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To report the efficacy of the oral hypoxia-inducible factor 2α inhibitor belzutifan in participants with von Hippel-Lindau disease-associated retinal hemangioblastomas in the LITESPARK-004 study. Subgroup analysis of the phase 2, single-arm, open-label LITESPARK-004 study. Adults with 1 or more von Hippel-Lindau disease-associated measurable renal cell carcinoma tumors not requiring immediate surgical intervention were eligible. Participants received oral belzutifan 120 mg once daily until disease progression or unacceptable treatment-related toxicity. Efficacy of belzutifan in retinal hemangioblastomas was a secondary end point, measured as response (improved, stable, or progressed) by independent reading center-certified graders based on color fundus imaging performed every 12 weeks using the investigator's preferred imaging standards. Additional assessments, where available, included OCT and ultra-widefield fluorescein angiography. Among 61 participants in LITESPARK-004, 12 had 1 or more evaluable active retinal hemangioblastomas in 16 eyes at baseline per independent reading center. As of April 1, 2022, the median follow-up for participants with ocular von Hippel-Lindau disease at baseline was 37.3 months. All 16 eyes were graded as improved, with a response rate of 100.0% (95% confidence interval, 79.4%–100%). No new retinal hemangioblastomas or ocular disease progression were reported as of data cutoff date. Eight participants underwent additional multimodal eye assessments performed at the National Institutes of Health study site. Among this subgroup, 10 of 24 hemangioblastomas in 8 eyes of 6 participants measured 500 μm or more in greatest linear dimension at baseline and were analyzed further. All 10 hemangioblastomas had a mean area reduction of 15% or more by month 12 and of 30% or more by month 24. Belzutifan showed promising activity against ocular von Hippel-Lindau disease, including capacity to control retinal hemangioblastomas, with effects sustained for more than 2 years while treatment is ongoing. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Background Spinal cord hemangioblastomas are rare benign and highly vascular tumors that develop either sporadically or as part of von Hippel–Lindau (VHL) disease. Generally, complete resection without significant neurologic deficit remains considerably challenging due to the risk of massive bleeding. The current study therefore aimed to describe en bloc resection of spinal cord hemangioblastomas according to the typical anatomical structures of peripheral lesions and evaluate the neurofunctional prognosis of this technique. Methods A total of 39 spinal cord hemangioblastomas from a series of 19 patients who underwent en bloc resection were retrospectively analyzed. In all cases, clinical and radiologic characteristics, as well as surgical tenets, were retrospectively determined and analyzed. Short- and long-term outcomes were analyzed using the McCormick grade and Odom's criteria. Factors significantly associated with poor neurologic function after en bloc resection were also determined. Results All 39 spinal cord hemangioblastomas, including 28 intramedullary, 2 intramedullary–extramedullary, and 9 extramedullary lesions, were located dorsally or dorsolaterally (100.0%). The most common lesion location was the thoracic segment (53.8%), with most of the lesions being accompanied by syringomyelia (94.7%). Long-term follow-up (mean: 103 ± 50.4 months) for prognosis determination revealed that 88.2% (15/17) of all cases had stable or improved neurofunctional outcomes according to the McCormick grade and Odom's criteria. Only one case with VHL disease developed recurrence 4 years after surgery. Additionally, statistical analysis showed that VHL disease was an independent prognostic factor associated with deteriorating neurologic function (p = 0.015). Conclusions En bloc resection facilitated satisfactory long-term functional outcomes in patients with spinal cord hemangioblastomas. Given that VHL disease was identified as a predictor of poor long-term outcomes, regular long-term follow-up of patients with VHL-associated spinal cord hemangioblastoma seems necessary. [ABSTRACT FROM AUTHOR]

Background: Central nervous system hemangioblastomas are the most prevalent manifestation of von Hippel‐Lindau (VHL) disease and remain the main cause of mortality. Surgical resection is the primary treatment strategy, but is not always possible, and should be used as restrictively as possible. There is an unmet need for less invasive treatment strategies, such as targeted therapy. Expression of somatostatin receptor 2A (SSTR2A) in VHL‐related hemangioblastomas has been described earlier, but the extent of expression in a larger population has yet to be determined. The authors hypothesize that a substantial subset of VHL‐related hemangioblastomas show SSTR2A expression, which may serve as a potential new treatment target. Methods: Patients who were surgically treated for a VHL‐related hemangioblastoma from 1990 until 2021 at the UMC Utrecht were included. Clinical data was derived from a clinical database. Tissue samples were histopathologically examined with use of hematoxylin and eosin staining, and immunohistochemical analysis of SSTR2A expression was performed. Results: Forty‐three tissue samples were obtained from 26 patients. Nine showed strong positivity for SSTR2A expression, whereas 13 showed moderate and 15 sparse expression. Three samples showed no expression of SSTR2A. The distribution showed right‐skewedness favoring a strong expression. SSTR2A expression colocalized with endothelial markers and not with stromal cells. Additionally, within‐patient variability for SSTR2A expression was described in 14 patients. Conclusion: SSTR2A is expressed in varying degrees in the majority of VHL‐related hemangioblastomas. Future treatment with somatostatin analogues or even peptide receptor radionuclide treatment may be considered for SSTR2A‐positive cases. There is a variable intrapatient expression of somatostatin receptor type 2A hemangioblastomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Intramedullary primary spinal cord tumors represent a heterogeneous group of very rare tumors. In cases of recurrence or high-grade tumors, radiotherapy, chemotherapy, or targeted therapies can be indicated. The purpose of this review is to clarify the actual knowledge about intramedullary primary spinal cord tumors in light of the latest progress made in their classification. Intramedullary primary spinal cord tumors are rare in adults and their classification has recently evolved. Their treatment most frequently relies on maximal safe surgical resection. Herein, we review, in light of the WHO 2021 classification of central nervous system tumors, the knowledge regarding the role of radiotherapy and systemic treatments in spinal ependymomas, spinal astrocytomas (pilocytic astrocytoma, diffuse astrocytoma, spinal glioblastoma IDH wildtype, diffuse midline glioma H3-K27M altered, and high-grade astrocytoma with piloid features), neuro-glial tumors (ganglioglioma and diffuse leptomeningeal glioneuronal tumor), and hemangioblastomas. In spinal ependymomas, radiotherapy is recommended for incompletely resected grade 2 tumors, grade 3 tumors, and recurrent tumors not amenable to re-surgery. Chemotherapy is used in recurrent cases. In spinal astrocytomas, radiotherapy is recommended for incompletely resected grade 2 astrocytomas and grade 3 or 4 tumors as well as recurrent tumors. Chemotherapy is indicated for newly diagnosed high-grade astrocytomas and recurrent cases. In hemangioblastomas not amenable to surgery, radiotherapy is an effective alternative option. Targeted therapies are playing an increasingly important role in the management of some intramedullary primary spinal cord tumor subtypes. BRAF and/or MEK inhibitors have demonstrated efficacy in pilocytic astrocytomas and glioneuronal tumors, belzutifan in von Hippel–Lindau-related hemangioblastomas, and promising results have been reported with ONC201 in diffuse midline glioma H3-K27M altered. [ABSTRACT FROM AUTHOR]

Introduction: Optic nerve and chiasm hemangioblastomas are rare tumors, occurring sporadically or in the context of von Hippel-Lindau (VHL) disease. They have only been portrayed in isolated case reports and small cohorts. Their natural history and therapeutic strategies are only scarcely described. To better characterize these rare tumors, we retrospectively analyzed an optic nerve and chiasm hemangioblastoma series of 12 VHL patients. By combining our own experience to a review of all known cases in literature, we intended to create treatment recommendations for optic nerve and chiasm hemangioblastomas in VHL patients. Methods: We reviewed two electronic databases in the hospitals of our senior authors, searching for VHL patients with optic nerve or chiasm hemangioblastomas. Clinical data were summarized. Tumor size and growth rate were measured on contrast enhanced MRI. Comparable data were collected by literature review of all available cases in VHL patients (Pubmed, Trip, Google and Google Scholar). Results: Of 269 VHL patients, 12 had optic nerve or chiasm hemangioblastomas. In 10 of 12 patients, tumors were diagnosed upon annual ophthalmoscopic/MRI screening. Of 8 patients who were asymptomatic at diagnosis, 7 showed absent or very slow annual progression, without developing significant vision impairment. One patient developed moderate vision impairment. Two symptomatic patients suffered from rapid tumor growth and progressive vision impairment. Both underwent late-stage surgery, resulting in incomplete resection and progressive vision impairment. One patient presented with acute vision field loss. A watchful-waiting approach was adopted because the hemangioblastoma was ineligible for vision-sparing surgery. One patient developed progressive vision impairment after watchful waiting. In the literature we found 45 patient cases with 48 hemangioblastomas. Discussion: When optic nerve and chiasm hemangioblastomas are diagnosed, we suggest annual MRI follow-up as long as patients do not develop vision impairment. If tumors grow fast, threaten the contralateral eye, or if patients develop progressive vision deficiency; surgical resection must be considered because neurological impairment is irreversible, and resection of large tumors carries a higher risk of further visual decline. [ABSTRACT FROM AUTHOR]

Spinal hemangioblastomas are often evaluated with catheter angiography for both workup and treatment planning. We report a unique longitudinal pulse-synchronous bouncing phenomenon observed during their angiographic evaluation and consider the association of pulse-synchronous bouncing with syringomyelia, another pathologic feature associated with hemangioblastomas. Preoperative spinal angiograms and associated magnetic resonance imagings (MRIs) obtained over a 16-year period at a single institution were retrospectively evaluated. Magnetic resonance imaging (MRI) parameters included lesion and syrinx location and size. Angiograms were evaluated for bouncing phenomena. Student's t-test and Chi square test compared characteristics between groups. Linear regression analyses evaluated maximum amplitude of dynamic motion and any associated syrinx. Nineteen hemangioblastoma patients had preoperative angiograms available for review. Eight exhibited bouncing behavior. Between the dynamic and nondynamic cohorts, there was no difference in presence or volume of syrinxes. Lesions in the dynamic cohort trended towards a cervical location (75% vs. 36.3%, P = 0.10). No significant correlation was found between bouncing amplitude and syrinx size (R2 = 0.023). Dural contact may be related to this dynamic behavior since other high-flow lesions like AVMs do not demonstrate this phenomenon, and AVMs are pial-based and more likely to contact stationary dura. Here, there were fewer lesions abutting the thecal sac in the dynamic cohort (50% vs. 81.8%, P = 0.14). Though no significant relationship was established between this bouncing behavior and syrinx formation, noted trends included a greater range of motion for cervical lesions and limited motion in tumors abutting the thecal sac. [ABSTRACT FROM AUTHOR]

Background: Pregnancy being an immunocompromised state, when complicated with neoplasm, challenges its management and outcomes. The study aims to find a middle path for optimum maternal, fetal, and oncological outcomes. Aim and objective: To understand a multidisciplinary approach towards care and management of cancers concomitantly prevalent with pregnancy and their outcomes. Methodology: An observational retrospective study was conducted at a Tertiary Care Hospital. Case description: This case series involves multiple cases diagnosed as neoplasms during pregnancy. Brain tumors in pregnancy are extremely rare. Here citing four cases with CNS tumors complicating the natural course of pregnancy. Also, including other tumors like 4 cases of Hematological malignancies during pregnancy. Conclusion: A multidisciplinary approach paves the way for optimum management of pregnancy with the neoplasm. Each case is unique and desires a new set of management protocols. The cases mentioned below describe the best possible treatment available and provided in various cases of neoplasms complicating pregnancy. [ABSTRACT FROM AUTHOR]

The identification of the VHL gene and its role in regulating the hypoxia-inducible factor signaling pathway has helped to revolutionize the treatment of renal cell carcinoma (RCC). Belzutifan is a novel small-molecule inhibitor of hypoxia-inducible factor 2α which has demonstrated efficacy in treating von Hippel–Lindau (VHL) disease, earning regulatory approvals for this indication. There is also early evidence for efficacy in sporadic RCC. Belzutifan has a favorable safety profile. Several clinical trials are currently ongoing, which should help in identifying this promising drug's role in RCC and beyond. This review summarizes the history, pharmacology and clinical evidence for belzutifan use to date, and also explores unanswered questions as they relate to this novel therapeutic agent. The novel drug belzutifan was developed after years of research in identifying the VHL gene and how genetic abnormalities in VHL may result in tumor growth. Belzutifan has been approved for use in patients with VHL disease – a rare familial disorder first described in the 19th century that presents with a variety of cancerous and noncancerous tumors, including kidney cancer. Growing evidence supports belzutifan's use in non-familial kidney cancer as well. This is important because most patients eventually develop resistance to the currently available cancer treatments, highlighting the need for drugs with a different mechanism of action. Belzutifan works by blocking a protein called HIF-2a, which causes tumor growth in patients with VHL disease. Belzutifan is well tolerated, with the most common side effects being low energy, hemoglobin and blood oxygen. This review summarizes the history, mechanism of action and research evidence to date supporting the use of belzutifan in VHL disease and cancer treatment. We also discuss future directions, including remaining clinical questions and areas of ongoing research. Executive summary Introduction Although the last decade has ushered in a new era of systemic therapy options for the management of metastatic renal cell carcinoma (RCC), including molecular targeted therapies and immune checkpoint inhibitors, most patients will eventually develop disease progression. This emphasizes the need for therapeutics with alternative mechanisms of action in the management of metastatic RCC. The VHL gene & its role in the cellular oxygen sensing pathway The VHL gene was identified in 1993, nearly a century after the first historical descriptions of von Hippel–Lindau (VHL) disease. VHL disease is caused by a germline variant in VHL, with an additional somatic inactivation/deletion of VHL in tumor cells. Variants in VHL may manifest in the absence of functional VHL protein, creating a cellular pseudohypoxic state whereby hypoxia-inducible factor (HIF) transcription factors are not degraded as they normally are in the presence of oxygen, ultimately leading to proangiogenic and tumorigenic gene expression. Belzutifan clinical pharmacology Belzutifan (MK-6482) is a first-in-class, second-generation HIF-2α inhibitor that selectively disrupts the heterodimerization of the HIF transcription complex, preventing downstream target gene transcription and resultant oncogenesis. Evidence to date suggests that belzutifan has a well-tolerated toxicity profile. The most commonly experienced side effects include fatigue, anemia and hypoxia. Clinical efficacy of belzutifan LITESPARK-001 was the first-in-human, phase I study of belzutifan that investigated its pharmacodynamics, pharmacokinetics and toxicity in 95 patients with locally advanced or metastatic solid tumors. In this study, belzutifan was well tolerated without dose-limiting toxicities, establishing 120 mg once daily as the recommended phase II dose. Belzutifan for VHL disease was first evaluated in the nonrandomized, phase II LITESPARK-004 study, in which 61 patients with VHL-associated, localized RCC were treated with belzutifan 120 mg orally daily. The demonstrated efficacy for RCC and non-RCC lesions led to the US FDA's approval of belzutifan in 2021 for the treatment of adult patients with VHL disease, with Health Canada and other regulatory bodies following suit. The interim analysis of the phase III study LITESPARK-005 was presented at the European Society for Medical Oncology Congress in 2023, showing superior objective response rate and progression-free survival for belzutifan compared with everolimus in previously treated patients with advanced RCC. Discussion To date, belzutifan has not been approved in any jurisdiction for treatment beyond VHL disease, for which the evidence is most robust. Growing evidence suggests belzutifan's efficacy in sporadic RCC; however, its place in the treatment algorithm has not yet been clearly established due the paucity of phase III trial evidence. There are numerous phase III trials evaluating the safety and efficacy of belzutifan in combination with other treatments in the second- and first-line and adjuvant settings for RCC. If belzutifan finds its way into the armamentarium of systemic therapy for metastatic RCC, this agent could be practice-changing beyond the VHL population. [ABSTRACT FROM AUTHOR]

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis. [ABSTRACT FROM AUTHOR]

Objectives: The superiority and usefulness of liquid material over particles for embolization have been a topic of debate due to differences in materials and techniques. This study aimed to identify the complications and outcomes associated with both embolization materials. Methods: This retrospective multicenter cohort study included 93 patients from an endovascular treatment registry, treated from January 1, 2018 to May 31, 2022. It included patients who underwent preoperative embolization for meningioma, solitary fibrous tumor/hemangiopericytoma, and hemangioblastoma. Data for patient characteristics, procedural factors, complications, and outcomes were collected from medical records. Results: A tortuous access route was the only factor independently associated with complications (p = 0.020). Although liquid material was more frequently used for embolization in relatively high-risk conditions, complication rates did not differ significantly between the groups (p = 0.999). In the liquid material group, the tip of the microcatheter could be guided closer to the tumor (p <0.001) using a distal access catheter and flow-guide microcatheters. The subgroup middle meningeal artery embolization had less operative bleeding in the liquid material group (p <0.001), whereas the particles group exhibited less intraoperative blood loss than the liquid material group (p = 0.006). Conclusion: The vascular tortuosity of the access route was only associated with complications in preoperative tumor embolization. Liquid material and particles showed no difference in complication rates. The use of particles in embolization may reduce intraoperative bleeding, but not in all cases can it be used safely. Therefore, a thorough understanding of the characteristics of both approaches and their relative advantages in clinical practice is essential to opt for the appropriate material according to the case. [ABSTRACT FROM AUTHOR]

Background: To date, real-world evidence around the clinical and economic burden related to von Hippel-Lindau (VHL) disease is limited. Therefore, this study characterized the prevalence, healthcare resource utilization (HRU), and economic burden of von Hippel-Lindau–associated central nervous system hemangioblastoma (VHL-CNS-Hb) and pancreatic neuroendocrine tumors (VHL-pNET) in the United States (US). Methods: Patients with VHL-CNS-Hb or VHL-pNET were identified from Optum's de-identified Clinformatics® Data Mart Database (2007–2020) and matched 1:5 to control patients without VHL disease or CNS-Hb/pNET. Prevalence rates of VHL-CNS-Hb and VHL-pNET (standardized by age and sex) in 2019 were estimated. HRU and healthcare costs (2020 US dollars) were compared between the VHL-CNS-Hb/VHL-pNET and control cohorts. Results: In 2019, US prevalence rates of VHL-CNS-Hb and VHL-pNET were estimated to be 1.12 cases per 100,000 (3,678 patients) and 0.12 cases per 100,000 (389 patients), respectively. Patients with VHL-CNS-Hb (N = 220) had more inpatient, outpatient, and emergency department visits and $49,645 higher annual healthcare costs than controls (N = 1,100). Patients with VHL-pNET (N = 20) had more inpatient and outpatient visits and $56,580 higher annual healthcare costs than controls (N = 100). Costs associated with surgical removal of CNS-Hb and pNET were particularly high. Conclusions: In this retrospective, claims-based study, both VHL-CNS-Hb and VHL-pNET were associated with substantial HRU and healthcare costs, particularly tumor reduction surgery–related costs. These findings provide important insight for healthcare payers regarding the expected real-world costs that enrollees with VHL-CNS-Hb and VHL-pNET may incur over the course of their disease. [ABSTRACT FROM AUTHOR]

Background: Patients affected by Von Hippel-Lindau (VHL) are prone to develop central nervous system neoplasms such as hemangioblastomas (HBs). Myxopapillary ependymoma (MPE) is not commonly associated with VHL disease. Case Description: We present the first case of a VHL patient affected by simultaneous silent cauda equina MPE and a symptomatic conus medullaris HB. The patient was first operated for systemic tumors and followed for asymptomatic HBs. Simple surveillance was maintained until neurological symptoms appeared. Regular followup demonstrated objective growth of the cystic conus medullaris tumor while the cauda equina lesion remained stable. Surgery was performed to avoid further neurological worsening. Histopathological examination showed conus medullaris HB and a nearby cauda equina MPE. Conclusion: Simultaneous spinal HBs and isolated MPE may exceptionally occur in VHL patients. [ABSTRACT FROM AUTHOR]

Approximately 50% of central nervous system tumors in children are primary posterior fossa tumors, ranking as the most common solid tumors in childhood. The most frequently encountered types are medulloblastoma, pilocytic astrocytoma, ependymoma, and brainstem gliomas. In addition, less common pathologies such as atypical teratoid/rhabdoid tumors, hemangioblastomas, schwannomas, cerebellar gangliocytomas, and epidermoid tumors are also present. This study comprehensively compiles the epidemiological, histopathological, radiological, and clinical characteristics of pediatric posterior fossa tumors considering current classifications, along with a detailed review of treatment approaches. [ABSTRACT FROM AUTHOR]

Background Hemangioblastomas pose an inherent surgical risk due to the potential for high intraoperative blood loss, especially in larger tumors. One approach to minimize this risk is to use preoperative embolization. Herein, we present our institutional experience treating large and giant cerebellar hemangioblastomas. Methods We performed a retrospective chart review of 19 patients with cerebellar hemangioblastomas that had a maximal diameter of >3 cm. We performed a literature review and included individual patient-level data that met our >3 cm diameter cerebellar hemangioblastoma inclusion criteria. Results Our cohort consisted of 19 patients that received a total of 20 resections for their cerebellar hemangioblastomas. Preoperative embolization was utilized in eight cases (38.1%). One patient experienced transient neurological complications after embolization (12.5%). Tumors of patients in the embolization group had larger median total, solid, and cystic volumes and were more likely to involve the cerebellopontine angle than those in the non-embolized group. Compared with non-embolized patients, embolized patients had less decrease in their hemoglobin, lower volumes of estimated blood loss, reduced rates of postoperative complications and permanent deficits, and greater instances of neurological improvement. The larger cohort (obtained from the combining our cohort with patients identified during a literature review) consisted of 99 patients with 39 receiving preoperative embolization. Conclusion It is important to examine individual patient characteristics when determining eligibility for preoperative embolization. However, improvements in endovascular techniques have made preoperative embolization a safe and effective procedure with minimal risks that can be performed in many patients. [ABSTRACT FROM AUTHOR]

Background - Hemangioblastoms are benign tumors that primarily occur in the central nervous system (CNS). They account for approximately 1.5-2.5% of all brain tumors and 7-12% of infratentorial tumors in adults. The most frequent association of hemangioblastoms is with von Hippel-Lindau (VHL) syndrome, which is characterised by a chromosomal mutation on 3p. In cases of VHL syndrome, these tumors can be found in various locations both within and outside the CNS. On the other hand, sporadic solitary hemangioblastoms, although uncommon, are typically limited to the posterior cranial fossa. The primary treatment option for these tumors is complete surgical removal, making surgery the preferred and most effective approach. Aims and objectives - The purpose of this study was to identify patients with solid and cystic posterior cranial fossa hemangioblastoms and explore the management challenges and outcomes associated with these tumors. Material and methods - This retrospective study included 6 patients admitted with radiologically diagnosed cerebellar hemangioblastoms under department of neurosurgery, GRMC and associated J.A. group of Hospitals from May 2021 to April 2023 who underwent surgery. No randomisation done. Results - The solid and cystic type of hemangioblastoma is typically the most prevalent form. Patients with this type often experience symptoms related to increased intracranial pressure (ICP). To address the tumors, all patients undergo complete removal through surgical resection. However, the occurrence of postoperative complications and mortality rates (16.6%) remains relatively high. This could be attributed to the limited literature available on adult posterior cranial fossa hemangioblastoms and the scarcity of surgical experience with such rare tumors. Conclusion- Overall, the prognosis and surgical outcomes for patients with hemangioblastomas are generally favourable. However, it should be noted that surgery for adult posterior cranial fossa hemangioblastomas is a demanding and challenging task. The complexity of the procedure, combined with the rarity of these tumors, contributes to the surgical challenges associated with their management. [ABSTRACT FROM AUTHOR]

Von Hippel‐Lindau disease is a rare inherited cancer‐predisposition syndrome. The authors report the updated recommendations for the multiorgan surveillance protocols. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 24-year-old woman with von Hippel-Lindau (VHL) syndrome, whose retinal capillary hemangioblastoma significantly improved after treatment with belzutifan. Topics discussed include the use of belzutifan in treating VHL-associated retinal hemangioblastomas, the drug's impact on tumor reduction, and the U.S. Food and Drug Administration (FDA) approval of belzutifan for treating VHL-related tumors.

Vertebral body location of hemangioblastomas (HB) is extremely rare. The authors report a case of spinal mass involving lower thoracic region with cord compression, approved to be spinal HB. A 57-year-old man presented to our center with eight months history of progressive intractable back pain and paraparesis. Admission computed tomography and magnetic resonance imaging (MRI) of the thoracolumbar spine demonstrated a lytic and expansile spinal mass with pedicle expansion and vivid contrast enhancement involving T11 and T12 vertebral bodies on the right side. He was a known case of von Hippel-Lindau (VHL) and he had history of 4th ventricular asymptomatic hemangioblastoma near Obex, multiple pancreatic cystic adenomas, multiple liver cysts, and right non-chromaffin adrenal mass. The patient underwent a T11-T12 partial transpedicular corpectomy with T5 to L3 posterior spinal fixation to bridge the invaded segment. The pathological and immunohistochemical findings were consistent with vertebral HB. Spinal HB although extremely rare, may be managed with subtotal tumor resection and fixation of normal adjacent vertebrae by cemented screws. [ABSTRACT FROM AUTHOR]

To elucidate the clinical characteristics of atypical retinal vascular proliferation in patients with von Hippel-Lindau (VHL) disease using OCT angiography (OCTA). Prospective, observational study. Fifty-seven consecutive patients with a diagnosis of VHL disease who visited Kyoto University Hospital between January 2019 and March 2022. Retinal hemangioblastomas (RHs) were assessed using multimodal imaging including OCTA. Retinal hemangioblastomas were classified into 2 phenotypes: nodular and flat. Nodular RHs were defined as typical RHs that were globular, well-circumscribed tumors, often accompanied with dilated feeder arterioles and draining venules. Flat RHs lacked a protruded red or colored mass, had variable and indistinct borders, and were not accompanied with feeder and draining vessels. The prevalence, distribution, and description of atypical flat RHs. Among 57 consecutive patients with VHL disease, 37 patients (64.9%) showed RHs in at least 1 eye. Bilateral RHs were seen in 23 patients (62.2%). Among 58 eyes of 37 patients with RHs, typical nodular RHs were detected in 54 eyes. Nodular RHs were seen mainly in the peripheral retina and occasionally in the peripapillary region, and they showed exudative changes in some cases. Flat RHs were detected in 7 eyes (12.1%). Four eyes showed only flat RHs, and 3 eyes showed both types in the same eye. Most flat RHs appeared as retinal hemorrhages or faint flat abnormal retinal vessels in the inner retina on the fundus examination, often within the macula area or peripapillary. In all eyes with flat RHs, OCTA showed abundant blood flow in the lesions. OCT revealed that flat RHs were seen mainly between the retinal nerve fiber layer and the ganglion cell layer, and occasionally within the inner nuclear layer. During a mean follow-up period of 20.4 ± 15.0 months, no flat RHs accompanied exudative change, tractional retinal detachment, or progression in size. Patients with VHL disease can demonstrate 2 distinct types of RHs: the classic nodular type and an atypical flat type. OCT angiography can be useful in improving the detection of atypical flat RHs, which can be difficult to detect clinically. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

Ultrasonography (US) provides real-time information on structures within the skull during neurosurgical operations. Superb microvascular imaging (SMI) is the latest imaging technique for detecting very low-velocity flow with minimal motion artifacts, and we have reported on this technique for intraoperative US monitoring. We combined SMI with administration of contrast agent to obtain detailed information during neurosurgical operations. Twenty patients diagnosed with brain tumor (10 meningiomas, 5 glioblastomas, 2 hemangioblastomas, 1 schwannoma, 1 malignant lymphoma, 1 brain abscess) underwent neurosurgery under US with SMI and contrast agent techniques. Vessel density and appearance time following contrast administration were analyzed. Flow in numerous vessels was not visualized by SMI alone, but appeared following injection of contrast agent in all cases. Flow in tumors was drastically enhanced by contrast agent in schwannoma, hemangioblastoma and meningioma, compared to normal brain tissue. Flows in the dilated and bent vessels of glioblastoma were also enhanced, although flow in hypoechoic lymphoma remained inconspicuous. The characteristics of tumor vessels were clearly visualized and tumor borders were demonstrated by the difference between tumor flow and brain flow, by the increased tumor vessel density and decreased appearance time of contrast agent compared to normal brain vessels. The combination of SMI and contrast agent techniques for intraoperative US monitoring could provide innovative flow images of tumor and normal brain. The neurosurgeon obtains information about tumor flow and tumor borderline before tumor resection. [ABSTRACT FROM AUTHOR]

Supratentorial hemangioblastomas are benign and highly vascularized neoplasms that appear most often in the spine and posterior cranial fossa. They can also be located in the supratentorial compartment of the brain. We conducted a systematic review of the literature to better understand the clinical insights of supratentorial hemangioblastoma in adults. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the authors reviewed the English-language literature in the PubMed/MEDLINE database on supratentorial hemangioblastoma in adults, published in the past 40 years. We analyzed the differences between sporadic hemangioblastomas and hemangioblastomas associated with von Hippel-Lindau disease. In addition, we compared the characteristics of supratentorial hemangioblastomas with infratentorial and spinal cord locations. We reviewed 92 articles, describing 157 supratentorial hemangioblastomas in a total cohort of 148 adult patients. Most articles reporting supratentorial hemangioblastomas were published in the United States. Supratentorial hemangioblastomas occur more frequently in women than men. The median age at the time of diagnosis was 44.48 years. The sellar/parasellar region was the most commonly tumor location, while the most common morphological type was the solid type. Almost 80% of hemangioblastomas were completely resected; the outcome was favorable in more than 3 fourth of patients. Given their rarity, the literature on supratentorial hemangioblastomas is limited and based mostly on case reports. Complete surgical resection is the first choice of treatment and is associated with a good treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Three‐dimensional (3D) contrast‐enhanced T1‐weighted flow‐sensitive black‐blood (CE‐T1WI FSBB) is a newly developed black blood sequence by adding motion probing gradient pulses to gradient echo (GRE) sequences, which has important value for the preoperative assessment of tumor brain blood supply vessels and intratumoral microbleeds. Purpose: To compare 3D CE‐T1WI FSBB and 3D contrast‐enhanced fast spin echo (FSE) sequence for T1WI for preoperative assessment of blood vessels and microbleeds in brain tumors and to investigate the correlation between visible vessels and microbleeds. Study type: Prospective. Subjects: One hundred and seventy‐five patients with brain tumors, 65 were male, 110 were female. Including histologically confirmed 73 meningiomas, 23 schwannomas, 20 gliomas, 7 hemangioblastomas, 5 metastases, 2 lymphomas, 2 hemangiopericytomas, 2 germ cell tumors, 1 craniopharyngioma, and 1 cholesteatoma. Field Strength/Sequence: A 3‐T, CE‐T1WI FSBB, GRE; 3‐T, CE‐T1WI, FSE. Assessment: Three neuroradiologists counted the number of intratumoral vessels on CE‐T1WI and CE‐T1WI FSBB images separately, and they counted the number of intratumoral microbleeds on CE‐T1WI FSBB images. Brain tumors were classified into grade I, grade II, and grade IV according to the World Health Organization (WHO) grading. Differences in the ability of CE‐T1WI FSBB and CE‐T1WI to display intratumoral vessels were compared. The mean counts of three observers were used to study the correlation between vessels and microbleeds. Statistical Tests: Two‐way random intraclass correlation coeficient (ICC) was used for inter‐reader agreement regarding intratumoral vessel and microbleed counts, and the linear regression analysis (with F‐test) was used to study the correlation between intratumoral vessels and microbleeds based on CE‐T1WI FSBB (α = 0.05). Results: Inter‐reader agreements for intratumoral vessel count on CE‐T1WI (ICC = 0.93) and CE‐T1WI FSBB (ICC = 0.92), and the agreement for intratumoral microbleed count on CE‐T1WI FSBB (ICC = 0.99) were excellent. There were statistically significant differences in intratumoral vessel counts between CE‐T1WI and CE‐T1WI FSBB using Mann–Whitney U ‐test: image readers could identify more intratumoral vessels on CE‐T1WI FSBB images, particularly for meningiomas, schwannomas, gliomas, and WHO grade I tumors. The number of intratumoral vessels had a significant positive effect on the number of intratumoral microbleeds (microbleeds = 5.024 + 1.665 × vessels; F = 11.51). Data Conclusion: More intratumoral vessels could potentially be identified using a 3D CE‐T1WI FSBB sequence compared to a CE‐T1WI sequence, and the number of intratumoral vessels showed a positive linear relationship with the number of intratumoral microbleeds, which might suggest that brain tumors with rich blood supply were more prone to intratumoral microbleeds. Evidence Level: 2 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Objective: Spinal hemangioblastomas (HBs) are a rare pathology, especially in the pediatric population. The natural history and long-term outcomes of pediatric patients with spinal HBs remain unclear due to their scarcity. Methods: A retrospective review of the clinical data and treatment outcomes of children with spinal HBs in our institution from 2012 to 2021 was conducted. Results: Thirty-nine pediatric patients were included, with an average age of 15.9 ± 2.9 years (range, 8-18 years), and 51.3% were female. Children were more likely to have von Hippel-Lindau (VHL) disease (p < 0.001), a family history of VHL (p < 0.001), multiple symptoms (p = 0.006), a shorter duration of symptoms (p < 0.001), and a larger lesion size (p = 0.004) and volume (p = 0.008) than their adult counterparts. The VHL-associated group of patients was more likely to present with multiple symptoms (p = 0.026), have a family history of VHL (p < 0.001), have multiple HBs (p < 0.001) and have synchronous intracranial lesions (p < 0.001) than the sporadic group. After surgery, 15 patients (38.5%) showed improved clinical outcomes, 17 patients (43.6%) remained unchanged, 4 patients (10.2%) worsened, and 3 patients (7.7%) died of tumor progression. During follow-up, there was a high rate of recurrence and repeated surgery, especially for children in the VHL-associated group. Conclusion: Pediatric patients with spinal HBs appear to have a higher relapse risk than their adult counterparts. Therefore, life-long follow-up of these patients is necessary, especially for VHL-associated cases. Surgery can benefit children with HBs and should be considered early to avoid irreversible neurological deterioration. [ABSTRACT FROM AUTHOR]

The perioperative risk of sporadic hemangioblastomas (HBs) and von Hippel-Lindau disease (VHL)–associated hemangioblastomas (VHL-associated HBs) remains unclear due to the rare prevalence of HB. Therefore, this study aimed to clarify risk factors for better surgical management of patients with HBs. A retrospective analysis of surgically treated HB patients registered in the Diagnosis Procedure Combination database of Japan, between 2010 and 2015, was performed. Age, sex, sporadic HBs or VHL-associated HBs, medical history, tumor location, hospital case load, postoperative complications, and Barthel index (BI) deterioration were assessed. We also evaluated the outcomes and factors of perioperative BI deterioration. In total, 676 patients with 609 intracranial lesions, 64 spinal lesions, and 3 with both types were eligible. Among them, 618 and 58 patients had sporadic HBs and VHL-associated HBs, respectively. The rates of perioperative BI deterioration were 12.5% and 12.2% for sporadic HBs and VHL-associated HBs, respectively. Perioperative mortality was 1.8% and 0% for sporadic HBs and VHL-associated HBs, respectively. Male sex, old age, high hospital case load, and medical history of diabetes mellitus were significantly associated with perioperative BI deterioration in all cases and sporadic HBs. Only medical history of diabetes mellitus was a significant risk factor for perioperative BI deterioration in VHL-associated HBs. No differences in perioperative BI deterioration rates between sporadic HBs and VHL-associated HBs were found. However, different risk factors for perioperative BI deterioration were identified. Consideration of these risk factors is recommended in all patients undergoing surgery for HB. [ABSTRACT FROM AUTHOR]

Both pilocytic astrocytoma (PA) and hemangioblastoma (HB) are common primary neoplasms of the posterior fossa with similar radiological manifestations. This study was conducted to evaluate the role of Radiomics in differentiating these two conditions in adults. After a retrospective search of our institutional imaging archive, adult patients with a known diagnosis of PA or HB were included. We reviewed each patient's most recent preoperative brain magnetic resonance imaging (MRI). The solid enhancing nodule of each lesion on post-contrast T1 sequence was manually segmented. Multiple Radiomics features were then extracted from each nodule using the Pyradiomics library. Subsequently, the most predictive features were identified by feature selection models. Following this, different machine learning (ML) models were constructed based on these selected features to classify lesions as PA or HB. Finally, we evaluated the performance of each model by leave-one-out cross-validation. With inclusion and exclusion criteria, 34 enhancing PA nodules and 39 HB nodules were selected. A total of 115 features were extracted from each enhancing nodule. Twelve characteristics were detected as most predictive of histopathological diagnosis. Among various ML models, the neural network had the best performance in differentiating these two conditions with an AUC of 0.9 and an accuracy of 82%. In this retrospective study, Radiomics MRI techniques demonstrated high performance in distinguishing adult posterior fossa PA from HB. Future development of Radiomics models may advance presurgical diagnosis of these two conditions when added to routine clinical practice and thus improve patient management. • Differentiation between hemangioblastoma and pilocytic Astrocytoma in the "adult" is challenging on conventional medical imaging. • However, an accurate preoperative diagnosis is crucial and can significantly alter patient management and surgical technique. • Our preliminary results regarding the application of Radiomics appear promising for this task, and we got an AUC of 0.9 without using any clinical information such as the patient's age. [ABSTRACT FROM AUTHOR]

Hemangioblastoma is a rare benign vascular tumor that occurs mostly in the cerebellum. The aim of the present study was to analyze the clinical characteristics of sporadic cerebellar hemangioblastoma and its surgical strategy. A total of 76 cases of sporadic cerebellar hemangioblastoma (42 males and 34 females; age, 46.4±13.9 years; age range, 23-72 years) admitted to the Department of Neurosurgery of the General Hospital of Northern Theater Command (Shenyang, China) from July 2012 to April 2021 were retrospectively analyzed. All patients had only one isolated tumor and underwent surgical resection. Their basic characteristics, serial radiographic examinations, surgical records and follow-up were analyzed. A total of 57 patients with cystic hemangioblastoma and eight patients with cystic solid hemangioblastoma directly underwent resection treatment. Of 11 patients with solid hemangioblastoma, 8 underwent vascular embolization prior to surgical resection. Furthermore, 3 patients with solid hemangioblastoma who were not embolized prior to surgery had intraoperative hemorrhage and poor prognosis. In addition, 3 patients underwent partial resection of the tumor and all of them suffered recurrence after the surgery. A total of 71 patients achieved good neurologic improvement. However, 5 patients had a poor prognosis after the initial surgery. In conclusion, total microsurgical resection is essential to improve the health status of patients with sporadic cerebellar cystic hemangioblastoma. In addition, preoperative embolization of arteries supplying solid hemangioblastomas can reduce intraoperative bleeding and improve prognosis. [ABSTRACT FROM AUTHOR]

This article discusses the case of a pregnant patient with von Hippel-Lindau syndrome (VHL) who presented with multiple hemangioblastomas in the central nervous system (CNS). Hemangioblastomas are common tumors associated with VHL and can significantly increase morbidity and mortality. The possible influence of pregnancy on the growth of these tumors remains unclear. The article presents the case of a 28-year-old pregnant patient with VHL who underwent microsurgical resection of three dominant lesions. The patient had a successful pregnancy and delivered a healthy baby. The article also discusses the progression of hemangioblastomas during pregnancy and the recommended treatment approaches. [Extracted from the article]

We present the case of 69-year-old woman who underwent preoperative embolization of a suprasellar hemangioblastoma supplied by the artery of foramen rotundum. To our best knowledge, this is the first such report in English. We review the literature focusing on feeding arteries of sellar and suprasellar hemangioblastomas. [ABSTRACT FROM AUTHOR]

Hemangioblastomas in the central nervous system are the most common manifestation of von Hippel-Lindau (VHL) disease. Because the growth rate of hemangioblastomas is unpredictable, regular follow-up is mandatory, focusing on clinical symptoms and imaging of the central nervous system. However, clinical symptoms may be subtle and nonspecific, and data about the relationship between the radiologic findings and clinical symptoms are sparse. This study aims to evaluate if and how findings of magnetic resonance imaging (MRI) regarding spinal hemangioblastomas are associated with symptoms of VHL disease, with special attention to peritumoral edema and spinal cysts. Serial spinal MRI scans of 43 genetically or clinically established VHL patients with at least 2 years of follow-up were reevaluated to examine the volume, growth rate, and location of spinal hemangioblastomas and the presence, size, and growth rate of peritumoral edema and cysts. Findings were compared with clinical symptoms using the Fisher exact test. We observed a total of 77 spinal hemangioblastomas in 28 patients. Eight of the 28 patients showed peritumoral edema and spinal cysts, and 1 patient showed peritumoral edema without cyst formation; 6 of these 9 patients showed clinical symptoms. Both peritumoral edema and spinal cysts were associated with clinical symptoms (P = 0.023 and P = 0.011, respectively). The presence of peritumoral edema and/or spinal cysts shown on MRI in VHL patients with spinal hemangioblastomas is associated with symptoms in more than half of the patients and may alert the clinician to intensify clinical and radiologic surveillance. [ABSTRACT FROM AUTHOR]

Background: Hemangioblastomas of the central nervous system are a prominent feature of von Hippel-Lindau-disease (vHL). Hemangioblastomas are known to secrete vascular endothelial growth factor (VEGF), suggesting a potential role of VEGF as a biomarker for tumor growth. Methods: Plasma VEGF samples from 24 patients with von Hippel-Lindau disease were analyzed by solid-phase proximity ligation assay (PLA). Levels were monitored over time together with numeric and volumetric CNS tumor burden, and compared to plasma VEGF levels in healthy controls. Results: The mean yearly progression in tumor volume was 65.5%. Yearly risk of developing one or several new CNS tumor(s) was 50%. No significant correlation between tumor burden and levels of VEGF was seen. VEGF levels in patients (31.55–92.04; mean 55.83, median 56.41) as measured by immunodetection in a solid-phase PLA did not differ significantly from controls (37.38–104.56; mean 58.89, median 54.12) (p = 0,266). Conclusion: The increase in total CNS tumor volume in vHL occurred in a saltatory manner. The risk of developing a new lesion was 50% per year. We found no evidence for VEGF secretion from CNS hemangioblastomas in vHL in circulating blood. Other potential biomarkers should be explored to assess progression of tumor burden in vHL. [ABSTRACT FROM AUTHOR]

Hemangioblastomas are benign, often cystic tumors occurring most commonly in the cerebellum. We describe resection of cystic cerebellar hemangioblastomas using an endoscope-assisted technique. We present a series of 9 cases and discuss the endoscopic technique for resection of cystic hemangioblastoma. Frameless neuronavigation was used in all cases. A small 1- to 1.5-cm corticotomy lined with Surgicel and patties allows access to the peritumoral cyst. Using bimanual microsurgical techniques and the 30-degree rigid endoscope to provide visualization, the mural nodule can be resected and the cyst cavity inspected. Complete resection of the mural nodule was achieved in all cases. One patient had a postsurgery pseudomeningocele requiring ventriculoperitoneal shunt. Hospital length of stay was short for all the patients. Endoscope-assisted resection is a safe and effective technique for surgical resection of cystic hemangioblastoma. [ABSTRACT FROM AUTHOR]

Hemangioblastomas (HBs) of the central nervous system are highly vascular neoplasms that occur sporadically or as a manifestation of von Hippel–Lindau (VHL) disease. Despite their benign nature, HBs are clinically heterogeneous and can be associated with significant morbidity due to mass effects of peritumoral cysts or tumor progression. Underlying molecular factors involved in HB tumor biology remain elusive. We investigated genome‐wide DNA methylation profiles and clinical and histopathological features in a series of 47 HBs from 42 patients, including 28 individuals with VHL disease. Thirty tumors occurred in the cerebellum, 8 in the brainstem and 8 HBs were of spinal location, while 1 HB was located in the cerebrum. Histologically, 12 HBs (26%) belonged to the cellular subtype and exclusively occurred in the cerebellum, whereas 35 HBs were reticular (74%). Unsupervised clustering and dimensionality reduction of DNA methylation profiles revealed two distinct subgroups. Methylation cluster 1 comprised 30 HBs of mainly cerebellar location (29/30, 97%), whereas methylation cluster 2 contained 17 HBs predominantly located in non‐cerebellar compartments (16/17, 94%). The sum of chromosomal regions being affected by copy‐number alterations was significantly higher in methylation cluster 1 compared to cluster 2 (mean 262 vs. 109 Mb, p = 0.001). Of note, loss of chromosome 6 occurred in 9/30 tumors (30%) of methylation cluster 1 and was not observed in cluster 2 tumors (p = 0.01). No relevant methylation differences between sporadic and VHL‐related HBs or cystic and non‐cystic HBs could be detected. Deconvolution of the bulk DNA methylation profiles revealed four methylation components that were associated with the two methylation clusters suggesting cluster‐specific cell‐type compositions. In conclusion, methylation profiling of HBs reveals 2 distinct subgroups that mainly associate with anatomical location, cytogenetic profiles and differences in cell type composition, potentially reflecting different cells of origin. [ABSTRACT FROM AUTHOR]

Hemangioblastomas are true benign vascular neoplasms arising from pluripotent mesenchymal stem cells that give rise to vascular endothelial cells and are most commonly found in the cerebellum, spinal cord, brainstem, and retina. These tumors may be isolated sporadic lesions or may be associated with hereditary genetic factors in the case of von Hippel-Lindau (VHL) syndrome. Spinal cord haemangioblastomas constitute 1.1% to 2.4% of all central nervous system tumors105, with the majority being single tumors that present in the fourth decade of life 106. In the pediatric population, sporadic spinal cord hemangioblastomas are exceedingly rare. The prevalence of spinal cord hemangioblastomas in children is increased among those with VHL syndrome. The thoracic cord is the most common site for spinal cord hemangioblastomas, followed by the cervical cord. Although these tumors are benign, they cause disabling symptoms due to spinal cord compression, syringomyelia, or hemorrhage from the tumor itself or from aneurysms that form on tumor-feeding arteries or intra-tumoral vessels., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Von Hippel Lindau(VHL)syndrome presents with cerebellar and spinal hemangioblastomas, renal cell cancer, neuroendocrine pancreatic tumor, and pheochromocytoma and it is caused by germline mutations in the VHL gene. Pathogenic germline variants in the succinate dehydrogenase A (SDHA) gene are associated with paraganglioma and pheochromocytoma. Here we report co-occurrence of germline pathogenic variants in both VHL and SDHA genes in a patient who presented with pancreatic neuroendocrine tumor. As these genes converge on the pseudo-hypoxia signaling pathway, further studies are warranted to determine the significance of co-occurrence of these variants in relation to tumor penetrance, disease severity, treatment response and clinical outcomes in this selected group of patients. [ABSTRACT FROM AUTHOR]

Introduction: Hemangioblastoma in the spine mainly occurs at the cervical and thoracic levels and is often associated with von Hippel-Lindau (VHL) syndrome. Here, we reported a quite rare case of spinal sporadic hemangioblastoma arising from the cauda equina. Case presentation: A 66-year-old woman presented with a 5-year history of low back and leg pain. Imaging revealed a hypervascular intradural extramedullary tumor in the lumbar region. Preoperative angiography helped to identify the feeding arteries and draining vein, and so facilitated subsequent tumor resection. The pain was dramatically improved but weakness of the left tibialis anterior and left extensor hallucis longus muscles persisted. Discussion: We reported a rare case of spinal hemangioblastoma arising from the cauda equina. Preoperative angiography may be useful for diagnosis and understanding of the anatomy of feeding veins. J. Med. Invest. 69: 312-315, August, 2022. [ABSTRACT FROM AUTHOR]

Background: Hemangioblastomas (HGBs) are highly vascular benign tumors, commonly located in the posterior fossa, and 80% of them are sporadic. Patients usually present with features of raised intracranial pressure and cerebellar symptoms. HGB can be classified as either mostly cystic or solids. Although the solid component is highly vascularized, aneurysm or hemorrhagic presentation is rarely described, having catastrophic results. Methods: We identified 32 consecutive patients with posterior fossa HBG who underwent surgery from 2008 through 2020 at our medical center. Tumors were classified as predominantly cystic or solid according to radiological features. Resection was defined as gross total (GTR) or subtotal (STR). Results: During the study period, 32 posterior fossa HGBs were resected. There were 26 cerebellar lesions and 4 medullar lesions, and in 2 patients, both structures were affected. Predominant cystic tumors were seen in 15 patients and solids in 17. Preoperative digital subtraction angiography (DSA) was performed in 8 patients with solid tumors, and 4 showed tumor-related aneurysms. Embolization of the tumors was performed in 6 patients, including the four tumor-related aneurysms. GTR was achieved in 29 tumors (91%), and subtotal resection in 3 (9%). Three patients had postoperative lower cranial nerve palsy. Functional status was stable in 5 patients (16%), improved in 24 (75%), and 3 patients (9%) deteriorated. One patient died 2 months after the surgery. Two tumors recurred and underwent a second surgery achieving GTR. The mean follow-up was 42.7 months (SD ± 51.0 months). Conclusions: Predominant cystic HGB is usually easily treated as the surgery is straightforward. Those with a solid predominance present a more complex challenge sharing features similar to arteriovenous malformations. Given the important vascular association of solid predominance HGB with these added risk factors, the preoperative assessment should include DSA, as in arteriovenous malformations, and endovascular intervention should be considered before surgery. [ABSTRACT FROM AUTHOR]

Background: Hemangioblastoma (HB) is a rare and highly vascularized tumor that originates from the central nervous system as well as other part of the body. They can appear sporadically or as part of von Hippel–Lindau (VHL) disease, a rare hereditary cancer syndrome. Although surgery can cure the majority of HBs, the disease shows a treatment-refractory challenge upon recurrence. HBs express a high amount of vascular endothelial growth factor (VEGF) which is responsible for angiogenesis and subsequently tumor progression. Anti-angiogenic treatment like bevacizumab has showed effect on HB, so we hypothesized that anlotinib could trigger HB regression via its inhibitory effect on VEGF. Case Presentation: We will share our experience in treating a 62-year-old woman with multiple recurrent lumbar and sacral cord HBs. She was treated with anlotinib (8mg qd d1-14, q3w) for three months and her follow up radiological examination demonstrated marked tumor regression which was evaluated as having partial response pursuant to RECIST 1.1 system. She is currently still receiving treatment of anlotinib orally and the lesions continuously reduced. Conclusion: We have reported that anlotinib can cause significant radiographic response in a patient with multiple recurrent lumbar and sacral cord HBs for the first time. This might enable a novel therapeutic approach for patients with multiple recurrent HB or those with multiple lesions such as in VHL disease which are difficult to resect surgically. [ABSTRACT FROM AUTHOR]

The prognostic factors for surgically removed spinal hemangioblastomas, the impact of VHL disease on outcome, and the role of intraoperative neuromonitoring are still not completely clear. The aim of this study was to review our experience with spinal hemangioblastomas in order to assess potential predictors of neurological outcome after surgery. All cases of spinal hemangioblastomas removed at two Italian academic institutions from 1985 to 2020 were reviewed. Data about clinical presentation and symptom duration, diagnosis of VHL, surgical approach, use of IONM, duration of hospital stay, follow-up, and modified McCormick grade before and after surgery were extracted. Sixty-one patients (31 F, 30 M) underwent 69 surgeries to remove 74 spinal hemangioblastomas (37 cervical, 32 thoracic, 5 lumbar). Improvement was found in 32.3% of cases, neurological condition remained stable in 51.6% of cases, and deteriorated in 16.1% of patients. A worsening trend in VHL patients and an improvement trend in non-VHL patients were detected, despite the lack of statistical significance. Laminotomy and use of IONM were found to be associated with better outcome, although no association was found between surgery without IONM and worse outcome. In most cases, patients affected by spinal hemangioblastomas can expect a good long-term outcome. In our experience, laminotomy seems to be associated with better outcome compared to laminectomy. While its absence is not associated with worse outcome, IONM seems to be associated with a better neurological outcome. Our study suggests that the more impaired the preoperative neurological condition, the worse the outcome. [ABSTRACT FROM AUTHOR]

Hemangioblastoma (HB) is one of the most common primary neoplasms of the posterior fossa in adults. Although single tumors can be sporadic, multiple tumors are almost always associated with von Hippel-Lindau (VHL) disease. In our case report, we are describing a 39-year-old woman with complaints of severe headache, pain, and numbness in both arms. She had a history of VHL disease. We performed contrast-enhanced cranial and cervical spine magnetic resonance imaging (MRI) examinations. Given the patient's history of VHL disease and characteristic MR imaging features of lesions, cranial and cervical HBs were considered for diagnosis. Surgical excision is the main treatment of these tumors and follow-up optimal imaging of these patients is crucial. In the screening of VHL patients, whole spinal axis imaging in conjunction with routine MRI studies must always be performed to rule out spinal HBs. [ABSTRACT FROM AUTHOR]