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Von Hippel‐Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web‐based application, REDCap, that thoroughly captures all VHL manifestation data. As an initial trial, information from 86 VHL patients from the University Health Network/Hospital for Sick Children was populated into the database. Analysis of this cohort showed missense variants occurring with the greatest frequency, with all variants localizing to the α‐ or β‐domains of VHL. The most prevalent manifestations were central nervous system (CNS), renal, and retinal neoplasms, which were associated with frameshift variants and large deletions. We observed greater age‐related penetrance for CNS hemangioblastomas with truncating variants compared to missense, while the reverse was true for pheochromocytomas. We demonstrate the utility of a comprehensive VHL database, which supports the standardized collection of clinical and genetic data specific to this patient population. Importantly, we expect that its web‐based design will facilitate broader international collaboration and lead to a better understanding of VHL. [ABSTRACT FROM AUTHOR]

Tumors secreting catecholamines, such as pheochromocytomas and paragangliomas, are rare and lifethreatening, due to their complications. They can be sporadic or occur in genetic syndromes, such as von Hippel-Lindau in which pheochromocytomas are observed in 10 to 20%. We report a case of a 42 years old male, who was sent in 2016 to our department for neurological symptoms related to cerebellar and central vestibular syndromes. His medical history revealed that at 8 years old he was operated for a symptomatic bilateral pheochromocytoma discovered by adrenergic symptoms and high blood pressure. Cerebral MRI showed intra- and extra-axial, supra- and infratentorial lesions causing supratentorial hydrocephalus associated with leptomeningeal dissemination deemed to be hemangioblastomas. One year later the patient started complaining of chronic diarrhea. The abdominal CT revealed three pancreatic tumors with radiological signs of pancreatic neuroendocrine tumors (PNETs) and a 12 mm mesenteric nodule presenting as a homogenously and typical for NET. The largest PNET had intensive fixation on octreotide scintigraphy. The association of pheochromocytomas, hemangioblastoma and pancreatic neuroendocrine tumors highlighted the diagnosis of VHL syndrome. The family history proved positive in a sibling with bilateral pheochromocytoma in infancy, retinal hemangioblastomas and cerebral hemangioblastoma. Genetic testing would have been useful, but in our case, it was lacking due to poor socio-economic conditions of the patient and absence of genetic testing in public hospitals. [ABSTRACT FROM AUTHOR]

Hemangioblastomas (HBLs) are highly vascular and cystic benign neoplasms. They form very small part of intracranial tumours and are often localized in the posterior fossa. Although most of them are sporadic, a significant group is accompanied with von Hippel-Lindau (VHL) syndrome. This case report presents a 57-year-old woman treated with total resection using micro-surgical technique and was diagnosed as HBL based on histopathologic findings. Contrast-enhanced cranial MRI of the patient with the complaints of spasms in the right side of body showed a right paracentral mass that caused midline shift. In literature, the previously reported cases of supratentorial HBL unaccompanied with VHL syndrome were searched in PUBMED, compiled and presented. It should be borne in mind that rare HBLs manifesting with various neurological symptoms may occur in the supratentorial region, and may not accompany with VHL syndrome. [ABSTRACT FROM AUTHOR]

The surgical resection of large supracerebellar hemangioblastomas (SHBs) is exceptionally challenging due to their vascularity and deep anatomic location and is associated with a high risk of postoperative complications and mortality. Access to the posterior incisural space can be achieved by either an infratentorial supracerebellar approach or occipital transtentorial approach (OTA). However, the optimal surgical strategy has not yet been established. Here, we report 2 cases of large SHBs that were successfully and safely resected via a unilateral OTA with multimodal assistance. Two patients presented to our hospital with ataxia due to large, solid SHBs. After preoperative embolization, gross total resection of the SHBs was achieved via an OTA. Furthermore, endoscopic assistance was used to resect the remnant portion of the tumor in the second patient. Both patients experienced transient ataxia but were discharged from the hospital without serious complications. The combination of an OTA with preoperative embolization and endoscopic assistance may reduce the intraoperative risk and contribute to improved outcome in patients with such clinically challenging tumors. [ABSTRACT FROM AUTHOR]

Hemangioblastomas are benign vascular neoplasms that may be associated with von Hippel−Lindau disease. They are more common in men, with a mean age of 36 years, and rarely affect the supratentorial region and, when present in this topography, do not have meningeal impairment. Diagnosis by the radiologic and histopathologic study is difficult, since they are rare and, therefore, forgotten diagnosis, besides they are differential diagnoses with other supratentorial neoplasms. The present report describes a case of a frontal hemangioblastoma in a 64-year-old woman who presented with seizures. Our imaging studies had as a main hypothesis a frontal meningioma because of dural tail sign, lack of edema, contrast enhancement pattern, and extra-axial location in the supratentorial region, in the frontal lobe, which is uncommon for a hemangioblastoma. The patient underwent microneurosurgery for tumor resection, and the excised tissue was submitted for anatomopathologic evaluation. This study clarified the diagnosis as hemangioblastoma. We followed up the patient at the outpatient clinic for 2 years, with clinical improvement, without tumor recurrence. We also compared the clinical, radiologic, epidemiologic, and anatomopathologic data of the reported case with data from a literature review conducted through the PubMed portal. Definitive treatment for these lesions is surgical resection. Physicians should be aware that supratentorial meningeal hemangioblastomas can be developed in a patient without von Hippel−Lindau disease and regular follow-up is mandatory. [ABSTRACT FROM AUTHOR]

Hemangioblastomas of the optic nerve are very rare tumors. They occur in association with Von Hippel-Lindau (VHL) syndrome; however, sporadic occurrences have been reported. We describe here a case of optic nerve hemangioblastoma in the absence of VHL and review the pertinent literature. A 33-year-old woman presented with gradually progressive vision loss in the right eye. On examination, the visual acuity on the right was hand movement close to face in all quadrants. Color discrimination was impaired. Fundoscopy revealed optic atrophy and no other retinal pathology. There was relative afferent pupillary defect in the right eye. No neurocutaneous markers were found. Imaging revealed lesion isointense on T1, hyperintense on T2/fluid-attenuated inversion recovery, and showing relatively homogenous enhancement on postcontrast study. Multiple flow voids were seen in the intracranial part of the lesion. The proximal part of the intraorbital right optic nerve was enlarged and tortuous with distended optic nerve sheath. A right single-piece fronto-orbital craniotomy was done. A reddish lesion seen involving the right optic nerve just proximal to the chiasm with multiple vessels and a distinct feeding vessel was seen supplying the tumor. The lesion was excised and the optic nerve was sacrificed approximately 1 cm proximal to the chiasm. The postoperative course was uneventful. Conclusions: Optic nerve hemangioblastoma is a rare occurrence and a high level of suspicion is required preoperatively in the absence of VHL syndrome. [ABSTRACT FROM AUTHOR]

Anterior inferior cerebellar artery (AICA) aneurysm is a rare cerebral entity, and its presentation in association with a hypervascularized tumor is even more exceptional. In this study, we describe a patient with rare coexistent pathologic conditions in combination with a cerebellar hypervascularized tumor with an outflow-related AICA aneurysm. A 1-stage procedure to remove both lesions was carried out after meticulous discussion with patient. Postoperative imaging demonstrated no residual aneurysm and total resection of the tumor, which was pathologically diagnosed as hemangioblastoma (HB). She made an excellent neurologic outcome and was discharged in unremarkable condition. At her 3-month follow-up visit, her condition remained stable for vasculopathologic states and neurologic functions. To our knowledge, this is the first published clinical experience regarding cerebellar HB coexistent with an AICA aneurysm that involved the efferent segment of the tumor's feeding vessel. Patients with coexistent vascular pathologic conditions should be aggressively treated, not by the wait-and-see practice, in case of unexpected rupture in the future. [ABSTRACT FROM AUTHOR]

von Hippel-Lindau disease–related hemangioblastoma is likely to occur in the cerebellum and accompany a cyst. As multiple hemangioblastomas commonly occur in von Hippel-Lindau disease, and multiple surgeries may thus be necessary, a minimally invasive surgical strategy is of great importance. We present 2 patients with von Hippel-Lindau disease–related hemangioblastomas successfully treated by a fully endoscopic transcranial approach via a short skin incision and a 2 cm × 2 cm small bony window. Before surgery, a three-dimensional virtual reality model was created to determine the ideal trajectory. Patient 1 had 2 serial large cystic tumors that equally contributed to obstructive hydrocephalus and were resected sequentially via a single endoscopic trajectory. Patient 2 had a progressive large cystic tumor that was resected endoscopically. Complete resection of the tumors was achieved without any complications in either patient. Small nodular tumors accompanying a large cyst are plausible candidates for endoscopic transcranial surgery. The spatial relationship of nodules, cyst, and cerebellar parenchyma is important to determine the applicability of the present technique. Preoperative three-dimensional virtual reality simulation helps assess the feasibility of this approach. [ABSTRACT FROM AUTHOR]

Hemangioblastomas (HBs) are benign, highly vascular tumors, often characterized by loss of function of the von Hippel–Lindau (vHL) gene. They are the most common central nervous system tumor observed in vHL syndrome. Loss of function of the vHL gene creates a "pseudo-hypoxic" state, causing overactivation of hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF)-related pathways. In some cases, HBs can rapidly increase in size during pregnancy to then present acutely, which most frequently occurs after the 20th gestational week. These changes in size usually occur from enlargement of the cystic component of the HB. Due to their preferred location in the posterior fossa near critical structures as well as along the spinal cord, such cases can present with severe neurological deficits, requiring urgent surgical intervention in a multidisciplinary setting. However, the reasons for this acute flare-up during pregnancy remain poorly understood, as are the reasons why this occurs in only a subset of tumors. Unveiling the etiology for this clinical scenario can affect the treatment of HBs, as it will contribute to the understanding of the pathophysiology of such a transformation from a quiescent lesion to a symptomatic one, not only in the setting of pregnancy. Identifying the correct triggers and the conditions initiating and mediating this switch will enable us to develop preventive medications which should allow us to keep the tumor in its quiescent phase. In this pathophysiological review, we investigate the association between HB growth and pregnancy based on an analysis > 40 such published cases. We suggest that the proangiogenic state of pregnancy is the leading etiology for this striking association, and to support the argument, we discuss its potential impact on HIF overexpression in a non-hypoxic manner through activation of the PI3K/Akt/mTOR pathway by proangiogenic factors. Specifically, we discuss the involvement of placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR-1) in various pathologic processes that can lead to the formation and growth of peritumoral edema and cysts, which are the primary causes for the development of any symptoms in HB. Both PlGF and VEGFR-1 are expressed at increased levels during pregnancy, and both have been reported as part of various pathological processes, including angiogenesis and tumorigenesis. The unique feature that both do essentially not show any significant negative impact on regular physiological processes makes them attractive therapeutic targets since very little side effects are expected. Further research into the effects of anti-PlGF or anti-VEGFR-1 therapy in HB is therefore recommended. [ABSTRACT FROM AUTHOR]

Von-Hippel Lindau (VHL) disease is rare neurocutaneous disorder arising from an inactivating mutation of the VHL gene on chromosome 3p35. The disease is inherited in an autosomal dominant fashion and predominantly involves tissues originating from the ectodermal germ layer. Although hemangioblastomas of retina and cerebellum are the most common clinical features, multiple-organ involvement in the form of renal cell carcinomas, spinal hemangioblastomas, renal cysts, and pancreatic cysts have also been reported. Hemangioblastomas of the spinal canal could present as cauda equina syndrome. We describe the case of a 55-year-old man with cauda equina syndrome as his first manifestation. An initial magnetic resonance imaging scan uncovered hemangiomas in the spinal canal. A thorough family history strongly suggested an autosomal dominant pattern of disease inheritance. Further physical examination and imaging revealed additional organ involvement consistent with VHL. We performed laminectomy and partial resection of hemangioblastoma for decompression. He recovered satisfactorily with his cauda equina syndrome resolving quickly post operation. No deterioration was apparent by the 12-month follow-up visit. To the best of our knowledge, this is the first case with cauda equina syndrome as the first manifestation of VHL disease. Laminectomy and partial resection of hemangioblastoma are safe and effective treatments to resolve impingement of the spinal cord. VHL disease resulting in hemangioblastoma in the spinal canal is rarely seen but should be included in the differential diagnosis of cauda equina syndrome to facilitate genetic counseling for the proband and offspring. [ABSTRACT FROM AUTHOR]

Background: Hemangioblastomas account for about 1%-3% of all central nervous system tumors. They are usually associated with the Von Hippel-Lindau syndrome and typically occur in the posterior fossa, or throughout the spinal neuraxis. Here, we report the unusual case of a sporadic cauda equina hemangioblastoma. Case Description: A 28-year-old Caucasian female patient presented with progressive low back pain of 2 months duration. The magnetic resonance (MR) revealed a heterogeneous intradural and extramedullary lesion at the L2 level; with intravenous contrast, there were vascular flow voids and surrounding vasogenic edema (i.e., measuring 4.1 cm × 3.5 cm). The patient underwent an L2 right hemilaminectomy under intraoperative neurophysiological monitoring. She was discharged the 4th postoperative day, neurologically intact. Literature describes 21 previous reports of sporadic isolated spinal hemangioblastomas. Conclusion: Although rare, sporadic, and isolated hemangioblastomas of the cauda equina should be included among the differential diagnoses of intradural spinal lesions, particularly when enhanced MR studies document serpentine flow voids. [ABSTRACT FROM AUTHOR]

Background: Spinal haemangioblastomas are rare benign but potentially devastating vascular tumours. They may occur sporadically or as a component of Von Hippel-Lindau (VHL) disease. There is a dearth of information about these tumours among Nigerians. This study aims to evaluate the clinical profile and outcome of surgery as well as the challenges of management of these tumours in a resource-limited country. Methods: We retrospectively analysed data from the records of patients who had surgery for spinal haemangioblastoma at our center between January 2004 and December 2018. Results: We operated 2 cases of spinal haemangioblastomas during the study period (1 male, 1 female). The patients were aged 25 and 50 years. Both patients presented with sensorimotor deficits but only one them had sphincteric dysfunction. The duration of symptoms was 2 weeks in one patient and 18 months in the other. The tumour was located in the thoracic region in both of them. One patient had extramedullary tumour while the had an intramedullary spinal tumour. Both patients were paraplegic at the time of surgery, for 3 days in one patient and more than 4 months in the second patient. Gross total tumour resection was achieved in both individual. The patient with short duration of symptoms and extramedullary tumour made a rapid post-operative neurological improvement while the one with long duration of symptoms and intramedullary tumour remained paraplegic until his demise 9 months after surgery. Conclusion: Spinal haemangioblastomas are rare tumours. Long duration of symptoms and intramedullary tumour location are predictors of unfavorable surgical outcome. [ABSTRACT FROM AUTHOR]

Purpose: Patients with von Hippel-Lindau (VHL) disease may develop various tumors, including neuroendocrine tumors of the pancreas (PNETs) and adrenal, central nervous system and retinal hemangioblastomas, kidney tumors and more. 68Ga-DOTATATE positron emission tomography (PET)/computerized tomography (CT) has been shown to be highly accurate for tumors with cells expressing somatostatin receptors. We aimed to assess the performance of 68Ga-DOTATATE PET/CT in patients with VHL disease.Methods: Patients with a diagnosis of VHL were enrolled in a prospective study and underwent surveillance imaging for pancreatic lesions (n = 301). The current analysis includes 73 evaluations with multiple imaging modalities of 36 patients (2.1 ± 0.8 evaluations/patient, range 1-4) for a head-to-head comparison of 68Ga-DOTATATE PET/CT, CT and/or MRI. In this post-hoc analysis we compared the detection rates of various imaging modalities for PNETs and for any extrapancreatic tumors located within the scan field of CT/MRI of the abdomen.Results: 68Ga-DOTATATE PET/CT detected a total of 206 lesions, CT detected 208 lesions and MRI detected 94 lesions in 61, 66 and 33 scans, respectively. 68Ga-DOTATATE PET/CT (3.4 ± 0.1 per scan) was superior than CT (3.2 ± 0.1 per scan, p = 0.02) with a similar trend when comparing with MRI (2.8 ± 0.1 per scan, p = 0.03) in detecting lesions in any anatomic locations.Conclusions: 68Ga-DOTATATE PET/CT had a significantly higher detection rate when compared with anatomic imaging for all lesions, and comparable detection rate for pancreatic lesions in VHL patients. Hence, given the higher accuracy and lower radiation exposure associated with 68Ga-DOTATATE PET/CT, its potential role in the surveillance of VHL-associated lesions should be further studied. [ABSTRACT FROM AUTHOR]

Abstract Optic nerve hemangioblastoma is a rare tumor that is usually unilateral and most commonly occurs in the context of von Hippel-Lindau disease. Differential diagnosis is based on clinical history and imaging. Magnetic resonance imaging with gadolinium enhancement is the most useful imaging modality as it can reveal flow voids and an absence of dural attachment, differentiating optic nerve hemangioblastoma from other more commonly encountered optic nerve tumors. Optic nerve hemangioblastoma are usually well-circumscribed vascular lesions composed of stromal cells and vascular endothelial cells. These lesions are diagnosed at a mean age of 37 years and can be asymptomatic, but over time, patients may develop reduction in vision, proptosis, and pain. Surgical excision is well described via orbital, transsphenoidal, or transcranial approaches. Given the risks associated with surgery, a stepwise conservative approach is advocated by most clinicians in the absence of severe symptoms. Although uncommon, this optic nerve tumor should be considered in young patients presenting with pain, proptosis, and optic nerve pallor, with or without a history of von Hippel-Lindau disease. [ABSTRACT FROM AUTHOR]

Background Hemangioblastomas (HBMs) are benign vascular neoplasms that most commonly arise within the cerebellum. Although other vascular lesions should be considered in the differential diagnosis, HBMs rarely resemble aneurysms on neuroimaging and only 1 case of a cerebellar HBM mimicking a posterior fossa aneurysm has been reported. Here we describe a retromedullary HBM that masqueraded as a distal posterior inferior cerebellar artery (PICA) medullary branch aneurysm. Case Description A 63-year-old asymptomatic male was incidentally diagnosed with an unruptured 3-mm left PICA aneurysm via computed tomography angiography during a workup for carotid stenosis. Two years later, the presumed aneurysm enlarged to 6.5 mm and prompted elective treatment. Endovascular treatment was unsuccessful, and the patient was immediately transitioned to a craniotomy for aneurysm clipping. After microsurgical dissection, the lesion was visualized on the posterior medullary surface with several small arterial feeders extending from the brainstem into the aneurysm dome, but no major parent vessel was observed. Because a clip could not be safely applied to these small vessels, they were instead coagulated and the lesion was completely resected. Final pathology revealed hemangioblastoma (World Health Organization grade I). Conclusions To our knowledge, this is the second case of HBM mimicking a PICA aneurysm. Given the rarity of PICA medullary branch aneurysms and their highly symptomatic nature, other etiologies, especially HBM, should be strongly considered when an apparent distal PICA aneurysm is diagnosed in an asymptomatic patient. If the lesion is unamenable to endovascular treatment, there should be high suspicion for HBM and subsequent craniotomy should be pursued. [ABSTRACT FROM AUTHOR]

Background: Hemangioblastomas (HB) are benign tumors of the central nervous system (CNS) that can appear sporadic or as part of von Hippel-Lindau (VHL) disease. It is often curable with surgical resection, but upon relapse, the disease exhibits a treatment-refractory course.Case report: A patient treated for sporadic cerebellar HB relapsed 12 years post-surgery. She developed disseminated disease throughout the CNS, including leptomeningeal manifestations. Repeat surgery and craniospinal radiation therapy were unsuccessful.Conclusion: This case is in line with previous publications on disseminated non-VHL HB. Available treatment options are inefficient, emphasizing the need for improved understanding of HB biology to identify therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Spinal hemangioblastomas account for 1-3% of all spinal cord tumors and are mostly intramedullary in location. Here, we report an intradural extramedullary hemangioblastoma of the thoracic spine, occurring in in a patient without von Hippel-Lindau disease. Case Description: A 58-year-old female had a 5-year history of progressive left lower extremity weakness. When the MR demonstrated an intradural/extramedullary lesion with a syrinx at the T2-3 level, she successfully underwent gross total tumor excision following which she neurologically improved. Conclusion: Here, we report a rare case of an intradural/extramedullary thoracic hemangioblastoma successfully excised at the T 2-3 level in a patient without von Hippel-Lindau disease. [ABSTRACT FROM AUTHOR]

Retinal hemangioblastomas are one of the most common and early manifestations of Von Hippel-Lindau disease. Early detection is the key in their management. When left untreated, these benign neoplasms may continue to grow and result in scleral infiltration and extraocular extension warranting enucleation of the globe. [ABSTRACT FROM AUTHOR]

Background: Hemangioblastomas (HBL) are benign tumors occurring sporadically or associated with Von Hippel-Lindau syndrome (VHL). Method: We present the pre-, per-, and postoperative course of a rare case with radicular HBL presenting with subarachnoid hemorrhage (SAH) in the frame of VHL. We describe the microsurgical approach. Conclusion: Complete microsurgical in bloc resection has been performed. Postoperative course was uneventful. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study., Objective: Cavernous malformations (CMs) and hemangioblastomas (HBs) of the spinal cord exhibit distinct differences in histopathology but similarities in the neurological course. The aim of our study was to analyze the clinical differences between the vascular pathologies and a benign tumor of the spinal cord in a perioperative situation., Methods: We performed a retrospective analysis of patients who had undergone surgery for lesions in the spinal cord between 1984 and 2015. Patients were screened for CMs and HBs as the primary inclusion criteria. General patient information, surgical data, and disease-specific data were collected from the records. Cooper-Epstein scores for clinical symptoms were evaluated preoperatively, at discharge, and at the 6-month follow-up., Results: A total of 112 patients were included, of which 46 had been diagnosed with CMs and 66 with HBs. Patients with CMs often demonstrated more preoperative neurological deterioration compared to those with HBs ( P < .05); accordingly, in took longer to diagnose HBs. Complete resection was possible for 96.8% of all patients with CMs and 90% of those with HBs. At the 6-month follow-up, patients with HBs more often presented with persisting neurologic impairment of the upper extremities compared to the CM patients ( P < .001)., Conclusion: CMs and HBs of the spinal cord have similarities but also exhibit significant differences in neurological presentation and perioperative course. Surgical therapy is the treatment of choice for symptomatic lesions, and complete surgical resection is possible in the majority of cases for both entities. Neurologic outcomes are usually favorable, although patients with HBs retain neurologic deficits more often., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Von Hippel Lindau is an inherited disease which leads to tumor growth, including hemangioblastomas in the central nervous system and retina. No pharmacological treatment has demonstrated efficacy. Propranolol is a beta-blocker widely used in some neurological and cardiac diseases, and its safety is known. We present a patient diagnosed with Von Hippel Lindau disease who was treated with propranolol for worsening migraine. The patient exhibited two asymptomatic hemangioblastomas, which showed no change in size during treatment with propranolol. Our case report suggests that propranolol could be effective in delaying the growth of hemangioblastomas in the central nervous system.

Highlights • Reciprocal effects between pregnancy and hemangioblastomas were not thoroughly clear. • Symptomatic treatment was the first choice for these patients, especially for those with spinal hemangioblastoma. • Safe urgent tumor resection was possible with careful maternal and fetal monitoring if necessary. • Both maternal and born fetal prognoses were favorable in the long run. Abstract The study aims to assess the management and maternal and fetal outcomes of pregnancies complicated by central nervous system (CNS) hemangioblastoma. Twenty-four female patients with CNS hemangioblastoma, who were pregnant in a tumor-burden status, were identified. Their medical charts, treatments, and follow-up materials were carefully reviewed. Of the included 24 CNS patients with hemangioblastoma (14 intracranial and 10 spinal hemangioblastomas), 5 patients (20.8%) were diagnosed with Von Hippel-Lindau disease (VHL). The median age of these patients at admission was 27.5 years. Intracranial hypertension was a common presenting symptom for patients with intracranial hemangioblastoma and was observed in 85.7% (12/14) of cases; the other 10 patients with spinal hemangioblastomas all suffered from paresthesia. Overall, 66.7% (16/24) of patients with CNS hemangioblastoma went through the gestational course with conventional observation; 16.6% (4/24) of patients accepted a ventriculo-peritoneal shunt (VPS) to delay the tumor resection; and 16.7% (4/24) of patients needed urgent tumor resection even when symptomatic treatments were given. Variable symptom improvement was seen when patients had follow-up visits at a median of 32.5 months. No maternal death or tumor recurrence was identified. For the fetal prognoses, one (4.2%) pregnancy ended in a spontaneous miscarriage and for (16.7%) pregnancies were interrupted; the other 19 (79.2%) live births were in good status without any congenital malformations. Symptomatic treatment was the first choice for pregnant patients with CNS hemangioblastoma. When needed, urgent tumor resection could be safely achieved with careful maternal and fetal monitoring. Both maternal and fetal prognoses were favorable during follow-up. [ABSTRACT FROM AUTHOR]

Hemangioblatomas are low grade, highly vascular tumors usually associated with VHL syndrome and most commonly occurs in the cerebellum. They very rarely occur in the spinal nerve roots and an origin in the filum terminale is exceptionl. A 47 year old man presented with low back pain, paresthesias and stiffness of the both lower limbs. He also had urinary retention and constipation. MRI showed an enhancing mass at the L5 vertebral level with multiple dilated and tortuous vessels at both poles of the tumor. Digital subtraction angiogram showed the tumor to be supplied by the anterior spinal artery and dural branches of lumbar arteries. At surgery, a well-defined tumor with orange red hue was found to be arising from the filum terminale. The tumor was excised en bloc. Histopathological examination showed hemangioblastoma which was confirmed with immunohistochemistry. Clinical symptoms improved significantly after surgery. A sporadic hemangioblastoma arising from the filum terminale should be considered as a rare cause of back pain and sciatica. Total excision of the tumor usually cures the patient. [ABSTRACT FROM AUTHOR]

Hemangioblastomas represent 3% of all central nervous system (CNS) tumors. The majority of CNS hemangioblastomas are infratentorial, with the cerebellum being the most frequent location, while 13% are found in the brainstem. Symptoms of brainstem hemangioblastomas can be very subtle and might therefore be overlooked or misinterpreted. We report the case of a patient with a hemangioblastoma at the junction of the medulla oblongata and the cervical spine and provide a brief review of the literature. [ABSTRACT FROM AUTHOR]

Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or peripheral sites have been reported to date, sporadically or in the setting of von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic analysis, using either the patient’s peripheral blood in 9 cases or paraffin embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9 cases in which DNA from peripheral blood lymphocytes was used, all with clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin embedded tumor tissues. The clinical features, histopathology, and molecular investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median age: 47 years) are presented herein. The histopathologic diagnosis was supported by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter methylation. Two of the present cases were already published with only limited or no molecular investigations. Four tumors of the present series were paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One tumor was von Hippel-Lindau disease-associated, 1 was classified as “hemangioblastoma-only VHLD”, 7 were sporadic, and one was unknown. All were histopathologically analogous to their counterpart located inside the central nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE, and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2 different extraneuraxial hemangioblastomas, and LOH in 4 (two as a double hit), all non-renal extraneuraxial hemangioblastomas. Methylation analysis failed to disclose promoter methylation in any case. In conclusion, we report eight new cases from the wide category of extraneuraxial hemangioblastomas (4 paraneuraxial, and 4 renal), one of which was von Hippel-Lindau disease-associated and 7 sporadic. VHL gene alterations were found not only in the von Hippel-Lindau disease-associated tumor, but − for the first time − also in 3 sporadic ones, two of which with novel mutations. [ABSTRACT FROM AUTHOR]

Purpose: Haemangioblastomas (HABLs) and pilocytic astrocytomas (PAs) are brain tumours presenting similar appearance and location in conventional magnetic resonance (MR) imaging. The purpose of our study was to determine whether a detailed analysis of diffusion (DWI) and perfusion (PWI) characteristics can be useful in preoperative differentiation of these tumours. Material and methods: The study group consisted of biopsy proven six HABLs and six PAs, which underwent preoperative standard MR examinations including PWI and DWI. In PWI relative cerebral blood volume (rCBV) and the shape of perfusion curves (parameters of peak height - rPH and percentage of signal recovery - rPSR) were analysed. All perfusion parameters were measured for the entire tumour core (mean rCBV, mean rPH, mean rPSR) and in regions with maximal values (max rCBV, max rPH, max rPSR). In DWI parameters of apparent diffusion coefficient (ADC) from the entire tumour core (mean ADC) and in regions with minimal values (min ADC) were evaluated. Results: Compared to PAs, HABLs presented significantly higher rCBV and rPH values and lower mean rPSR value. PAs showed significantly lower rCBV and rPH values and higher mean rPSR value. Mean rCBV showed no overlap in the values between HABLs and PAs, and thus it provided the highest accuracy in differentiating between them. Max rPSR, mean ADC, and min ADC did not show any significant differences. Conclusions: High rCBV values and deep perfusion curves with only partial return to the baseline are characteristic features of HABLs differentiating them from PAs, which show lower rCBV values and perfusion curves overshooting the baseline. Diffusion parameters are not useful in differentiation of these tumours. [ABSTRACT FROM AUTHOR]

Background Hemangioblastomas usually occur in the cerebellum and are often a component of von Hippel-Lindau disease. Edema-like changes along the optic tract are commonly observed in association with tumors in the sellar and suprasellar regions, such as craniopharyngiomas and pituitary adenomas. Here, we describe a case of sporadic suprasellar hemangioblastoma with edema-like changes along the optic tract that completely resolved after surgery. Case Description The patient was a 28-year-old woman with failing vision and a bitemporal hemianopia. Magnetic resonance imaging revealed a tumor accompanied by a 10-mm cyst. Fluid-attenuated inversion recovery axial magnetic resonance imaging revealed a hyperintense region along the optic tract. Other regions of the central nervous system were normal. Endoscopic transsphenoidal surgery was performed, and the histopathologic findings confirmed hemangioblastoma. Six months after surgery, the edema-like change along the optic tract had disappeared. The patient is doing well without pituitary insufficiency, pituitary hormone medications, or signs of tumor recurrence. In addition, the genetic test was negative for von Hippel-Lindau mutations. Conclusions When examining a patient with suprasellar tumor, clinicians must consider the possibility of hemangioblastoma. Adequate treatment can improve the edematous change and visual disturbance. [ABSTRACT FROM AUTHOR]

The aim of this study is to compare the optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA) features of retinal capillary hemangioblastoma (RCH). This is an observational case series of three patients with von Hippel-Lindau (VHL) disease and one patient with juxtapapillary RCH. All patients underwent FFA with a mydriatic fundus camera and OCTA with swept-source angio OCT. The FFA and OCTA characteristics of tumors were compared. In our series, FFA could identify tumors as small as the width of a third-order retinal artery, which was missed on clinical examination. OCTA identified these tiny tumors, but only those closer to the posterior pole. Both FFA and OCTA could identify the intrinsic vasculature and feeder vessel in juxtapapillary RCH. On OCTA, the tumors were better defined than in FFA. The depth of the lesion can be identified on OCTA. Feeder and the draining vessels could be identified precisely in OCTA than FFA, particularly in small tumors. OCTA can identify tumors in VHL missed on clinical examination. It can identify the feeder vessel and intrinsic vasculature of sessile juxtapapillary RCH and aids in its diagnosis. Tumors are better defined in OCTA than FFA due to the absence of leakage. However, FFA can identify nearly all the early tumors, but OCTA fails to image the peripheral tumors due to its smaller field and prolonged acquisition time. Technological advances and the development of wide-field OCTA in the future can be helpful in identifying all the unsuspected tumors in VHL disease. [ABSTRACT FROM AUTHOR]

Hemangioblastomas are benign tumors of the central nervous system (CNS) that may occur either sporadically or as part of von Hippel–Lindau (VHL) disease, in which they coexist with a series of other tumors outside the CNS. Because of their low mitosis rate, hemangioblastomas usually have slow-growing and late manifestations, but may cause sudden neurological symptoms if tumor hemorrhage occurs. Few studies have evaluated the impact of pregnancy on the evolution of hemangioblastomas. Some authors have reported tumor growth in women with VHL disease, but no such association was observed by others. The influence of pregnancy on sporadic hemangioblastomas remains largely unexplored. We report here the case of a pregnant woman whose first manifestation of sporadic spinal hemangioblastoma was life-threatening, rapidly progressive dysautonomia. In addition, we discuss the role of pregnancy in the triggering of symptoms, as well as the possibility of medically indicated delivery for the management of these tumors. [ABSTRACT FROM AUTHOR]

Introduction: Hemangioblastomas [75% sporadic, 25% with Von Hippel Lindau (VHL) disease] are highly vascular, benign lesions. The surgical nuances, management, and complication avoidance in brain-stem hemangioblastomas (BHs) have been studied.Material and Methods: Over 18 years, 27(mean age: 29 years; range 15-60 years) consecutive cases of BH underwent microsurgical excision. All patients were assessed clinico-radiologically for neurological deficits and screened for VHL disease. Outcome of the patients was based on Karnofsky Performance Status scale (KPS).Results: 12 out of 19 (70.4%) patients with hydrocephalus underwent a cerebrospinal fluid (CSF) diversion procedure. Lower cranial nerve palsy was present in 10 (37%) patients and motor weakness in 13 (48%). The tumours [mean size 3.34 ± 1.06 cm, range: 1.4-5.5 cm; 11 solid, rest solid-cystic; 18 (66.7%) subpial and 9 (33.33%) intramedullary] were divided into four categories based on size: A: <2 cm (n = 5,18.5%); B: 2-3 cm (n = 10,37%); C: 3-4 cm (n = 6,22.2%); D: >4 cm (n = 6,22.2%). Their location was at posterior cervicomedullary junction (n = 12); pontomedullary junction (n = 7); pons (n = 3), medulla (n = 3) and ponto-mesencephalic region (n = 2). Multiple flow voids were seen in >50% patients with tumour >2 cm. 5 patients had syringomyelia; and, 8 had diffuse cervical cord expansion. Two patients with a large vascular tumour underwent preoperative embolization. Six patients had VHL disease; one underwent bilateral adrenalectomy for refractory hypertension; and, the another, nephrectomy for renal cell carcinoma. Twenty-six patients underwent a midline suboccipital craniectomy; and, 1 with a cerebellopontine angle tumour, a retromastoid craniectomy. 15 patients underwent total excision; 10 patients, near-total (<10% remaining) excision, and 2 patients, a subtotal (>10% remaining)) excision. Three patients (2 with VHL disease) expired due to exsanguinating hemorrhage, spreading venous thrombosis and aspiration pneumonitis, respectively. At follow-up visit (median: 25 ± interquartile range 2-56months), 17 patients had improved KPS, 4 remained in same status and 3 (recently operated, on tracheostomy) had worsened KPS.Conclusions: Significant improvement is achievable in neurological status in patients following successful extirpation of a brain-stem hemangioblastoma, despite a turbulent perioperative period. Leaving tumour capsule adherent to the brain-stem often helps in preserving brain-stem function. Postoperatively, the patients should be monitored for their respiratory and lower cranial nerve status to prevent aspiration pneumonitis. [ABSTRACT FROM AUTHOR]

Background: Supratentorial hemangioblastoma is an uncommon lesion with few data available. Resemblance to other tumours represents a struggle concerning pre-operative diagnosis and management. Objectives: The aim of this study was to review the current literature, integrating two new cases with uncommon features. Methods: A search of English language peer-reviewed articles in PubMed®, Cochrane Library®, Google Scholar® and summary of the current knowledge. Results: A total of 162 cases, with no predominance between von Hippel–Lindau disease and wild-type sporadic lesions. The frontal lobe is the most common topography, followed by the pituitary stalk, with image resemblance to a glioma or a metastasis. From these, 20 cases revealed dural attachment, mimicking a meningioma. Symptoms are due to mass effect or epilepsy, with low haemorrhagic risk. Clinical outcome on supratentorial hemangioblastoma depends on resection extension, with no recognised complementary treatment. Post-operative follow-up is essential, even in wild-type, sporadic cases, concerning recent reports of tumour dissemination. Conclusions: This review compiles the main characteristics of supratentorial hemangioblastoma, that despite its rarity, should be a concern on differential diagnosis, treatment planning and expected prognosis. [ABSTRACT FROM AUTHOR]

Circulating endothelial cells (CECs) detach from the intima monolayer after endothelial damages. Their circulating endothelial progenitors (CEPs) represent less than 0.01% of nucleated blood cells. Increased levels of CECs and CEPs have been detected in patients with several types of cancer, suggesting that they could be a useful blood-based marker for detecting a tumor, or for monitoring its clinical course. However, their routine monitoring is time consuming and technically challenging. Here, we present a flow cytometry method for quantifying such cells in a cohort of patients with hemangioblastoma (HB). HB is a rare benign tumor, responsible for 1–2.5% of primary intracranial tumors and up to 10% of spinal cord tumors, and for which no tools are available to predict the onset or recurrence in patients undergoing surgical removal of tumor mass. This method allowed us to accurately quantifying CEC and CEP before and after surgery. CEPs are present at high levels in HB patients than control before intervention, and decrease after tumor removal, suggesting that their percentage could represent a valid tool to monitor the disease onset and recurrence. [ABSTRACT FROM AUTHOR]

Background Spinal hemangioblastomas account for 1%–5% of all spinal cord tumors. Although spinal hemangioblastomas are rare, it is exceedingly rare to have a case of intradural extramedullary hemangioblastoma of the spine, especially in isolation without von Hippel-Lindau syndrome. The purpose of this report is to present a rare case of intradural extramedullary hemangioblastoma of the cauda equina and a literature review. Case Description An 82-year-old man presented with an intradural mass at the L4 spinal level on magnetic resonance imaging. Given the benign appearance on magnetic resonance imaging and lack of radiculopathy, the decision was made to observe the patient. Over the course of 4 years, the tumor enlarged and caused left lower extremity radicular pain. Posterior laminectomy and tumor excision was performed. Owing to intimate involvement with multiple nerve roots, subtotal resection was performed. Immunohistopathologic analysis revealed a highly vascular and cellular tumor, with findings consistent with intradural extramedullary hemangioblastoma. The patient ultimately underwent CyberKnife radiosurgery for residual tumor, with improvement in neurologic symptoms. Follow-up studies at 2 years failed to show any tumor growth. Conclusions Literature review revealed cauda equina intradural extramedullary spinal hemangioblastoma to be a rare diagnosis. Furthermore, this was a sporadic case without associated von Hippel-Lindau syndrome. Only 20 previous cases have been reported. Immunohistopathologic analysis was required to make the diagnosis. Radiosurgery appears to be useful in cases of residual tumor after subtotal tumor resection. [ABSTRACT FROM AUTHOR]

The field of hematopoietic and vascular developmental research owes its origin to the chick embryo. Many key concepts, such as the hematopoietic stem cell, hemangioblast and hemogenic endothelium, were first proposed in this model organism. Genetically tractable models have gradually replaced the chick in the past two decades. However, advances in comparative genomics, transcriptomics and promoteromics promise a re-emergence of the chick embryo as a powerful model for hematopoietic/vascular research. This review summarizes the current status of our understanding of early blood/vascular development in the chick, focusing primarily on the processes of primitive hematopoiesis and early vascular network formation in the extraembryonic and lateral plate mesoderm territories. Emphasis is given to ontological and molecular association between the blood and endothelial cells and to the evolutionary relationship between the hemangioblasts, common precursors for the blood and endothelial lineages, and the coelomic epithelial lining cells. Links between early blood/vascular development and later definitive hematopoiesis are also discussed. Finally, potential applications of the chick model for comparative and omics-level studies of the blood/vascular system are highlighted. [ABSTRACT FROM AUTHOR]