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.