FINAL DIAGNOSIS: (CENTRAL) NEUROCYTOMA
Central neurocytomas are typically intraventricular tumors in young adults and over 100 cases have been reported since the entity was first described in 1982. The most common location is supratentorially in the lateral ventricles near the foramen of Monro or in the septum pellucidum. Morphologically, these tumors are easily confused with oligodendrogliomas or clear cell variants of ependymomas. To make matters more confusing, the neuronal essence may be identified, but the term "neuroblastoma" or "PNET" used for diagnosis, resulting in unnecessary therapy, but with an outcome considerably less bleak than implied by such diagnostic terms. Widespread recognition by neuropathologists, neurosurgeons and neuroradiologists of the central neurocytoma and its incorporation into the WHO pantheon of CNS tumors has diminished these mis-identifications. Neurocytomas are rare before age 10 years, but over 60% present between the ages of 20-40. About 20% occur between ages 10-20 (1). In most cases the history of clinical symptoms is short (less than eight months) but in some patients symptoms can be present for as long as three years. A few cases have been discovered incidentally. Clinical symptoms are usually related to increased intracranial pressure (headache, papilledema) or, in some, visual disturbances. More rarely, symptoms such as mental disturbances, pyramidal signs, hormonal dysfunction or seizures have been associated with neurocytomas (1).
Radiologically, the tumors are identified as intraventricular masses, which are sometimes quite large. Calcification can be identified by CT scans. MRI shows the mass to be isointense with cortex, or showing slightly high signal in T1- and T2-weighted images and proton-density spin echo sequences. Typically there is homogenous enhancement following contrast medium administration, but the pattern may be more heterogeneous if there is calcification or cystic areas.
Grossly, the tumor is typically well-demarcated from the surrounding tissue and usually grayish, friable. About 40% have a gritty texture due to numerous microcalcifications.
Microscopically the tumor cells are bland, monotonous, and contain round nuclei with a delicate "salt and pepper" chromatin pattern. The cells have scanty or ill defined cytoplasm and are embedded in an eosinophilic matrix which has a fine, fibrillar texture. Clear cell areas are usually present and may tempt the unwary into a diagnosis of oligodendroglioma, however, they are rarely a prominent component of the histologic pattern. In other areas, there may be a paucity of cells with irregularly shaped patches of matrix. Sometimes tumors cells may exhibit a streaming pattern. In a few cases rosettes have been reported, however, these have been reported as absent in most cases. Necrosis and endothelial proliferation are rare and mitoses are uncommon. Proliferation studies have shown most cases to have MIB-1 labeling indices of <1%.
Immunohistochemically, the tumors are nearly always strongly positive for NSE and synaptophysin and less so for other neuronal markers such as neurofilament, neuron-associated class III beta-tubulin and the microtubule associated proteins MAP2 and tau. In nearly all cases, tumor cells are negative for GFAP, although occasionally, they may show reactive glial cells near the edges.
Electron microscopy invariably shows numerous 60-160 nm dense core granules and 40-60 nm clear vesicles as well as microtubules. Intermediate filaments are not usually present and there are often numerous cellular processes. Synaptic formation is a confirmatory finding, but is not invariably present and appears to have no bearing on the biologic behavior of the tumor (1).
The microscopic appearance, immunohistochemical profile and ultrastructural features of this case confirm the neuronal origin of this tumor. The histologic features are that of a central neurocytoma, however, this case is unusual in that the tumor was not intraventricular. Instead, it was located along the orbital surfaces of the left frontal lobe, involving the olfactory bulb and surrounding the optic tract, optic chiasm as well as the internal carotid, middle cerebral and anterior cerebral arteries of the Circle of Willis. Although extraventricular sites, such as in this case, are exceptional, there have now been several reports of neurocytomas occurring in the cerebral hemispheres (2, 3,4) as well as in the spinal cord (5). These cases appear to have outcomes as favorable as their more common intraventricular brethren.
In this case, the neurosurgeons felt that the tumor had been completely resected and four months after her surgery an MRI scan showed no recurrence. With total resection, cures are possible, but even with incomplete resection several years will elapse before there is a recurrence. The role of radiotherapy in the treatment of primary, incomplete resected tumors or recurrences is still uncertain. In a few cases, there has been histologic evidence of "anaplasia" consisting of focal necrosis, vascular proliferation and marked mitotic activity. Follow-up has been reported in two of these cases and show no recurrence after 40 and 48 months (1). Thus, the prognostic implications of such histologic features are not certain.
Contributed by Ronald L. Hamilton, M.D.