Unusual malignant glioneuronal tumors of the cerebrum of adults: a clinicopathologic study of three cases

Abstract

Malignant glioneuronal tumors of the brain are rare and poorly characterized. Herein, we report the clinicopathologic features of three examples with unusual morphologies including both glial and neuronal differentiation. Hematoxylin and eosin-stained slides were reviewed in all cases. Immunohistochemical stains were performed on formalin-fixed, paraffin-embedded sections. Transmission electron microscopy (EM) was performed on both formalin-fixed (n=1) and paraffin embedded tissue (n=2). The immunogold technique for localization of GFAP was also performed. Two patients were male and one was female, age 66, 84, and 34 years, respectively. Radiologic studies demonstrated hyperdensity on CT (n=3), multicentricity (n=2), and a cortical based solid component with a cystic extension into underlying white matter (n=2). At surgery, all three tumors were superficial and relatively circumscribed. Histologically, they were composed of large epithelioid cells (n=3), spindle cells (n=1), and poorly differentiated smaller cells with high nuclear/cytoplasmic ratios (n=1). Brisk mitotic activity and coagulative non-palisading necrosis were present in all cases. The tumors were immunopositive for GFAP (n=3), S-100 (n=3), synaptophysin (n=3), chromogranin (n=3), Neu-N (n=2), and neurofilament protein (n=2). Stains for EMA were negative. EM demonstrated convincing neurosecretory granules in one case, some in filament-containing cells immunogold labeled for GFAP. Two patients expired 3-5 weeks after surgery. True malignant neoplasms with glial and neuronal differentiation do occur in the central nervous system of adults and may pursue a highly aggressive course. The use of minimal diagnostic criteria, e.g., immunoreactivity for a single antigen like neurofilament protein, may not be sufficient and should be discouraged.

Ewing’s Sarcoma and Peripheral Primitive Neuroectodermal Tumor in Adults: Different Features of a Rare Neoplasm

“…Malignant small cell tumors of the chest wall and/or the lung have been described several years ago in children and young adults only [3]. In comparison, central primitive neuroectodermal tumors (cPNETs) are defined as a group of monomorphous, small cell examples of malignant, primary central nervous system neoplasms with neuronal and glial differentiation [4]. The peak incidence of tumors of the EFT is reported to be at the age of 15 years, while they rarely occur in adults [2].…”

The ‘rosette‐forming glioneuronal tumor’ of the fourth ventricle

“…Three of the four patients showed evidence of tumor recurrence but were still surviving 4, 13, and 10 years from initial presentation. Unusual highly malignant multicentric cortical‐based glioneuronal tumors of the cerebrum have also been recently described 18 in contrast to the usually indolent behaviour of glioneuronal tumors apart from the glioneuronal tumor with neuropil‐islands.…”

“…The rosette-forming glioneuronal tumor of the fourth ventricle (RGTFV) 8 is one of recently described glioneuronal tumor variants. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] In particular RGTFV needs to be distinguished from glioneuronal tumor with neuropil-like islands/rosetted glioneuronal tumor and papillary glioneuronal tumor (PGT). 19 RGTFV and PGT have been added in the 2007 WHO classification of brain tumors.…”

Malignant glioneuronal tumor of the adult cerebrum with neuropil-like islands involving “proliferating nodules”: confirmatory report of an unusual variant

“…Indeed, diagnostic criteria for purported neuronal diVerentiation tend to range from expression of neuronal markers in isolated cells to dysplastic neurons, to suggestive architectural patterns [9,13]. While the increasing sensitivity of detection methods clearly is at odds with the speciWc relevance of results thus obtained, reproducible patterns are being searched for in order for meaningful entities to be singled out.…”

“…On the one hand, neuropil-like islands can be conceived as transitory structures that may eventually either undergo deWnite gangliocytic maturation-thus evolving into complex glioneuronal tumors of the type described by Rodriguez et al [9]-or end up submerged by the mitotically active astrocytic bulk of tumor. This hypothetic scenario has actually been lent some support by cases requiring second surgery, in which the neuronal component was reported as either not being present from the outset [8] or vanishing during tumor progression [12].…”