The morphologic spectrum of oligodendrogliomas includes tumors that are traditionally misinterpreted as “diffuse fibrillary astrocytomas.” These consist of isolated neoplastic oligodendrocytes that are entrapped in a background composed of axons and fibrillary reactive gliosis. In some cases, a genetic deletion is present in the 1p19q locus. A series of 153 “pure” supratentorial oligodendrogliomas composed of “classic” or pseudo-“diffuse fibrillary oligodendrogliomas” showed that two-thirds of the tumors were exclusively isolated tumor cells (type III) and that only one-third exhibited both isolated tumor cells and solid tumor tissue components (type II). The type II tumor destroys brain parenchyma and forms new micro-blood vessels, whereas isolated tumor cells do not destroy the parenchyma and are not associated with microangiogenesis. Clinically, a neurologic deficit occurs in about 57% of type II but in only 8% of type III oligodendrogliomas. On MRI, contrast enhancement is observed in type II oligodendrogliomas (64%) but is usually not seen in type III. The biologic behavior of these tumors seems to be closely related to the pattern of tumor growth. Emergence of microangiogenesis within a tumor that at first grows slowly with a type III pattern signals more aggressive behavior (18).

MRI typically reveals oligodendrogliomas to be hyperintense on spin density and T2-weighted images. Their signal is often heterogeneous owing to small cysts, calcification, or prior hemorrhage. Calcification is especially common and may be seen best on CT.

Statistics show anaplastic transformation in 50% of patients 10 years after diagnosis. Anaplastic transformation may be suspected on the basis of PET studies, because anaplastic oligodendrogliomas show a higher methionine and [¹⁸F]FDG fixation than low-grade oligodendrogliomas. Radiotherapy and chemotherapy with gadolinium enhancement are usually indicated for recurrences (19). Survival for patients with anaplastic oligodendroglioma is about 3 years.

Low-grade astrocytomas associated with chronic seizures constitute a distinct clinicopathologic group of tumors that arise in young hosts (20 to 40 years old). These low-grade gliomas usually have an indolent course. An important factor in achieving long-term seizure control is complete removal of the lesion to tumor-free margins. In addition, complete resection of the tumor may be the most effective treatment for control of low-grade glioma growth. Margins may be limited by functional cortex, leading to partial tumor excision. For low-grade gliomas in the temporal lobe, additional medial temporal resection may be required. This is most often predicted preoperatively by MRI that shows the lesion infiltrating the hippocampus or hippocampal atrophy. Decisions about extralesional hippocampal resection should be based on evaluation of this presumed dual pathology using several variables in addition to hippocampal atrophy, including seizure history, video-EEG, semiology, proximity of the tumor to the hippocampus, and the neuropsychological profile of the patient, especially with regard to memory function (20).

On MRI, low-grade astrocytomas usually appear homogeneous, although some tumors have cystic components. The signal is hyperintense on double-echo sequence and hypointense on T1-weighted images. Calcification is seen on CT in the minority of low-grade astrocytomas, compared with the strong majority of oligodendrogliomas; however, because astrocytomas are the most common overall, any tumor with calcification is most likely to be of this type.

There appears to be a significant decrease in the risk of tumor recurrence in patients who undergo aggressive resection (100% 10-year survival) compared with patients who have anything less than gross-total resection (21). Gender, type of symptoms, length of preoperative symptoms, and timing of radiation therapy (immediate postoperative versus delayed radiotherapy) are not known to be significant
in determining outcome, length of survival, recurrence, and/or incidence of transition to more malignant tumors. Within the population of patients with low-grade astrocytomas, those with chronic epilepsy usually have the best prognosis. Tumors associated with chronic epilepsy are much less likely to become more malignant over time (21). Irradiation can be used to reduce intractable seizure frequency in some patients with unresectable (biopsy-proven) low-grade astrocytoma (19). Focal radiation treatment may reduce seizures by more than 75% in 80% of cases, and the MRI often shows a tumor response to radiation that correlates with reduced seizure frequency (19). In patients who became seizure free, seizure recurrence is usually associated with tumor progression (14).

Ganglioglioma may be the most common cause of tumor-related chronic epilepsy (22,23). The current World Health Organization (WHO) classification defines ganglioglioma as a neoplasm composed of neoplastic neural (ganglion cells) and glial elements (24). Ganglioglioma accounts for 0.4% to 9% (17) of primary brain tumors diagnosed at different institutions. It has been described in many parts of the central nervous system but is most commonly found in the temporal lobe (25,26).

The tumor has been localized by MRI or CT scans in the temporal (70%), frontal (10%), parietal (8%), and occipital (3%) lobes. MRI is able to detect the tumor with a very high degree of sensitivity, but findings are infrequently specific for ganglioglioma. On MRI, a wide variety of signals may be found (23), such as gadolinium enhancement in 60%, mass effect in 45%, cystic change in 30%, and cerebral edema in 5%. CT scan, suggested by Tampieri and colleagues (23), shows abnormality in 70%, with calcification in 35% of these, but is reported as normal in the other 30%.

Histologically, the tumors are composed of large polymorphic ganglion cells (pyramidal-like neurons), with vesicular nuclei and prominent nucleoli admixed with a neoplastic glial element, most often astrocytic. Mild perivascular chronic inflammation and vascular endothelial proliferation are usually found. Cortical dysplasia—generally adjacent to but separate from the tumor—is present in 40% of the cases described in the literature (22).

Good seizure control is seen in patients with resected ganglioglioma, despite years of medically resistant seizures: 80% of patients are seizure free (Engel class I) at 6 months, 72% at 1 year, and 63% at 2 years (22). Good outcome may be achieved, despite scalp EEG findings that may conflict with tumor location, and is more likely when surgery is performed relatively soon after epilepsy onset. MRI features such as presence or absence of gadolinium enhancement, mass effect, and cystic change had no measurable influence on the seizure outcome after tumor resection. Malignant degeneration is a rare consequence of these tumors, but the glial component can become anaplastic. No strong statistical data are available to indicate the frequency of such transformations.

DNETs are a group of supratentorial cortically based lesions that superficially resemble mixed oligoastrocytomas, oligodendrogliomas, and astrocytomas. Clinically, these tumors are associated with complex partial seizures beginning before the age of 20 years, with no neurologic deficit and no stigmata of phakomatosis (27). In the revised WHO classification, DNETs have been incorporated into the category of neuronal and mixed neuronoglial tumors. This classification describes a histologic variant characterized by the following criteria: cortical location, multinodular architecture (the nodule consisting of astrocytoma-like variants, oligodendrogliomas, or oligoastrocytomas), and foci of dysplastic cortical disorganization, showing a columnar structure perpendicular to the cortical surface. Daumas-Duport (28) described a glioneuronal element that was demonstrated to be specific and sufficient for diagnosing DNETs. Even if some of these tumors show a high MIB-1 labeling index, the spectrum of DNETs includes a simple form with a unique glioneuronal element. DNET is a surgically curable tumor of young patients with intractable partial seizures (29).

Daumas-Duport and colleagues (29) reported a series of 39 cases of neuroepithelial tumors associated with medically intractable complex partial seizures. The age at onset of symptoms ranged from 1 to 19 years (mean, 9 years). In addition to the chronic nature of the seizures (range, 2 to 18 years; mean, 9 years), one third of the patients showed radiologic features such as focal cranial deformity, indicating that the tumors had an early onset and were long-standing. In most cases, CT scans showed a “pseudo-cystic,” welldemarcated, low-density appearance, associated in some cases with focal contrast enhancement (18%) or calcified hyperdensity (23%). MRI signals are hypo and hyper on T1 and T2 sequences, respectively. No edema, but possible gadolinium enhancement, can be seen. In a few cases, DNET was associated with neurofibromatosis type 1. The tumor involved primarily the temporal lobe (62%) but also occurred in the frontal lobe (31%). Although tumor removal was considered incomplete or subtotal in 17 patients (44%), long-term follow up (range, 1 to 18 years; mean, 9 years) showed neither clinical nor radiologic evidence of progression in any patient. Comparison of the survival data of the 13 subjects who had undergone postoperative radiotherapy with the 26 who had not indicated that radiation therapy was of no obvious benefit. The identification of DNET has therapeutic and prognostic implications because aggressive therapy can be avoided, thus sparing these young patients the deleterious long-term effects of radiotherapy or chemotherapy.

Pleomorphic xanthoastrocytoma is a relatively rare brain tumor of adolescents and young adults, characterized by its superficial location, sometimes associated with a cyst, and by frequent involvement of the meninges. Temporal lobe localization helps explain why epilepsy predominates as a
presenting symptom. Histology shows intracellular lipid inclusions, hypervascularization, and in all cases an arachnoidal component. The tumor is slow-growing, despite features of histologic atypia that place it in WHO grade II or III on the basis of elevated mitotic counts and the presence of punctiform necrosis. Immunostaining with the proliferation marker MIB-1 is present in only 2% of cells in the grade II group, whereas 5% show labeling in grade III. All pleomorphic xanthoastrocytomas express some amount of glial fibrillary acidic protein and are shown to elaborate a characteristic pericellular reticulin network. Surgical treatment is considered to offer the best survival outcome. Tumor recurrence with confirmed anaplasia still occurs in about 20% of cases at a mean postoperative follow up of 5 years, and survival for patients with recurring anaplastic xanthoastrocytomas is about 2 years.