title: Epithelioid Glioblastomas and Anaplastic Epithelioid Pleomorphic Xanthoastrocytomas--Same Entity or First Cousins?
abstract: Epithelioid glioblastoma (eGBM) and pleomorphic xanthoastrocytoma (PXA) with anaplastically transformed foci (ePXA) show overlapping features. Eleven eGBMs and 5 ePXAs were reviewed and studied immunohistochemically. Fluorescence in situ hybridization for EGFR amplification, PTEN deletion and ODZ3 deletion was also performed, with Ilumina 450 methylome analysis obtained in five cases. The average age for eGBM was 30.9 (range 2-79) years, including five pediatric cases and a M : F ratio of 4.5. The ePXA patients had a M : F ratio of 4 and averaged 21.2 (range 10-38) years in age, including two pediatric cases. Six eGBMs and two ePXAs recurred (median recurrence interval of 12 and 3.3 months, respectively). All tumors were composed of solid sheets of loosely cohesive, "melanoma-like" cells with only limited infiltration. ePXAs showed lower grade foci with classic features of PXA. Both tumor types showed focal expression of epithelial and glial markers, retained INI1 and BRG1 expression, occasional CD34 positivity, and lack of mutant IDH1 (R132H) immunoreactivity. BRAF V600E mutation was present in four eGBMs and four ePXAs. ODZ3 deletion was detected in seven eGBMs and two ePXAs. EGFR amplification was absent. Methylome analysis showed that one ePXA and one eGBM clustered with PXAs, one eGBM clustered with low-grade gliomas, and two eGBMs clustered with pediatric-type glioblastomas. Common histologic, immunohistochemical, molecular and clinical features found in eGBM and ePXA suggest that they are closely related or the same entity. If the latter is true, the nomenclature and WHO grading remains to be resolved.
authors.affiliation: Department of Pathology, University of California, San Francisco, CA.
authors.forename: Sanda
authors.initials: S
authors.lastname: Alexandrescu
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Korshunov
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore.
authors.forename: Siang Hui
authors.initials: SH
authors.lastname: Lai
authors.affiliation: Department of Pathology, Good Samaritan Hospital, San Jose, CA.
authors.forename: Salma
authors.initials: S
authors.lastname: Dabiri
authors.affiliation: Department of Pathology, Apollo Specialty Hospital, Chennai, India.
authors.forename: Sushama
authors.initials: S
authors.lastname: Patil
authors.affiliation: Department of Pathology, Children's Hospital of Alabama, Birmingham, AL.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Indiana University, Indianapolis, IN.
authors.forename: Chie-Schin
authors.initials: CS
authors.lastname: Shih
authors.affiliation: Department of Pathology, Indiana University, Indianapolis, IN.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Bonnin
authors.affiliation: Department of Pathology, Texas Health Presbyterian Hospital, Dallas, TX.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Baker
authors.affiliation: Department of Pathology, Scripps Clinic, La Jolla, CA.
authors.forename: Emma
authors.initials: E
authors.lastname: Du
authors.affiliation: Department of Pathology, Children's Hospital Central California, Madera, CA.
authors.forename: David W
authors.initials: DW
authors.lastname: Scharnhorst
authors.affiliation: Department of Pediatric Oncology, Children's Hospital Central California, Madera, CA.
authors.forename: David
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN.
authors.forename: David W
authors.initials: DW
authors.lastname: Ellison
authors.affiliation: Department of Pathology, University of California, San Francisco, CA.
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: BRAFV600E; ODZ3; epithelioid; glioblastoma; pediatric; pleomorphic; prognosis; xanthoastrocytoma