Oligodendroglioma with ganglioglioma-like maturation: the histopathological diagnostic challenge of a brain neoplasm with aberrant neuronal component – A case report and review of the literature
- IRCCS Ospedale Policlinico San Martino, Anatomic Pathology Unit, Genoa, Italy,
- DISC, University of Genova, Genova, Italy.
- Radiology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
- Medical Oncology Unit, Ospedale Policlinico San Martino, Italy.
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal-Infant Sciences, University of Genoa, Genoa, Italy.
Gabriele Gaggero, Anatomic Pathology Unit, Ospedale Policlinico San Martino, IRCCS, Genoa, Italy.
DOI:10.25259/SNI_792_2022Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Gabriele Gaggero1, Luca Carlin2, Luca Valle1, Giulia Gnocchi3, Elisa Bennicelli4, Pietro Fiaschi5. Oligodendroglioma with ganglioglioma-like maturation: the histopathological diagnostic challenge of a brain neoplasm with aberrant neuronal component – A case report and review of the literature. 23-Dec-2022;13:587
How to cite this URL: Gabriele Gaggero1, Luca Carlin2, Luca Valle1, Giulia Gnocchi3, Elisa Bennicelli4, Pietro Fiaschi5. Oligodendroglioma with ganglioglioma-like maturation: the histopathological diagnostic challenge of a brain neoplasm with aberrant neuronal component – A case report and review of the literature. 23-Dec-2022;13:587. Available from: https://surgicalneurologyint.com/surgicalint-articles/12076/
Background: Oligodendroglioma with ganglioglioma-like maturation is a rare entity not included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. To date, only a few cases were described in the literature. We report a case of this tumor, along with a review of the previous case reports/ series.
Case Description: A 63-year-old man with a left frontal mass and a 2-month history of seizures underwent surgical resection in our center. Grossly, the specimen appeared as a yellowish mass with prominent hemorrhagic component. Microscopically, the lesion was composed by small round cells often surrounded by a clear halo and, near the hemorrhagic area, by scattered large cuboidal cells with vesicular nuclei and prominent eosinophilic nucleoli. On immunohistochemical stains, both cells components tested positive for ATRX, p53, and GFAP; larger ganglion-like cells showed synaptophysin and chromogranin-A expression. IDH1 codon 132 mutation, 1p-19q-codeletion, and MGMT methylation were observed. Eventually, a diagnosis of oligodendroglioma (the WHO grade II) with ganglioglioma-like maturation was rendered. The patient received adjuvant chemotherapy and is currently alive and asymptomatic.
Conclusion: Recognition of ganglioglioma-like maturation in oligodendrogliomas may prevent undertreatment of these neoplasms. To this end, fluorescence in situ hybridization assays are crucial for defining the 1p-19q status.
Keywords: 1p-19q, Ganglioglioma-like maturation, Oligodendroglioma
For the 1st time, the 2016 World Health Organization Classification of Tumors of the Central Nervous System (CNS) added molecular parameters to histological features to define many tumor entities. In fact, the diagnosis of oligodendroglioma and anaplastic oligodendroglioma requires the demonstration of both IDH1 or IDH2 mutation and codeletion of chromosomal arms 1p and 19q.[
Despite it represents a crucial innovation, this classification does not define a subgroup of oligodendrogliomas characterized by the presence of aberrant neuronal differentiation. These tumors were first described by Perry et al. in 2002 and 2010 and defined as “oligodendrogliomas with neurocytic differentiation” and “oligodendroglial neoplasms with ganglioglioma-like maturation.”[
Knowing the existence of this, although very rare, histotype does not constitute merely a microscopic descriptive peculiarity, rather represents a crucial differential diagnostic crossroads between oligodendroglioma and ganglioglioma, with important clinical consequences: in fact, while oligodendroglioma (beyond the histological subtype) is still a diffuse glial neoplasm, ganglioglioma, on the other hand, represents an entity with extremely mild biological behavior.
More in detail
Gangliogliomas are rare slow-growing neuroepithelial tumors, composed by both neoplastic ganglion and glial cells, usually affecting children and young adults with a male predominance. They are preferentially located in the temporal lobe, but they can occur throughout all the CNS.[
On the other hand, oligodendrogliomas are usually diffusely infiltrating, low grade, and slow-growing gliomas with tumor cells resembling oligodendrocytes (monomorphic rounded nuclei with a surrounding artifactual halo giving the cells the so-called “fried egg” appearance).[
IDH-mutant and 1p/19q codeleted oligodendrogliomas typically show nuclear expression of ATRX (absent in most IDH-mutant diffuse astrocytomas) and no mutant-type p53 nuclear staining (often present in IDH-mutant astrocytomas). Ki-67 proliferation index is usually <5%. Nuclear atypia and occasional mitosis are compatible with the diagnosis of an oligodendroglioma (the WHO grade II tumor), but marked mitotic activity (at least six mitotic figures per high-power field), prominent microvascular proliferation, and spontaneous necrosis are indicators of anaplastic oligodendroglioma (corresponding to the WHO grade III).
In this differential clinical-diagnostic context, to the best of our knowledge, only few cases of oligodendroglioma with ganglioglioma-like maturation have been described.[
With the aim of collecting data to better characterize this rare entity, we present an oligodendroglioma displaying ganglion cells, including its histological and immunohistochemical findings and a review of the related literature.
A 63-year-old man presented to our hospital with a 2-month history of epileptic seizures. A head CT was performed revealing a left frontal large inhomogeneous isohypodense area, with tenuously hyperdense components and numerous focal calcium deposits, probably related to a productive lesion.
The MRI showed a large area of altered signal of uneven appearance with both cortical and white matter involvement, hyperintense on T1-weighted images, related to the known heteroplastic productive lesion. Within the lesion, small postcontrast agent hyperintense spots seemed to be appreciated. The characteristics of the MRI images in accordance with the CT images were suggestive of oligodendroglioma. No other lesions were found on whole body CT. Surgical removal of the lesion and pathological examination was performed.
The lesion appeared as a 5 cm coarse yellowish mass with a hemorrhagic component involving about half of the specimen.
After fixation in 10% buffered formalin, the entire surgical specimen was sampled according to standard procedures and embedded into paraffin. Serial 4-μm thick sections were stained with hematoxylin-eosin for conventional histology. Immunohistochemistry was performed on the paraffin sections with the following antibodies: synaptophysin (SP15, Ventana, Arizona, USA), Chromogranin A (LK2H10, Ventana, Arizona, USA), GFAP (EP672Y, Ventana, Arizona, USA), p53 (DO-7, Ventana, Arizona, USA), CD34 (QBEnd/10, Ventana, Arizona, USA), ATRX (D-5, Santa Cruz, Texas, USA), and Ki-67 (30-9, Ventana, Arizona, USA). The reactions were visualized using DAB detection.
Point mutations of IDH1 (codons 105/132), IDH2 (codons 140/172), and e BRAF (codon 600) were searched by real-time polymerase chain reaction. Hypermethylation of the MGMT promoter was verified by Pyrosequencing. The 1p/19q status was investigated with fluorescence in situ hybridization (FISH).
Microscopically, the lesion was composed by small round cells with slightly hyperchromatic nuclei often surrounded by a clear halo embedded in a fibrillary matrix. Near the degenerative hemorrhagic area, the lesion was hypercellular with scattered large and squared-shape cells, vesicular nuclei, and prominent eosinophilic nucleoli resembling ganglion cells. No anaplastic cells, mitoses, endothelial proliferation, or necrosis could be seen.
The lesion exhibited distinctive immunohistochemical profiles. Larger ganglion-like cells showed expression of synaptophysin and chromogranin-A, but no CD34 expression [
(a) Hematoxylin-Eosin: large neuronal cells can be seen between small round oligodendrocytes. (b) ATRX immunohistochemical staining: a diffuse staining is present in neoplastic cells. (c). Chromogranin immunohistochemical staining: An intense granular pattern is expressed in large neuronal cells. (d) CD34 immunohistochemical staining: neither small oligodendrocytes nor large neuronal cells expressed this marker. Scale bars: 75 μm (a-c); 150 μm (b and d).
Finally, the case was diagnosed as oligodendroglioma WHO grade II with ganglioglioma-like maturation, IDH1-mutated, and 1p/19q codeleted.
After 2 months from the surgery (subtotal resection of the tumor), the patient received chemotherapy for 7 months, due to an increasing of the residual lesion on RM and PET scans. The patient is currently alive and asymptomatic.
This case showed considerable diagnostic difficulties: in particular, the histopathological coexistence of glial cells with cytological similarities to oligodendrocytes, together with neuronal cells (ganglion-type), places oligodendroglioma, and ganglioglioma among the main differential diagnosis: two entities so similar histologically, as different in their molecular profile and respective clinical outcome since ganglioglioma usually has an indolent behavior compared with other neoplasms with diffuse glial component.
Immunophenotypic features (no expression of CD34 and expression of ATRX by ganglion-like cells) and molecular findings (IDH1 mutation and 1p/19q codeletion) lead us to conclude that our case was a rare example of oligodendroglioma with ganglioglioma-like maturation. Very few cases of this tumor to date have been described, and the characteristics of each are shown in
As previous authors have stated, recognition of ganglioglioma-like maturation in oligodendrogliomas may prevent misdiagnosis and undertreatment of these neoplasms.[
Declaration of patient consent
Patient’s consent not required as patient’s identity is not disclosed or compromised.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
1. Bailey P, Bucy PC. Oligodendrogliomas of the brain. J Pathol Bacteriol. 1929. 32: 735-51
2. Blümcke I, Wiestler OD. Gangliogliomas: An intriguing tumor entity associated with focal epilepsies. J Neuropathol Exp Neurol. 2002. 61: 575-84
3. Dudley RW, Torok MR, Gallegos DR, Mulcahy-Levy JM, Hoffman LM, Liu AK. Pediatric low-grade ganglioglioma: Epidemiology, treatments, and outcome analysis on 348 children from the surveillance, epidemiology, and end results database. Neurosurgery. 2015. 76: 313-20
4. Hirose T, Nobusawa S, Nakazato Y, Sasaki A. A case of oligodendroglioma with prominent neuronal differentiation. Hum Pathol. 2013. 44: 2353-9
5. Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, VandenBerg SR. Ganglioglioma: An ultrastructural and immunohistochemical study. Cancer. 1997. 79: 989-1003
6. Louis DN, Perry A, Reifenberger G, von Deimling A, FigarellaBranger D, Cavenee WK. The 2016 world health organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 2016. 131: 803-20
7. Luyken C, Blümcke I, Fimmers R, Urbach H, Wiestler OD, Schramm J. Supratentorial gangliogliomas: histopathologic grading and tumor recurrence in 184 patients with a median follow-up of 8 years. Cancer. 2004. 101: 146-55
8. Park JH, Cha YJ, Chang JH, Lee SK, Kim SH. A rare case of oligodendroglioma with gangliocytic differentiation in a 31-year-old male: Importance of genetic testing for IDH1/2. Brain Tumor Pathol. 2020. 37: 95-9
9. Perry A, Burton SS, Fuller GN, Robinson CA, Palmer CA, Resch L. Oligodendroglial neoplasms with ganglioglioma-like maturation: A diagnostic pitfall. Acta Neuropathol. 2010. 120: 237-52
10. Perry A, Scheithauer BW, Macaulay RJ, Raffel C, Roth KA, Kros JM. Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications. J Neuropathol Exp Neurol. 2002. 61: 947-55
11. Tanaka Y, Nobusawa S, Yagi S, Ikota H, Yokoo H, Nakazato Y. Anaplastic oligodendroglioma with ganglioglioma-like maturation. Brain Tumor Pathol. 2012. 29: 221-8
12. Vajtai I, Arnold M, Vassella E. Oligodendroglioma with neurocytic differentiation and characteristic loss of heterozygosity on chromosomes 1p and 19q. Acta Neuropathol. 2005. 110: 520-2
13. Wesseling P, van den Bent M, Perry A. Oligodendroglioma: Pathology, molecular mechanisms and markers. Acta Neuropathol. 2015. 129: 809-27
14. Yamashita S, Yokogami K, Niibo T, Takeishi G, Ikeda T, Miyata S. Oligodendroglial ganglioglioma. Brain Tumor Pathol. 2011. 28: 311-6