Chordoid Glioma of the Third Ventricular with Rare Patterns and Mutation in PRKCA: a case report and review of literature

Background: Chordoid gliomas are rare, low-grade neoplasms of the third ventricle. In the updated 4th edition of the 2016 WHO classication of tumours of the CNS, it described some three less common histological patterns and rare tissue patterns. Case presentation:Here we reported a case with all the uncommon patterns. It was a 52-year-old woman with dizziness and blurred vision. Imaging showed a solid tumor located in the third ventricle with a well-circumscribed border. Histological, almost tumor cells formed into atypical glands with different sizes and irregular shapes in an abundant of solid or loosely collagen matrix. Some tumor cells formed into papillary patterns, micro-papillary patterns. pseudoglandular patterns. Some focal tumor cells were spindle-shape. Only few epithelioid tumor cells formed into clusters and cords embedded into a myxoid stroma like the chordoma. No anaplastic features were identied in any lesion. Immunohistochemically, all the tumor cells were strong reactivity for TTF-1. Some tumor cells strong but focal reactivity for GFAP, NEU-N, and CD34. It showed a recurrent D463H missense mutation in PRKCA. All these ndings conrm that the diagnosis was chordoid glioma of the third ventricular. Conclusions: There may be lots of histopathological features in one chordoid glioma case. It maybe suggested that PRKCA D463H mutation and TTF-1 positive may help to diagnose it.


Background
Chordoid gliomas of the third ventricular are extremely rare entities in the central nervous system. Histologically, they are most often composed of clusters and couds of epithelioid tumor cells within a variably mucinous stroma. It was reported in the literature that it also had a rare special histological structure, such as pappilary [5]. Here we report a case with less common and rare patterns such as pappilary, alveolar, pseudoglandular, solid, fusiform and brosing. Till now, we had no found a case in the literature with all these histological structures.

Case Presentations
A 52-year-old woman presented with dizziness and blurred vision for six months without causative factor. The patient did not have any other discomforts. The general physical and neurological examination was normal. CT scans showed that there was a solid tumor in the third ventricle with densely enhanced and characteristically exhibited a well-circumscribed border (Fig 1). The MRI scan showed that isointensity on T1WI, and hyperintensity on T2WI. After Gddiethylenetriamine pentaacetic acid (Gd-DTPA) administration, the tumor showed homogeneous (Fig 2). The MRI diagnosis was germ cell tumor.
During surgery, the tumor located at the optic cross and the end plate pool, which pushing the bilateral optic nerves downward. The tumor was hard with rich blood supply. It adhered to the surrounding tissues tightly. The patient had gross total resection. In gross specimen, the tumor tissue was grayish yellow and broken into piles with the size 2.5x1.0x1.0cm.
Microscopically, the border between the tumor and adjacent brain was well de ned, with no evidence of tumor in ltration (Fig 3). There were many histological patterns. We introduced them according to the proportion of these histological patterns. Almost tumor cells formed into various forms glands with different sizes and irregular shapes invading the brous stroma (Fig 4). The tumor cells cubic or polygonal, some cells have long protrusions linked to the wall of the ducts. Cells have abundant cytoplasmic eosinophils (Fig 5). In some areas there were rare tumor cells formed into clusters or cords or gland in an abundant of solid or loosely collagen matrix (Fig5, 6). Some tumor cells arranged along the central brovascular core and formed into papillary structures and even secondary papillaries. The tumor cells anchored to blood vessels by short, shout cytoplasmic processes. Unipolar cytoplasmic processes anchor neoplastic cells to stromal blood vessels in formations of radial, papillary or ribboned pro les. These columnar or subtly tapered processes were shorter and stouter than those of perivascular pseudorosettes and do not collect as an ependyma pseudorosettes which with anuclear zones (Fig 7).
Many tumor cells have nuclear inclusions and nuclear grooves (Fig 8). Some areas the tumor cells formed into micro-papillary structures (Fig 9).The cytoplasm of some tumor cells was vacuolated. The nucleus located at the edge of the cell. These cytoplasmic vacuole-like cells came together to form a pseudoglandular (Fig 10).There were some focal areas that the tumor cells were spindle-shaped. This pattern made the tumor parenchyma and stroma was unclear (Fig 11). There were few areas that the epithelioid tumor cells formed into clusters and cords embedded into a myxoid stroma like the chordoma (Fig 12). There were varied degrees lymphoplasmacytic in ltrate in the tumor and the periphery brain tissue (Fig 13). No anaplastic features were identi ed in any lesion. Mitotic gures were absent in the tumor.
Here we performed genomic pro ling on the case. It identi ed a recurrent D463H missense mutation in PRKCA, which localizes in the kinase domain of the encoded protein kinase C alpha (PKCα) (Fig 17).
The pathological diagnosis was chordoid glioma of the third ventricular.
The patient was alived 15 months after surgery without any adjuvant therapy.

Discussion
To date, approximately 100 cases of chordoid glioma have been reported in the literatures. They most occur frequently in adults. Chordoid gliomas occupy the anterior portion of the third ventricle, with larger tumors also lling the middle and posterior aspects. They generally arise in the midline and displace normal structures in all directions as they enlarge (2). While there were a few reports that chordoid glioma located outside the third ventricle, such as hemisphere, thalamus, parieto-temporal extra-ventricular, juxtaventricula et al (8). This made the diagnosis di cult and had challenges. Considering these entities may be not limited to the third ventricle, the nomenclature may require an amendment with more clinical and radiological evidence supports.
Most chordoid glioma patients had signs and symptoms of obstructive hydrocephalus, including headache, nausea, vomiting and ataxia. Other clinical features include endocrine abnormalities re ecting hypothalamic compression, visual eld disturbances due to compression/displacement of the optic chiasm, and personality changes including psychiatric symptoms and memory abnormalities.
In imaging, chordoid gliomas present as solid or cystic-solid and characteristically exhibit a wellcircumscribed border within the third ventricle. On MRI, the solid portion of tumors showed isointense or hypointensity on T1-weighted and hyperintensity in most cases on T2WI. (8).
In microscopy, chordoid gliomas are most often composed of clusters and couds of epithelioid tumor cells within a variably mucinous stroma that typically contains a lymphoplasmacytic in ltrate. Neoplastic nuclei are moderate in size, ovoid, and relatively uniform. Mitoses are absent in most tumors, when present, they are rare. A stroma lymphoplasmacytic in ltrate, often containing numerous Russell bodies, is a consistent nding. In the updated 4th edition of the WHO Classi cation of Tumours of the CNS (2016) (4) described that maybe there were three less common histological patterns had been reported: a solid pattern with sheets of polygonal epithelioid tumor cells without mucinous stroma, a fusiform pattern with groups of spindle-sheped cells among loose collagen, and a brosing pattern with abundant brosis. The brosing pattern tends to be more common in older patients. Other (rare) tissue patterns include pappilary [3], alveolar, and pseudoglandular patterns. Individual tumor cells have abundant esoinophilic cytoplasm. In some cases, limited glial differentiation in the form of coarsely brillar processes can also be seen. Reactive astrocytes, Rosenthal bres, and often chronic in ammatory cells including lymphocytes, plasma cells, and Russell bodies are seen in adjacent non-neoplastic tissue. In our case, there were common pattern and three less common patterns and three rare patterns. Such case was really rare.
The immunohistochemical feature of chodoid glioma is the tumor cells strong reactivity for GFAP, vimentin and TTF-1. CD34 is positive focally. Immunoreactivity for S100, EMA and cytoderatin is variable.
Neuronal and neurosendocrine markers, such as synaptophysin, neuro laments, and chromograin-A, are consistently negative. The proliferation is low. Neither IDH mutation nor BRAF V600E mutation were found in the literature. In our case, there were focal tumor cells positive for NeuN which had no related literature reports retrieved.
Goode et al reported that all the 13 chordoid gliomas had a recurrent D463H missense mutation in PRKCA, which localizes in the kinase domain of the encoded PKCα (2). Our case had D463H missense mutation and had no D294G mutation in PKCα.
Differential diagnosis of histopathology 1. Adenocarcinoma brain metastases: The patient has a history of adenocarcinoma of other organs. Immunohistochemical, the CKp was strong positive.  Figure 1