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Background Intramedullary spinal cord tumors (IMSCTs) are rare, heterogenous lesions that are usually enhanced on preoperative magnetic resonance imaging (MRI) because of a damaged blood-brain barrier. Sodium fluorescein is a dye that accumulates in areas of the central nervous system with a damaged BBB. Given the pattern of MRI contrast enhancement of the majority of IMSCTs, the use of this fluorescent tracer could improve tumor visualization and quality of resection. In this article, we present the first experience with the application of fluorescein-guided technique for surgical removal of IMSCTs. Methods Eleven patients (6 men, 5 women; mean age, 50.1 years), harboring 5 ependymomas, 3 hemangioblastomas, 1 astrocytoma, 1 pilocytic astrocytoma, and 1 glioneuronal tumor forming rosettes were included. Sodium fluorescein (5 mg/kg) was injected immediately after patient intubation. Tumors were removed with microsurgical technique and standard neurophysiological monitoring, under YELLOW 560 filter (Pentero 900) visualization. Surgical reports were reviewed regarding usefulness and grade of fluorescein staining. Postoperative MRI was performed within 72 hours after surgery, and postoperative clinical outcome was registered. Results No adverse events were registered. Fluorescent staining was reported in 9 of 11 cases (82%), all of them enhancing on preoperative MRI (100% of ependymomas, 100% of pilocytic astrocytomas, 100% of hemangioblastomas). No fluorescence was reported in 1 astrocytoma and 1 glioneuronal tumor–forming rosette. Intraoperative fluorescence was considered helpful for tumor resection in 9 of 11 cases (82%). Gross total resection was obtained in 8 of 11 cases (72.7%). Conclusions Our results suggest that fluorescein-guided surgery is a safe and effective technique that can be used during the surgical resection of IMSCTs presenting with contrast-enhancement on preoperative MRI. [ABSTRACT FROM AUTHOR]

Objective Hemangioblastomas with enhanced cyst walls represent a rare radiologic presentation of hemangioblastomas with poor understandings. We aimed to summarize the clinical and radiologic features, important differential diagnosis, surgical strategy, and clinical outcome of this rare entity. Methods From June 2008 to March 2017, 12 patients with cystic hemangioblastomas presenting with enhanced wall thickness on MRI were treated in our department. The clinical presentations, radiologic investigations, surgical treatment, neurologic outcome, and recurrence rate were evaluated. Important preoperative differential diagnosis and surgical strategy of this entity were discussed. Results Twelve patients with cystic hemangioblastomas presenting with an enhanced cyst wall on magnetic resonance imaging were analyzed retrospectively. There were 5 male and 7 female subjects, with a mean age of 41.4 years (range, 13–78 years) and an average duration of symptoms before diagnosis of 2.23 months (range, 0.5–8.0 months). Radiologically, enhancement of both tumoral nodule and cyst were observed in 8 patients, while pure ring-enhanced cyst without typical tumoral nodule was found in 4 patients. Histopathologic examination confirmed the diagnosis of hemangioblastomas, and the enhanced cyst wall and mural nodule shared the same histopathologic pattern. Postoperative complications occurred in only 1 patient with postoperative cerebellar hemorrhage. During follow-up, 8 patients achieved favorable neurologic outcomes (Karnofsky score: 100) without recurrence; however, 4 patients experienced local tumor recurrence after the initial surgery. Conclusions Hemangioblastomas with enhanced cyst wall possess distinctive radiologic features, and they are frequently misdiagnosed preoperatively. Favorable tumor control can be achieved only when gross total resection of both the tumor nodule and cyst wall are performed. Close follow-up is necessary because of the high recurrence rate in this subset of hemangioblastomas. [ABSTRACT FROM AUTHOR]

Introduction: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. Case presentation: A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. Conclusions: This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria. RFA appears to be safe in terms of oncological radicalism and in renal function preservation. In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue. [ABSTRACT FROM AUTHOR]

Hemangioblastomas (HBs) are uncommon tumors characterized by the presence of inactivating alterations in the von Hippel-Lindau ( VHL) gene in inherited cases and by infrequent somatic mutation in sporadic entities. We performed whole exome sequencing on 11 HB patients to further elucidate the genetics of HBs. A total of 270 somatic variations in 219 genes, of which there were 86 mutations in 67 genes, were found in sporadic HBs, and 184 mutations were found in 154 genes in familial HBs. C: G>T: A and T: A>C: G mutations are relatively common in most HB patients. Genes harboring the most significant mutations include PCDH9, KLHL12, DCAF4L1, and VHL in sporadic HBs, and ZNF814, DLG2, RIMS1, PNN, and MUC7 in familial HBs. The frequency of CNV varied considerably within sporadic HBs but was relatively similar within familial HBs. Five genes, including OTOGL, PLCB4, SCEL, THSD4, and WWOX, have CNVs in the six patients with sporadic HBs, and three genes, including ABCA6, CWC27, and LAMA2, have CNVs in the five patients with familial HBs. We found new genetic mutations and CNVs that might be involved in HBs; these findings highlight the complexity of the tumorigenesis of HBs and pinpoint potential therapeutic targets for the treatment of HBs. [ABSTRACT FROM AUTHOR]

Background: Pediatric hemangioblastomas are rare, and the clinical features, timing of surgical intervention, optimal treatment, and clinical outcomes are still unclear. Methods: We performed a retrospective study of all patients with CNS hemangioblastomas who were treated at West China Hospital from January 2003 to March 2015. Patients under the age of 16 years were included in the study. The medical records of these patients were reviewed and statistically analyzed. Results: Twenty-five children (15 females and ten males, [mean age 12.6 ± 4.7 years, range 1-16 years]) presented with hemangioblastomas. Tumors were detected in the cerebellum, brainstem, and spinal cord in 40, 28, and 32% of patients, respectively. Sixteen children (64%) had VHL syndrome. The most frequent symptoms were those related to increased intracranial pressure. The mean duration of symptoms was 1.5 ± 2.1 months. Preoperative hydrocephalus was noted in 11 children (44%). Gross total resection was achieved in all children. Clinical symptoms improved in 19 children (76%), unchanged in four children (16%), and aggravated in two children (8%), respectively. The mean follow-up was 44.5 ± 32.3 months. Five patients (20%) experienced disease progression. Using univariate analysis, both tumor-associated cysts ( P = 0.027) and VHL disease ( P = 0.032) were significantly related to postoperative outcomes. Conclusions: Pediatric hemangioblastomas have many different clinical features compared with adult cases. A high degree of suspicion for VHL disease should be raised in pediatric hemangioblastomas. Despite many challenges involved, surgical outcomes for pediatric hemangioblastomas are favorable. Lifelong follow-up is mandatory to detect the disease progression. [ABSTRACT FROM AUTHOR]

Background: Intramedullary hemangioblastomas are rare benign vascular tumors, infrequent in pediatric patients. Clinical symptoms vary according to the age of presentation, tumor size, location, and concomitant syringomyelia. This is the second reported case of hemangioblastoma presenting with acute hydrocephalus. Case presentation: A 3-month-old infant with acute hydrocephalus was asymptomatic after a ventriculoperitoneal shunt was placed. She returned 3 months later with irritability, acute paraplegia, and respiratory distress. Magnetic resonance imaging (MRI) showed an intramedullary T8-T9 tumor with syringomyelia. She underwent surgical resection with good results during the 6-month follow-up. Conclusion: Intramedullary tumors may present as hydrocephalus and other nonspecific symptoms, with invariably delayed diagnosis in children, but must be considered in suspicious cases. [ABSTRACT FROM AUTHOR]

Background: Posterior fossa hemangioblastomas are WHO grade I benign lesions with a surprisingly high recurrence rate. This study determines the factors responsible for recurrence and the clinico-radiological and histopathological differences between primary ( group A; n = 60) and recurrent/symptomatic residual (group B; n = 24) tumors. Methods: Radiologically, tumors were differentiated into cystic, cystic with a mural nodule, solid-cystic/microcystic and solid. Surgery was undertaken via a midline or lateral suboccipital approach. Histopathology differentiated them into reticular, cellular or mixed subtypes. Results: Truncal-appendicular ataxia in group A and von Hippel-Lindau (VHL) disease and raised intracranial pressure in group B were the predominant presentations. VHL patients in group B had a longer duration of symptoms (median 72 months) than those with non-VHL recurrences (median: 36 months). Multicentric mural nodules ( n = 9/24, 37.50%, P = 0.0001) and bilateral cerebellar hemispheric involvement ( n = 6/24, 25%, P = 0.0003) were exclusively seen in the preoperative radiology of group B tumors. Brainstem involvement was seen in the tumors of ten (16.67%) patients in group A and six (25.00%) patients in group B. One subset of patients required several resurgeries for repeated recurrences. Abnormal vascular proliferation and papillary projections into adjacent brain, and highly cellular stroma were unique histological features at recurrence. Total resection was achieved in 45 group A and 19 group B patients. The outcome based on the Karnofsky performance scale (KPS) was assessed at follow-up at 6 weeks (A: n = 60, B: n = 24): KPS0: A = 4, B = 1; KPS10-40 (dependent): A: 4, B = 5; KPS50-70 (independent for daily needs): A = 36, B = 16; KPS80-100 (fully independent): A = 16; B = 2. Conclusions: In recurrent/residual tumors, the radiological as well as histopathological features showed a distinctive change toward a more aggressive nature. Higher incidences of multiple mural nodules, bilateral spread, remote recurrence and VHL disease at preoperative radiology; as well as proliferative angioarchitecture, an irregular brain tumor interface and highly cellular stroma at histology were found in these patients compared to their primary counterparts. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Purpose: To examine the clinical profile and surgical complications in patients with spinal hemangioblastomas and to evaluate the long-term outcome in them. Overview of Literature: Although considered to be histologically benign, hemangioblastomas may cause significant neurological deficits. The proportion of spinal hemangioblastomas associated with von Hippel-Lindau (VHL) disease has been estimated be 13%-59%. Preoperative neurological function correlates with postoperative neurological status. Studies have shown no difference in outcomes between sporadic and VHL-associated spinal hemangioblastomas. Methods: This retrospective study included 14 consecutive patients treated for spinal hemangioblastomas at our institute between January 2000 and June 2013. The mean follow-up period was 5 years. Magnetic resonance imaging of the complete neuraxis was performed in all cases, and preoperative embolization was performed in two cases. Results: In total, 14 patients underwent 18 surgeries, of which 15 were for spinal hemangioblastomas. Of all the patients, 86% had motor weakness and 79% presented with sensory disturbances. Preoperative McCormick functional grades were grade I in 7 (50%), grade II in 3 (21%), and grade III in 4 (29%) patients; 50% patients were diagnosed with VHL disease. All patients underwent complete resection of the tumor. Eight patients experienced deterioration in their neurological status in the immediate postoperative period; among them, five had gradual improvement. At 5-year follow-up, 11 (78.57%) patients showed good functional outcomes. Conclusions: Microsurgical excision of spinal hemangioblastomas can cause postoperative morbidity, mainly in the form of neurological deterioration. Almost half of our patients had deterioration in the McCormick grade in the immediate postoperative period. However, a complete microsurgical excision can result in good long-term functional outcomes, as most of the immediate postoperative neurological deterioration in our patients was reversible. There was no difference in the long-term functional outcomes between sporadic and VHL-associated spinal hemangioblastomas. [ABSTRACT FROM AUTHOR]

Objectives Hemangioblastomas in the cerebellopontine angle (CPA) are uncommon and have rarely been reported. They may be easily misdiagnosed because of the atypical location and clinical and imaging features. The present study aimed to characterize clinical and radiologic features, treatment strategies, and outcomes in these rare lesions and to investigate various factors that may affect postoperative outcomes. Methods The medical records of patients with CPA hemangioblastomas who underwent surgery from 2003–2016 at the West China Hospital were reviewed retrospectively and statistically analyzed. Results Twenty-three patients (14 males and 9 females) presented with CPA hemangioblastomas. Eight patients (34.8%) had von Hippel-Lindau (VHL) syndrome. Gross total resection was achieved in 22 patients (95.6%). The mean follow-up was 45.1 ± 36.2 months (range 3–144 months). After surgery, the symptoms improved in 18 cases (78.3%), remained unchanged in 3 cases (13%), and were aggravated in 2 cases (8.7%). Four patients showed local recurrence during follow-up (17.4%). Patients with cystic hemangioblastomas had a better neurologic improvement ( P = 0.041) compared with patients with solid tumors. Furthermore, patients with maximal diameter of tumors >3 cm ( P = 0.035) or solid tumors ( P = 0.018) showed a higher incidence of postoperative complications. The local recurrence was correlated with VHL disease ( P = 0.027). Conclusions Although hemangioblastomas of the CPA are challenging lesions to treat surgically, they can be removed safely when these lesions are appropriately diagnosed and treated. Patients with VHL disease are more likely to have a local recurrence. A regular follow-up is recommended to detect the local and distant recurrence, even if the clinical course is benign and the tumor is totally resected. [ABSTRACT FROM AUTHOR]

We report a case of sporadic isolated hemangioblastoma arising from the retroperitoneum and provide a review of the scarce literature regarding this very rare tumor. Furthermore, we thoroughly describe the pathologic features and the broad differential diagnosis that should always be included in the study of any retroperitoneal soft tissue mass to arrive at the final diagnosis. [ABSTRACT FROM AUTHOR]

Hemangioblastoma tends to occur in the infratentorial regions and rarely in the supratentorial regions. This tumor is strongly associated with von Hippel-Lindau disease (VHLD), especially in the supratentorial regions, with only 12 cases of suprasellar hemangioblastoma unrelated to VHLD. However, all these cases were diagnosed based on clinical screening and confirmation of family history. We report a case of suprasellar hemangioblastoma that was successfully removed through an extended transsphenoidal approach and diagnosed as a sporadic case unrelated to VHLD by immunohistochemical examination. A 67-year-old woman had mild diabetes insipidus and a visual field defect. Head magnetic resonance imaging revealed a suprasellar tumor compressing the optic chiasm upward. The tumor was totally removed without complication through an extended transsphenoidal approach. Postoperative histologic examination disclosed large vacuolated stromal cells and rich capillary networks, and the diagnosis was established as hemangioblastoma. Clinical screening and confirmation of family history revealed no specific results, and additional immunohistochemical staining showed diffuse cytoplasmic expression of anti-VHLD gene-derived protein (pVHL). We emphasize that pVHL immunohistochemical evaluation would be wise to adopt, especially for patients with a high risk of VHLD related to younger age and supratentorial lesions. [ABSTRACT FROM AUTHOR]

Objective It is sometimes difficult to make a differential diagnosis between brain metastases and hemangioblastomas in the posterior fossa. We assessed whether high b value diffusion-weighted image (DWI) at b = 4000 could differentiate these tumors. Methods We acquired DWI at 3-T magnetic resonance imaging with b = 1000 and b = 4000 seconds/mm 2 in histologically confirmed 12 patients of hemangioblastoma without von Hippel-Lindau disease and 16 patients with brain metastases originating at the posterior fossa. Apparent diffusion coefficient (ADC) values were measured by manually placing regions of interest on ADC maps at the site of enhanced tumor confirmed on contrast-enhanced T1- weighed image. ADC was expressed as the minimum (ADC MIN ), mean (ADC MEAN ), and maximum (ADC MAX ) values. Results All the ADC values of hemangioblastomas were statistically higher than those of metastatic tumor in both b = 1000 and b = 4000 ( P < 0.0001 in ADC MIN , ADC MEAN , and ADC MAX ; Mann-Whitney U test). With the cutoff value at 0.6 × 10 −3 mm 2 /second, the positive predictive value of ADC MIN at b = 4000 was higher than that of ADC MIN at b = 1000 (100% vs. 89.3%, logistic analysis) to differentiate hemangioblastomas from brain metastases. Moreover, we studied the pathologic subtype of hemangioblastoma and confirmed that ADCs (b = 4000 MIN ) of cellular subtype were statistically lower than those of reticular subtype ( P = 0.03; Mann-Whitney U test). Conclusions High b value DWI reflects diffusion more accurately than does regular b value. Our results showed that ADC calculation by high b value (b = 4000) DWI at 3-T magnetic resonance imaging is clinically useful for differentiating hemangioblastomas from brain metastases. [ABSTRACT FROM AUTHOR]

Hemangioblastoma is a well-circumscribed, highly vascular, lipid-rich and low-grade tumor of uncertain histogenesis. Its histopathological features have been well established. Herein, we present a case of cerebellar hemangioblastoma in a 43-year-old woman. Histologically, the tumor was predominantly composed of cellular areas showing eosinophilic or vacuolated stromal cells arranged in nests and sheets. Focally, conventional reticular areas could be seen. Additionally, in some areas, the stromal cells were arranged radially around blood vessels, exhibiting perivascular pseudorosette structures, which were similar mostly to those of ependymomas. Immunohistochemically, the stromal cells markedly showed diffused staining for Vimentin, S-100, CD56, NSE, inhibin-a, podoplanin, alpha-Thalassemia/mental retardation syndrome X and carbonic anhydrase IX, and were negative for cytokeratin, epithelial membrane antigen, oligodendrocyte transcription factor 2, neuronal nuclear antigen, synaptophysin, isocitrate dehydrogenase 1 (R132H), P53 and CD34. Interestingly, the reticular and cellular areas either showed no or individual scattering of the GFAP-positive cells, respectively, while, the perivascular pseudorosette areas strongly and diffusely expressed GFAP. Nuclear mitosis and necrosis were not observed. The MIB-1 antibody labeling index was especially low (about 3%). Based on these findings, the patient was diagnosed with cerebellar hemangioblastoma. In the present case, we documented a distinctive histological appearance of perivascular pseudorosettes in hemangioblastoma and provided the evidence for stromal cells with glial differentiation. [ABSTRACT FROM AUTHOR]

Background: Imaging and histology of clear-cell ependymoma and cerebellum-based hemangioblastoma are similar; distinguishing between them is a diagnostic challenge. Case presentation: A 62-year-old Chinese woman presented with an intermittent headache of 8 years' duration. Computed tomography and magnetic resonance imaging revealed a mass in the cerebellum. Neurological imaging suggested hemangioblastoma (HB). Histologically, the tumor included cellular and paucicellular areas, in which cells were arranged in nests or diffusely distributed; and a highly vascular area, in which tumor cells were arranged in clusters and separated by capillaries. At low magnification, the tumor mimicked cellular HB, but at high magnification, tumor cells showed clear cytoplasm instead of the vacuolated cytoplasm typically observed in HB. Moreover, spindly, bipolar elements resembling tanycytes were observed within the nest structures. Although these features indicated the possibility of ependymoma, neither true ependymal rosettes nor an ependymal-lined profile was observed. The tumor was characterized by prominent vascularity, but glomeruloid formation was absent. We saw pleomorphism in foci of some tumor giant cells, but pathologic mitosis and palisaded necrosis were absent. Most tumor cells were positive for glial fibrillary acidic protein and S100. Epithelial membrane antigen was expressed with a paranuclear dot-like or a ring-like pattern. The Ki-67 index was approximately 2%. Considering the patient's symptom, neurological imaging, and pathological findings, she was diagnosed as cerebellar ependymoma (WHO grade II). Conclusions: Here, we report a case of ependymoma with overlapping clear-cell and tanycytic features, and review the literature to evaluate its real incidence. Pathologists should consider this rare diagnosis when confronted with a similar presentation. [ABSTRACT FROM AUTHOR]

This study evaluated the clinical features, treatment strategies and outcomes of solid hemangioblastomas in 28 patients diagnosed with hypervascular lesions in the posterior fossa. Preoperative embolization of the feeding arteries had limited effects, with only 7 patients benefitting from it for the reduction of intraoperative hemorrhage. The tumor was completely removed in all patients, and 22 patients had a full recovery, while 6 patients, all of whom had van Hippel Lindau disease, developed recurrences. The present study demonstrated that meticulous en bloc surgical resection was the optimal treatment for solid hemangioblastomas of the posterior fossa. For large tumors, preoperative embolization was critical for preventing postoperative morbidity. Given the improvements in microsurgical techniques and the understanding of the tumor vascular pattern, total tumor removal associated with a low mortality rate could be achieved. [ABSTRACT FROM AUTHOR]

Purpose Positional nystagmus is usually caused by peripheral vestibular disorder, mostly benign paroxysmal positional vertigo (BPPV). However, positional nystagmus is also encountered in central lesions. We aimed to determine clinical characteristics of the structures responsible for central positional nystagmus (CPN) associated with brain tumors. Methods All four patients (3 men; range = 19–77 years) had an evaluation of spontaneous and positional nystagmus using video-oculography. Brain MRIs were performed in all patients. Results All patients showed apogeotropic positional nystagmus during supine roll tests, and had an initial diagnosis of BPPV. Except for the positional nystagmus, findings of neurological examination were normal. Because all subjects were initially diagnosed with BPPV, canalith repositioning maneuvers were applied repeatedly but without a success. Brain MRI finally disclosed brain tumors involving the midline cerebellar structures around the fourth ventricle and the nodulus. The pathological diagnosis was hemangioblastoma in two and metastatic tumor in the others. Conclusions An apogeotropic type of CPN may be an isolated finding in patients with a cerebellar tumor. Even in patients with isolated apogeotropic positional nystagmus, a central lesion should be sought especially when refractory to repeated canalith repositioning maneuvers. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to determine the expression of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and endothelial tyrosine kinase receptor (Tie-2) in central nervous system (CNS) hemangioblastomas (HBs) and explore the correlation with peritumoral cyst formation. Method A total of 22 paraffin-embedded specimens derived from 11 cyst-associated and 11 solid solitary CNS HBs were collected for streptavidin-peroxidase immunohistochemical staining. The expression levels of Ang-1, Ang-2 and Tie-2 in cystic and solid HBs were estimated and compared according to the integrated optical density (IOD) of staining in the sections. To further confirm the differential expression of Ang-1 and Ang-2 between cystic and solid HBs, an additional 9 frozen specimens from 5 cyst-associated and 4 solid solitary HBs were collected for Western blot analysis. Clinical histories and radiological records of the patients were reviewed retrospectively. Results Compared to normal cerebellum tissue, Ang-1, Ang-2 and Tie-2 were prominently overexpressed in both the stromal cells and endothelial cells of CNS HBs. The expression of Ang-2 and the ratio of Ang-2/Ang-1 in the cystic group were significantly higher than those in the solid group. The intensity of Ang-2 expression in the cystic group was negatively correlated with age. There was no correlation between the expression level of the proteins and sex, tumor location, tumor volume or cyst volume. Conclusions Ang/Tie signaling is upregulated in HBs and is likely associated with the process of intense vascularization and cyst formation. Higher Ang-2 levels and a higher Ang-2/Ang-1 ratio may contribute to cyst formation by increasing the vascular permeability. The decrease in Ang-2 expression with advanced age in cystic-associated HBs may be associated with the reduced growth rate of peritumoral cysts among elderly patients. Ang-2 shows great potential as an effective therapeutic target of symptomatic CNS HBs associated with cysts. [ABSTRACT FROM AUTHOR]

Hemangioblastoma (HB) is mainly located in the brain and the spinal cord. The tumor is composed of two major components, namely neoplastic stromal cells and abundant microvessels. Thus, hyper-vascularization is the hallmark of this tumor. Despite the identification of germline and/or epigenetic mutations of Von Hippel Lindau ( VHL) gene as an important pathogenic mechanism of HB, little is known about the molecular signaling involved in this highly vascularized tumor. The present study investigated the key players of multiple angiogenic signaling pathways including VEGF/VEGFR2, EphB4/EphrinB2, SDF1α/CXCR4 and Notch/Dll4 pathways in surgical specimens of 22 HB. The expression of key angiogenic factors was detected by RT2-PCR and Western blot. Immunofluorescent staining revealed the cellular localization of these proteins. We demonstrated a massive upregulation of mRNA levels of VEGF and VEGFR2, CXCR4 and SDF1α, EphB4 and EphrinB2, as well as the main components of Dll4-Notch signaling in HB. An increase in the protein expression of VEGF, CXCR4 and the core-components of Dll4-Notch signaling was associated with an activation of Akt and Erk1/2 and accompanied by an elevated expression of PCNA. Immuofluorescent staining revealed the expression of VEGF and CXCR4 in endothelial cells as well as in tumor cells. Dll4 protein was predominantly found in tumor cells, whereas EphB4 immunoreactivity was exclusively detected in endothelial cells. We conclude that multiple key angiogenic pathways were activated in HB, which may synergistically contribute to the abundant vascularization in this tumor. Identification of these aberrant pathways provides potential targets for a possible future application of anti-angiogenic therapy for this tumor, particularly when a total surgical resection becomes difficult due to the localization or multiplicity of the tumor. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the clinical course after early surgical treatment with excision of retinal hemangioblastomas (RHs) before development of major complications. Methods Interventional case series of four eyes (four patients) with a peripheral RH that had not yet been treated by laser or cryotherapy prior to surgery. All eyes underwent 23-gauge vitrectomy with lesion excision. One patient underwent ligation of the feeder vessel prior to lesion excision. Best-corrected visual acuity and clinical course were assessed during a follow-up period of at least 4 years. Results Four patients (mean age 27.3 years; range 19-32) were included, of whom two had von Hippel-Lindau syndrome. Visual acuity improved in three patients (mean 4.8 lines; range 3-10) and remained stable at 0.0 logMAR in one patient. There were no intraoperative complications. Postoperative complications included transient mild vitreous haemorrhage ( n = 2), and local epiretinal membrane formation at the excision location ( n = 1). At 4 years postoperatively, there were no long-term complications. There was one case of a new lesion, which was effectively treated with laser. Conclusion Vitrectomy with RH excision seems to be an effective approach for larger RHs and could be considered an early treatment option in selected cases. Postoperative complications were limited in scope of this case series. Important points to consider during vitrectomy are effective closure of feeder and draining vessels as well as complete removal of posterior hyaloid and epiretinal membranes in order to avoid postoperative vitreous haemorrhage and proliferative vitreoretinopathy. [ABSTRACT FROM AUTHOR]

Mammalian cells sense changes in oxygen and transduce that information into adaptive changes in gene expression using a conserved pathway that converges on the heterodimeric transcription factor called hypoxiainducible factor (HIF), which contains a labile alpha subunit and a stable beta subunit. In the presence of oxygen, the alpha subunit is hydroxylated on one (or both) of two highly conserved prolyl residues by an Egg-Laying Defective Nine (EglN) [also called Prolyl Hydroxylase Domain (PHD)] dioxygenase, which recruits an ubiquitin ligase complex containing the VHL tumor suppressor gene product. Germline VHL mutations cause von Hippel-Lindau (VHL) disease, which manifest as angiogenic tumors such as hemangioblastomas and kidney cancers. Somatic VHL inactivation and deregulation of HIF (especially HIF2a) drives sporadic kidney cancers and an HIF2a inhibitor is showing promise for this disease. VHL, EglN1, and HIF2a polymorphisms have been linked to familial polycythemia and adaptation to high altitude. Orally available EglN inhibitors are being developed for the treatment of anemia and ischemic diseases. [ABSTRACT FROM AUTHOR]

OBJETIVO: descrever uma experiência e as técnicas para abordagem destas lesões com ênfase nos aspectos microcirúrgicos. MÉTODOS: foram relatados nove casos consecutivos de pacientes submetidos à ressecção de lesões intramedulares operados entre 2000 e 2008. A escala funcional de McCormick foi usada para avaliar o status funcional dos pacientes RESULTADOS: a idade dos pacientes variou de 13 a 45 anos (média de 27,1 anos). Quatro (44,4%) pacientes eram homens e cinco (55,5%), mulheres. Dois pacientes tinham a doença de von Hippel-Lindau, com outros hemangioblastomas associados. Conforme a localização, sete (77,7%) pacientes tinham lesões na região cervical (dois deles com tumores na transição crânio-cervical) e dois (22,2%) tinham lesões na região torácica. Todos os pacientes tiveram ressecção total das lesões, sendo que três apresentaram leve piora clínica no pós-operatório imediato. Após seis meses do procedimento cirúrgico, dois pacientes apresentaram melhora clínica, enquanto sete mantinham-se funcionalmente iguais ao período pré-operatório. CONCLUSÕES: o conhecimento anatômico e de técnicas microcirúrgicas adequadas permite a ressecação total destas lesões sem agregar morbidade adicional.OBJETIVOS: describir una experiencia y las técnicas para abordaje de esas lesiones, enfatizando los aspectos microquirúrgicos. MÉTODOS: fueron relatados nueve casos consecutivos de pacientes sometidos a resección de lesiones intramedulares, operados entre 2000 y 2008. La escala funcional de McCormick fue usada para la evaluación del status funcional de los pacientes RESULTADOS: la edad de los pacientes varió de 13 a 45 anos (media de 27,1). Cuatro (44,4%) pacientes eran hombres y cinco (55,5%), mujeres. Dos pacientes eran portadores del enfermedad de von Hippel-Lindau, con otros hemangioblastomas asociados. Conforme la localización, siete (77,7%) pacientes tenían lesiones en la región cervical (dos con tumores en la transición cráneo-cervical) y dos (22,2%) tenían lesiones en la región torácica. Todos los pacientes tuvieron resección total de los tumores, siendo que tres tuvieron deterioración clínica leve en el post-operatorio inmediato. Después de seis meses del procedimiento quirúrgico, dos pacientes presentaron mejoras clínicas, mientras seis se mantuvieron funcionalmente iguales al periodo pre-operatorio. CONCLUSIONES: el conocimiento anatómico y de técnicas microquirúrgicas adecuadas permite la resección total de estos tumores sin agregar morbididad adicional.OBJECTIVES: to report an experience and to present a surgical technique to achieve total resection and cure. METHODS: nine consecutive cases of intramedullary haemangioblastomas, operated between 2000 and 2008 are presented. The functional scale proposed by McCormick was used to evaluate the patients' neurological status. RESULTS: age at presentation varied from 13 to 45 (average 27.1) years. Four (44.4%) patients were male and five (55.5%), female. Two patients had an associated von Hippel-Lindau disease, with others haemangioblastomas. According to the site of presentation, seven (77.7%) were localized at the cervical region (including two at the cervico-medullary junction), and two (22.2%) at the thoracic level. Total resection was achieved in all cases. Three patients had some functional worsening immediately after surgical procedure. After six months, there were no patients with functional worsening comparing with the pre-operative status and two patients had clinical improvement. CONCLUSIONS: adequate knowledge of anatomy and the correct use of microsurgical techniques allowed total resection of these tumors with minimal morbidity and maximum functional recovery.

Spinal nerve root hemangioblastomas present mostly as intradural-extradurally. Purely extradural spinal nerve root hemangioblastoma is a very rare entity. In this study, we aimed to analyze epidemiological perspectives of purely extradural spinal nerve root hemangioblastomas presented in English medical literature in addition to our own exemplary case. PubMed/MEDLINE was searched using the terms "hemangioblastoma," "extradural," "spinal," and "nerve root." Demographical variables of age, gender, concomitant presence of von Hippel-Lindau (VHL) disease; spinal imaging and/or intraoperative findings for tumor location were surveyed from retrieved articles. There are 38 patients with purely extradural spinal nerve root hemangioblastoma. The median age is 45 years (range = 24-72 years). Female:male ratio is 0.6. Spinal levels for purely extradural spinal nerve root hemangioblastomas, in order of decreasing frequency, are thoracic (48.6%), cervical (13.5%), lumbar (13.5%), lumbosacral (10.8%), sacral (8.1%), and thoracolumbar (5.4%). Concomitant presence of VHL disease is 45%. Purely extradural spinal nerve root hemangioblastomas are very rare and can be confused with other more common extradural spinal cord tumors. Concomitant presence of VHL disease is observed in less than half of the patients with purely extradural spinal nerve root hemangioblastomas. Surgery is the first-line treatment in these tumors. [ABSTRACT FROM AUTHOR]

Central nervous system hemangioblastomas occur sporadically and in patients with von Hippel-Lindau (VHL) disease due to a VHL germline mutation. This mutation leads to enhanced transcription of chemokine receptor 4 (CXCR4), its ligand (CXCL12) and vascular endothelial growth factor A (VEGFA). We aimed to determine in VHL-related and sporadic hemangioblastomas CXCR4, CXCL12, and VEGFA protein expression and to correlate this to hemangioblastoma size and expression in normal surrounding tissue. 27 patients with a hemangioblastoma were included for analysis of immunohistochemistry of tissue, MRI and DNA. Hemangioblastomas overexpress CXCR4, CXCL12, and VEGFA compared to normal surrounding tissue. In sporadic hemangioblastomas the mean percentage of CXCR4 positive hemangioblastoma cells was 16 %, SD 8.4, in VHL-related hemangioblastomas 8 %, SD 4.4 ( P = 0.002). There was no relation between preoperative tumor size and CXCR4 or CXCL12 expression. Compared to normal surrounding tissue CXCR4, CXCL12, and VEGFA were overexpressed in hemangioblastomas. Most interestingly, sporadic hemangioblastomas overexpress CXCR4 compared to VHL-related hemangioblastoma. [ABSTRACT FROM AUTHOR]

Background Solid cerebellar hemangioblastomas are highly vascular lesions and may cause catastrophic hemorrhage during excision. Methods This retrospective study enrolled 10 patients (7 men and 3 women, with a mean age of 38.2 ± 12.5 years) with solid cerebellar hemangioblastomas. All patients had a solitary tumor and underwent surgical resection of the lesion through a suboccipital approach. The basic features, serial radiographic examinations, and operative records were analyzed. Results The most common presenting symptoms were headache (100%), ataxia (100%), and long tract manifestations (60%). Three patients had experienced failed surgery previously due to massive intraoperative bleeding. Three patients were confirmed as having Von Hippel–Lindau disease. The average size of the tumor was 40.7 ± 8.7 mm in its maximal diameter (range 25–58 mm). Total endovascular occlusion obtained in six patients, near total occlusion in three patients, and incomplete occlusion in one patient. Nine (90.0%) patients underwent gross total resection and one (10.0%) underwent partial resection. After the primary surgery, eight (80.0%) patients experienced improvement in their symptoms, two (20.0%) maintained their pre-treatment status, and none showed neurological deterioration following tumor resection. Blood loss during surgery after embolization was minimal and controllable. Conclusion Preoperative embolization improves safety and efficacy of the microsurgical excision of such tightly located very vascular tumors. Embolization changes the concept of this lesion surgery into piecemeal removal rather than a total mass extraction technique. Liquid agents are superior to particles in obliteration of such lesions. [ABSTRACT FROM AUTHOR]

Background: von Hippel-Lindau (VHL) disease is a rare hereditary tumor syndrome caused by VHL gene mutations that is characterized by heterogeneous phenotypes such as benign/malignant tumors of the central nervous system, retina, kidney, adrenal gland, and pancreas. The genotype-phenotype correlation has not been well characterized in the Korean population so far. Therefore, this study aimed to evaluate the VHL mutation spectrum and genotype-phenotype correlations in Korean VHL patients. Methods: Thirteen unrelated subjects with VHL mutations were included. Direct sequencing and multiplex ligation-dependent probe amplification were performed. Consequently, the clinical manifestations and family histories of the subjects were evaluated. Results: We identified 10 different VHL mutations. The c.160_161delAT frameshift mutation was novel. Missense mutations clustered in 2 domains (α domain in exon 1; β domain in exon 3). The most frequently observed mutation was c.208G > A (p.Glu70Lys). Milder phenotypes were observed in subjects with de novo mutations. Age-specific risk for CNS hemangioblastoma was significantly higher in subjects carrying missense mutations within the HIF-α binding site (P < 0.05). Conclusions: This study provides insight into the genotype-phenotype correlation in that amino acid substitutions in the HIF-α binding site may predispose patients to age-related risks of CNS hemangioblastoma. [ABSTRACT FROM AUTHOR]

Object: The purpose of this study was to analyze the surgical outcome and complications of a single-center series of medulla oblongata (MO) hemangioblastomas. Methods: We retrospectively reviewed the medical charts of all medulla oblongata hemangioblastomas operated on at our institution between 1996 and 2015. All patients had a pre- and postoperative MRI and a minimum follow-up of 6 months. Patients were scored according to the Karnofsky Performance Scale (KPS) and McCormick Scale at the moment of admission, discharge and the last follow-up. Results: Thirty-one surgical procedures were performed on 27 patients (16 females and 11 males). The mean age was 33 years, and 93 % of patients had von Hippel Lindau (VHL) disease. Three patients experienced very complicated postoperative courses, with one case ending in the death of the patient. Two patients required tracheostomy. According to McCormick's classification, 7 (23 %) of the 31 operations resulted in aggravation and 23 (74 %) in no change. Considering the seven patients with aggravation at discharge, four patients (60 %) returned to their preoperative status, one (14 %) improved but remained below his preoperative McCormick grade and two (29 %) did not improve. At last follow-up, KPS was ameliorated in 53 %, stable in 40 % and worsened in 7 % of cases. Conclusion: Surgery of medulla oblongata hemangioblastomas is a challenging procedure characterized by an acceptable morbidity. Transient morbidity is not negligible even if the long-term outcome is in most cases favorable. A compromised neurological condition seems to be the best predictor of unfavorable outcome. [ABSTRACT FROM AUTHOR]

A 45-year-old gentleman presented with headache, dizziness, and unsteadiness of gait. On imaging, he was found to have a cerebellar and a spinal intramedullary hemangioblastoma. To rule out Von Hippel-Lindau (VHL) disease, we did screening of the whole abdomen with ultrasonography followed by contrast-enhanced computed tomography of the abdomen, and surprisingly, the patient was having bilateral adrenal pheochromocytoma and a hepatic cyst. A diagnosis of VHL disease was made on this basis. The patient was operated and he made a very good recovery. We are reporting this interesting case because of its typical findings and its rarity. Disease management and review of literature were also discussed at the end. [ABSTRACT FROM AUTHOR]

Introduction: Well-differentiated papillary thyroid carcinoma generally (PTC) have a favorable prognosis. This metastasis is rare in the central nervous system. Brain metastasis has a relatively poor prognosis. We present a rare case of cerebellar metastasis, one that mimics a solid type cerebellar hemangioblastoma and because of which it was very hard to reach accurate preoperative diagnosis. Accurate diagnosis was challenging because of the similar imaging and histopathological findings for these two tumors. Case description: A brain lesion was detected by routine medical checkup of the brain with MRI in a 49-year-old woman 2 years after thyroidectomy for well-differentiated PTC. Gadolinium-enhanced MRI showed a homogeneous prominently enhanced lesion with surrounding enhanced dilated vessels in the left cerebellar hemisphere. Digital subtraction angiography showed a strongly stained lesion fed by the peripheral branch of the left posterior inferior cerebellar artery with drainage into the inferior vermian vein, revealing arteriovenous shunting. The most like likely preoperative diagnosis was felt to be that of a solid cerebellar hemangioblastoma. Gross total resection of the tumor was achieved by bilateral suboccipital craniotomy, and intraoperative pathological analysis suggested hemangioblastoma. Histopathological findings showed proliferation of vacuolated sheeted tumor cells with clear and eosinophilic cytoplasm and numerous thin-walled microvessels, consistent with hemangioblastoma. However, the final diagnosis was brain metastasis of the follicular variant of PTC due to a partial thyroid follicle-like pattern including eosinophilic fluid pathologically and positive TTF-1 immunostaining. Discussion and evaluation: Since presented rare case of cerebellar metastasis of PTC was very similar to solid type cerebellar hemangioblastoma on imaging and histopathological findings, accurate diagnosis was challenging. Moreover, it is extremely rare for a cerebellar metastasis to occur as an initial distant metastasis of PTC, and hemangioblastoma is the most common primary cerebellar neoplasm in adults. This epidemiological data was also one of the reason of difficulty to reach preoperative accurate diagnosis. Conclusions: To the best of our knowledge, there are no other reports of challenging diagnosis case of these two tumors in the literature. Brain metastasis of a well-differentiated PTC could be a relatively poor prognostic factor, and accurate diagnosis and suitable surgical therapy or radiotherapy are needed. [ABSTRACT FROM AUTHOR]

Background: The most common type of vascularized tumor located in the posterior incisural space in older patients is the falcotentorial meningioma. Solid hemangioblastomas are rarely found in this particular area of the brain. To the best of our knowledge, the case of only one patient harboring a hemangioblastoma not associated with Von Hippel-Lindau disease has been previously reported in the literature in this anatomic region. Regarding age presentation, it is rare for sporadic hemangioblastoma in any part of the brain to occur in older patients; only two cases have previously been reported, and neither were in this anatomical space. A solid hemangioblastoma represents a surgical challenge because of its high vascularization, very similar to an arteriovenous malformation, and it should be removed en bloc to prevent significant intraoperative bleeding.Case Presentation: We report here the case of a 63-year-old white male patient with a sporadic hemangioblastoma located in the posterior incisural space mimicking a tentorial meningioma. It was completely removed en bloc via an infratentorial supracerebellar approach with an excellent outcome.Conclusions: A hemangioblastoma should be considered among the differential diagnosis of hypervascularized masses in the posterior incisural space, even in cases of solid tumors, in older patients, or in the absence of Von Hippel-Lindau disease. These tumors located in the posterior incisural space represent a challenge, and the infratentorial supracerebellar approach provides panoramic exposure to allow safe resection. [ABSTRACT FROM AUTHOR]

Background: Leptomeningeal dissemination of hemangioblastomas (HB) of the central nervous system (CNS) is extremely rare. Few studies have reported leptomeningeal involvement in sporadic HB or in HB associated with von Hippel-Lindau syndrome. The clinical and radiological features of leptomeningeal involvement in HB after surgery have not been described in detail. Materials and methods: This retrospective case review involved patients from three different tertiary referral centers with leptomeningeal dissemination of HB after surgery for the primary mass. A literature review was also performed to describe the clinical and radiological characteristics and long-term outcomes of patients who developed leptomeningeal dissemination after initial surgical resection. Results: This study included seven patients, five males and two females, ranging in age from 36 to 54 years. Incidence of leptomeningeal dissemination in patients with HB was about 4.3 % (3/69). It appeared at a mean 94.9 months (range, 39-204 months) after gross total resection of CNS HBs. Three of the seven patients died 5, 38, and 79 months, respectively, after diagnosis of leptomeningeal dissemination. Review of the literature identified 21 patients with characteristics of leptomeningeal dissemination similar to those in our series. Conclusions: Leptomeningeal dissemination of HB is a rare pattern of long-term recurrence. Long-term outcomes may be fatal. The long developmental period suggests that early detection and aggressive management may improve prognosis in patients with CNS leptomeningeal dissemination of HB. [ABSTRACT FROM AUTHOR]

Cyst formation in meningioma is rare and furthermore, cyst formation in angiomatous variant of meningioma is extremely rare. Here, we are reporting an unusual angiomatous variant of meningioma with extensive cystic changes mimicking supratentorial hemangioblastoma. The tumor was detected in a 42-year-old woman who presented with left-sided hemiparesis. Magnetic resonance imaging of the brain revealed a large-sized cystic tumor with a contrast-enhancing nodule in the right posterior frontal region. Total excision of the tumor was achieved and left hemiparesis improved. [ABSTRACT FROM AUTHOR]