Two novel tumours with NTRK2 fusion in the methylation class of extraventricular neurocytomas, including one intraventricular.

We report here about two novel tumours classified as extraventricular neurocytomas (EVN) using DNA-methylation profiling, associated with NTRK2 fusions instead of the usual FGFR1 alterations so far attributed to this tumoural entity. We present the second detailed case of an intraventricular presentation in the MC EVN. Our findings broaden the spectrum of MC EVN and have implications in terms of diagnosis, therapy and terminology.

Central Neurocytoma with Extensive Intratumoral Hemorrhage: A Case Report.

BACKGROUND Central neurocytoma (CN) is a rare neuronal tumor of neuroepithelial origin. It has been assigned to World Health Organization classification grade 2. These tumors are usually benign and located in the anterior half of the lateral ventricle, though they can also be found in the third and fourth ventricles. Left untreated, a CN can cause blockage of cerebrospinal fluid, thus leading to hydrocephalus. CNs are exceedingly uncommon, making up just 0.1-0.5% of primary intracranial tumors. The tumors typically develop in people aged 20 to 40. There are no official guidelines on how to treat CN, so treatment options are often individualized on the basis of specific case findings. CASE REPORT A 39-year-old man with an uncomplicated medical history presented with dizziness, increasingly worse headaches, presyncope, and a loss of appetite. Radiological data and postoperative histopathological and histochemical analysis led to the diagnosis of CN with extensive intratumoral hemorrhage. Surgical resection of the tumor was proposed to the patient, to which he agreed. CONCLUSIONS CN is a benign tumor, but it can cause serious or life-threatening complications. Gross total resection of the tumor is recommended if possible, and if deemed beneficial to the patient's clinical condition. This case reports the symptoms of a patient with CN, who underwent gross total resection and showed no sign of any residual tumor tissue on postoperative MRI. By reporting these types of cases, we can take necessary steps ahead of widespread agreement on optimal treatment of patients with neurocytomas.

Central neurocytomas in children: Clinicopathologic features and long-term surgical outcomes.

PURPOSE: Pediatric central neurocytomas (PCNs) is an extremely rare entity, and very few reports have exclusively focused on the clinicopathologic features and surgical outcomes of PCNs. METHODS: This study was undertaken to elucidate the clinical and pathological characteristics and long-term surgical outcomes of PCNs. RESULTS: Fourteen consecutive patients with pathologically verified PCNs were identified, including 9 girls and 5 boys, with a mean age of 15.2 ± 3.9 years (range 3-18 years). Children tended to present with symptoms of increased intracranial pressure (ICP) (p = 0.003), an acute clinical course (p = 0.044), and a shorter duration of symptoms (p = 0.019) than their adult counterparts. Surgery was performed under the guidance of a neuronavigation system and intraoperative ultrasound; gross total resection (GTR) was achieved in 12 patients (85.7%), and subtotal resection (STR) was achieved in two patients (14.3%). One child received adjuvant radiotherapy (RT) owing to the atypical features of the lesion. During a mean follow-up of 90.2 ± 37.0 months (range 42-156 months), one patient (7.1%) with atypical features experienced lesion relapse 2 years after surgery and received RT, and the symptoms of all children were relieved. CONCLUSION: Surgery can benefit children with CNs and ensure relatively long-term progression-free survival. RT can be administered to patients with residual or relapsed lesions.

A Clinicopathological and Molecular Analysis of Sellar/Suprasellar Neurocytoma Mimicking Pituitary Adenoma.

Objective: To investigate the clinicopathological characteristics, molecular genetic characteristics and prognosis of extraventricular neurocytoma located in the sellar/suprasellar region. Methods: Seven archived tumor samples derived from 4 patients with neurocytoma in the sellar/suprasellar region were collected from the First Affiliated Hospital of Fujian Medical University and the Affiliated Hospital of Qingdao University and retrospectively analyzed for clinical manifestations, imaging features, and histopathological features. Neuronal and pituitary biomarkers and molecular features were detected in these tumor tissues by immunohistochemistry and FISH or Sanger sequencing. The related literature was reviewed. Results: Three patients were female, while 1 was male, with an average age of 35.5 years (range: 27 to 45 years). The initial manifestations were mainly headache and blurred vision in both eyes. The first MRI examination showed marginally enhancing masses in the intrasellar or intra- to suprasellar region. The diagnosis of pituitary adenomas was based on imaging features. The levels of pituitary hormones were normal. Histologically, the tumor cells were arranged in a sheet-like, monotonous architecture and were uniform in size and shape with round to oval, exquisite and hyperchromatic nuclei, which densely packed close to one another and were separated only by a delicate neuropil background. There was no evident mitosis, necrosis or microvascular proliferation. The three cases of recurrent tumors were highly cellular and showed increased mitotic activity. Immunohistochemically, the tumor cells were positive for syn, CR, CgA, and vasopressin and were focally positive for NeuN, TTF-1, NF, CK8, vimentin, and S100 proteins. Other markers, including IDH1, BRAF VE1, Olig-2, and EMA, were negative. Pituitary transcription factors and anterior pituitary hormones were negative. Molecular genetic testing showed that the tumor cells lacked IDH gene mutations, LOH of 1p/19q, MYCN amplification, and EGFR alteration. With a median follow-up of 74.5 months (range 23 to 137 months), 3 patients relapsed at 11, 50, and 118 months after the initial surgery. Conclusion: The morphological features and immunophenotypes of neurocytoma in the sellar/suprasellar region are similar to those of classic central neurocytoma. The prognosis is relatively good. Gross-subtotal resection and atypical subtype may be related to tumor recurrence.

Recurrent cerebellar liponeurocytoma with anaplastic features at initial presentation: A case report.

BACKGROUND: Cerebellar liponeurocytoma is a rare entity with fewer than 100 reported cases and series in the available literature to date. Although the cerebellum remains the typical primary site, the entity has been shown to demonstrate increased aggressiveness and malignant progression with multiple recurrences. CASE DESCRIPTION: We present a unique case in a 64-year-old gentleman of a cerebellar liponeurocytoma with multiple recurrences and progressive anaplasia. The tumor showed anaplastic features at first presentation and recurred in a more aggressive fashion in a short 2-year period despite surgical debulking and post-operative radiotherapy. It re-recurred within 6 months with subsequent re-debulking without further radiotherapy. At latest follow-up almost 3 years since surgical management of the patient's second recurrence, the patient remains well with minimal neurological impairment and no radiological signs of recurrence. CONCLUSION: Cerebellar liponeurocytoma may present with increasingly atypical histological features that may warrant more aggressive post-operative treatment to prevent disease recurrence and clinical deterioration. This may include a more aggressive surgical resection margin and consideration of adjuvant radiotherapy in all cases.

Cerebellar liponeurocytoma in an elderly patient: DNA methylation profiling as a helpful diagnostic tool.

AIM: Cerebellar liponeurocytoma is a rare primary cerebellar neoplasm that mostly occurs in adults, however, it is rare in the elderly. MATERIALS AND METHODS: We report, in a 79-year-old female, a recurrent vermian cerebellar mass that was previously diagnosed as primary cerebellar tumor with neuroendocrine differentiation. The recurrent lesion showed anaplastic features and lipidization. RESULTS: DNA methylation profiling was performed for the recurrent tumor, which showed a high score match for cerebellar liponeurocytoma. CONCLUSION: This report confirms the usefulness of DNA methylation profiling for the diagnosis of challenging CNS tumors.

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.

Olfactory neurocytoma as a unique cause of chronic SIADH.

A 32-year-old man was found to have a nasal mass on DOTATATE positron emission tomography (PET) scan to investigate the cause of his syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient presented 6 years earlier with malignant hypertension followed by a second emergency admission for hyponatraemia. Multiple scans and blood tests over 6 years yielded no cause for his SIADH. Nasendoscopy was unremarkable. A PET scan prompted endoscopic sinus surgery which resulted in the resection of a mass in the anterior hiatus semilunaris. The histological findings were fitting with a diagnosis of a neurocytic-type tumour favouring an olfactory neurocytoma. Following resection, the patient remains well and is cured of his SIADH. An olfactory neurocytoma although rare should be considered as a benign differential for a mass in the nasal space. This case demonstrates how an olfactory neurocytoma can present as a cause of SIADH.

Atypical Central Neurocytoma: An Investigation of Prognostic Factors.

OBJECTIVE: Central neurocytoma is a rare nervous tissue benign neoplasm. A subset of central neurocytoma has unfamiliar aggressive tendency: so-called atypical central neurocytoma (ACN). This retrospective study aims to analyze the prognostic factors and the impact of various therapy tools on atypical central neurocytoma. METHODS: Twenty-two patients diagnosed with ACN between January 2009 and March 2018 were included. Data collected included the patient's age, gender, tumor location, presenting symptoms, and treatment received. Patients were followed up to detect recurrence and to assess survival. RESULTS: Median overall survival was 57 months, with a 5-year survival of 35%. Better survival was observed for patients <35 years old (66 vs. 47 months; P = 0.061) and patients with gross total resection over subtotal resection or biopsy (76, 45, and 22 months, respectively; P < 0.0001). Patients with a tumor located in the posterior half of the lateral ventricle had better survival, with no statistical significance (P = 0.053). Multivariate analysis showed prognostic significance with the extent of resection (P = 0.000). Progression-free survival ranged from 6 to 82 months, with a median value of 38 months and showed a significant relation with subtotal resection compared with biopsy (P = 0.006). Recurrence was less in patients who received radiotherapy and was statistically significant (P = 0.007). CONCLUSIONS: Long-term survival is possible for patients with atypical central neurocytomas treated with surgery and postoperative radiation. Multivariate analysis confirmed that gross total resection was an independent prognostic factor for survival. Adjuvant radiotherapy reduces tumor recurrence, especially after incomplete surgery.

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.

Progeny in an Inhospitable Milieu-Solitary Intraventricular Metastasis From a Triple-Negative Breast Cancer Mimicking Central Neurocytoma: Case Report and Review of Diagnostic Pitfalls and Management Strategies.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the most invasive subtypes of breast cancer, with high rates of visceral metastases and recurrence. Choroid plexus metastasis from breast cancer is infrequent despite a high incidence of brain parenchymal metastasis. METHODS: We report a case of solitary metastasis to the choroid plexus from a TNBC that masqueraded as central neurocytoma, and we review the PubMed database for similar cases focusing on their diagnostic challenges and management strategies. RESULTS: A 28-year-old woman with a history of TNBC presented with recurrent seizures, headache, and vomiting. Imaging studies depicted a well-defined lesion in the right anterior lateral ventricle that was attached to the septum pellucidum. After an initial radiological diagnosis of central neurocytoma, she deteriorated rapidly with intraventricular hemorrhage requiring emergency transcallosal microsurgical tumor decompression. Histopathological examination and immunohistochemistry confirmed breast carcinoma as the origin of the intraventricular mass. A review of the PubMed database identified only 2 case reports of choroid plexus metastases from breast cancer reported thus far. CONCLUSIONS: Choroid plexus metastases are exceedingly infrequent and can be mistaken for the more common central neurocytoma. The intraventricular milieu is inhospitable suggesting some extracranial carcinomas develop traits that help them to thrive in the acellular cerebrospinal fluid. Intraventricular mass lesions with a history of primary neoplasm should raise suspicion for choroid plexus metastases. A high index of suspicion despite excellent control of the primary tumor and the absence of systemic metastases is indispensable.

Histogram Analysis Parameters ADC for Distinguishing Ventricular Neoplasms of Ependymoma, Choroid Plexus Papilloma, and Central Neurocytoma.

BACKGROUND To determine if histograms of ADC can be used to differentiate ventricular ependymomas, choroid plexus papillomas (CPPs), and central neurocytomas (CNCs). MATERIAL AND METHODS We retrospectively reviewed records from 185 patients from 1 January 2014 to 1 November 2018. We finally included a total of 60 patients: 36 (60.00%) had histologically confirmed ependymomas, 10 (16.67%) had CPPs, and 14 (23.33%) had CNCs, as determined by routine MRI scanning at 3.0T. The ADC histogram features were derived and then compared by Kruskal-Wallis test (they were not normally distributed). Bonferroni test was used to compare the 2 groups and then we determined the ROC. RESULTS Ependymomas had significantly higher mean, perc.01%, perc.10%, perc.50%, perc.90%, and perc.99% than CNCs. Ependymomas had significantly lower skewness than CNCs. Histogram metrics derived from mean, perc.01%, perc.10%, perc.50%, and perc.90% were significantly lower in the CNCs group than in the CPPs group. CPPs showed significantly lower skewness than CNCs. A threshold value of 86.50 for perc.50% to predict ependymomas from CNCs was estimated (AUC=0.97, sensitivity=97.20%, specificity=85.70%). Optimal diagnostic performance to predict CPPs from CNCs (AUC=0.96, sensitivity=100.00%, specificity=85.70%) was obtained when setting Perc.50%=84.00 as the threshold value. CONCLUSIONS The ADC histogram analysis may help to discriminate ependymomas, CPPs, and CNCs.

Tetraventricular Atypical Central Neurocytoma.

BACKGROUND: Central neurocytomas are benign tumors accounting for <0.5% of all intracranial tumors. They are usually intraventricular, the most common site being the lateral ventricles, and are associated with good prognosis if they are completely resected surgically. CASE REPORT: We report the case of a middle-aged woman who was evaluated for recent-onset headache and for whom magnetic resonance imaging of the brain was suggestive of a solid cystic intraventricular mass spanning all the ventricles. The patient underwent subtotal excision of the mass, with intraoperative neuromonitoring. The result of Histopathologic examination was suggestive of atypical neurocytoma. The patient had complete neurologic recovery in spite of immediate postoperative deficits. CONCLUSIONS: Gross total resection should be the goal in all patients with central neurocytoma, but it may be limited because of proximity of the tumor to eloquent areas, especially in large tumors. Intraoperative neuromonitoring plays a pivotal role in maximal safe resection of such large tumors. Tetraventricular atypical central neurocytoma is a very rare entity; and this case could be, to the best of our knowledge, only the second reported case.

Central Neurocytoma - A Rare Brain Tumor.

Central neurocytoma are rare, slow growing, intraventricular tumors of neuronal origin, typically located in the lateral ventricles, near the Foramen of Monroe with characteristic imaging features. They generally occur in young age with favorable prognosis. With clinical, histological and immunohistochemical background, we report a case of central neurocytoma.

Prognosis and treatment outcomes of central neurocytomas: clinical interrogation based on a single center experience.

INTRODUCTION: Central neurocytoma (CN) is a very rare neuronal neoplasm. The clinical implications of the potential prognostic factors for these lesions, including tumor atypia, have therefore not been clarified. METHODS: Forty CN patients were enrolled and reclassified as typical or atypical in accordance with an MIB-1 labeling index (LI) of above and below 2%. RESULTS: We classified our retrospective study cohort as 21 (52.5%) typical and 19 (47.5%) atypical CN cases. No significant differences were found in terms of sex, mean age, mean tumor size or tumor location between these groups. Recurrences occurred in 2 (9.5%) typical and 6 (33.3%) atypical cases. The typical CN 2-,3- and 5-year PFS rates were 100%, 100%, 92.3%, and those for the atypical group were 93.8%, 78.1%, 65.1%, respectively (p = 0.02). The PFS rates did not statistically differ by treatment modality (gross total resection alone, subtotal resection (STR) alone and STR plus radiation therapy (RT) or radiosurgery (RS)) either in the whole cohort (p = 0.75) or in the typical CN and atypical CN subgroups (p = 0.45 and 0.98, respectively). An atypical histology was the only prognostic indicator of recurrence by univariate analysis (hazard ratio: 5.40, p = 0.04). CONCLUSIONS: An atypical lesion (MIB-LI > 2%) is an important prognostic indicator in CN. The clinical implications of the extent of resection for CN patients are still debatable. The use of STR plus RT or RS may be a viable treatment strategy for CN but different therapeutic and follow-up approaches for atypical CN will be needed.

Liponeurocytoma: Systematic Review of a Rare Entity.

OBJECTIVE: Liponeurocytoma is a rare benign tumor of the central nervous system, which develops mainly in adult patients within the posterior fossa. The World Health Organization has categorized this entity in its last classification of 2016 as a benign grade II tumor. Histopathologic characteristics contain neuronal and variable astrocytic differentiation with foci of lipomatous distinction. Only a few case reports and case series have been reported and the knowledge of this tumor is limited. General treatment guidelines do not exist. The aim of this study was to analyze the literature to create treatment guidelines. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to search existing online databases between January 1, 1978 and May 15, 2018. RESULTS: A systematic review of the literature found 73 patients (40 female, 33 male) with liponeurocytoma, in 59 of whom (80.8%) the disease occurred in the posterior fossa. The Ki-67/MIB-1 proliferation index was described in 58 patients, showing a mean value of 3.73% ± 4.01%. Follow-up was performed in 49 patients, with a median length of 52.02 ± 50.52 months, showing tumor recurrence in 14 patients (28.57%). Tumor recurrence was observed in only 1 patient (1/12, 8.33%) after adjuvant radiotherapy, whereas tumor recurrence was seen in 13/29 patients (44.83%) who did not receive adjuvant radiotherapy. CONCLUSIONS: Liponeurocytomas are rare benign tumors, occurring mainly in the cerebellum. The therapy of choice is surgery. Postoperative radiotherapy seems to decrease the risk of tumor recurrence and should be offered to the patient.

Patterns of care and survival outcomes in patients with an extraventricular neurocytoma: An individual patient data analysis of 201 cases.

INTRODUCTION:: Extraventricular neurocytoma is a rare neuronal tumor arising outside the ventricles. However, because of its rarity, its optimum treatment remains undefined. MATERIALS AND METHODS: We intended to perform an individual patient data analysis to examine the patterns of care and prognostic factors involved in the treatment of extraventricular neurocytomas. PubMed, SCOPUS, and Google Scholar were searched with the following MeSH terms: "Neurocytoma, Extra ventricular neurocytoma, Spinal neurocytoma AND treatment, Survival" to find all possible publications pertaining to EVN. RESULTS: From 108 publications, we retrieved 201 patients of extraventricular neurocytoma. Their median age was 30 years (range: 0.6-78 years). Sixty seven patients were in the pediatric (age ≤20 years) age group. There was a bimodal age distribution. Surgical details were available for 132 cases, and 51.5% underwent a gross total resection whereas 41.7% underwent a subtotal resection. Adjuvant radiation was used in 40% cases. For the entire cohort, the median progression free survival was 77 months (53.3-100.7). However, we could not find an impact of any of the prognostic factors on survival. CONCLUSION: An extraventricular neurocytoma is a very rare disease with varied presentations and different sites of origin. Gross total resection remains the standard of care. Adjuvant radiation may be used for salvage. However, radiation therapy after subtotal resection of an atypical neurocytoma may be administered.