Malignant gliomas with primitive neuroectodermal tumor-like components: a clinicopathologic and genetic study of 53 cases.
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.
Perry
Arie
A
Division of Neuropathology, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA. aperry@wustl.edu
Miller
C Ryan
CR
Gujrati
Meena
M
Scheithauer
Bernd W
BW
Zambrano
Sandro Casavilca
SC
Jost
Sarah C
SC
Raghavan
Ravi
R
Qian
Jiang
J
Cochran
Elizabeth J
EJ
Huse
Jason T
JT
Holland
Eric C
EC
Burger
Peter C
PC
Rosenblum
Marc K
MK
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
D018906:Antineoplastic Agents, Alkylating; D011518:Proto-Oncogene Proteins; D003606:Dacarbazine; D000077204:Temozolomide