Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity

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✓ Clinical and pathological features of 52 infants and children with atypical teratoid/rhabdoid tumor (ATT/RhT) of the central nervous system are defined. This tumor is typically misdiagnosed as a primitive neuroectodermal tumor (PNET) primarily because 70% of ATT/RhTs contain fields indistinguishable from classic PNETs. Separation of these two tumor types is crucial because the prognosis for ATT/RhT is grim even when treatment includes surgery with or without radio- and/or chemotherapy.

These tumors are most common in infants less than 2 years of age. The cases described in this study arose intracranially in all but one instance, although one-third had already spread throughout the subarachnoid space at presentation. Clinical signs and symptoms and radiological features do not distinguish ATT/RhTs from PNETs. The tumors are composed entirely (13%) or partly (77%) of rhabdoid cells. Seventy percent contain fields of typical PNET alone or in combination with mesenchymal and/or epithelial elements. The immunohistochemical profile is unique: epithelial membrane antigen, vimentin, and smooth-muscle actin are positive in the majority of tumors and markers for germ-cell tumors are consistently negative.

Abnormalities of chromosome 22 distinguish ATT/RhTs from PNETs, which typically display an i(17q) abnormality.

Article Information

Address reprint requests to: Lucy Balian Rorke, M.D., Department of Pathological Anatomy, The Children's Hospital of Philadelphia, 324 South 34th Street, Philadelphia, Pennsylvania 19104–4399.

© AANS, except where prohibited by US copyright law.

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Figures

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    Left: Axial T2-weighted image showing a mass (arrows) in the left cerebellar hemisphere involving the left lateral aspect of the pons and projecting exophytically into the subarachnoid space. The signal intensity of the mass is predominantly isointense to the cortical gray matter. Within the mass there are areas of higher signal intensity consistent with fluid-filled cavities. Center: Axial T1-weighted image after gadolinium injection showing homogeneous enhancement of the mass. Right: Axial T1-weighted image after gadolinium injection showing an ependymal site of tumor dissemination (arrowhead).

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    Upper Left: Photomicrograph showing a typical field of rhabdoid cells that are large and have distinct cell borders. Note large round single or double nuclei with one prominent nucleolus. Upper Right: Photomicrograph showing a field of classic primitive neuroectodermal tumor from the same neoplasm shown in Fig. 1 left. Note the striking difference in histological features between these two views. Lower Left: Photomicrograph showing a characteristic field of neoplastic mesenchymal tissue in atypical teratoid/rhabdoid tumor (ATT/RhT). Note spindled character of the cells. Lower Right: Photomicrograph showing focus of squamous epithelium in mesenchyme in same ATT/RhT pictured in upper left. H & E, original magnification × 100.

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    Tumor sections stained with H & E for histological investigation. Left: Photomicrograph showing typical primitive neuroectodermal tumor (PNET) in left upper portion and classic rhabdoid cells in right lower field. Original magnification × 50. Right: Photomicrograph showing large nest of PNET and smaller less well defined nests of similar cells in mesenchymal field of the same tumor shown in Fig. 2 upper left and right. Original magnification × 20.

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    Tumor sections stained for histological investigation, original magnification × 100. Left: Photomicrograph of rhabdoid cells stained for presence of epithelial membrane antigen (EMA) showing positive membrane and cytoplasmic staining. Immunoperoxidase method for EMA. Right: Photomicrograph of rhabdoid cells stained for presence of vimentin showing striking positivity of the entire perikaryon. Immunoperoxidase method for vimentin.

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    Tumor sections stained for histological investigation, original magnification × 100. Left: Photomicrograph of rhabdoid cells stained for presence of smooth-muscle actin (SMA) showing positive reaction in scattered cells. Immunoperoxidase method for SMA. Right: Photomicrograph showing nests and scattered rhabdoid cells staining positively for glial fibrillary acidic protein (GFAP). Immunoperoxidase method for GFAP.

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    Tumor sections stained for histological investigation, original magnification × 100. Left: Photomicrograph of a field of rhabdoid cells showing striking positive reaction for neurofilament protein (NFP) in a proportion of cells. Immunoperoxidase method for NFP. Right: Photomicrograph showing scattered rhabdoid cells staining positively for presence of AE1-keratin.

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    Electron micrograph of typical rhabdoid cell displaying bundles of intermediate filaments within the perikaryon (arrows). Bar = 1 µm.

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