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INTRODUCTION

Glial cells are non-neuronal cells in the central nervous system that surround, protect, and sustain the neurons The two most numerous normal glial cell types in the CNS are the astrocyte and the oligodendrocyte. During embryologic development, the neuropithelial lining cells first produce neuroblasts, the progenitors of neurons. As soon as neuroblast production ceases, this same neuroepithelial lining begins to produce glioblasts, which differentiate into astrocytes and oligodendrocytes.⁷ Recent studies suggest that both oligodendrocytes and at least some astrocytes are derived from the same progenitor cells.^1,3,16 Astrocytes normally serve a sustentacular function, i.e. they support and sustain neurons. Oligodendrocytes normally serve an insulating function, i.e. they serve to myelinate within the central nervous system. In sum, both oligodendrocytes and type 2 astrocytes are derived from a common precursor, and, despite their very different functions, they have a close embryologic relationship.

Excluding ependymal tumors and mixed neuronal-glial tumors, the World Health Organization essentially recognizes two types of glial tumors: “Astrocytic tumours” and  “Oligodendroglial tumours”.⁹ Glial tumors are envisioned as astrocytic, oligodendroglial, or some combination of these two ("oligoastrocytomas"), as well as special variants or subtypes thereof. These are also graded on a scale of 1 to 4, to reflect expected degrees of aggressiveness.

This is a logical phylogenetic system, if one assumes that these tumors express differentiation toward astrocytes, oligodendrocytes, or both. There is an elephant in the room, however: there is no hard evidence that “oligodendroglial” tumors mimic differentiation toward normal oligodendrocytes. This was simply an historical assumption based upon the observation of some morphologic similarities between “oligodendroglioma” cells and normal oligodendrocytes, coupled with the supposition that normal oligodendrocytes “should” have a neoplastic counterpart. (Note that we are not saying that this assumption is necessarily incorrect—we are simply noting that it remains unproven.)  To further complicate the story, there is evidence to suggest that “oligodendrogliomas” arising in the temporal lobe, insula, and diencephalon, are clinicopathologically distinct from oligodendrogliomas arising in the frontal, parietal, and occipital lobes.¹¹

HISTOLOGY OF GLIOMAS

Glial tumors (gliomas) exhibit amazingly varied morphologies. In fact, the most common glial tumor was once known as “glioblastoma multiforme” precisely because its appearance is so variable. Nevertheless, all glial tumors express a glial immunophenotype (a.k.a. antigenic expression), and demonstrate glial differentiation. In the everyday practice of pathology, antigenic expression is one of the most objective means of determining tumor differentiation. Unfortunately, there are no differential antigenic tests to separate “astrocytoma” from “oligodendroglioma”. Rather, there are simply a constellation of soft morphologic features that are suggestive of “oligodendroglial differentiation”, including cellular monomorphism, nuclear roundness, perineuronal satellitosis, secondary structure formation, artifactual cytoplasmic retraction, scanty cytoplasm, calcifications, branching capillaries, and mucin-filled microcysts.

Ironically, "oligodendroglioma" is largely defined by what it lacks—namely glial processes; indeed, the name ­oligodendroglioma means few processes. Many of the classic morphologic features are consequences of this lack. Also ironically, the most famous microscopic feature (the clear “fried egg” cell) is actually an artifact of slow fixation, which is not found in frozen sections or in rapidly fixed biopsies.

The morphologic features of oligodendroglioma tend to be highly subjective and are fraught with marked interobserver variability. Furthermore, small sample size often exacerbates these problems, since both “astrocytic” and “oligodendroglial” neoplasms of all grades can exhibit regional heterogeneity.


Figure 1. Oligodendroglial neoplasm: Note the marked tendency of tumor cells to cluster around neurons (“perineuronal satellitosis”).
 

CLINICAL FEATURES OF GLIOMAS

The majority of patients with oligodendrogliomas present with seizures or chronic seizure disorders. The typical patient is a young to middle-aged male with an indolent presentation. Other common presentations include headache, increased intracranial pressure, focal neurologic deficits, and mental status changes.^8,9,13

PROGNOSIS AND TREATMENT OF GLIOMAS

Survival statistics vary widely, probably because of lack of universally accepted diagnostic criteria. Median survival is highly dependent upon Grade.^4,12,17,18 Low-grade oligodendrogliomas probably have a median survival of greater than 10 years, whereas Grade III oligodendrogliomas (“anaplastic oligodendrogliomas”) have median survival estimates ranging from <1 yr to 3.9 yrs. Grade for grade, “oligodendrogliomas” have a somewhat longer survival than “astrocytomas”, and mixed gliomas (“oligoastrocytomas”) have an intermediate prognosis, although the relative proportions of cell types do not seem to matter.¹⁷