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Grading Gangliogliomas: a Short Case Series With Clinico-Imagistic and Immunohistopathological Correlations
Objectives: Ganglioglioma (GG) represents an extremely rare tumor of the central nervous system, which is composed of two different cellular populations: a glial cell population and a neuronal cell population, the former being the one which will establish the histologic grade of the tumor. The current World Health Organization (WHO) Classification of Tumors of the Central Nervous System divides gangliogliomas into benign (WHO grade I) and malignant (WHO grade III). Several scientific studies acknowledge that some tumors are difficult to grade but, due to the scarcity of cases as well as the lack of multicentric epidemiological data, there are no extensive studies regarding this matter in the neuropathology literature.
Material and methods: We report a short case series of three patients with ganglioglioma who were admitted and treated at the Neurosurgery Department of “Bagdasar Arseni” Emergency Hospital. The patients had different clinical presentations, varying from migraines and epileptic seizures to development of a large, slowly growing tumor. Tissue fragments were obtained through surgical resection and sent to the Pathology Department for microscopic investigation.
Outcomes: Histopathologic examination revealed both components of the tumor, supporting the diagnosis of ganglioglioma, albeit the glial component featured different histologic grade in each tumor. The tumor diagnosed as grade II lacked mitoses, but showed conspicuous atypia and numerous multinucleated cells. Immunohistochemistry revealed immunoreactivity for synaptophysin, chromogranin A and neurofilament in the neuronal component and GFAP positivity in the glial component of the tumor. Neurofilament showed an unusual pattern of staining, in which areas with benign features showed patchy positivity, while areas with malignant features and striking nuclear pleomorphism were completely negative.
Conclusion: Due to the completely different clinical outcome, we strongly believe that a grade II ganglioglioma should be differentiated from a grade III GG, based on the lack of mitoses, necrosis and microvascular proliferation. The differentiation between grade II GG and grade I GG should be made on the cellular pleomorphism of both components (glial and neuronal). Based on our experience, we conclude that immunohistochemistry could aid in this differentiation through markers like: Ki67, neurofilament, CD34 and chromogranin A. We strongly believe that further immunohistochemical research on larger study groups will eventually lead to a consensus regarding definitive criteria for grade II gangliogliomas.
Keywords: ganglioglioma, histological grading, glioneuronal neoplasms.