Brain Pathology Case of the Month - August 2005

FINAL DIAGNOSIS:  OLIGODENDROGLIOMA, WHO GRADE II WITH NEUROCYTIC DIFFERENTIATION.

DISCUSSION:

Recently four cases of this new and distinctive glioneuronal tumor composed primarily of oligodendroglioma and, to a lesser extent, neurocytoma-like regions with rosette formation have been described ¹. Based on clinicopathologic and genetic features the authors devised the term "oligodendroglioma with neurocytic differentiation". There are striking clinical, morphological and genetic similarities between these and the present case. All were frontal lobe tumors. Three of the four arose in the left hemisphere. The mean age of onset was 43 years. The tumors carried overlapping morphological and immunohistochemical features of oligodendrogliomas and central neurocytomas. In one of the four microcalcifications were noted. Despite extensive morphological overlap, there are distinct clinicopathologic and genetic alterations in oligodendrogliomas and central neurocytomas. In contrast to oligodendrogliomas often arising in the frontal lobe, central neurocytomas are rare neoplasms principally found adjacent to the foramen of Monro ^{2, 3.} Extraventricular tumors with neurocytoma- like morphology should therefore include the differential diagnosis of an oligodendroglioma with neurocytic differentiation.

Genetically, the incidence of combined LOH 1p and 19q, the "molecular signature" for the majority of oligodendroglial neoplasms ⁴, is very low in central neurocytomas ⁵. Furthermore, central neurocytomas with LOH 1p and LOH 19q show randomly distributed allele losses affecting single chromosomal loci only ⁵. Molecular pathology proves to be a feasible diagnostic tool in these cases. Indeed, as in our case, combined LOH 1p and LOH 19q was demonstrated in three of the four reported tumors for all informative loci ¹. Incidentally, all these tumors - like the presented one here were located in the left frontal lobe.

The histogenesis of oligodendroglioma is still not understood. So far the O-2A cell, identified in rodent models with the ability to differentiate along either oligodendroglial or astrocytic lines depending on cell culture conditions is considered a potential progenitor cell ⁶. Recently, Williams et al. have isolated a precursor cell from the rat cerebral cortex capable of generating both neurons and oligodendrocytes proposing the existence of a "N-O" precursor cell ⁷. While oligoastrocytomas might be explained by the existence of an O-2A precursor cell, oligodendrogliomas with neurocytic differentiation might originate from the "N-O"- cell. It is unknown, however, if "O-2A" -cells or "N-O" -cells exist in humans at all. While these tumors might answer questions as to the origin of oligodendroglial neoplasms in the future, it is important for today's neuropathologist to be aware of this variant of oligodendrogliomas.

Their clinical course, despite a tendency of recurrence, seems benign. Moreover, alternative therapeutic strategies arise, if LOH 1p and LOH 19q is demonstrated, as in this case. Oligodendrogliomas with allelic losses on these chromosomes proofed to be chemosensitive tumors and patients with these tumors were longer recurrence free and had an longer overall survival time ^{8, 9.}

REFERENCES:

1. Perry A, Scheithauer BW, Macaulay RJ et al. Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol. 2002;61:947-955
2. Hassoun J, Soylemezoglu F, Gambarelli D et al. Central neurocytoma: a synopsis of clinical and histological features. Brain Pathol. 1993;3:297-306
3. von Deimling A, Janzer R, Kleihues P, Wiestler OD. Patterns of differentiation in central neurocytoma. An immunohistochemical study of eleven biopsies. Acta Neuropathol (Berl). 1990;79:473-479
4. Perry A. Oligodendroglial neoplasms: current concepts, misconceptions, and folklore. Adv Anat Pathol. 2001;8:183-199
5. Tong CY, Ng HK, Pang JC et al. Central neurocytomas are genetically distinct from oligodendrogliomas and neuroblastomas. Histopathology. 2000;37:160-165
6. Raff MC, Miller RH, Noble M. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature. 1983;303:390-396
7. Williams BP, Read J, Price J. The generation of neurons and oligodendrocytes from a common precursor cell. Neuron. 1991;7:685-693
8. Smith JS, Perry A, Borell TJ et al. Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol. 2000;18:636-645
9. Cairncross JG, Ueki K, Zlatescu MC et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst. 1998;90:1473-1479

Contributed by Wolf Mueller, Ulrike Lass, Julian Veelken, Friedrich Reuter, Andreas von Deimling

International Society of Neuropathology