Virtual Microscope
A 17 month-old girl with a cerebellar-pontine angle tumor
Elizabeth Rushing, M.D., Col.
Department of Neuropathology and Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, D.C.
Clinical Information: The patient was a 17 month-old baby girl who presented with a 2-week progressive walking difficulties. According to her mother's description, she was not able to climb or walk normally. There were also falls, asymmetric gait and loss of balance. The patient also started tilting her head to the left more often. An MRI performed in an outside hospital demonstrated a large, enhancing mass involving the right posterior fossa with extension into the cerebellar-pontine angle. There was no sign of hydrocephalus or imaging evidence to suggest spinal dissemination. The cerebral spinal fluid was negative for atypical cells. The mass was surgically excised. The specimen submitted for pathologic examination contains multiple, creamy yellow to tan, slightly firm fragments of tissue, 5.0 x 4.0 x 0.8 cm in toto. The following is a slide of one of the paraffin blocks.
Diagnosis: Atypical teratoid rhabdoid tumor (ATRT), WHO grade IV.
Pathology: The slide available through the virtual microscope is representative of all the tissue blocks submitted for examination. At low-power, there is a densely packed, cellular tumor with a variable amount of interlacing stroma. In some areas, the tumor cells appear in small cell nests, with artifactual spaces between the cells, probably resulting from formalin fixation. On higher magnification, many of the nuclei of the neoplastic cells are large, pleomorphic and harbor prominent nuclei. A moderate amount of cytoplasm is present in most cells. It is not uncommon to find tumor cells with a "big belly" of cytoplasm and an eccentric nucleus. Some of these "big bellies" contain a round inclusion-like body. These cells represent the so-called "rhabdoid" cells.
The rhabdoid features of this tumor are well appreciated in the intraoperative cytologic preparation, which is a very effective mean for detecting rhabdoid cells. These features are also rather obvious in frozen sections. Rhabdoid cells in ATRT can range from uncommon to abundant. These cells are quite variable in size, with rather small rhaboid cells in the current case. In some examples of ATRT, the rhabdoid cells can be quite large and not uncommonly multinucleated. Diagnosis for those cases is usually straight forward.
Immunohistochemistry: The tumor cells are negative for BAF 47, which is strong evidence in favor of the diagnosis of ATRT. Note that the endothelial cells are positive and serve as internal controls. Practically all the tumor cells are strongly positive for vimentin. Since this tumor is polyphyenotypic, neoplastic cells are focally positive for neurofilament proteins (NFP), glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), and cytokeratin (CK) CAM5.2 and AE1/AE3. The tumor cells are negative for desmin, smooth muscle actin, synatpophysin, and placental alkaline phosphatase (PLAP). For suspicious lesions that arise from and around the sellar and pineal region, germ cell tumor must be entertained in the differential diagnosis.
Fluorescent in situ hybridization: No deletion of chromosome 22q11.2 was demonstrated.
Comment: The morphology, immunohistochemical and clinical features are consistent with a diagnosis of ATRT. The lack of immunoreactivity for BAF 47 indicates that the protein product of INI1 gene is not expressed. Deletion of the INI1 gene on chromosome 22q11.2 is seen in about 90% of ATRTs, which leads to absence of expression of the gene product. In the case under discussion, it is most likely that a specific type of mutation occurred that led to lack of expression of the protein product. See another case of ATRT