Histological spectrum of oligodendroglial tumors: Only a subset shows 1p/19q codeletion

Vani Santosh 
 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Correspondence Address:
Dr. Vani Santosh
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru - 560 029, Karnataka
India

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Until recently, histological examination has been the gold standard for establishing the diagnosis of diffuse gliomas. However, with evolving molecular genetics and awareness of biomarkers, attempts at prognostic stratification using histomolecular classification are being made with increasing success. The molecular genetic changes specific to a distinct set of gliomas have finally made their way into routine neuropathological diagnosis. The latest World Health Organization (WHO) update on central nervous system (CNS) tumors (2016) takes into account genetic testing along with histology to define an entity that is following the International Society of Neuropathology (ISN) Haarlem guidelines.[1],[2] Among the diffuse gliomas, oligodendrogliomas are known to harbour a distinctive genetic profile, i.e., the 1p19q codeletion along with isocitrate dehydrogenase (IDH) mutation.[2]

In this issue of the journal, Pai et al., present a large series of 676 cases of both pediatric (n = 18) and adult (n = 658) diffuse gliomas composed of complete or partial oligodendroglial component, which were diagnosed over a 7-year period in a single institution. This is certainly the largest series from India investigating 1p19q codeletion status. The tumors included oligodendroglioma (OD) and anaplastic oligodendroglioma (AOD), oligoastrocytoma (OA), and anaplastic oligoastrocytoma (AOA), as well as glioblastoma with an oligodendroglial component (GBM-O).[3]

The various methods of carrying out the 1p19q assay are elegantly described in this paper. As expected with the 1p19q codeletion status, the authors show a frequency of 59.24% in histological OD and AOD, 13.28% in OA and AOA, and 5.1% in GBM-O. Interestingly, in the pediatric age group, 1p/19q codeletion was seen in 25% of pure ODGs and in 10% of mixed ODGs. Thus, the authors have attempted to identify canonical ODG tumors within the broad histological spectrum of diffuse gliomas, and their results are in line with previous reports.[4],[5]

The authors state that the possible reason of a relatively lesser percentage of codeletion in their study may have been the inclusion of cases across different age groups, locations, and histological subtypes.[3] There were cases of GBM-O, of which 5.2% were codeleted, which is also similar to previous studies.[5] The authors also re-emphasize the lower frequency of p53 overexpression in pure ODG tumors, which is in agreement with the existing literature.[6] Not surprisingly, an inverse correlation between 1p/19q codeletion and p53 protein overexpression was noted. The authors conclude that adult patients with pure ODG histology, frontal location, presence of calcification, and p53 protein nonpositivity had statistically significant correlation with the 1p/19q codeletion. This observation underscores the importance of histology, which is of prime importance while evaluating any diffuse glioma.[3]

However, what is lacking in this study is the data on isocitrate dehydrogenase (IDH) mutations (which the authors admit), as well as alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression.[3] The current WHO update on CNS tumors (2016)[1] takes into consideration molecular parameters in addition to histology for defining the diffuse glioma entities. Accordingly, IDH mutation and 1p19q codeletion status have become entity defining features for ODG and AOD tumors. Loss of ATRX expression and p53 expression would help to identify diffuse astrocytomas and anaplastic astrocytomas, which are considered characteristic, even though not mandatorily required for the diagnosis.[2]

The authors also discuss the favorable prognostic benefit of 1p19q codeletion status, as noted in various studies, along with additional mutations of IDH and telomerase reverse transcriptase (TERT) promoter,[7],[8] even though they have not demonstrated the same in their study. In a previous study from our group, we demonstrated the prognostic value of the histomolecular subgroups of anaplastic grade III gliomas. In that study, anaplastic oligodendrogliomas (defined by 1p19q codeletion and IDH mutations) had the best prognosis. While the IDH-mutant anaplastic astrocytomas had an intermediate prognosis, the IDH wild-type anaplastic astrocytomas were associated with the worst prognosis; once again reiterating that molecular biomarkers in diffuse gliomas can be utilized to provide a prognostically relevant classification.[9]

From the observation in the present series and previously reported cases, pediatric oligodendrogliomas appear to be a histologic entity without a defining molecular signature. It is possible that there is more than one molecular pathway underlying the pathogenesis of this entity.[10] Here, the authors have noted 1p19q codeletion in 25% of pure ODG cases and 10% of mixed tumors. While this finding is in agreement with some of the previous studies,[11] the same was not observed in others.[12] The authors justify that these findings highlight the occurrence of the adult type (1p/19q mediated) type of ODG in the pediatric age group, especially in older children.

The present study reiterates the fact that 1p19q assay using the fluorescence in situ hybridization technique needs to be an integral part of diffuse glioma diagnosis, and that the codeletion status is an absolute requirement for the identification of canonical type of ODG. In fact, the current WHO update on CNS tumors (2016)[2] provides an algorithm for the approach to the diagnosis of diffuse gliomas, which has three tiers; histology, IDH status, and other genetic parameters which includes the 1p19q assay.

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