title: Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases.
abstract: Central nervous system neoplasms with combined features of malignant glioma and primitive neuroectodermal tumor (MG-PNET) are rare, poorly characterized, and pose diagnostic as well as treatment dilemmas. We studied 53 MG-PNETs in patients from 12 to 80 years of age (median = 54 years). The PNET-like component consisted of sharply demarcated hypercellular nodules with evidence of neuronal differentiation. Anaplasia, as seen in medulloblastomas, was noted in 70%. Within the primitive element, N-myc or c-myc gene amplifications were seen in 43%. In contrast, glioma-associated alterations involved both components, 10q loss (50%) being most common. Therapy included radiation (78%), temozolomide (63%) and platinum-based chemotherapy (31%). Cerebrospinal fluid (CSF) dissemination developed in eight patients, with response to PNET-like therapy occurring in at least three. At last follow-up, 27 patients died, their median survival being 9.1 months. We conclude that the primitive component of the MG-PNET: (i) arises within a pre-existing MG, most often a secondary glioblastoma; (ii) may represent a metaplastic process or expansion of a tumor stem/progenitor cell clone; (iii) often shows histologic anaplasia and N-myc (or c-myc) amplification; (iv) has the capacity to seed the CSF; and (v) may respond to platinum-based chemotherapy regimens.
authors.affiliation: Division of Neuropathology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA. aperry@wustl.edu
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Miller
authors.forename: Meena
authors.initials: M
authors.lastname: Gujrati
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: Sandro Casavilca
authors.initials: SC
authors.lastname: Zambrano
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Jost
authors.forename: Ravi
authors.initials: R
authors.lastname: Raghavan
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Cochran
authors.forename: Jason T
authors.initials: JT
authors.lastname: Huse
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burger
authors.forename: Marc K
authors.initials: MK
authors.lastname: Rosenblum
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D016259:Genes, myc / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009362:Neoplasm Metastasis; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011878:Radiotherapy / Q000379:methods; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011518:Proto-Oncogene Proteins; D003606:Dacarbazine; D000077204:Temozolomide