The role of single fraction Gamma Knife radiosurgery for intraventricular central neurocytomas and the utility of F-18 fluroethyltyrosine: two case reports.

BACKGROUND: Primary treatment of central neurocytomas is surgical resection. Gamma Knife surgery is considered a valuable therapeutic option in case of residual (after subtotal resection) or recurrent central neurocytomas. Here, we focused on the role of F-18 fluroethyltyrosine as a marker to document tumor progression after initial resection, in the context of an atypical central neurocytoma. We also describe MIB-1's role in evaluating therapeutic decision-making. CASE PRESENTATION: Two patients with central neurocytomas were treated by Gamma Knife surgery in our center. The first case (31-year-old Caucasian male) had atypical central neurocytoma. Four and a half years after surgical resection, magnetic resonance imaging and F-18 fluroethyltyrosine documented clear progression of residual central neurocytoma, further treated by Gamma Knife surgery (18 Gy at 50%, target volume 1.4 cc, and prescription isodose volume 1.8 cc). The initial post-Gamma Knife surgery clinical course was uneventful, with progressive volumetric reduction of residual tumor up to 4.5 years, when out-of-field recurrence was suspected and confirmed by local F-18 fluroethyltyrosine hyperactivity. Second single-fraction Gamma Knife surgery was performed (18 Gy at 50%, target volume 0.49 cc, prescription isodose volume 0.72 cc). The second (32-year-old Caucasian female) had previous subtotal resection and typical central neurocytoma. Seven years later, she had residual tumor progression. Single-fraction Gamma Knife surgery was performed (16 Gy at 50% isodose line, target volume 1.7 cc, and prescription isodose volume 2.5 cc). Last follow-up showed tumor volume reduction. Follow-up magnetic resonance imaging showed important volumetric reduction of both treated lesions. CONCLUSIONS: In atypical central neurocytomas, F-18 fluroethyltyrosine could be used as postoperative examination to detect small tumor remnants, follow-up evaluation following the Gamma Knife surgery or, in select cases, following surgical resection. The role of MIB-1 is important in therapeutic decision-making, as tumors with MIB-1 exceeding 2% are characterized by more aggressive clinical course. Single-fraction Gamma Knife surgery remains a valuable therapeutic option for postoperative residual atypical central neurocytomas and central neurocytoma recurrences.

Comparison of surgery with or without adjuvant radiotherapy in treating central neurocytoma: a single-center retrospective real-world study.

PURPOSE: To investigate the efficacy and safety of adjuvant radiotherapy (RT) in patients with central neurocytoma (CN). METHODS: The study included 68 patients with CN retrospectively, was further divided into surgery + RT group (31 patients) and surgery alone group (37 patients). Progression-free survival (PFS), overall survival (OS), and adverse reactions (AEs) were compared between the two groups. RESULTS: The median follow-up duration was 82.2 (interquartile range, 64.7-104.5) months. Patients in the surgery + RT group tended to have longer PFS than those in the surgery alone group (5-year PFS rate: 92.7% vs. 86.3%; P = 0.074). There was no significant difference in OS between the two groups (5-year OS rate: 96.8% vs. 94.3%; P = 0.639). Subgroup analysis revealed a significant improvement in PFS in patients receiving RT after surgery in patients who underwent subtotal resection (STR) (P = 0.045). In the overall population, univariate multivariate analysis revealed that gross total resection (GTR) (P = 0.002), tumor location in the unilateral ventricle (P = 0.008), and MIB-1 (Ki-67) labeling index (LI) < 5% (P = 0.009) were favorable independent prognostic factors for PFS. Whereas tumor location in the unilateral ventricle (P = 0.043) was a favorable independent prognostic factor for OS. Moreover, RT patients experienced AEs (Grade 1-2, well-tolerated). CONCLUSION: Adjuvant RT in the treatment of CNs showed satisfactory safety, and postoperative RT could improve PFS in STR patients. Furthermore, GTR, tumor development in the unilateral ventricle, and MIB-1 LI < 5% were found to be favorable factors affecting the prognosis of CNs.

MRI features of an atypical case of extraventricular neurocytoma: A case report.

RATIONALE: Central neurocytoma occurring outside the ventricles is known as extraventricular neurocytoma (EVN). EVN is rare and its magnetic resonance imaging (MRI) findings vary greatly and overlap with the imaging features of other intracerebral primary tumors. PATIENT CONCERNS: A 21-year-old woman with an intrauterine pregnancy of 18+2 weeks complained of dizziness and headache for 3 months. DIAGNOSIS: A 8.6 cm × 5.8 cm × 3.7 cm space-occupying lesion was seen in the right frontal lobe on MRI, with mixed long signals on T1-weighted imaging and mixed slightly long signals on T2-weighted imaging, slightly hyperintense on T2-weighted imaging fluid attenuated inversion recovery images, and a large-scope long T1-weighted imaging and long T2-weighted imaging cystic component at the center of the lesion. A thick fence-like enhancement of the solid component at the periphery of the lesion was observed after injecting a contrast medium, while the internal cystic component was not enhanced. The MRI diagnosis was of glioma. The lesion was pathologically confirmed as an atypical central neurocytoma of the right frontal lobe. INTERVENTIONS: Resection of the lesion and postoperative radiotherapy. OUTCOMES: The patient was lost to follow-up. LESSONS: EVN can be considered as a differential diagnosis for lesions occurring in the cerebral hemispheres of young patients with cystic degeneration, thick fence-like enhancement, and peritumoral edema on MRI.

Gamma Knife radiosurgery for the treatment of central neurocytoma: a single-institution experience of 25 patients.

Central neurocytomas (CNs) are extremely rare tumors that account for 0.1-0.5% of all intracranial neoplasms. Recently, Gamma Knife radiosurgery (GKRS) has become a treatment option in patients with CN. We aimed to evaluate the efficacy and safety of GKRS in 25 CN patients and review the results along with relevant literature. GKRS patient database was searched, and 25 patients who underwent GKRS for CN between 2009 and 2018, were evaluated retrospectively. The study cohort included 15 female and ten male patients with a median age of 32 years (range, 5-60). The most common presenting symptom was headache (88%). The neurological examination was unremarkable in all patients, except for one patient with decreased vision. Twenty patients (80%) had a history of surgical resection. Most of the tumors (92%) were located in the ventricles, and the median tumor volume was 4.8 cm3 (range, 0.8-28.1). The median marginal dose was 14 Gy (range, 12-15) to a median isodose of 50% (range, 40-50). Following a median follow-up of 80 months (range, 36-138), local tumor control was achieved in 100% of patients. Distant recurrence was observed in one patient (4%). No adverse radiation effect was observed. Regarding non-specific post-GKRS symptoms, one patient experienced a prolonged headache, and one epileptic patient experienced a brief partial seizure. In our patient cohort, GKRS yielded favorable local tumor control (100%) during a median follow-up of 6.6 years. Our series demonstrates that GKRS is an effective and safe treatment option for patients with primary or residual CNs.

[Choice optimisation of radiation therapy technique for central neurocytomas from literature data]. / Optimisation du choix de la technique d'irradiation des neurocytomes centraux à partir des données de la littérature.

Neurocytomas represent 0,25 to 0,5 of brain tumours. These tumours have neuronal differentiation. It's a young adult disease. The main treatment is neurosurgery. The place of other therapies is still unclear, noticeably with regards to radiotherapy. This review aim is to determine the place and the modalities of radiotherapy in the management of neurocytomas. A literature search using PubMed allowed to select the most relevant studies. Finally, 22 studies were selected according to pre-established criteria to answer the problem. All studies were retrospective studies except one. The analysis conclusion defined radiotherapy as a treatment of choice in selected patients, when surgical resection was incomplete or when tumour was atypical.

Central neurocytoma originating in third ventricle with expansion into the cerebral aqueduct and fourth ventricle: Case report and review of literature.

BACKGROUND: Central Neurocytomas (CNs) are rare brain tumors, making up less than 1% of all primary tumors within the CNS. They are commonly located in the lateral ventricles, and often present with visual changes and symptoms of obstructive hydrocephalus. Histopathology shows characteristics similar to ependymomas and oligodendrogliomas, however tumor cells display neuronal differentiation, and immunohistochemical stains typically for synaptophysin. Gross total resection is the most important prognostic indicator of survival. CASE DESCRIPTION: We describe the case of a 48-year-old male with a CN originating in the third ventricle with expansion through the cerebral aqueduct into the fourth ventricle. He presented with bi-frontal headaches, imaging revealed an avidly enhancing tumor occupying the inferior third ventricle, cerebral aqueduct, with expansion into the fourth ventricle. An interhemispheric craniotomy with a transcallosal transchoroidal approach to the third ventricle was performed, this provided a trajectory that paralleled the long axis of the tumor. Postoperative imaging confirmed a near total resection with linear residual enhancement on the anterior wall of the fourth ventricle. Intensity modulated radiotherapy was performed, 7-month follow-up imaging was clean. CONCLUSION: CNs are rare brain tumors, most commonly located within the lateral ventricles. We describe a rare case of a CN spanning from the third ventricle into the cerebral aqueduct and fourth ventricle. To our knowledge, this is only the fourth reported case of such a tumor. Surgical approach must be carefully selected, as gross total resection is the most important prognostic indicator.

Cerebellar Neurocytoma with Excellent Response to Radiotherapy.

BACKGROUND: Extraventricular neurocytoma (EVN) is a rare neurocytoma occurring in the brain parenchyma outside the ventricular system that shares similar biological behaviors and histopathologic characteristics with central neurocytoma. Reports of EVN localized in the brainstem and cerebellum are relatively uncommon. In addition, few cases with radiotherapy as the only treatment have been reported and their outcomes were unclear. CASE DESCRIPTION: We report a case of pathologically confirmed EVN of the brainstem and cerebellum in a 43-year-old male who presented with unprovoked nausea and dizziness. The patient received radiotherapy only and showed a favorable outcome during the 2-year follow-up period. CONCLUSIONS: These results suggest that patients with EVN who are treated with radiotherapy without surgery may have a favorable prognosis.

Atypical extraventricular neurocytoma: A case report.

Atypical extraventricular neurocytoma (EVN) is a rare condition characterized by diffuse tumor cell hyperplasia, increased neovascularization, increased necrosis, and aggressive characteristics. A case of a 25-year old man who presented with atypical EVN in his left parietal - occipital flaps is reported. Magnetic resonance imaging (MRI) revealed a well-defined globular mass with heterogeneous signals in the left parietal lobe, and mild perilesional edema. After left parietal craniotomy and tumor excision, pathologic examination of the resected tissue revealed that the lesion was localized mainly in the white matter and imbued with tumor cells possessing round hyperchromatic nuclei with perinuclear halos and increased microvascular proliferation. The patient underwent radiotherapy at 21st postoperative day. Over the past 26 months, the patient has been regularly followed up, and so far no neurologic deficits have been observed. The latest MRI showed that the tumor bed was stable with slight peritumoral edema. The results of clinical, histopathological and immunohistochemical examinations indicate that atypical EVN is a rare neoplasm with unique radiographic and pathologic characteristics. It possesses more aggressive properties than typical EVN.

Radiosurgery for Central Neurocytoma.

The classification of central neurocytoma (CN) by the WHO was upgraded to grade 2 in 1993 as it was recognized that at least some of these tumors can exhibit more aggressive behavior. Currently, as of 2016, CN is classified as WHO grade 2. Indeed, some atypical variants have been reported and residual postsurgical tumor is believed to have the potential for malignant transformation. Although gross total resection is usually curative for CN (5-year survival rate 99%), it is achieved in nearly 30-50% of cases due to its central location. Adjuvant treatments should be deliberately considered for the optimal management of CN. Recently, stereotactic radiosurgery is increasingly proposed as an adjuvant treatment for CN.

Surgical Management of Primary Cerebellopontine Angle Melanocytoma: Outcome, Recurrence and Additional Therapeutic Options.

OBJECTIVE: Meningeal melanocytomas of the central nervous system are extremely rare, with an incidence of 1 per 10 million individuals. Cases of primary cerebellopontine angle melanocytoma (PCPAM) have only been described in single case reports. The goal of the present study was to analyze the surgical management of PCPAM, with a particular focus on early and late treatment outcomes and recurrence rates. METHODS: The patients who had undergone surgery for PCPAM from January 2004 to May 2018 were identified by a local database query. The patients were evaluated for initial symptoms, pre- and postoperative facial and cochlear nerve function, complications, and recurrence rate by reviewing the patients' medical records. RESULTS: We identified 4 patients with PCPAM of >1500 cerebellopontine angle lesions (∼0.2%) that had been surgically treated at our department in the past 14 years. Of the 4 patients, 2 were men and 2 were women, with a mean age of 47 years. Anatomical facial and cochlear nerve preservation was achieved in all 4 patients. One patient experienced a new moderate facial palsy immediately after surgery (House-Brackmann grade III). Of the 4 patients, 3 had undergone radiotherapy and 1 had undergone ion beam therapy for tumor recurrence (6 years after surgery). Of the 4 patients, 3 had presented with tumor recurrence at 2, 3, and 6 years of follow-up respectively. The long-term follow-up examination had not yet been conducted for 1 patient. CONCLUSIONS: At long-term follow-up, 3 patients had developed recurrence. Because of the high recurrence rate of PCPAM, we believe that radiotherapy in addition to surgery should be considered in the future to avoid early recurrence.

Atypical central neurocytoma with novel EWSR1-ATF1 fusion and MUTYH mutation detected by next-generation sequencing.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

Tumor control of third ventricular central neurocytoma after gamma knife radiosurgery in an elderly patient: A case report and literature review.

RATIONALE: Central neurocytoma is rare benign tumor that occurs in high probability in young adults in the lateral ventricle. Herein, we report an unusual case of an elderly woman who was diagnosed with central neurocytoma isolated to the third ventricle. This deeply located tumor was effectively treated using gamma knife radiosurgery (GKR). PATIENT CONCERNS: A 79-year-old woman was admitted to hospital with gait disturbance and cognitive dysfunction. DIAGNOSIS: Brain magnetic resonance imaging (MRI) revealed a homogenously enhancing multilobulated mass in the posterior third ventricle measuring 1.8 cm in size. The tumor was diagnosed as a central neurocytoma isolated to the third ventricle. INTERVENTIONS: Neuronavigation-guided endoscopic third ventriculostomy and biopsy were performed. One week following surgery, GKR was performed using a prescribed dose of 14 Gy with 50% isodose lines, and a target volume of 1.62 cc. OUTCOMES: Three months after GKR, brain MRI revealed a decrease in the size (to 1.4 cm) of the multilobulated strong enhancing mass in the posterior third ventricle, and the patient's symptom of confusion was improved. LESSONS: Previous studies have reported that tumors in unusual locations, such as those isolated to the third ventricle, are different according to age, either in young children or elderly individuals. Although complete surgical resection is an effective treatment for central neurocytoma, it is often difficult to approach these tumors through surgery. GKR could, therefore, be an alternative primary treatment option for deeply located central neurocytomas in elderly patients.

Stereotactic radiosurgery for hypervascular intracranial tumors.

OBJECTIVE: To evaluate the safety and efficacy of SRS treatment of central neurocytomas (CNCs), cavernous sinus hemangiomas (CSHs), and glomus tumors (GTs); and to compare upfront stereotactic radiosurgery (SRS) and adjuvant SRS in the treatment of these hypervascular tumors. METHODS: This was a retrospective review of consecutive CNCs, CSHs, and GTs treated with SRS between 1993 and 2017. Tumor response was categorized based on volumetric analysis on magnetic resonance imaging: (1) tumor regression [> 10% decrease in tumor volume (TV)]; (2) stable tumor (≤ 10% change in TV); or (3) tumor progression (> 10% increase in TV). RESULTS: Sixty hypervascular tumors (CNC: 28; CSH: 16; GT: 16) underwent SRS between 1993 and 2017. Margin doses were 13 Gy, 12 Gy, and 14 Gy for CNCs, CSHs, and GTs, respectively. Tumor regression was observed in 54 tumors (90%) with initial SRS after a median follow-up of 82 months. Relative reductions in TVs for CNCs were 38%, 52%, and 73% at 12, 24, and 48 months, respectively. Relative reductions in TVs for CSHs were 51%, 68%, and 88% at 12, 24, and 48 months, respectively. Relative reductions in TVs for GTs were 22%, 31%, and 47% at 12, 24, and 48 months, respectively. Upfront SRS was performed in 26 patients (43%). No difference in relative TV reductions were found between upfront and adjuvant SRS. Adverse radiation effects were observed in five patients. No mortality was encountered. CONCLUSION: SRS for hypervascular tumors is associated with high rates of tumor regression with low risk of complications. No significant difference in rates of relative TV reduction were found between upfront and adjuvant SRS. Hence, upfront SRS may be considered in select patients.

Rapid tumor growth with glial differentiation of central neurocytoma after stereotactic radiosurgery.

Although stereotactic radiosurgery (SRS) is effective for central neurocytoma (CN), the long-term outcome of SRS remains unclear. We present a case of recurrent CN that was diagnosed 10years after surgical resection and consecutive stereotactic radiotherapy. The patient was treated with SRS for the recurrent tumor, but underwent two-staged surgery once again due to rapid tumor growth. Histological features of the recurrent tumor were consistent with the diagnosis of CN. However, an increased Ki-67 proliferation index (3.4%), aberrant angiogenesis and glial differentiation of the tumor cells were observed, which were not identified in the initial CN. In addition, vascular endothelial growth factor (VEGF) and VEGF receptor were highly expressed in the recurrent tumor cells, as well as in the vascular endothelial cells. Our case suggests that malignant transition with aberrant angiogenesis and glial differentiation may be attributable to SRS.

Treatment Results of Gamma Knife Radiosurgery for Central Neurocytoma: Report of a Japanese Multi-Institutional Cooperative Study.

OBJECTIVE: Central neurocytoma (CN) is a rare benign neuronal tumor, and a limited number of reports have described the usefulness of radiosurgery for a relatively large group of patients. We evaluated the effectiveness and outcomes of Gamma Knife radiosurgery (GKS) for CN in a Japanese multi-institutional study. METHODS: We performed retrospective analysis of 36 patients with CN who were treated with GKS in 12 institutes in Japan. All patients underwent surgery before GKS. The median tumor volume at GKS was 4.9 mL (range, 0.07-23.4 mL), and the median radiation dose prescribed to the tumor margin was 15 Gy (range, 10-20 Gy). The median follow-up period was 54.5 months (range, 3-180 months). RESULTS: The local tumor progression-free survival rates at 5 and 10 years were 94% and 86%, respectively. Three patients developed distant dissemination 16-90 months later. Overall progression-free survival was unrelated to the prescribed dose (<15 Gy vs. ≥15 Gy, P = 0.62), tumor size (<6 mL vs. ≥6 mL, P = 0.46), gender (P = 0.36), age (<30 vs. ≥30 years, P = 0.37), target of GKS (residual vs. recurrence, P = 0.90), and type of enhancement (homogeneous vs. inhomogeneous, P = 0.19). Two permanent complications occurred with 1 intratumoral hemorrhage and 1 radiation injury. CONCLUSIONS: GKS is effective for CN because of its high rate of long-term local tumor control. GKS may have a potential role as a primary treatment for asymptomatic, relatively small tumors in the absence of hydrocephalus without surgical resection.

[Multiple primary liponeurocytoma of the central nervous system].

We report a unique case of primary multiple liponeurocytoma. Liponeurocytoma is a rare benign tumor (Grade II) of the posterior cranial fossa with neural- or probably astrocytic-lineage cells; the tumor stroma contains mature adipocytes. This case is the thirty-eighth case of this pathology reported in the world literature and the first case of multiple form of this disease. We have provided a sufficiently thorough neuroradiological and histological picture that allows one to differentiate between a liponeurocytoma and other histological variants. Recommendations for the tactics for managing patients with this rare disease are proposed based on the analysis of treatment of this pathology reported in the world literature.

Extraventricular neurocytoma treated with 177Lu DOTATATE PRRT induction and maintenance therapies.

A 64-year-old woman with a 30-year history of recurrent sellar masses presented with severe headache and rapidly progressive visual field loss in the left eye. She was diagnosed with an extraventricular neurocytoma, which was octreotide positive, and was referred for PRRT (peptide receptor radionuclide therapy) with 177Lu [DOTA0,Tyr3]octreotate (DOTATATE). After 4 induction and 4 maintenance treatment cycles, her headaches resolved, her vision improved, and her sellar mass stabilized. The use of 177Lu DOTATATE PRRT in the management of extraventricular neurocytoma warrants further research.

The management of central neurocytoma: radiotherapy.

Intraventricular neurocytomas (IVNs) are rare tumors of neuronal differentiation, accounting for 0.1% to 0.5% of all primary brain tumors. Complete surgical resection is highly recommended, but at least one-third to one-half are subtotally resected. Stereotactic radiosurgery (SRS) and conventional radiotherapy have been used for management of residual and recurrent tumors, but the optimal treatment following subtotal surgical resection is less clear. Although there are trends toward higher local tumor control and survival rates with lower complications among IVNs treated with SRS, higher quality data are required to confirm these findings.

The management of residual or recurrent central neurocytoma.

Treatment following neurosurgical resection or biopsy of a central neurocytoma depends on the pathologic analysis and proliferative activity demonstrated, the extent of surgical resection, the neuroanatomic location and accessibility of residual tumor, and the patient's postoperative condition. The risks and benefits of additional surgery, radiation therapy, and/or chemotherapy should be weighed and individualized based on these factors and guided by the existing literature.

Clinical outcome and quality of life after treatment of patients with central neurocytoma.

Central neurocytoma (CN) is an uncommon, deep-seated tumor of the central nervous system. Optimal treatment strategies and long-term outcomes are not well established. The mainstay of initial treatment CN is total surgical resection whenever possible; however, CNs cannot be resected completely in more than half of patients. Advances in alternative and adjuvant treatments and their role in the treatment of CN is becoming significant. This article provides an overview of the clinical outcomes of various treatment modalities, recent advances, and recommendations for the treatment of CN, emphasizing functional outcomes and the quality of life.