Atypical extra-ventricular ganglioneurocytoma.
Ganglioneurocytoma was first described by Nishio and coll. in 1990 (4) as a tumor composed of a combination of mature neuronal cells. This lesion has histological features similar to those of neurocytoma, with the addition of ganglionic differentiation. Ganglioid differentiation throughout the tumor is required for the diagnosis while cases with ganglionic cells restricted to focal areas should not be defined as ganglioneurocytoma (2). Ganglioneurocytoma is more commonly extraventricular (EV) (1) and it may involve the cerebral hemispheres and spinal cord. To the best of our knowledge this represents the only reported extra-axial case. The radiological appearance of EV ganglioneurocytoma may often be that of a cystic mass and heterogeneous contrast enhancement is frequently found, which may suggest high-grade glioma. As shown in the present case, ganglioneurocytoma may also radiologically mimic meningioma.
The main histological differential diagnosis of EV ganglioneurocytoma is represented by oligodendroglioma, due to the presence in both entities of small cells with round nuclei and clear cytoplasm. The presence of atypical cells, vascular proliferation and necrosis may suggest high-grade glioma. Immunohistochemistry is helpful for the distinction of these tumors. Indeed EV ganglioneurocytoma is diffusely positive for synaptophysin and negative for GFAP. Although synaptophysin positivity has been shown in some oligodendrogliomas, in these tumors immunoreactivity is less than that of EV ganglioneurocytomas which are strongly reactive both in the neuropil and in the perinuclear cytoplasm. In addition, the absence of olig-2 expression argues against the diagnosis of a glial tumor. Finally, while oligodendrogliomas are mainly IDH-1 positive, EV neurocytomas (with ganglioid differentiation or not) are IDH-1 negative (3). Ganglioglioma may be also an important differential diagnosis as the glial component can show oligodendroglial-like morphology. Again, the complete absence of GFAP stains in the tumor helps the differential diagnosis.
At present, ganglioneurocytoma does not figure as a separate entity in the WHO Classification of central nervous system (CNS) tumors, but it is considered as a variant of EV neurocytoma and graded as WHO grade II. The clinical behavior as well as the prognostic impact of the histological features of EV neurocytoma (with ganglioid differentiation or not) are not well characterized. However, it was suggested that tumors showing vascular proliferation, necrosis, mitotic activity > 3/10 HPF or Ki-67 labeling index > 3% should be designated as "atypical" for their higher recurrence risk (1). However, the presence of atypical features does not warrant an up-grading of the lesion to WHO grade III and complete surgical resection seems to be the most relevant prognostic factor for these neoplasias (1).
Contributed by Valeria Barresi, MD, Maria Caffo, MD, Luana Licata, MD, Filippo Flavio Angileri, MD