Background

Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms

PATHOGENESIS	CHARACTERIZATION
Central neurocytomas are genetically distinct from oligodendrogliomas and neuroblastomas. Tong CY, Ng HK, Pang JC, Hu J, Hui AB, Poon WS. Department of Anatomical & Cellular Pathology and Neurosurgical Unit, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.	Histopathology 2000 Aug;37(2):160-5 Abstract quote AIMS: Central neurocytoma is a rare central nervous system tumour typically found in the lateral ventricles and at the septum pellucidum. Histologically, it resembles oligodendrogliomas and yet ultrastructurally, it shows neuronal differentiation. Its molecular oncogenesis is not known. The aim of this study was to examine whether major genetic events found in oligodendrogliomas and neuronal tumours, namely allelic deletions of chromosomes 1p and 19q and N-myc amplification, can be found in central neurocytomas. As there was one report describing gain of chromosome 7 in central neurocytomas, we also examined epidermal growth factor receptor (EGFR) amplification, as the EGFR gene is located at chromosome 7p. METHODS AND RESULTS: Nine central neurocytomas and matched blood samples were examined for loss of heterozygosity (LOH) of 1p and 19q13.2-13.4 with 23 finely mapped microsatellite markers. N-myc amplification was studied by fluorescence in-situ hybridization using paraffin-embedded sections. EGFR amplification was tested for by differential PCR. Six of nine (67%) tumours showed LOH at one or more loci at 1p and 5/9 (56%) of cases showed LOH at 19q. However, common regions of deletion cannot be identified. The majority of informative markers are retained at 1p (84%) and 19q (86%). Only one tumour showed amplification of N-myc and none of the cases showed amplification of EGFR. C ONCLUSION: Central neurocytomas are genetically distinct from oligodendrogliomas, and chromosomes 1p and 19q probably do not play an important role in their pathogenesis. N-myc and EGFR amplification are rare.
Detection of chromosomal imbalances in central neurocytomas by using comparative genomic hybridization. Yin XL, Pang JC, Hui AB, Ng HK. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong.	J Neurosurg 2000 Jul;93(1):77-81 Abstract quote OBJECT: Central neurocytomas are rare neuronal tumors commonly found in the intraventricular regions. Little is known about the tumorigenesis of these neoplasms. The aim of this study was to provide an overview of genetic imbalances in central neurocytomas. METHODS: In this study, comparative genomic hybridization was used to identify DNA sequence copy number changes (losses and gains) in a series of 10 central neurocytomas. Tumor DNA and normal reference DNA were differentially labeled and allowed to cohybridize to normal metaphase chromosomes. After hybridization and fluorescent staining of the bound DNA, regions of gain or of loss of DNA sequences were detected as changes in the tumor/normal fluorescence intensity ratio along the target metaphase chromosomes. A gain of DNA sequence was detected in chromosomes 2p, 10q, and 18q. A protooncogene, Bcl2, which maps to 18q21, was evaluated by immunohistochemical analysis to determine its role in the formation of central neurocytomas. CONCLUSIONS: In this study the authors identified recurrent genetic changes on chromosomes 2p, 10q, and 18q in central neurocytomas and highlighted chromosomal regions for additional mapping and cloning of candidate genes that are important in the development of central neurocytomas.

 

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
Ganglioneurocytoma mimicking a malignant tumor: case report with a literature review of the MRI appearance of neurocytomas and gangliogliomas. Chan A, McAbee G, Queenan J, Manning A. Department of Pediatrics (Neurology), School of Osteopathic Medicine, University of Medicine & Dentistry of New Jersey, 40 E. Laurel Rd, Suite 100, Stratford, NJ 08084, USA.	J Neuroimaging 2001 Jan;11(1):47-50 Abstract quote A 14-year-old girl presented with symptoms of increased intracranial pressure after her head was squeezed at a party. MRI demonstrated a mass that was hypointense to brain on T1WI and heterogeneous in signal on PD and T2WI; compression of the ventricle, midline shift, and mild ventriculomegaly also were present. Contrast enhancement was extensive and heterogeneous, mimicking a malignant tumor. Neuropathology revealed a ganglioneurocytoma.
In vivo proton magnetic resonance spectroscopy of central neurocytomas. Kim DG, Choe WJ, Chang KH, Song IC, Han MH, Jung HW, Cho BK. Department of Neurosurgery, Seoul National University College of Medicine, Korea.	Neurosurgery 2000 Feb;46(2):329-33; discussion 333-4 Abstract quote OBJECTIVE: The authors report on the metabolic features of central neurocytomas observed during in vivo single-voxel proton magnetic resonance spectroscopy. METHODS: Volume-selective single-voxel proton magnetic resonance spectroscopy was performed with a 1.5-T unit using a point-resolved spectroscopy sequence (TR/TE = 2000 ms/135 and 270 ms) to obtain spectra of a single 8-cc voxel. The subjects were five patients in the Department of Neurosurgery of Seoul National University Hospital whose central neurocytomas had been diagnosed histologically. The peak intensities of compounds containing choline (Cho), N-acetylaspartate, creatine/phosphocreatine, and lactate were analyzed. RESULTS: The ratios of Cho to creatine/phosphocreatine and Cho to N-acetylaspartate were significantly higher than ratios in normal brains. A lactate signal was present, and an unidentified signal was also observed at 3.55 ppm, which might have been produced by inositol or glycine. CONCLUSION: A combination of the signal at 3.55 ppm and a prominent Cho peak seems to be a characteristic feature of central neurocytomas. Volume-selective single-voxel proton magnetic resonance spectroscopy could provide additional information to aid in diagnosing this condition.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
Extraventricular Neurocytomas Pathologic Features and Clinical Outcome Daniel J. Brat, M.D., Ph.D.; Bernd W. Scheithauer, M.D.; Charles G. Eberhart, M.D., Ph.D.; Peter C. Burger, M.D. From the Departments of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia (D.J.B.); Mayo Clinic, Rochester, Minnesota (B.W.S.); and Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A. (C.G.E., P.C.B.).	Am J Surg Pathol 2001;25:1252-1260 Abstract quote Neurocytic neoplasms usually arise within the lateral ventricles, generally as circumscribed, slowly growing masses curable by total resection. Both subtotal resection and histologic atypia are associated with an increased risk of recurrence. In contrast, neurocytic neoplasms situated within brain parenchyma, so-called “extraventricular neurocytomas” (EVNs), are not as well characterized. The relationships between histologic features and extent of resection versus clinical behavior have not been defined. We evaluated pathologic features, clinical data, and neuroimaging of 35 examples. The tumors occurred in 18 males and 17 females, age 5–76 years (median 34 years). All tumors involved the cerebrum. On imaging, EVNs were solitary, variably contrast-enhancing, and often (57%) cystic. Tumor cells were arranged in sheets, clusters, ribbons, or rosettes, in association with fine neuropil dispersed in broad zones that separated cell aggregates. Ganglion cell differentiation was seen in 66%. All tumors showed strong synaptophysin immunoreactivity. Despite the lack of apparent astrocytes in hematoxylin and eosin-stained sections, focal glial fibrillary acidic protein reactivity was seen in 46%. Eleven EVNs were designated “atypical” based on the presence of necrosis, vascular proliferation, or elevated mitotic activity (3 mitoses/10 high power fields). Nineteen tumors were subtotally resected or biopsied, whereas 14 were totally resected grossly. Seventeen patients underwent radiotherapy (mean 55 Gy). In 30 cases with follow-up, 10 tumors recurred, 3 causing death at 6, 14, and 43 months. All 10 recurrences followed subtotal resection. No totally resected tumors recurred. Thus, the majority of EVNs are well differentiated and appear unlikely to recur after gross total resection. Subtotal resection, atypical histologic features, and high cell proliferation rates correlate with recurrence.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
Central neurocytoma: a correlative clinicopathologic and radiologic analysis. Sgouros S, Carey M, Aluwihare N, Barber P, Jackowski A. Department of Neurosurgery, Birmingham Neuroscience Centre, Queen Elizabeth Hospital, England.	Surg Neurol 1998 Feb;49(2):197-204 Abstract quote BACKGROUND: Central neurocytoma was described as a well differentiated tumor of neuronal origin, distinct from ganglion cell tumors and neuroblastoma. An initially perceived benign biologic behavior has been questioned by subsequent reports of anaplastic and recurrent tumors. We report six cases of central neurocytoma, with variable clinical and pathologic features that stimulate discussion on the management of these tumors. METHODS: Of the 95 oligodendrogliomas treated in our institution in the last 40 years, three tumors were reclassified as central neurocytomas on histologic reappraisal. Three additional cases prospectively diagnosed as central neurocytomas are reported. The clinical, pathologic, and radiologic features are reviewed. RESULTS: Early recurrence, not related to malignant histologic features, was noted in two patients who had not received postoperative radiotherapy. Anaplastic histologic changes were not accompanied by malignant biologic behavior in another patient. Neither patient with recurrent tumor was controlled by radiotherapy alone. Chemotherapy with carboplatin reduced tumor size temporarily in one of these patients. CONCLUSION: An entirely benign nature for this tumor is questioned and it appears that there may be malignant variants. Surgery should aim for maximum possible excision, as the location of the tumor allows. The role of postoperative radiotherapy remains controversial and may be considered in cases of subtotal excision of tumors with anaplastic histologic features. Chemotherapy may be of benefit in cases recurring despite surgery and radiotherapy.
Central neurocytoma with malignant course. Neuronal and glial differentiation and craniospinal dissemination. Elek G, Slowik F, Eross L, Toth S, Szabo Z, Balint K. Hospital of Hungarian Railways, Departments of Pathology Pathology of MAV Hospital at Pest, Podmaniczky u 11, Budapest, H-1062, Hungary.	Pathol Oncol Res 1999;5(2):155-9 Abstract quote Central neurocytoma is a benign neuronal tumor of young adults in the lateral cerebral ventricles with characteristic X ray and light microscopic findings. In many respects typical central neurocytoma is reported below, with recurrence in the third month requiring reoperation. Death ensued in the fifth postoperative month. Subsequent histology proved progressive vascular proliferation and increasing, unusual glial differentiation of the neuronal tumor. At autopsy tumorous seeding blocked the liquor circulation. A thin tumorous layer covered the surface of all ventricles, the cerebellum and medulla oblongata. The GFAP positive cells out-numbered the synaptophysin positive ones. Increase of GFAP positivity and vascular proliferation of the central neurocytoma may be alarming signs suggesting a malignant course in addition to the other atypical features.
Pigmented central neurocytoma: case report and literature review. Ng TH, Wong AY, Boadle R, Compton JS. Department of Tissue Pathology, Westmead Hospital, Sydney, Australia.	Am J Surg Pathol 1999 Sep;23(9):1136-40 Abstract quote A case of pigmented central neurocytoma is reported. The tumor showed histologic, immunophenotypic, and ultrastructural features of central neurocytoma. The pigment consisted of an intimate association of lipofuscin and neuromelanin. Pigmented neuroepithelial tumors are rare, and the pigments may be neuromelanin or melanin. Pigmented central neurocytoma has not been described to date. The low proliferation rate of the tumor suggests a delayed turnover of tumor cells as a possible cause of lipofuscin accumulation. Autocatalytic peroxidation of lipofuscin is a possible mechanism of neuromelanin formation.
Histopathological variants of central neurocytoma: Report of 10 cases. Favereaux A, Vital A, Loiseau H, Dousset V, Caille J, Petry K. Laboratoire d'Anatomie Pathologique et de Neuropathologie, Universite Victor Segalen, Bordeaux.	Ann Pathol 2000 Dec;20(6):558-63 Abstract quote Central neurocytoma is a rare neuronal tumor affecting young adults and usually located in the lateral ventricles. Post-operative prognosis is generally good. Histologically, central neurocytoma is composed of isomorphous small round or ovoid cells alternating with irregularly shaped patches of fibrillary matrix similar to the neuropile. In a series of 10 cases, two central neurocytomas were histologically "atypical" at first examination. One was intra-ventricular, and the second had an intra-parenchymatous juxta-ventricular location. Both were highly cellular with mitotic activity, and tumor necrosis was seen in one. Neuronal differentiation was assessed by synaptophysin immunoreactivity in all 10 cases and by ultrastructural examination in four, including the two "atypical" forms. Neuronal differentiation was less marked in these "atypical" forms, one also presenting focal GFAP immunoreactivity. The proliferative potential was determined by MIB-1 labeling index and compared with clinical outcome. The eight classical central neurocytomas had a MIB-1 labeling index < 2.3%, whereas the two "atypical" forms had a MIB-1 labeling index > 5.2% and both recurred. We think that there is a spectrum of small-cell neuronal tumors. The two extremes could be the central neurocytoma and the primary cerebral neuroblastoma, while the intermediate forms might be qualified as "atypical neurocytoma". In our series, the histological and immunohistochemical criteria of biological aggressiveness appeared to be high mitotic activity, tumor necrosis, loss of neuronal differentiation and high MIB-1 labelling index.
So-called malignant and extra-ventricular neurocytomas: reality or wrong diagnosis? A critical review about two overdiagnosed cases. Vallat-Decouvelaere AV, Gauchez P, Varlet P, Delisle MB, Popovic M, Boissonnet H, Gigaud M, Mikol J, Hassoun J. Department of Pathology,Lariboisiere Hospital, Paris, France.	J Neurooncol 2000 Jun;48(2):161-72 Abstract quote Central neurocytoma (CN) is described as a rare intra-ventricular benign neuronal tumor of the brain. Two primary tumors first diagnosed as malignant and extra-ventricular neurocytomas are reported here. Histologically, the tumor of the first patient, a forty-one-year-old man, consisted of monotonous cells with round nuclei, but no fibrillar background. The second tumor, in a nineteen-year-old girl, showed areas of moderately pleomorphic round cells, with numerous rosettes and ganglion cell differentiation, in an abundant fibrillary network. Both presented calcifications. Mitoses were more frequent in recurrences and spinal locations than in the primaries. All tumors stained strongly for synaptophysin, and GFAP was partly positive in the first case only. Patients received post-surgical radiotherapy and were still alive eight and six years, respectively, after initial surgery. The interpretation of atypical cases, such as ours is not easy: the diagnoses finally retained were oligodendroglioma in the first case and ganglioneuroblastoma in the second case. Furthermore, neurocytomas atypical either by their unusual topographical or histological presentation or by their poor prognosis, have been frequently entitled in this way on synaptophysin positivity. So, we were prompted to reassess the entity of CN, seventeen years after the first description, to re-appreciate the reality of anatomo-clinical variants and to discuss the value of synaptophysin positivity in these tumors. In conclusion, it seems preferable to individualize true classical CN, which has a favorable outcome, from so-called extra-ventricular, atypical and anaplastic, clinically malignant neurocytomas for which complementary treatment is required.
Cerebellar liponeurocytoma. Case report and review of the literature. Jackson TR, Regine WF, Wilson D, Davis DG. Department of Surgery, University of Kentucky Medical Center, Lexington 40536-0084, USA.	J Neurosurg 2001 Oct;95(4):700-3 Abstract quote Cerebellar liponeurocytoma is a rare tumor of the posterior fossa that has many morphological similarities to medulloblastoma and neurocytoma. Recently the World Health Organization working group for classification of central nervous system neoplasms adopted the term "cerebellar liponeurocytoma" to provide a unified nomenclature for a tumor variously labeled in the literature as lipomatous medulloblastoma, lipidized medulloblastoma, medullocytoma. neurolipocytoma, lipomatous glioneurocytoma, and lipidized mature neuroectodermal tumor of the cerebellum. The rarity of this tumor and paucity of pertinent information regarding its biological potential and natural history have resulted in the application of various treatment modalities. It is suggested in the available literature that these lesions have a much more favorable prognosis than typical medulloblastomas, and that adjuvant therapy for liponeurocytoma need not be as extensive as that administered for medulloblastomas.
Central neurocytomas express photoreceptor differentiation. Mena H, Morrison AL, Jones RV, Gyure KA. Department of Neuropathology, Armed Forces Institute of Pathology, Washington, DC.	Cancer 2001 Jan 1;91(1):136-43 Abstract quote BACKGROUND: Central neurocytomas are composed of mature neuronal elements, frequently arranged in rosettes similar to those present in pineocytomas. This suggests the possibility of similar patterns of differentiation, including photoreceptor differentiation. The authors analyzed the immunoreactivity of central neurocytomas for retinal S-antigen, neuronal, glial, and neuroendocrine markers. METHODS: Thirty-three central neurocytomas were analyzed with reference to their clinicopathologic characteristics, immunoreactivity, and the possibility that anaplastic histologic features correlated with aggressive clinical behavior. RESULTS: There were 18 male and 15 female patients. The median age at diagnosis was 30 years (range, 3-69 years). All of the tumors with specified location were related to the ventricles. Thirty-two tumors were diagnosed at surgery and 1 at autopsy. Histologic features included mineralization (20 of 33), foci of necrosis (4 of 33), chronic inflammation (4 of 33), ganglion cell differentiation (1 of 33), and lipomatous differentiation (1 of 33). None of the lesions had significant nuclear pleomorphism, mitotic activity, or vascular endothelial proliferation. Immunohistochemistry included expression of synaptophysin (33 of 33), neuron specific enolase (31 of 33), S-100 protein (25 of 33), retinal S-antigen (14 of 24), somatostatin (8 of 27), glial fibrillary acidic protein (4 of 33), neurofilament protein (3 of 22), and leucine enkephalin (1 of 27). At follow-up, 15 of 23 patients were alive an average of 8.1 years (range, 0.91-35.9 years) after surgery. CONCLUSIONS: Central neurocytomas behave as slowly growing neoplasms that remain confined within one or several supratentorial ventricles and are associated with long survival after surgical excision. Malignant forms with aggressive clinical behavior were not found. The neoplastic cells can express photoreceptor differentiation possibly relating central neurocytomas to pineocytomas. Adipocyte differentiation may be present, and the possibility of a relation between the central neurocytoma and cerebellar liponeurocytoma should be entertained.
Central Liponeurocytoma David H. George, M.D. Bernd W. Scheithauer, M.D. From the Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, U.S.A.	Am J Surg Pathol 2001;25:1551-1555 Abstract quote The 2000 World Health Organization has included cerebellar liponeurocytoma in the category of glioneuronal tumors of the central nervous system. Once termed medullocytoma and considered an embryonal tumor, a variant of medulloblastoma, its indolent behavior and morphologic features prompted this nosologic change. Biphasic in appearance, the tumor consists of well-differentiated neurons with the cytology of neurocytes in addition to a population of lipidized cells resembling mature adipose tissue. Such tumors occur in older adults and have a relatively good prognosis. Linking the concept of liponeurocytoma to its occurrence in the cerebellum unnecessarily obscures the existence of similar neoplasms at other sites, such as among classic central neurocytomas of the lateral and third ventricles. Indeed, two such cases have briefly been reported. To these, we add a third example, the first to be ultrastructurally examined. Our case provides evidence that the lipid vacuoles progressively accumulate and coalesce within cells retaining neurocytic features. Thus, these distinctive lesions are the result of tumoral lipidization, rather than true adipose metaplasia.

 

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
A study of proliferative markers in central neurocytoma. Sharma MC, Rathore A, Karak AK, Sarkar C. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.	Pathology 1998 Nov;30(4):355-9 Abstract quote To gain a better insight into the biological behavior of central neurocytomas, various proliferative indices were studied in these tumors and correlated with the histological features as well as the clinical outcome. Twenty cases of neurocytoma were selected over a 16 year period (1980-1995), which accounted for 0.28% of all intracranial tumors reported at this centre. Treatment consisted of surgical resection (total 14, subtotal six) followed by radiotherapy. Except for five patients who died of surgical complications, the remaining 15 were all alive and well during the follow-up period, varying from six months to 72 months (average 32 months). Thirteen tumors showed benign histological characteristics (Group I) while seven showed mitoses + necrosis (Group II). The proliferative index was assessed in formalin-fixed paraffin-embedded tissue of 17 cases using the silver nucleolar organiser region (AgNOR) technique and immunohistochemical staining for proliferating cell nuclear antigen (PCNA-PC10 antibody) and Ki-67 antigen (MIB-1 monoclonal antibody). The AgNOR counts ranged from 1.2 to 2.6 (mean 1.9 +/- 0.4), PCNA labeling index (LI) from 0.1 to 5.5 (mean 2.5 +/- 1.8) and MIB-1 LI from 0.1 to 3 (mean 0.8 +/- 0.02). There was no significant difference in any of these parameter values between histological Groups I and II, except that MIB-1 LI tended to be higher in Group II tumors. Further, there was no significant correlation between these proliferative indices and the mitotic rate of the tumors as well as the survival of the patients. A longer follow-up will be required to determine the relationship between proliferative markers and outcome as well as to bring out any heterogeneity in their biological behavior. Since these are relatively rare tumors, multicentric pooling of data will be required to reach a definitive consensus regarding their biological aggressiveness and consequentially, the use of radiotherapy in their treatment. The present report is a contribution in this direction.
ELECTRON MICROSCOPY
Intraventricular neurocytoma with prominent myelin figures. Park SH, Ostrzega N, Akers MA, Vinters HV. Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.	Ultrastruct Pathol 1999 Sep-Oct;23(5):311-7 Abstract quote A case is reported of intraventricular neurocytoma that had characteristic light microscopic findings of neurocytoma with prominent intracytoplasmic concentric lamellar structures mimicking myelin sheaths. On routine H&E-stained sections, this tumor showed intracytoplasmic vesicular bleb-like structures having eosinophilic cores that were consistent with ultrastructural concentric lamellar structures. Immunohistochemically, this tumor was immunoreactive for synaptophysin and neurofilament, but negative for antibody to glial fibriallary acidic protein. Electron microscopic findings fulfilled the criteria for neurocytoma, with the presence of neurosecretory granules and neurotubules. These findings may suggest dual differentiation of this tumor into neurocytes and oligodendrocytes.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Oligodendroglioma

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Central neurocytoma: clinical, immunohistologic, and biologic findings of a human neuroglial progenitor tumor. Valdueza JM, Westphal M, Vortmeyer A, Muller D, Padberg B, Herrmann HD. Department of Neurosurgery, University Hospital Hamburg-Eppendorf, F.R.G.	Surg Neurol 1996 Jan;45(1):49-56 Abstract quote BACKGROUND: Central neurocytomas are rare brain tumors recognized by their typical radiologic and histologic features. In general, a good prognosis is achieved by total removal. The histogenesis is still under debate, but a neuronal origin is widely assumed. METHODS: This study presents the clinical and immunohistologic findings of five patients and the results of cell culture experiments of two patients with central neurocytoma treated surgically between 1983 and 1993. RESULTS: The patient age at diagnosis ranged from 21 to 30 years (mean, 25 years). The male-to-female ration was 1:4. Raised intracranial pressure due to hydrocephalus was the main cause of the clinical manifestations. Total resection was achieved in two cases. Four patients received radiotherapy. One patient suffered a recurrence 1 year after surgery, requiring a second resection and radiotherapy. Follow-up studies took place between 1 and 10.5 years (mean, 7.1 years). To date, all patients are free of their tumors. Two patients suffered from permanent memory disturbances after surgery. Immunohistochemistry confirmed the neuronal nature of the tumors. Cell-culture studies, which have been carried out for the first time, demonstrated concomitant expression of neuronal (synaptophysin) and glial (GFAP) markers. CONCLUSION: Total removal is the therapy of choice. In tumor recurrence or limited surgery (e.g. due to severe affliction of the fornical structures), radiotherapy has shown to be efficacious. The cell-culture experiments give new insight on the histogenesis of central neurocytoma, indicating that the tumor arises from an undifferentiated precursor cell with the capacity of bipotential neuroglial differentiation.
Atypical central neurocytoma. Soylemezoglu F, Scheithauer BW, Esteve J, Kleihues P. Department of Pathology, University Hospital, Zurich, Switzerland.	J Neuropathol Exp Neurol 1997 May;56(5):551-6 Abstract quote The proliferative potential of central neurocytomas was determined in a biopsy series of 36 cases and compared with clinical outcome. T he mean size of the growth fraction, as determined by MIB-1 labeling index (MIB-1 LI) at first biopsy, was 2.8 +/- 2.5 with a range of 0.1 to 8.6%. Neurocytomas with an MIB-1 LI > 2% comprised 39% of cases and showed a close correlation with the presence of vascular proliferation (p = 0.0006). The Kaplan-Meier analysis showed a highly significant difference in disease-free survival between the 2 groups (p = 0.0068). Over an observation time of 150 months, there was a 22% relapse among patients with an MIB-1 LI less than 2% and a 63% chance of relapse among those with an MIB-1 LI greater than 2%. We propose the term "atypical central neurocytoma" for the latter subset, corresponding to WHO grade II.
The natural history of a recurrent central neurocytoma-like tumor. Wharton SB, Antoun NM, Macfarlane R, Anderson JR. Department of Histopathology, Addenbrookes Hospital, Cambridge, UK.	Clin Neuropathol 1998 May-Jun;17(3):136-40 Abstract quote The central neurocytoma was first recognized as a distinct entity in 1982. The original description was of a low grade, intraventricular neoplasm composed of uniform cells showing neuronal differentiation, and having a very favorable prognosis after surgery. Subsequently rare cases have been described showing malignant histological features but retaining the morphological characteristics that justify inclusion in this category. The behavior of such cases has yet to be determined. We report a case of a longstanding intraventricular tumor showing neuronal differentiation in which repeated recurrences following surgery have revealed evidence of increasing nuclear pleomorphism, mitotic activity and glial differentiation. We suggest that this tumor broadens further the clinical and pathological spectrum of central neurocytoma.
Central neurocytoma: histologic atypia, proliferation potential, and clinical outcome. Mackenzie IR. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.	Cancer 1999 Apr 1;85(7):1606-10 Abstract quote BACKGROUND: Although central neurocytomas are considered benign, recent reports suggest that some patients with histologic atypia and/or elevated proliferation potential may have a poor outcome. METHODS: A retrospective review identified 15 cases of central neurocytoma. Clinical follow-up was available for 14 patients. Each tumor was evaluated for the presence of atypical histologic features, including cellular pleomorphism, endothelial proliferation, and necrosis. The proliferation potential was assessed by MIB-1 immunohistochemistry. The correlation among histology, MIB-1 labeling index (MIB-1 LI), and clinical outcome was evaluated. RESULTS: Histologic atypia was identified in 3 tumors (20%). The MIB-1 LI ranged from 0.1% to 6.0%, and 5 cases (33%) had an MIB-1 LI >2%. The correlation between histologic atypia and MIB-1 LI was poor, with only 1 tumor having both atypia and MIB-1 LI >2%. Clinical follow-up ranged from 13 to 255 months postoperatively (mean, 68 months). Although most patients were alive and well at last follow-up, three developed symptomatic recurrence and one died as a result of increased tumor growth. The tumors from all 4 patients with a poor outcome had MIB-1 LI >2%, but only 1 had histologic atypia. CONCLUSIONS: The proliferation potential of central neurocytoma is a useful predictor of clinical outcome, whereas histologic atypia alone is not prognostically significant. It would be appropriate to recognize a subgroup of central neurocytomas with elevated proliferation potential as WHO Grade 2 lesions. The terms "atypical" and "anaplastic" are not appropriate to describe these lesions, as they imply a certain histologic appearance. The most accurate designation would be "proliferating neurocytoma."
Intraventricular neurocytoma: a clinicopathological study of 20 cases with review of the literature. Sharma MC, Sarkar C, Karak AK, Gaikwad S, Mahapatra AK, Mehta VS. Department of Pathology, All India Institute of Medical Sciences, New Delhi - 110029, India	J Clin Neurosci 1999 Jul;6(4):319-323 Abstract quote The clinicopathological features of 20 cases of central neurocytomas are described. They accounted for 0.28% of all intracranial tumours diagnosed during a 16 year period (1980-1995). Lower mean age of the patients at diagnosis (23.1 years), male preponderance (M:F=1.8:1) and higher incidence of involvement of the right lateral ventricle (10/20 cases) were noted in this series, in contrast to reports from Western literature. Total removal of the tumour was done in 14 cases while the remaining six underwent partial resection. Morphogically, the tumours had a striking resemblance to oligodendrogliomas (11/20 had been earlier diagnosed as oligodendrogliomas) and an interesting finding was the presence of dilated vascular channels in 12/20 tumours. The diagnosis was confirmed in all cases by immunohistochemistry and/or electron microscopy. While 18 cases were histologically benign, two had features of atypical neurocytoma. Five patients died due to postoperative complications. The remaining patients received postoperative radiation and their follow-up revealed that all of them were doing well at 12 to 72 months after surgery. These neoplasms should be suspected in any young patient with radiological evidence of an intraventricular lesion; for their differentiation from gliomas, immunohistochemistry and electron microscopy should be done. This is important because, unlike gliomas, these tumours have a relatively favourable prognosis and their current treatment of choice is complete surgical removal without adjuvant chemo- or radiotherapy.
Benign central neurocytoma. Ashkan K, Casey AT, D'Arrigo C, Harkness WF, Thomas DG. Departments of Neurological Surgery and Neuropathology, National Hospital for Neurology and Neurosurgery, London, England.	Cancer 2000 Sep 1;89(5):1111-20 Abstract quote BACKGROUND: "Central neurocytoma" is classically considered as an intraventricular benign tumor, largely based on data from small retrospective series. The authors present prospective data on 12 patients with tumors diagnosed as central neurocytoma, to highlight the diverse nature of this tumor and challenge the classic notion. METHODS: Between 1991 and 1997, 12 patients had tumors diagnosed prospectively as "central neurocytoma". Clinical, radiologic, and histologic data were collected, and Karnofsky performance score was evaluated for each patient. Proliferation marker studies were performed using Ki-67 labeling index. RESULTS: In two patients, the tumors were located in atypical locations, namely, the parietal lobe and the spine. Aggressive behavior characterized by clinical and radiologic evidence of tumor progression was noted in two additional patients. In both these cases, unusually high proliferation rates of 5.3% and 11.2% were noted. Total excision of the tumor, when possible, was the treatment of choice. Postoperative radiotherapy to the residual tumor may be of benefit in patients with clinically aggressive tumors, or those with high proliferation rates. CONCLUSIONS: Given the findings of this study, it is suggested that the traditional concept of central neurocytoma as a benign intraventricular tumor warrants reconsideration.
TREATMENT
Chemotherapy in patients with recurrent and progressive central neurocytoma. Brandes AA, Amist?a P, Gardiman M, Volpin L, Danieli D, Guglielmi B, Carollo C, Pinna G, Turazzi S, Monfardini S. Department of Medical Oncology, Azienda Ospedale-Universit?a, Padova, Italy.	Cancer 2000 Jan 1;88(1):169-74 Abstract quote BACKGROUND: Recurrent central neurocytoma is very rare and to the authors' knowledge data regarding its response to chemotherapy currently are not available. METHODS: Three patients with progressive neurocytoma received chemotherapy after their informed consent was obtained. Disease recurred in two patients after surgery and radiotherapy and in one patient after surgery. The treatment regimen was comprised of etoposide, 40 mg/m(2)/day, for 4 days; cisplatin, 25 mg/m(2)/day, for 4 days; and cyclophosphamide, 1,000 mg/m(2), on Day 4; this cycle was repeated every 4 weeks. RESULTS: Stabilization of disease was observed in 2 patients and complete remission was observed in 1 patient; at last follow-up, these responses had been maintained for 15 months, 18 months, and 36 months, respectively. CONCLUSIONS: In this small series, this therapeutic regimen led to long term disease reduction, and merits further study.
Stereotactic radiosurgery for residual neurocytoma. Report of four cases. Tyler-Kabara E, Kondziolka D, Flickinger JC, Lunsford LD. Department of Neurological Surgery, University of Pittsburgh, Pennsylvania, USA.	J Neurosurg 2001 Nov;95(5):879-82 Abstract quote The purpose of this report was to review the results of stereotactic radiosurgery in the management of patients with residual neurocytomas after initial resection or biopsy procedures. Four patients underwent stereotactic radiosurgery for histologically proven neurocytoma. Clinical and imaging studies were performed to evaluate the response to treatment. Radiosurgery was performed to deliver doses to the tumor margin of 14, 15, 16, and 20 Gy, depending on tumor volume and proximity to critical adjacent structures. More than 3 years later, imaging studies revealed significant reductions in tumor size. No new neurological deficits were identified at 53, 50, 42, and 38 months of follow up. The authors' initial experience shows that stereotactic radiosurgery appears to be an effective treatment for neurocytoma.
Gamma knife radiosurgery of recurrent central neurocytomas: a preliminary report. Bertalanffy A, Roessler K, Dietrich W, Aichholzer M, Prayer D, Ertl A, Kitz K. Department of Neurosurgery, University of Vienna, Medical School, Waehringer Guertel 18-20, A-1090, Austria.	J Neurol Neurosurg Psychiatry 2001 Apr;70(4):489-93 Abstract quote OBJECTIVES: A series of three recurrent central neurocytomas treated by gamma knife radiosurgery (GKRS), which were initially totally resected, are described. Up to now, no reports exist on this treatment modality for this rare tumour entity. METHODS: Three male patients, aged between 20 and 25 years, presented with large intraventricular tumours. Total tumour removal was achieved by a single surgical procedure (one patient) or two operations (two patients). Neuropathological investigation showed a central neurocytoma, immunohistochemically all three tumours expressed a neuronal antigenic profile typical for neurocytomas, and the MIB-1 proliferation index ranged from 2.4% to 8.7%. Each patient experienced a tumour recurrence after 5 to 6 years. The recurrence was multifocal in two and a singular tumour mass in one patient. Gamma knife radiosurgery was performed. The tumours were enclosed within the 30% to 60% isodoseline, and delivered a tumour marginal dose of 9.6 to 16 Gy. During the follow up period, the patients were tested clinically and the volume of the tumours was measured on MRI. RESULTS: Within follow up periods of 1 to 5 years, control MRI showed a significant decrease of the tumour mass in all cases. None of the patients developed new neurological symptoms after GKRS. Two patients returned to work in their previous employment, whereas one patient remained permanently disabled due to a pre-existing visual impairment and abducens palsy. CONCLUSION: GKRS proved to be a useful tool in the treatment of recurrent central neurocytomas. Tumour control and even tumour shrinkage can be achieved with a single procedure and a low risk of morbidity.

Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.

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