PEDIATRIC MALIGNANT GLIOMA WITH TUBULORETICULAR INCLUSIONS AND MYCN AMPLIFICATION - REPORT OF A CASE WITH IMMUNOHISTOCHEMICAL, ULTRASTRUCTURAL, FLOW CYTOMETRIC, KARYOTYPIC, AND SOUTHERN BLOT ANALYSIS

Background. The authors described unusual pathologic features in a lef t frontal lobe malignant glioma in a 3 1/2-year-old boy. The pathology was similar in the initial excision and two subsequent recurrences at 9 and 11 months and at autopsy, when extensive subarachnoid spread wa s noted. Methods. The tumor was studied by conventional histology, imm unohistochemistry, flow cytometry, transmission electron microscopy (T EM), immune electron microscopy (IEM), and cytogenetic and Southern bl ot analysis. Results. The tumor revealed two different histologic patt erns. One component showed large cells with eosinophilic cytoplasm, ve sicular nuclei with prominent nucleoli, eosinophilic perinuclear inclu sions, and immunoreactivity for glial fibrillary acidic protein (GFAP) and vimentin. The other component consisted of undifferentiated cells with hyperchromatic nuclei and scanty cytoplasm. By TEM, the perinucl ear aggregates were composed of tubuloreticular inclusions, which were also observed in endothelial cells within the tumor vasculature. By I EM, the intermediate filaments in the tumor cell cytoplasm were decora ted with GFAP. Flow cytometric results revealed a marked increase in t he S-phase (48%), whereas cytogenetic analysis of short-term cultures showed an abnormal karyotype containing marker chromosomes and double minutes. In the second resection, additional karyotypic abnormalities were noted, including 1p- and several additional markers. The first an d second resections showed MYCN amplification by Southern Blot analysi s in the 60- to 80-fold range. Conclusions. This tumor presents unique histologic, ultrastructural, and cytogenetic findings as well as MYCN amplification that is notable for a pediatric malignant glioma. Tubul oreticular inclusions were a prominent feature in this tumor, which ag ain is unique for a glioma.