Brain Pathology Case of the Month - March 1997



The patient had a good postoperative course and recovered her baseline functional status in a few weeks. A metastatic work up including spinal MRI showed no evidence of disease. She was included in the "Baby POG" protocol, and received two rounds of cyclophosphamide plus vincristine followed by one round of cis-platinum and VP-16. Post-chemotherapy evaluation revealed a minimal response, with an estimated 20% reduction in the residual tumor. She received a second course of the same treatment, but her follow-up MRI revealed further progression of the disease and dissemination of the tumor seven months after the diagnosis.


Atypical teratoid/rhabdoid tumor of the central nervous system (ATRT) is an aggressive childhood neoplasm sharing histopathologic features with both central primitive neuroectodermal tumors (cPNET) and peripheral malignant rhabdoid tumors (MRT). Cytogenetic and other molecular studies have determined these tumors to have closer relationship to MRT. While the most common cytogenetic abnormality in cPNETs involves chromosome 17 i(17q), both ATRT and MRT share monosomy of chromosome 22 2, or at least genetic losses in the distal part of the long arm of chromosome 22 3. The putative mechanism of tumorigenesis is inactivation of a still to be defined tumor supressor gene (TSG) distinct from the NF-2 gene, located in the distal long arm of chromosome 22. The same, or a different but closely placed, TSG may be responsible for the development of meningiomas.4 Of special interest in this case is the presence of a constitutive ring chromosome 22 abnormality in this child. Ring chromosome 22 generally involves loss of the distal part of the long arm of the chromosome, including the locus for the putative TSG. In fact, childhood meningiomas and multiple meningiomas have been previously described in patients with constitutional ring chromosome 22 5,6. To my knowledge, this is the first case of ATRT presenting in a patient with ring chromosome 22. Further molecular studies are being performed to determine the status of the other allele in the neoplastic tissue. Ota et al., 7 after studying two MRT cell lines (one of renal and the other of extrarenal origin) by immunocytochemical, ultrastructural and cytogenetic techniques, concluded that in both cases the cells have neuroectodermal as well as mesenchymal differentiating potential. Based on this pluripotentiality, they suggest a neural crest origin and propose to classify MRT as a subtype of cPNET.

The most extensive and recent review of ATRT with detailed clinical, radiologic and pathologic description of 52 cases is that of Rorke et al. 8 Histopathologically, all tumors contain groups of rhabdoid cells in differing proportions. A minority of the tumors are exclusively composed of rhabdoid cells, and the rest have an admixture of rhabdoid with cPNET, mesenchymal and / or epithelial components. The immunohistochemical pattern of staining varies among the different components, but the rhabdoid cells are almost uniformly positive for epithelial membrane antigen, Vimentin and smooth muscle actin. GFAP, cytokeratin and neurofilament antibodies immunoreact with the rhabdoid component of most cases, both in the intracranial (ATRT) as well as the extracranial locations (MRT) 9,10. Desmin is immunoreactive in the rhabdoid component of a minority of tumors.

The admixture of different histologic patterns in the majority of ATRT of the CNS is a subject of much interest. Unlike teratomas, the other type of tumor composed of cells of mixed embryologic origin in which the cell of origin is a germ cell, the cell of origin in ATRT is unknown.


  1. Hunter AGW, Ray M, Wang HS, Thompson DR. Phenotypic correlations in patients with ring chromosome 22. Clinical Genetics 1977;12:239-49
  2. Biegel JA, Rorke LB, Packer RJ, Emanuel BS. Monosomy 22 in rhabdoid or atypical tumors of the brain. J Neurosurg 1990;73:710-4
  3. Besnard-Guérin C, Cavenee W, Newsham I. The t(11;22)(p15.5;q11.23) in a retroperitoneal rhabdoid tumor also includes a regional deletion distal to CRYBB2 on 22q. Genes Chromosom Cancer 1995;13:145-50
  4. Peyrard M, Fransson I, Xie YG et al. Characterization of a new member of the human beta-adaptin gene family from chromosome 22q12, a candidate meningioma gene. Hum Mol Genet 1994;3:1393-9
  5. Arinami T, Kondo I, Hamaguchi H, Nakajima S. Multifocal meningiomas in a patient with a constitutional ring chromosome 22. J Med Genet 1986;23:178-80
  6. Petrella R, Levine S, Wilmot PL, Ashar KD, Casamassima AC, Shapiro LR. Multiple meningiomas in a patient with constitutional ring chromosome 22. Am J Med Genet 1993;47:184-6
  7. Ota S, Crabbe DCG, Tran TN, Triche TJ, Shimada H. Malignant rhabdoid tumor: a study with two established cell lines. Cancer 1993;71:2862-72
  8. Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurgery 1996;85:56-65
  9. Fischer HP, Thomsen H, Altmannsberger M. Malignant rhabdoid tumors of the kidney expressing neurofilament proteins. Path Res Pract 1989;184:541-7
  10. Wick MR, Ritter JH, Dehner LP. Malignant rhabdoid tumors: a clinicopathologic review and conceptual discussion. Sem Diagnost Pathol 1995;12:233-48

Contributed by Contributed by Ana Rubio, MD, PhD

International Society of Neuropathology