMA/SMA.

These results are discussed in view of current debates over the histogenesis of CNS PNET and ATRT, and in reference to the classification of rhabdoid tumors as an entity or phenotype.
Alpha-internexin expression in medulloblastomas and atypical teratoid-rhabdoid tumors.

Kaya B, Mena H, Miettinen M, Rushing EJ.

Department of Pathology, John A. Burns School of Medicine, The Queen's Medical Center, Honolulu, HI, USA.
Clin Neuropathol. 2003 Sep-Oct;22(5):215-21. Abstract quote  

OBJECTIVE: To determine whether medulloblastomas and atypical teratoid/rhabdoid tumors express alpha-internexin, an intermediate filament protein that is expressed in normal neurons undergoing maturation and differentiation.

MATERIALS AND METHODS: 28 medulloblastomas and 5 atypical teratoid/rhabdoid tumors were examined for the immunohistochemical expression of alpha-internexin, as well as the neuronal markers peripherin and synaptophysin, and glial fibrillary acidic protein.

RESULTS: Overall, 21 of 28 medulloblastomas (75%) expressed alpha-internexin. More specifically, alpha-internexin expression was observed in 6 of 10 (60%) classic medulloblastomas, 12 of 14 (86%) desmoplastic medulloblastomas, 2 of 3 (67%) nodular medulloblastomas, and in one medullomyoblastoma. Similarly, 4 of 5 (80%) atypical teratoid/rhabdoid tumors expressed alpha-internexin. The extent of staining for alpha-internexin tended to be less than that of synaptophysin for both medulloblastomas (75% vs 93%) and atypical teratoid/rhabdoid tumors (80% vs 100%). In contrast to alpha-internexin, peripherin was expressed in only 4 medulloblastomas and one atypical teratoid/rhabdoid tumor.

CONCLUSIONS: Alpha-internexin is expressed in the majority of medulloblastomas and atypical teratoid/rhabdoid tumors, indicating that these primitive tumors usually exhibit neuronal differentiation.

Immunohistochemical Analysis of hSNF5/INI1 in Pediatric CNS Neoplasms.

Judkins AR, Mauger J, Ht A, Rorke LB, Biegel JA.

Departments of *Pathology and Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA.
Am J Surg Pathol. 2004 May;28(5):644-650. Abstract quote  

Atypical teratoid/rhabdoid tumor (AT/RT) may be misdiagnosed as primitive neuroectodermal tumor/medulloblastoma (PNET) and occasionally as other tumors. Molecular genetic analysis of AT/RT demonstrates deletion and mutation of the hSNF5/INI1 gene in most cases, with decreased or absent expression at the RNA or protein level.

Immunohistochemistry with an antibody to INI1 was performed to determine whether this would be a sensitive and specific means of assessing INI1 loss in pediatric brain tumors. Fifty-three tumors consisting of 20 AT/RTs, 10 PNETs, and 23 other central nervous system tumors were examined. No nuclear staining was found in all 20 AT/RTs. Most other central nervous system tumors demonstrated nuclear staining. Eight cases in which classification as AT/RT or PNET was difficult were also examined.

Seven cases had no chromosome 22 deletion or INI1 mutation; INI1 antibody showed nuclear staining in these cases. One case was a recurrent tumor with features consistent with an AT/RT. INI1 immunostaining was negative in this case, and a mutation in INI1 was subsequently identified.

Immunohistochemical staining with an INI1 antibody correlates with molecular findings in AT/RT and may be useful in confirming the histologic diagnosis. INI1 immunostaining may have particular utility in the analysis of tumors with indeterminate histologic features or atypical immunophenotypic profiles.


Survival Poor prognosis
Prognostic Factors  

Association between DNA content and tumor suppressor gene expression and aggressiveness of atypical teratoid/rhabdoid tumors.

Berrak SG, Ozek MM, Canpolat C, Dagcinar A, Sav A, El-Naggar A, Langford LA.

Division of Pediatric Hematology-Oncology, Marmara University Medical Center, Istanbul, Turkey.
Childs Nerv Syst. 2002 Oct;18(9-10):485-91. Epub 2002 Jul 23. Abstract quote  

OBJECTS: Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive neoplasms that afflict infants and young children. The objective of this retrospective study was to determine the association between DNA content (DNA ploidy, cell cycle analysis), tumor suppressor gene (p53, pRb, p16, and MMAC/PTEN) expression and the biologic aggressiveness of these tumors.

METHODS: Eight tumors from 7 patients (1 girl, 6 boys; median age 4+/-6.7 months) were studied. Two patients had DNA aneuploidy and 5 patients manifested diploid DNA content at diagnosis. The proliferative index of the tumors ranged from 10% to 28% (median, 12+/-6.4%). The single tumor with a low proliferative index (i.e., <10%) was aneuploid. Immunohistochemical evaluation of p53, pRb, p16, and MMAC/PTEN expression patterns showed that most of the tumors contained more cells with abnormal pRb and p16 expression than cells with abnormal p53 and MMAC/PTEN expression. Expression of tumor suppressor genes, however, was inhomogeneous.

CONCLUSION: Our findings led us to conclude that AT/RT of childhood is characterized by a high proliferative index and DNA aneuploidy. The high expression of abnormal pRb and p16 and the low expression of abnormal p53 and MMAC/PTEN indicate alteration of the G1-to-S phase step in the cell cycle, which could be an explanation for the aggressive nature of these tumors.
Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy.

Tekautz TM, Fuller CE, Blaney S, Fouladi M, Broniscer A, Merchant TE, Krasin M, Dalton J, Hale G, Kun LE, Wallace D, Gilbertson RJ, Gajjar A.

Department of Hematology-Oncology, Mail Stop 260, St Jude Children's Research Hospital, 332 N Lauderdale St, Memphis, TN 38105, USA.
J Clin Oncol. 2005 Mar 1;23(7):1491-9. Abstract quote

PURPOSE: To describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH).

PATIENTS AND METHODS: Primary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed.

RESULTS: Thirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%) were significantly better than those for younger patients (EFS, 11% +/- 6%; OS, 17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy.

CONCLUSION: Children presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.
Cerebral atypical teratoid/rhabdoid tumor of infancy: long-term survival after multimodal treatment, also including triple intrathecal chemotherapy and gamma knife radiosurgery--case report.

Hirth A, Pedersen PH, Wester K, Mork S, Helgestad J.

Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
Pediatr Hematol Oncol. 2003 Jun;20(4):327-32. Abstract quote  

Cerebral atypical teratoid/rhabdoid tumors (AT/RT) of infancy are highly malignant and have a poor prognosis.

The authors report on one case with long-term survival. The patient was a 1 year-old boy presenting with a large AT/RT in the right temporal lobe. He was treated with complete surgery, followed by multiagent chemotherapy. Later he had a second resection and intrathecal chemotherapy and Gamma knife radiosurgery was added to the treatment.

Except for a well-controlled temporal epilepsy, the boy is doing well after 6 years follow-up. AT/RT should be treated in a multimodal way. Intrathecal chemotherapy and Gamma knife radiosurgery of single recurrent or residual tumors might increase survival.

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Last Updated July 15, 2005

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