CENTRAL-NERVOUS-SYSTEM ATYPICAL TERATOID RHABDOID TUMORS OF INFANCY AND CHILDHOOD/

In 1987, a distinctive brain tumor arising in young children was first described. This tumor contained neuroepithelial, peripheral epithelia l, and mesenchymal elements, but lacked divergent tissue differentiati on characteristic of malignant teratomas. It was originally designated as atypical teratoid tumor, but because of the prominent rhabdoid com ponent, the tumor designation was modified to atypical teratoid/rhabdo id tumors (AT/RT) of infancy and childhood. AT/RTs occur most commonly in infants under 2 years of age, often have central nervous system (C NS) dissemination, do not respond to therapy, and typically are fatal within 1 year. Most are located in the cerebellum (65%), but they may arise at any CNS site. Histologically, various patterns can be present within the same tumor, but they all have a population of rhabdoid cel ls, and 70% contain fields typical of a primitive neuroectodermal tumo r (PNET/medulloblastoma). Less frequently, malignant mesenchymal tissu e and/or an epithelial component are found. Necrosis and brisk mitotic activity are common. The immunocytochemical profile is complex, but g erm cell markers are consistently negative. Ultrastructural features v ary and depend on the site sampled, but whorled bundles of cytoplasmic intermediate filaments are a distinctive finding in cells of the rhab doid component. The authors report 4 AT/RTs (2 males, 2 females, age r ange 6 months to 4 1/2 years, 3 cerebellar, 1 cerebral). All cases sho wed a variety of histologic patterns with necrosis. Typical rhabdoid c ells, PNET areas, undifferentiated bland large cell regions, dense con nective tissue, and solid clusters of epithelial cells were present. I mmunocytochemistry showed strong vimentin reactivity,whereas epithelia l membrane antigen, cytokeratin, glial fibrillary acidic protein, S-10 0 protein, desmin, and smooth muscle actin were present to a lesser ex tent in most cases. Germ cell markers were negative. Ultrastructurally , many cells contained aggregates of cytoplasmic intermediate filament s, and some cells had a basal lamina on one aspect. Cells with interdi gitating cytoplasmic borders were seen and rare cells had microtubules . Cytogenetic studies were normal in 2 cases. Follow-up has shown that 3 children have died of disease (<1 year after diagnosis) and 1 child is alive with disease (18 months after diagnosis). Separation of AT/R T from PNET based on histopathologic and biologic evaluation is import ant, because AT/RTs are aggressive tumors with a dismal prognosis and currently there is no effective treatment. Neither clinical signs and symptoms nor radiologic features will distinguish AT/RTs from PNETs.