title: Gliosarcoma with epithelial differentiation: immunohistochemical and molecular characterization. A case report and review of the literature.
abstract: Few reported cases of gliosarcomas or glioblastomas with epithelial-like areas exist. Most cases were originally diagnosed as metastatic carcinoma. Focal expression of glial fibrillary acidic protein has helped characterize these tumors as having a glial origin. We report a case of gliosarcoma with multifocal, extensive areas of well-differentiated carcinoma; demonstrating squamous and glandular differentiation. The expression of glial fibrillary acidic protein and epithelial phenotype were mutually exclusive. We performed extensive immunohistochemical analyses and comparative genotypic analysis using microdissection to secure representative glial and epithelial components. Loss of heterozygosity was analyzed with a panel of 12 polymorphic microsatellite markers designed to indicate allelic loss and situated in proximity to known tumor suppressor genes located on chromosomes 1p, 9p, 10q, 17p and 19q. We found comparable patterns of acquired allelic loss between the glial and carcinomatous components, strongly supporting the monoclonal origin of this neoplasm. This case represents an extreme form of phenotypic divergence in a malignant glioma, and constitutes a difficult diagnostic challenge. This heterogeneity reflects the potential for a range of phenotypic expression in malignant gliomas that needs to be recognized. We suggest microdissection genotyping as a molecular technique to better characterize these tumors.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. ozolekja@upmc.edu
authors.forename: John A
authors.initials: JA
authors.lastname: Ozolek
authors.forename: Sydney D
authors.initials: SD
authors.lastname: Finkelstein
authors.forename: Marta E
authors.initials: ME
authors.lastname: Couce
mesh_terms: D000368:Aged; D015415:Biomarkers; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology*; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D018316:Gliosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7; D007633:Keratins / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D019656:Loss of Heterozygosity; D008297:Male; D012196:Review Literature as Topic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D015415:Biomarkers; C400901:CAM 5.2 antigen; D005904:Glial Fibrillary Acidic Protein; C507497:KRT7 protein, human; D053552:Keratin-7; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D007633:Keratins