Management of neurocytomas: case report and review of the literature

The purpose of this report is to review the available literature on the presentation, pathology, and treatment of central nervous system (CNS) neurocytomas. A case report of an extraventricular neurocytoma is presented along with a comprehensive literature search of patients with a diagnosis of CNS neurocytoma. CNS neurocytomas are rare neoplasms, with fewer than 240 cases reported in the literature. The majority of neurocytomas are found in the ventricular system of the brain. Immunohistochemistry is frequently used to help distinguish this tumor from other CNS neoplasms. MIB-1 proliferation index is commonly used in an attempt to predict biologic behavior. Little is known about the management of patients with this tumor, because most reports are from the pathologic literature and contain sparse information regarding clinical management. Neurocytomas are rare CNS tumors with varied biologic behavior. MIB-1 index may help direct adjuvant therapy. An excellent prognosis can be expected if a gross total resection is achieved. Postoperative radiation therapy (RT) may be considered after subtotal resection. Otherwise, RT is an option for medically inoperable or recurrent disease.     

Extraaxial neurocytoma in the skull base

Extraventricular neurocytoma is an uncommon neuronal tumor, located outside the cerebral ventricles, which shows histological features similar to those of central neurocytoma. Most extraventricular neurocytomas are situated in the intraaxial regions of the central nervous system. We report a rare case of an extraaxial neurocytoma in the sphenocavernous-petroclival region that was successfully treated by radiation therapy following partial removal and pathological evaluation of the tumor.     

Central Neurocytoma: A Review

Central neurocytomas are rare intraventricular neoplasms of the central nervous system, compromising 0.25-0.5% of brain tumors. The diagnosis and management of these tumors remains controversial since most clinical series are small. Typically, patients with central neurocytomas have a favorable prognosis, but in some cases the clinical course is more aggressive. Although histological features of anaplasia do not predict biologic behavior, proliferation markers including MIB-1 might be more useful in predicting relapse. The most important therapeutic modality is surgery, and a safe maximal resection confers the best long-term outcome. In cases of a subtotal resection,'standard external beam radiation can be added or radiation can be delayed until tumor progression occurs. Smaller residual tumor volumes or recurrences can be treated with more conformal radiation or focused radiosurgery. Re-operation for recurrence should be considered if the procedure can be safely performed. Chemotherapy may be useful for recurrent central neurocytomas that cannot be resected and have been radiated, although long-term responses have not been reported for chemotherapy. Overall, this paper reviews the findings of the larger studies and highlights some of the important case reports that contribute to the current management of central neurocytomas.     

Primary neurocytoma of the spinal cord: a case report and review of literature

Summary Most central neurocytomas (CN) and spinal neurocytomas (SN) have a bland well-differentiated histologic picture and uneventful clinical course. However, rare examples showing histologic atypia, recurrence and even CSF dissemination have been reported. Herein we report a case of recurrent spinal neurocytoma in a 24-year-old male who presented with a 2-month history of weakness and numbness of the left upper and lower limbs, and was previously operated at the same site 10 months ago. MRI revealed a contrast enhancing intramedullary mass involving C5-T1 region. Radiologic and operative impression at both surgeries was that of a glioma, possibly anaplastic. Histologic and immunohistochemical features in both resections were those of an atypical neurocytoma. The tumor showed rare mitoses, focal mild vascular proliferation in both specimens, and necrosis in the initial specimen. MIB1 labeling indices were 9 and 10%, respectively. Based on the analysis of this case and limited data from the literature, it is hypothesized that SN shows a histopathologic picture, immunoprofile and biologic behavior very similar to CN. However, the presence of histologic atypia and increased MIB1 index in SN appear to more closely correlate with tumor recurrence and a worse overall outcome, in part due to their location in the critical region of cervical spinal cord. Therefore, we hypothesize that SN with atypia requires a close clinical follow up. As in CN, radiation therapy is perhaps best reserved for atypical, progressive and recurrent SN.     

Central,Extraventricular and Atypical Neurocytomas: a Clinicopathologic Study of 35 Cases from Pakistan Plus a Detailed Review of the Published Literature

Background: Central neurocytomas are rare neuronal neoplasms with a favorable prognosis. They are typically located in the lateral ventricles of the brain and mostly histologically correspond to WHO grade II with a Mib 1 labelling index of <2%. Similar tumors located in the cerebral hemispheres and spinal cord, for example, are called "extraventricular neurocytomas". A few tumors histologically show atypia, mitoses, vascular proliferation and/or necrosis and a Mib 1 index >2 % and are designated as "atypical neurocytomas. Aim: The aim of our study was to describe the common as well as unusual morphologic features and the role of various immunohistochemical stains in the diagnosis of these rare tumors. Materials and Methods: We retrieved and reviewed 35 cases diagnosed between 2001 and 2015. Results: Sixty percent of patients were males, and the mean age was 26 years. 31 cases (88.6%) were intraventricular and 4(11.4%) were extraventricular. Histologically, 6 cases (17.1%) were compatible with "atypical neurocytomas". All cases showed the classic morphology comprising nests and sheets of uniform, round cells with uniform round to oval nuclei with finely speckled chromatin and perinuclear cytoplasmic clearing (halos). All cases also showed delicate, fibrillary, neuropil-like matrices. Other common histologic features included capillary-sized blood vessels in a branching pattern in 57.1%, foci of calcification in 34.3% and perivascular pseudorosettes in 20%. Rare findings included Homer- Wright or true rosettes in 8.6% and ganglioid cells in 2.9%. Synaptophysin was the most consistent and valuable marker, being positive in almost all cases. GFAP positivity in tumor cells was seen in 25.7% of cases. Follow up was available in 13 patients. Of these 9 had histologically typical and 4 had atypical tumors. Only 1 (with an atypical neurocytoma) died, probably due to complications of surgery within one month, while 12 (including 3 with atypical neurocytomas) remained alive. Recurrence developed in 1 of these 12 patients (histologically consistent with typical morphology) almost 9 years after surgery. Only 4 patients, including 2 with atypical tumors, received postoperative radiotherapy, all with surgery in 2010 or later. Overall, prognosis was excellent with prolonged, recurrence free survival and most patients, even without receiving radiation therapy, were alive and well for many years, even a decade or more after surgery, without developing any recurrence, indicating the benign nature of these neoplasms.     

Neurocytomas: long-term experience of a single institution

There is a lack of studies reporting on outcomes of control and treatment toxicities for neurocytomas. A 25-year retrospective review of a tertiary center's experience with neurocytomas was completed to report on these outcomes. All cerebral neurocytoma cases (19 patients; median age, 31 years; range, 18-62 years; 18 intraventricular and 1 extraventricular) treated between 1984 and 2009 were analyzed, including central pathology and radiology reviews. Median follow-up was 104.5 months (range, 0.75-261.7 months). Primary treatment was surgery alone (n = 18 patients), followed by surgery and adjuvant radiotherapy (n = 1). The crude local control rate after surgery was 68% for all cases (cerebral neurocytomas) and 74% for central neurocytomas. Salvage therapies included further surgery (n = 4), radiation (n = 3), and chemotherapy (n = 1). Ten-year Kaplan-Meier overall and relapse-free survival rates were 82% and 62% and 81% and 57%, respectively, for all cases and for central neurocytomas only. The median overall survival and relapse-free survival were 104.5 and 79.3 months, respectively, for all cases and for central neurocytomas. Ten patients had grade 3/4 toxicity, and 1 patient had a grade 5 perioperative hemorrhage that resulted in death 23 days after surgery. Late grade 3/4 toxicities occurred in 9 patients. Three patients had permanent grade 2 motor or cognitive deficits. We provide the first report outlining toxicities and survival outcomes in a series of 19 patients. Our experience suggests that initial surgery provides durable local control rates in two-thirds of patients, with low risk for significant permanent deficits. Salvage therapy with surgery and/or radiation provides durable local control in tumors that recur after surgery.     

Rapid shrinkage of remnant central neurocytoma after gamma knife radiosurgery: a case report

Central neurocytomas are typically benign tumors that have high local control rates after gross total resection. Radiotherapy for residual or recurrent central neurocytomas is controversial.We report a 30-year-old male with a central neurocytoma in the lateral ventricle. The tumor was subtotally resected through a transcallosal approach, and subsequently treated with gamma knife radiosurgery. The tumor had shrunken markedly by 2 months after radiosurgery and remained unchanged during the one year follow-up period.Gamma knife radiosurgery may be an option for effective treatment of patients with residual or recurrent central neurocytomas.     

中枢神经细胞瘤的M砒和DWI诊断及鉴别诊断

本组收集2002年9月～2011年2月苏州大学附属第一医院收治的8例CNC中,男性4例、女性4例,年龄22～55岁,中位年龄31-3岁。6例患者因头痛、呕吐及视物模糊等颅高压症状入院。     

Central neurocytomas express photoreceptor differentiation

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.     

Primary central nervous system primitive neuroectodermal tumors (CNS-PNETs) of the spinal cord in children: four cases from the German HIT database with a critical review of the literature

Approximately 30-50% of patients with intracranial primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) develop spinal metastases. In contrast, primary spinal CNS-PNETs are extremely uncommon. The database and study records of the German/Austrian brain tumor trials HIT 91, HIT SKK 92, and HIT 2000 were retrospectively reviewed to describe clinical features, treatment modalities, and outcome of children with primary CNS-PNETs of the spinal cord who were registered as observational patients. Out of 1,248 patients with medulloblastomas or CNS-PNETs registered in the HIT database four patients (female, n = 3) with primary CNS-PNETs of the spinal cord were identified. Age at diagnosis was 10, 16, 23, and 174 months. Location of primary tumors was medulla oblongata-T3, C2-T1, T10-L2, T7-T10. Two patients had metastatic disease at diagnosis. Complete and incomplete resection was performed in one patient each, whereas two patients underwent a biopsy only. Two patients received chemotherapy only, in accordance with the HIT 91 trial (sandwich chemotherapy arm). They developed disease progression and died six months after diagnosis. One patient was given chemotherapy in accordance with the HIT 2000 trial followed by craniospinal radiotherapy and four courses of maintenance chemotherapy. The patient is in complete remission almost four years after diagnosis. The fourth patient developed disease progression while receiving induction chemotherapy. Hence, chemotherapy was switched to a modified Head Start protocol. After three cycles he underwent double autologous stem cell transplantation and craniospinal irradiation. Forty months after diagnosis the patient is alive and well, but surveillance MRIs still show nodular enhancing lesions in the area of the primary tumor and intracranial meningeal enhancement. Primary CNS-PNETs of the spinal cord probably require multimodal treatment including radiotherapy to achieve sustained tumor control.     

Ependymal tumors

Opinion statement Ependymal tumors are rare malignancies that arise from the cells that line the ventricles and central canal of the spinal cord. Although they are more common in children, adults may also be effected by ependymal tumors. Prognosis is dependent on tumor location, histology, especially for myxopapillary tumors that tend to occur in the lumbar spine, extent of surgical resection, and stage of disease. Standard therapy consists of complete resection when feasible. The exact role of adjuvant radiotherapy in patients with radiographically confirmed complete resection is poorly defined. Patients with known residual disease may benefit from local radiation therapy, but the extent of radiation field and total dose are controversial. Even in patients treated with involved field radiotherapy, most relapses occur within the original tumor bed, thus local control remains the biggest obstacle to effective therapy. Chemotherapy has little impact against this tumor and has no role in the adjuvant setting, outside of a well designed clinical trial, with the possible exception of children younger than 5 years in an effort to delay radiation. A minority of patients may respond to one of several chemotherapy regimens at the time of recurrence, but the impact of this therapy is limited. Newer treatment strategies are needed.     

Clinical Course of Central Neurocytoma with Malignant Transformation—An Indication for Craniospinal Irradiation

Central neurocytoma is generally considered to be a benign tumor and the literature suggests that a cure may be attained by surgery ± adjuvant focal irradiation. However, there is a need for change in the therapeutic strategy for the subgroup of patients with aggressive central neurocytoma. An example case is presented and the literature on central neurocytoma cases with malignant features and dissemination via the cerebrospinal fluid is reviewed and the radiotherapeutic strategies available for central neurocytoma treatment is discussed. Nineteen cases including the present report with a malignant course and cerebrospinal fluid dissemination have been described to date, most of them involving an elevated MIB-1 labeling index. Our case exhibited atypical central neurocytoma with an initially elevated MIB-1 labeling index (25–30 %). The primary treatment included surgery and focal radiotherapy. Three years later the disease had disseminated throughout the craniospinal axis. A good tumor response and symptom relief were achieved with repeated radiation and temozolomide chemotherapy. Central neurocytoma with an initially high proliferation activity has a high tendency to spread via the cerebrospinal fluid. The chemo- and radiosensitivity of the tumor suggest a more aggressive adjuvant therapy approach. Cases with a potential for malignant transformation should be identified and treated appropriately, including irradiation of the entire neuroaxis and adjuvant chemotherapy may be considered.     

Primary cerebral neuroblastoma (neurocytoma) in adults

Summary We report a case of a third ventricular neuroblastoma (neurocytoma) in a 66 year old man. A stereotactic needly biopsy was performed to obtain a tissue diagnosis and was followed by total resection. We elected not to give radiation or chemotherapy and to follow the patient closely with serial CT scans. Presently, 48 months postoperatively, the patient is free of tumor by head CT scan and able to live independently. We reviewed the literature of primary cerebral neuroblastomas/neurocytomas occurring in adults (15 years of age) and found 32 cases. Our patient is the oldest of this group with a mean age of 32 ± 14 years (S.D.). The location of the 33 neoplasms was intraventricular in 17 cases (52%) and intraparenchymal in 16 cases. The male to female ratio was 2: 1. Of the 17 patients having a minimal follow-up period of 5 months (mean 51 months), five developed recurrences after 5 to 144 months (mean 50 months) compared to 12 patients without recurrence after a 6- to 72-month follow-up period (mean 52 months). Recurrences occurred statistically significantly more often in parenchymal neuroblastomas/neurocytomas than in intraventricular tumor locations.     

Adult intradural primary spinal cord tumors

Primary spinal cord tumors represent 4.5% of all central nervous system neoplasms. They are either intradural intramedullary or intradural extramedullary. Intramedullary tumors are predominantly intrinsic gliomas (astrocytomas and ependymomas). Spinal ependymomas can usually be completely removed by separating the tumor from the spinal cord and, when complete, no further therapy is required. Astrocytomas, by contrast, infiltrate the myelon, and therefore surgery is frequently incomplete. Intradural extramedullary tumors are mostly benign (WHO grade 1) and comprise either peripheral nerve sheath tumors (neurofibromas and schwannomas) or meningiomas. Complete resection can be performed on both lesions and is often curative. Radiotherapy is indicated for primary malignant tumors (WHO grade 3 and higher) and for patients in whom surgery is contraindicated. For grade 1 and 2 tumors, the role of radiotherapy is controversial. Chemotherapy is reserved for recurrent primary spinal cord tumors with no other options. However, the lack of clinical trials for these tumors is problematic. Consequently, treatment is similar to that for intracranial histologies. Early recognition of the signs and symptoms of primary spinal cord tumors facilitates early treatment, potentially minimizes neurologic morbidity, and improves outcome. Primary treatment for almost all spinal cord tumors is surgery, with predictors of outcome being preoperative functional status, grade of tumor, and extent of resection.     

Central neurocytomas with MIB-1 labeling index over 10% showing rapid tumor growth and dissemination

SummaryObjective and importance Central neurocytoma is recognized as a indolent intraventricular tumor arising from the ependyma around the foramen of Monro and anterior part of the lateral ventricles, and well demarcated from the brain parenchyma. Surgical removal can be curative without postoperative therapy. However, malignant central neurocytoma refractory to even aggressive treatment is known.Clinical presentation We report two cases of extraventricular central neurocytomas with significant vascular proliferation, mitoses, and MIB-1 labeling index of more than 10%.Intervention Subtotal removal for the one patient and open biopsy for other followed by radiotherapy with chemotherapy were performed. However, the disease progressed and dissemination occurred. Both patients subsequently died 23 and 18 month after the histological diagnosis was established.Conclusion Extraventricular central neurocytoma may present with frequent vascular proliferation and high MIB-1 labeling index. Even if they lack malignant histological findings like frequent mitosis and/or necrosis, the prognosis for such patients is very poor.     

Central neurocytoma: histologic atypia, proliferation potential, and clinical outcome

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."     

脊柱转移性肿瘤的评分和局部治疗

脊柱转移瘤的分类评分方法基于肿瘤的恶性程度、患者的神经系统功能、骨破坏情况及预后, 评价简单适用, 预测性较强。进行预计生存期评估和系统评价, 可以指导患者的个体化治疗, 明确具有手术适应证的患者可以通过姑息手术、瘤内切除或全脊椎切除术, 或选择合适的微创手术方式和入路, 结合采用立体定向放射治疗和调强放射治疗等措施, 达到肿瘤局部控制、维持神经功能, 改善生存质量的目的。经皮椎体成形术、射频消融、脊柱内窥镜等现代微创外科理念和技术将在脊柱转移性肿瘤治疗方面发挥更大的作用。      

Primary central nervous system germ cell tumors

Opinion statement The prognosis of primary germ cell tumors (germinal neoplasms) of the central nervous system varies, depending on the histology and size of tumor and the extent of disease at diagnosis. Although some patients receive therapy without a tissue diagnosis, it is strongly recommended that tumor tissue samples be obtained for accurate histologic diagnosis. Modern neurosurgical navigation techniques have made tissue sampling by stereotactic biopsy a safe and rapid method of determining tumor histology. Depending on tumor location, open surgical biopsy may be required in some patients. Typically, germinomas are exquisitely radiosensitive, although pre-irradiation chemotherapy reduces the total radiation exposure and may increase the cure rate. Induction cisplatin-based chemotherapy, followed by low-dose involved field radio-therapy, has excellent overall and relapse-free survival rates and is the optimal treatment for patients with germinomas. This combined chemoradiotherapy approach is associated with minimal endocrinopathy and minimal neurocognitive dysfunction. Patients with relapses after low-dose radiation therapy can respond well to salvage therapy (chemotherapy or chemoradiotherapy) without significant sequelae. Patients with nongerminomas respond best to chemotherapy combined with radiation, although the response and cure rates are lower compared to germinomas. Patients with residual masses and normal tumor markers after primary therapy should have a second-look resection because most patients have residual teratoma or necrotic tissue and can be spared additional chemotherapy or radiation. Pure mature teratomas are cured only by surgical extirpation. Immature central nervous system teratomas appear to benefit from radical surgical resection, but higher doses of locally directed radiotherapy are required with no benefit from the usual chemotherapy.     

Central Neurocytoma with Craniospinal Dissemination

Central neurocytoma was first described by Hassoun et al. in 1982. The tumor is a rare benign tumor of the central nervous system, usually located in the lateral ventricles. Most reported cases are histologically and clinically benign. Several cases with recurrence have been described. Including the case presented here, only seven cases with craniospinal dissemination have been reported. None of the previous cases with dissemination had histological atypia but most did have a high MIB-1 labeling index (MIB-1 LI). Our patient had a high MIB-1 LI (4.6%) and dissemination was found to have advanced through the anterior horns of the lateral ventricles and to the spinal cord at the T4 level. The patient underwent partial resection of the tumor with follow-up radiation treatments for the residual tumor and dissemination. After the radiation, the size of the tumor decreased. The report of this case will be helpful in the treatment of disseminated central neurocytoma.