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MedPharmRes, 2020, 4 15 MedPharmRes journal of University of Medicine and Pharmacy at Ho Chi Minh City homepage: http://www.medpharmres.vn/ and http://www.medpharmres.com/ Case report Central neurocytoma: Report of a rare case and literature review Ai Nhan Thi Lea*, Quynh Tho Ngoc Lea, Anh Hien Thi Hob, Anh Thu Phan Danga a Department of Pathology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; b Department of Radiology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam. Received July 13, 2020: Revised September 10, 2020: Accepted September 17, 2020 Abstract: Central neurocytoma (CN) is an uncommon brain tumor arising primarily in the lateral ventricular near the foramen of Monro and approximately accounting for 0.1-0.5% of all primary tumors of the central nervous system. We report a case of neurocytoma located in the fourth ventricle and extended into the third ventricle. The tumor is composed of uniform round cells with immunohistochemical features of neuronal differentiation. CN is probably a differential diagnosis with oligodendrogliomas and ependymoma. Morphology and immunohistochemical findings associated with clinical and radiological characteristics may support CN diagnosis. Keywords: neurocytoma, ependymoma, oligodendroglioma, immunohistochemistry. 1. INTRODUCTION Central neurocytoma (CN) is a rare tumor that was first individualized by Hassoun et al. in the 1980s [1]. According to the Central brain Tumor Registry of the United States, representing approximately 100% of the US population, the annual incidence rate of CN was 0.022 per 100 000 between 2006 and 2014 [2]. Central neurocytoma until 2020 has 500 known cases worldwide [3], mostly comprising of case reports and short series from individual specialties. This kind of tumor typically occurs in the lateral ventricular near the foramen of Monro. It is composed of uniform round cells that show evidence of neuronal differentiation on immunohistochemistry and electron microscopy. CN has been clinically misdiagnosed as ependymomas of the foramen of Monro or intraventricular oligodendrogliomas due to overlapping radiological and microscopic features [4]. Nonetheless, the usual benign clinical course and the neuronal differentiation of central neurocytoma designates it as a distinct entity [4]. Because of its rarity, the diagnosis of this neoplasm remains controversial and may be tricky in some instances. Herein, we report a case of central neurocytoma in a young middle-age male patient that was initially diagnosed as ependymoma. We also review clinical, radiological, histopathological, and immunohistochemical characteristics for CN comprehensive diagnosis. 2. CASE PRESENTATION A 32-year-old man suffered from constant headaches and frequent vertigo for over a month, then presented with sudden, severe vomiting and vertigo. Physical examination showed neither papilledema nor neurological deficits. Magnetic resonance imaging (MRI) revealed T1 hypointense, T2 hyperintense fairly-marginated inhomogeneously enhancing mass of size 42x50x55 mm in the left cerebellopontine angle, which partially located in the third ventricle and extended through the foramina of Luschka and the aqueduct of Sylvius into the fourth ventricle (Figure 1-3), which showed heterogeneous gadolinium enhancement with scattered necrosis, hemorrhage, and calcifications (Figure 4 & Figure 5)). The lesion compressed bilateral hippocampi and *Address correspondence to Ai Nhan Thi Le at the Department of Pathology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; E-mails: ltanhan.nt18@ump.edu.vn DOI: 10.32895/UMP.MPR.4.4.3 © 2020 MedPharmRes 16 MedPharmRes, 2020, Vol. 4, No. 4 Le et al. Fig. 1. T1- weighted axial (left) and coronal (right) images from brain MRI displayed a mass among the left cerebellopontine angle located in the third ventricle of the fourth ventricle. Fig. 2. [Brain MRI]. On T1- weighted sagittal image, the mass is almost isointense to grey matter Fig. 3. [Brain MRI]. T2- weighted axial (left) and FLAIR axial (right) images show heterogeneous and slight hyperintensity the left cerebellar hemisphere, pushed the brainstem and the cerebellar vermis to the right, obstructed the cerebral aqueduct, and caused supratentorial ventricular system dilatation. The imaging and clinical symptoms suspected an ependymoma with ventricular dilatation. The patient underwent external ventriculostomy and microsurgical tumor removal. Microscopic features showed uniform, small-to-mediumsized cells with rounded to oval nuclei, finely stippled chromatin, and inconspicuous nucleoli, along with scant cytoplasm, which arranged radially around small central blood vessels as a pseudo-rosette pattern mimicking ependymoma (Figure 6). Fibrillary nucleus-free areas irregular rosette in pineocyomas are also focally presented (Figure 7). Microcalcifications were scattered (Figure 8A). Arborizing capillary blood vessels were detectable, but Central neurocytoma: A case report and literature review microvascular proliferation was absent (Figure 8B). Necrosis, mitoses, and abnormal mitotic figures were not found. Immunohistochemical staining showed diffuse and strong cytoplasmic expression for synaptophysin and NSE, whereas indisputably negative for GFAP, CK, EMA, and vimentin. After surgery, intraventricular fluid accumulation and ventricular dilatation did not regress. A brain computed MedPharmRes, 2020, Vol. 4, No. 4 17 topography (CT) scan two weeks later showed profuse fluid accumulation and dilation of the supratentorial ventricular system, slight fluid accumulation around the left cerebellar hemisphere, brainstem, and also in the left cerebellopontine angle; the left cerebellar hemisphere and brainstem were still compressed. The patient suffered from left-sided hemiplegia, right abducens nerve palsy, and lack of consciousness recovery. Fig. 4. [Brain MR]. Post-contrast T1-weighted axial image (left) in comparison with non-contrast T1-weighted sagittal image reveals heterogeneous enhancement Fig. 5. mIP-image (left) and SWI-image (right) from brain MRI display areas of hemorrhage and calcifications Fig. 6. Uniform tumor cells arranged radially around small central blood vessels forming perivascular pseudo-rosette growth pattern, which mimicked ependymomas (H&E staining, 20X) 18 MedPharmRes, 2020, Vol. 4, No. 4 Le et al. Fig. 7. Fibrillary nucleus-free areas irregular rosettes in pineocyomas also focally presented (H&E staining, 40X) A B Fig. 8. Micro-calcifications (A) and arborizing capillary blood vessels(B). (H&E staining, 40X) Fig. 9. Immunohistochemical staining results showed diffuse and strong cytoplasmic positive for synaptophysin (left) and NSE (right). 3. DISCUSSION In literature, CN usually affects young adults and is located in the lateral and third ventricles, obstructing the liquor drainage- headaches and other symptoms of raised intracranial pressure, rather than distinct neurological deficits [4]. Our patient had a similar sign of a typical neurocytoma with sudden onset. Clinical features such as severe headaches, vertigo, and projectile vomiting can appear or surge dramatically due to intraventricular hemorrhage within the tumor, which causes severe obstructive hydrocephalus. In this case, MRI showed a relatively large mass lesion, which was partially located in the third ventricle and extended through the foramina of Luschka and the aqueduct of Sylvius into the fourth ventricle. The tumor had TW1- intermediate intensity, FLAIR- hyperintensity, and heterogeneous gadolinium enhancement with necrosis areas and microcalcifications, which corresponded with the radiological features of CN [4]. Images of the blood accumulation and the ventricular dilatation confirmed tumor hemorrhage and obstructive hydrocephalus complication. Imaging differential diagnosis of CN depends on involved sites and patient’s age [5]. Tumors involve lateral ventricle in young adults include oligodendrogliomas, subependymal giant cell astrocytomas, ependymomas, and low grade or pilocytic astrocytomas [5]. Astrocytomas and ependymomas may involve other sites of the ventricular system, but usually without intratumoral calcifications [5]. Central neurocytoma: A case report and literature review MedPharmRes, 2020, Vol. 4, No. 4 19 Macroscopically, neurocytoma presents as a soft, ovoid, lobulated, or nodular mass that is generally well circumscribed. The neoplasm is usually grayish, resembling the grey matter, with areas of hemorrhage [6]. In our case, the tumor was 42x50x55 mm in size, grayish, and hemorrhagic. ependymoma rather than CN [9, 10]. Nevertheless, characteristics of nuclear roundness with speckled chromatin and comparatively poorly-defined perivascular rosettes suggest neurotic origin, which is confirmed by synaptophysin immunoreactivity along with no expression of GFAP [6]. Microscopically, typical central neurocytoma is welldifferentiated with the benign histological feature, which is composed of uniform cells with rounded nuclei, finely spackled chromatin, and present variable nucleoli, along with scant eosinophilic cytoplasm and in some areas has small cells with perinuclear halos, which resemble oligodendroglioma [7]. Tumor cells are usually closely arranged but may also be set within a background of finely filamentous stroma with neuropil-like quality. In some places, tumors display high cellular density alternating with fibrillary/acellular networks [6]. The latter growth pattern mainly appears perivascular and has a fine fibrillary neuropil matrix mimicking pseudorosettes of ependymoma. In many cases, thin-walled arborizing blood vessels and foci of calcification are readily identified [4]. Anaplastic histological features are characterized by brisk mitotic activity, microvascular proliferation, and necrosis. And tumors with these features are so-called atypical central neurocytoma. The terminology is also applied for CN with a Ki-67 proliferation index above 2 or 3%, even if no anaplastic features are found [4]. In our case, microscopic features revealed cytological characteristics of a typical CN. Tumor cells are arranged radially around small central blood vessels forming a perivascular pseudo-rosette growth pattern, mimicking ependymomas. Although microvascular proliferation was presented, other anaplastic histological features such as necrosis and brisk mitotic activity were absent. Regarding prognosis, CN is generally benign, with a cure of an extended resection. Overall survival rate at 3 and 5 years after gross total resection was 95% and 85%, respectively, versus 55% and 45% after subtotal resection [11]. In one multicenter study of 71 patients, incomplete resection was predictive of poor outcome [12]. The patient presenting tumor hemorrhage and supratentorial ventricular system dilation, cerebellum, and brainstem compression along with uncomplete tumor resection may deal with unfavorable outcomes. The neuronal differentiation of tumor cells was confirmed by a typical immunohistochemical expression such as diffuse and strong reactivity for synaptophysin and NSE, along with obvious non-expression for GFAP. Strong immunostaining for synaptophysin has been recognized as the most reliable diagnostic marker [4, 7]. Typically, synaptophysin immunoreactivity is noted in the neuropil, especially in fibrillary zones and perivascular cell-free areas, and not in the cell bodies of normal neurons [4]. Immunostaining for neuron-specific enolase (NSE) also determined the neuronal nature of the neoplasm. The significance of GFAP staining herein is to identify the presence of glial cell differentiation; thus, it is used to exclude diagnoses of oligodendroglioma, astrocytomas, and ependymoma. Although most studies have shown that GFAP is expressed only in entrapped reactive astrocytes, it has also been reported in CN cells by some authors [8, 9]. Because of the fore-mentioned overlapping histological appearances, there is a wide variety of differential diagnoses of CN, in which the two most common are oligodendroglioma and ependymoma. Oligodendroglial tumors and CN can have cytoplasmic vacuoles and monomorphic histologic appearances, which can hardly be differentiated from each other [9]. However, intraventricular localization, along with histological features of anuclear neuropil islands, salt and pepper chromatin, eosinophilic granular bodies, and lack of infiltrated brain parenchyma may suggest a diagnosis of central neurocytoma [9]. Immunoreactivity for synaptophysin and NSE may support the diagnosis. An intraventricular tumor with a solid, non-infiltrating pattern along with perivascular pseudo-rosettes is likely a feature of an 4. CONCLUSION Central neurocytoma, a kind of neurocyte tumor, occurs mostly in the lateral and third ventricle and usually affects young adults. The neoplasm shares some similar radiological features, histologic appearance with oligodendroglioma or ependymoma, and shows specific neuronal immunoreactivity. Due to rare incidence, CN is probably misinterpreted with other tumors such as oligodendrogliomas and ependymoma. From our practical case and review of the literature, imaging and clinical symptoms provide an approach for initial diagnosis of CN; however, histological and immunohistochemical appearance shows excellent importance for diagnosis confirmation. ETHICS STATEMENT Written informed consent was obtained from the patient’s next of kin for the publication of this case report. A copy of the consent form is available for review by the Editor of this journal. AUTHOR CONTRIBUTIONS Conceptualization: Ai Nhan LT, Quynh Tho LN. Investigation: Ai Nhan LT, Quynh Tho LN Visualization: Anh Hien HT Writing—original draft: Ai Nhan LT. Writing—review & editing: Anh Thu PD., Ai Nhan LT CONFLICT OF INTEREST The authors declare that they have no potential conflicts of interest. FUNDING No funding to declare. ORCID ID Ai Nhan Thi Le https://orcid.org/0000-0003-4573-1619 Anh Thu Phan Dang 0904 https://orcid.org/0000-0002-4062- Quynh Tho Ngoc Le 7062 https://orcid.org/0000-0002-9407- Anh Hien Thi Ho 2468 https://orcid.org/0000-0003-3067- REFERENCES 20 MedPharmRes, 2020, Vol. 4, No. 4 1. Hassoun J, Gambarelli D, Grisoli F, Pellet W, Salamon G, Pellissier JF, et al. Central neurocytoma. An electron-microscopic study of two cases. Acta neuropathologica. 1982;56(2):151-6. Epub 1982/01/01. doi: 10.1007/bf00690587. PubMed PMID: 7064664. 2. Tish S, Habboub G, Jones J, Ostrom QT, Kruchko C, Barnholtz-Sloan JS, et al. The epidemiology of central and extraventricular neurocytoma in the United States between 2006 and 2014. Journal of neuro-oncology. 2019;143(1):123-7. Epub 2019/03/13. doi: 10.1007/s11060-019-031449. PubMed PMID: 30859483. 3. Orphanet Report Series. Prevalence of rare diseases: Bibliographic data. Rare Diseases collection. January 2020;Number 1(Diseases listed in alphabetical order). 4. Cavenee WK, Louis DN, Ohgaki H, Wiestler OD. WHO classification of tumours of the central nervous system: WHO Regional Office Europe; 2007. 156 p. 5. Chen CL, Shen CC, Wang J, Lu CH, Lee HT. Central neurocytoma: a clinical, radiological and pathological study of nine cases. Clinical neurology and neurosurgery. 2008;110(2):129-36. Epub 2007/11/21. doi: 10.1016/j.clineuro.2007.09.023. PubMed PMID: 18022760; PubMed Central PMCID: PMCPMC2702989. 6. Sharma MC, Deb P, Sharma S, Sarkar C. Neurocytoma: a comprehensive review. Neurosurgical review. 2006;29(4):270-85; discussion 85. Epub Le et al. 7. 8. 9. 10. 11. 12. 2006/08/31. doi: 10.1007/s10143-006-0030-z. PubMed PMID: 16941163. Kleinschmidt-DeMasters BK, Tihan T, Rodriguez F. Diagnostic pathology: neuropathology: Elsevier Health Sciences; 2016. 189 p. Söylemezoglu F, Scheithauer BW, Esteve J, Kleihues P. Atypical central neurocytoma. Journal of neuropathology and experimental neurology. 1997;56(5):551-6. Epub 1997/05/01. doi: 10.1097/00005072199705000-00011. PubMed PMID: 9143268. von Deimling A, Janzer R, Kleihues P, Wiestler OD. Patterns of differentiation in central neurocytoma. Acta neuropathologica. 1990;79(5):473-9. doi: 10.1007/BF00296105. Kleinschmidt-DeMasters BK, Tihan T, Rodriguez F. Diagnostic pathology: neuropathology: Elsevier Health Sciences; 2016. 56 p. Rades D, Fehlauer F, Lamszus K, Schild SE, Hagel C, Westphal M, et al. Well-differentiated neurocytoma: what is the best available treatment? Neuro-oncology. 2005;7(1):77-83. Epub 2005/02/11. doi: 10.1215/s1152851704000584. PubMed PMID: 15701284; PubMed Central PMCID: PMCPMC1871623. Vasiljevic A, François P, Loundou A, Fèvre-Montange M, Jouvet A, Roche PH, et al. Prognostic factors in central neurocytomas: a multicenter study of 71 cases. The American journal of surgical pathology. 2012;36(2):220-7. Epub 2012/01/19. doi: 10.1097/PAS.0b013e31823b8232. PubMed PMID: 22251941.