Department of Pathology

Case of the Month April 2002

13 month-old boy with history of nausea and vomiting

Linh Vi, M.D., Jeffrey Stead, M.D., Sydney Schochet, M.D.

Diagnosis:

Atypical Teratoid/Rhabdoid Tumor

Discussion

Atypical teratoid/rhabdoid tumor (AT/RT) has been defined by the World Health Organization as a malignant CNS tumor manifesting in children and composed of rhabdoid cells, with or without fields resembling a classical primitive neroectodermal tumor (PNET), epithelial tissue, and neoplastic mesenchyme [1]. This tumor was described for the first time in 1987. It contained neuroepithelial, peripheral epithelial, and mesencymal elements but lacked divergent tissue differentiation characteristic malignant teratomas [1,2,3,4].

Histologically, various patterns may be present in the same tumor (PNET, medulloblastoma (MB), malignant mesenchymal tissue and/or epithelial component as well as germ cell components)[1,2,3,4,5]. However, AT/RTs described have had a population of rhabdoid cells, which ultrastructurally contained intermediate filaments. Because of morphological diversity, this tumor has been mistaken for PNET when it was localized at the supratentorial site or for meduloblastoma when it occurred at the posterior fossa. From an immunohistochemical standpoint, AT/RT tumors have expressed immunoreactivity with cytokeratin, EMA, GFAP, vimentin, synaptophysin, chromogranin, and smooth muscle actin [1,5] with a high MIB-1 labeling index [8]. The markers for germ cell tumors were constantly negative [2,3,4].

Nearly 90% of CNS AT/RTs have demonstrated monosomy or a deletion of chromosome 22 by fluorescent in-situ hybridization. Other chromosomal aberrations such as ring chromosome 22 [7], and complex rearrangements of chromosome 6 and 11, [9] have been reported.

AT/RTs are extremely rare in adults. Most have been reported in children less than two years old with a male to female ratio of 2. Localization of these tumors was: posterior fossa 52%, supratentorial 39%, multifocal 5% [1]. Survival ranged from 9 months to 5 years [1,3,5,6,8]. Most patients die within a year of diagnosis [1,5]. Therefore the differential diagnosis between AT/RT (median survival 15.4 months) versus PNET/MB (median survival 154.4 months) [8] and other pediatric CNS neoplasms is extremely important.

References

1. World Health Organization Classification of Tumors of the Nervous System, LYON, 2000. P 145-148

2. Oka H., Scheithauer BW: Clinicopathological characteristics of atypical teratoid/rhabdoid tumor. Neuro Med Chir (Tokyo) 1999 Jul; 39(7):510 -7;discussion 517-8 Bhattacharjee, Hicks J, Langford L et al: Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood. Ultrastruct Pathol 1997 Jul-Aug;21(4):369-7

3. Rorke LNB, Packer RJ, Biegel JA: Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. Neurosurg 1996 Jul;85(1):56-65

4. Burger PC, Yu IT, Tihan T et al. Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and chilhood frequently mistaken for meduloblastoma: a pediatric oncology group study. Am J Surg Pathol 1998 Sep;22(9):1083-92

5. Hilden JM, Waterson J, Longee DC, Moertel CL et al. Central nervous system atypical teratoidtumor/rhabdoid tumor: response to intensive therapy and review of literature. Neurooncol 1998 Dec;40(3):265-7

6. Rubio A. March 1997—4 year old girl with ring chromosome 22 and brain tumor. Brain Pathol 1997; Jul;(3):1027-8

7. Ho DM, Hsu CY, Wong TT et al. Atypical teratoid/rhabdoiod tumor of the central nervous system: a comperative study with primitive neuroectodermal tumor/meduloblastoma. Acta neuropathol (Berl) 2000 May;99(5):482-8

8. Lopez-Gines C, Cerda Nicalas M, Kepes J et al. Complex rearrangement of chromosomes 6 and 11 as the sole anormaly in atypical teratoid/rhabdoid tumors of the central nervous system. Cancer Genet Cytogenet 2000 Oct 15;122 (2):149-52