Malignant Variant of the Central Neurocytoma

KISEP J Korean Neurosurg Soc 35 : 313-316, 2004

Case Report Malignant Variant of the Central Neurocytoma

Yu-Seok Choi, M.D.,1 Yeung-Jin Song, M.D.,1 Ki-Yeong Huh, M.D.,2 Ki-Uk Kim, M.D.1 Department of Neurosurgery,1 Pathology,2 College of Medicine, Dong-A University, Busan, Korea

Central neurocytoma is a rare, well-differentiated neuronal tumor and is usually located in the lateral or third ventricle of young adults. Its overall prognosis is excellent with a low proliferative index. The majority of previously reported malignant variants rarely did recurred after tumor removal and regarded as benign tumor despite of histopathological malignant feature. Nevertheless, we experienced a case of malignant variant of the central neurocytoma with high proliferative index(Ki-67 labeling index >30%), which showed recurrence immediately after surgery and died within 3 months POD. Here, we describe the case with a review of the literatures.

KEY WORDS : Central neurocytoma·Recurrence·Ki-67 labeling index.

Introduction

entral neurocytoma, first C reported by Hassoun et al.9) in 1982, has been known to occur in the ventricles of young adults. By the light microscopical exam- B ination, central neurocytoma is A C similar to oligodendroglioma or Fig. 1. A : Axial T1-weighted enhanced magnetic resonance image showing an slightly high signal ependymoma, and its post-operative intensity mass on third ventricle and Rt. lateral ventricle ant. and post. horn with parenchymal invasion prognosis is excellent6,9,12,14,15,25). combined with calcification. B, C : Coronal, Sagittal TI-weighted enhanced magnetic resonance image showing intratumoral cystic lesion with inhomogenously slightly enhanced ventricular mass Nevertheless, von Deimling et containing calcification and tumor invasion into the thalamus and basal ganglia with obstructive al.24) first reported a case of central hydrocephalus. neurocytoma showing malignant feature in 1990. Since then, some studies have reported that Case Report central neurocytoma showed malignancy in rare cases, and its incidence accounts for 5% of total central neurocytomas. 6-year-old boy was under a 2-year follow-up for Moreover, histopathology established that central neurocy- A increasing head circumference and enuresis via our toma showed malignancy in some cases, although its department of pediatrics. He was referred to us with chief recurrence rate is very low and prognosis is excellent4,19). We complaints of paraparesis and IICP symptoms including experienced a case of malignant variant of the central nausea, vomiting, papillary edema. neurocytoma, of which diagnosis was established on the basis Brain MRI scan, T1WI revealed a calcified large mass of 6 of definite histopathology, and very high proliferative index. 5 6.5cm in the right thalamus and basal ganglia with The patient died of recurrence about 3 months after surgery. slightly higher signal than the brain parenchyma and in the Here, we describe the case with a review of the literatures. 3rd ventricle, the body of the lateral ventricle. On Gd-DTPA enhanced image, the mass was inhomogeneous and had cyst and accompanying calcification. Received：July 28, 2003 Accepted：October 27, 2003 Moreover, hydrocephalus was detected(Fig. 1). The mass Address for reprints：Ki-Uk Kim, M.D., Department of Neurosurgery, College of Medicine, Dong-A University, 3ga-1 was resected subtotally via right anterior transcallosal app- Dongdaeshin-dong, Seo-gu, Busan 602-715, Korea roach. Intraoperatively, tumor originated from the lateral Tel : 051) 240 - 5246, Fax : 051) 242 - 6714 ventricle and invaded into the 3rd ventricle. Partial resection E-mail : kukim@mail. donga. ac. kr was performed due to severe hemorrhage and ill-defined

VOLUME 35 March, 2004 313 Malignant Neurocytoma

3rd ventricle as well as the right thalamic region associated with ventricular hemorrhage(Fig. 2). Light microscopically, cells had round-to-oval nuclei and pale cytoplasm, similar to low-grade oligodendroglioma, but in some densely clustered area, the nuclei of the tumor cells showed the features bizarre giant cells with hyperchromatism and polymorphism, and mitotic figures, suggestive of malignancy. Immunohistochemical staining revealed that the cells were A B strongly positive to synaptophysin, and had a high MIB-1 labeling index over 30%. Referred to Yale University School Fig. 2. A, B : Postoperative computed tomography scan showing right side extraventricular catheter insertion and residual of Medicine in the US, the present case was confirmatively intraventricular mass, parenchymal mass with calcification. Lt. lateral diagnosed with malignant variant of the central neurocytoma ventricle post. horn demonstrating intraventricular hemorrhage. with its hyperproliferative activity (Fig. 3). On the POD 10, after EVD catheter removal, he exhibited generalized tonic clonic seizure and deteriorated. He under- went EVD on the left frontal horn and thereafter recovered. Intraoperatively, his CSF profile was RBC 2340/mm3, WBC 460/mm3 (lymphocyte 60%), protein 300mg/dL and glucose 128mg/dL, suggestive of aseptic meningitis. However, CSF A B cytology demonstrated no evidences of malignancy. On the POD 24, he was transferred to other hospital due to worsening mental status. On the POD 54, brain MRI scan revealed that the mass was inhomogeneous and recurred in the anterior horn of right lateral ventricle and brain parenchyma with hydrocephalus persisted and ependymal enhanc- C D ement suggestive of meningitis(Fig. 4). Fig. 3. A : Densely cellular area revealed pleomorphic, hyperchr- On the POD 72, his mentality change to comatose and then omatic cellular nucleus and bizzar giant cell(H&E,×40). B : Mitotic died of cardiac arrest and respiratory distress. figure of cell nucleus is showing, suggestive of malignancy (H&E,× 200). C : Immunohistochemical stainings revealing positive reaction for synaptophysin and internuclear graular deposition (original Discussion magnification×400). D : Photomicrograph showing staining for Ki-67 antigen with MIB-1 monoclonal antibody with focally over 30% of ince central neurocytoma was first described by Hassoun cell positive (original magnificaion×400). S et al.9) in 1982, only 20 cases have been reported tumor boundary followed by EVD on right lateral ventricle. between 1982 and 1989. With the advancement of Post-operative brain CT scan showed the residual mass in the immunohistochemistry and electron microscopy in the 1990s, 107 cases of central neurocytoma, formerly misdiagnosed as oligodendroglioma or ependymoma, have been established through the reev- aluation between 1990 and 19935). Since then, the number of cases has been abruptly increased to reach about 500 until 2001 world- A B C wide. The main features of central Fig. 4. A : Axial T1-weighted nonenhanced magnetic resonance image demonstrating recurred neurocytoma was a lateral ventri- mass in right ant. horn containing calcification and parenchymal area 54 days after surgery. B, C : cle location, a resemblance to olig- Coronal, Sagittal T1-weighted enhanced magnetic resonance image demonstrating a inhomogenously slightly enhancement mass in recurred right ant. horn and third ventricle with odendroglioma or ependymoma persistent hydrocephlaus still is showed. on light microscopic and image

314 J Korean Neurosurg Soc 35 YS Choi, et al.

Table 1. Review of the case reports diagnosed with extraventricular origin and extraventricular extension of al.11) reported that MIB-1 intraventricular origin in the central neurocytoma labeling index is the only Reports Symptoms Tumor location useful parameter for evaluation Ashkan et al1) Interscapular pain C6-T1 spinal cord Seizure Parietal lobe of proliferative activity of central 6) Coca et al 3) Limb numbness T10-11 spinal cord neurocytoma. Fujimaki et al. Hamilton7) Headache, vomiting Frontal lobe reported that central neuroc- Harada et al8) Seizure Frontal lobe ytoma showed Ki-67 index Kim et al13) Seizure Frontal lobe ranging from 1 to 5.6% and 17) Nishio et al Seizure Frontal lobe had similar proliferative activ- Seizure Frontal lobe ity to malignant meningioma Seizure Temporal lobe or malignant astrocytoma. Sgouros et al19) Headache, visual disturbance Occipital lobe 1) Tatter et al22) Limb parasthesia C2-C6 spinal cord In addition, Ashkan et al. Limb parasthesia C3-C4 spinal cord reported that central neuroc- Our case Headache, vomiting, Rt. thalamus, basal ganglia ytoma showed Ki-67 index paraparesis, left arm tremor area ranging from 0.4 to 11.2%; 60% of total cases showed Ki- Table 2. Comparison of immunohistochemical analysis (Malignant central neurocytoma) 67 index of > 2%; and there Kim DG et al.15) Kim CH et al.13) Our case was significant correlation bet- Mitosis + + + ween Ki-67 index and clinical Vascular proliferation + - + outcome. In Korea, two cases Necrosis - - + of the central neurocytoma Pleomorphism - + + reported showing histopatho- Parenchymal invasion - Frontal lobe Rt. BG, thalamus Proliferative index 7.3%* 10% 30% logical malignancy with a Ki- 13,15) *DNA flow cytometry usage index, BG : basal ganglia 67 index of 7.3% and 10% . The present case showed Ki- finding, occurrence in young adults, neuronal origin seen by 67 index of 30%, much higher than the maxi-mum value of electron microscopic and immunohistochemical examination, 11.2% ever reported, and died of recurrence about 3 months and benign course with postoperative favourable prognosis. after surgery, supported that there is significant correlation Many authors have reported that histological variants between Ki-67 index and clinical outcome. showing clinical malignancy were identified, its incidence When atypical central neurocytoma occurred in a child, the was extremely low and prognosis was similar to that of radiopathological finding for differentiation neurocytoma benign central neurocytoma1,15,16,23-25). from primitive neuroectodermal tumor(PNET) or cerebral To date, central neurocytoma has been reported have neuroblastoma is ventricular location, neuronal differention, predilection mostly occuring in the ventricle. However, some which is characterized by immunohistochemical staining recent studies noted that central neurocytoma of extrave- marker such as synaptophysin, neuron specific enolase and ntricular origin or intraventricular origin invading into brain synpase-like structure was seen on electron microscopic parenchyma, including the present case(Table 1). examination. Although central neurocytoma is known as benign tumor, As noted earlier, in spite of the histopathological evidence atypical central neurocytoma has been established according of malignancy, the present case showed the different clinical to revised WHO classification in 200213,21,25). Atypical central outcome from other cases on the basis of the difference in neurocytoma is defined as a condition with a labeling index proliferative activity(Table 2). As in the case of benign of > 2% and with definite histopathology of vascular central neurocytoma, the complete resection is the gold proliferation, mitotic figure and necrosis. Especially in cases standard treatment and the postoperative radiotherapy is with malignant atypical central neurocytoma, MIB-1 labeling effective for malignant counterpart. In cases with difficulty in index(Ki-67), DNA flow cytometry and 201Tl-SPECT have the complete resection, including the present case, the partial been widely accepted as the prognostic indicators, rather than resection should be done because of ill-defined margin from the histopathological findings. In a study using 201Tl- adjacent parenchymal tissue as well as hemorrhage and the SPECT, 1H-MRS and MIB-1 labeling index, Kanamori et difficulty in hemostasis due to hypervascularization1,12). Many

VOLUME 35 March, 2004 315 Malignant Neurocytoma studies have reported that the radiotherapy for residual tumor cases. Acta Neuropathol 56 : 151-156, 1982 10. Hassoun J, Soylemezoglu F, Gambarelli D, Figarella BD, Von AK, is clinically effective in patients with central neurocytoma Kleihues P : Central neurocytoma : a synopsis of clinical and showing malignancy or recurrence1,2,10,17,25). histological features. Brain Pathol 3 : 297-306, 1993 201 The present case indicated that MIB-1 labeling index is an 11. Kanamori M, Kumabe T, Shimizu H, Yoshimato T : Tl-SPECT, 1H-MRS, and MIB-1 labeling index of central neurocytoma : three important parameter for prognosis and postoperative course case reports. Acta Neurochir 144 : 157-163, 2002 in patients with central neurocytoma. 12. Kim BT, Joo KS, Chang JC, Shin WH, Choi SK, Byun BJ : Surgical pitfall : 2 cases of central neurocytoma. J Korean Neurosurg Soc 28 : 402-405, 1999 Conclusion 13. Kim CH, Jung HW, Hwang SG, Chi JG : Cerebral central neurocytoma with high proliferative index. J Korean Neurosurg Soc 33 : 195-198, 2003 e experienced a case of malignant variant of the 14. Kim DG, Chi JG, Park SH, Chang KH, Lee SH, Jung HW, et al : W central neurocytoma with high proliferative index(Ki- Intraventricular neurocytoma : clinicopathological analysis of seven cases. J Neurosurg 76 : 759-765, 1992 67 labeling index >30%), which showed the immediate 15. Kim DG, Kim JS, Chi JG, Park SH, Jung HW, Choi KS, et al : recurrence and died 3 months after surgery. Here, we describe Central neurocytoma : proliferative potential and biological the case with a review of the literatures. behavior. J Neurosurg 84 : 742-747, 1996 16. Mrak RE : Malignant neurocytic tumor. Hum Pathol 25 : 747-752, 1994 References 17. Nishio S, Morioka T, Suzuki S, Fukui M : Tumor around the foramen of monro. J Clinical Neurosci 9 : 137-141, 2002 1. Ashkan K, Adrian TH, Corrado D, William F, David GT : Benign 18. Paul K, David NL, Bernd WS, Lucy BR, Guido R, Peter CB, et al : The central neurocytoma : A double misnomer? Cancer 89 : 1111-1120, WHO classification of tumors of the nervous system. J Neuropathol 2002 Exp Neurol 61 : 215-225, 2002 2. Barbosa MD, Margaret B, Timothy J, James L : Intraventricular 19. Sgouros S, Carey M, Aluwihare N, Barber P, Jacowski A : Central neurocytoma : A clinical and pathological study of three cases and neurocytoma : a correlative clinicopathologic and radiologic analysis. review of the literature. Neurosurgery 26 : 1045-1054, 1990 Surg Neurol 49 : 197-204, 1998 3. Coca S, Moreno M, Martos JA, Rodriguez J, Bareena A, Vaquero J : 20. Sgouros S, Jackowski A, Carey MP : Central neurocytoma without Neurocytoma of spinal cord. Acta Neuropathol 87 : 537-540, 1994 intraventricular extension. Surg Neurol 42 : 335-339, 1994 4. Elek G, Slowik F, Eross L, Toth S, Szabo Z, Balint K : Central 21. Soyleme ZF, Scheithauer BW, Esteve J, Kleihues P : Atypical neurocytoma with malignant course. Pathology Oncol Res 5 :155- central neurocytoma. J Neuropathol Exp Neurol 56 : 551-556, 159, 1999 1997 5. Francesco M, Renato S, Maria LDC, Paolo C, Arcangelo G, Giorgio 22. Tatter SB, Borges LF, Louise DN : Central neurocytoma of the I : Central neurocytoma : clinico-pathological study of 5 cases and cervical spinal cord. Report of two cases. J Neurosurg 81 : 288-293, review of the literature. Clin Neurol Neurosurg 97 : 219-228, 1995 1994 6. Fujimaki T, Matsuno A, Sasaki T, Toyoda T, Matsuura R, Ogai M, 23. Tomura N, Hirano H, Watanabe O, Watarai J, Itoh Y, Mineura K, et et al : Proliferative activity of central neurocytoma. Measurement of al : Central neurocytoma with clinically malignant behavior. AJNR tumor volume doubling time. J Neurooncol 32 : 103-109, 1997 Am J Neuroradiol 18 : 1175-1178, 1997 7. Hamilton R : Frontal lobe tumor in 11year old girl. Brain Pathol 7 : 24. von Deimling A, Janzer R, Kleiheus P, Wiestler OD : Patterns of 713-714, 1997 differentiation in central neurocytoma. An immunohistochemical 8. Harada M, Morioka T, Nishio S, Fukui M : Neurocytoma in the left study of eleven biopsies. Acta Neuropathol 79 : 473-479, 1990 frontal lobe. No Shinkei Geka 19 : 89-92, 1991 25. Yasargil MG, von Ammon K, von Deimling A, Valavanis A, 9. Hassoun J, Gambarelli D, Grisoli F, Pellet W, Salamon G, Pellisier Wichmamm W, Wiestler OD : Central neurocytoma : Histopathological JF, et al : Central neurocytoma : An electromicroscopic study of two variants and therapeutic approach. J Neurosurg 76 : 32-37, 1992

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