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BACKGROUND: Von Hippel-Lindau (VHL) disease is a rare autosomal dominant disorder that predisposes patients to develop multiple cysts and tumors, such as hemangioblastomas (HBs) and clear cell renal cell carcinoma (ccRCC), due to mutations in the VHL tumor suppressor gene. While treatment of HBs varies based on their characteristics and has improved patient survival, it still involves high morbidity and mortality, leading to ongoing debates and studies to refine therapy strategies. Recent developments include the emergence of Belzutifan, a novel inhibitor targeting hypoxia-inducible factor 2α (HIF-2α), which has shown promising results in ongoing trials, particularly for patients not immediately requiring surgery. METHODS: This systematic review and meta-analysis aimed to comprehensively evaluate the efficacy and safety of Belzutifan for treating HBs associated with VHL disease. Search was conducted across Medline, Embase, Cochrane, and Web of Science databases. Statistical Analysis was performed, with proportions and 95 % confidence intervals. Statistical analyses were carried out using R Studio. RESULTS: Ten studies were selected, comprising 553 patients. The population mean age was 40 (24-65), and 50 % of the population was formed by males. In terms of proportion, 6 analyses were performed: Disease Stability of 31 % [95 %CI:14 %-47 %; I2 = 2 %]; Disease Progression of 2 %[95 %CI:0 %-9 %; I2 = 0 %]; Partial Response of 75 % [95 %CI:54 %-96 %; I2 = 58 %]. Complete response of 1 % [95 %CI:0 %-7 %; I2 = 0 %];and Side effects, anemia 81 % rate [95 % CI:54 %-100 %; I2 = 94 %], and fatigue rate of 79 % [95 % CI:54 %-100 %;I2 = 94 %]. CONCLUSION: Results indicate that Belzutifan effectively stabilizes disease, reduces tumor progression, and achieves significant therapeutic responses, although side effects like anemia and fatigue were noted.

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Background: Hemangioblastomas are benign vascular neoplasms, World Health Organization grade I, with the most frequent location in the cerebellum. Complete microsurgical resection can be a challenge due to excessive bleeding, which is why preoperative embolization takes importance. Case Description: Two clinical cases are presented, a 25-year-old woman and a 75-year-old man, who presented with intracranial hypertension symptoms due to obstructive hydrocephalus; a ventriculoperitoneal shunt was placed in both cases; in addition, they presented with cerebellar signs. Both underwent embolization with ethylene vinyl alcohol copolymer, with blood flow reduction. After that, they underwent microsurgical resection within the 1st-week post embolization, obtaining, in both cases, gross total resection without hemodynamic complications, with clinical improvement and good surgical outcome. It is worth mentioning that surgical management is the gold standard that allows a suitable surgical approach, like in our patients, for which a lateral suboccipital craniotomy was performed. Conclusion: Solid hemangioblastomas are less frequent than their cystic counterparts. The treatment is the surgical resection, which is a challenge and always has to be considered as an arteriovenous malformation in the surgical planning, including preoperative embolization to reduce perioperative morbidity and mortality and get good outcomes.

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BACKGROUND: Hemangioblastomas (HBs) are highly vascular tumors linked to substantial morbidity and mortality. Recently, interventional neuroradiology has evolved rapidly, spurring interest in preoperative embolization as a possible HB treatment. PURPOSE: This study evaluates the effectiveness and safety of preoperative embolization in managing HB. METHODS: Adhering to PRISMA guidelines, this meta-analysis considered randomized and nonrandomized studies meeting specific criteria, encompassing intracranial HB and preoperative embolization. Primary outcomes were preoperative embolization efficacy and safety. Complications were classified as major (cerebellar ischemia, ischemic strokes, intratumoral hemorrhage, subarachnoid hemorrhage) and minor (transient nystagmus, slight facial nerve palsy, nausea, transient dysarthria, hemiparesis, hemisensory impairment, thrombotic complications, extravasation). RESULTS: Thirteen studies involving 166 patients with preoperative embolization before HB resection were included. Two studies using the Glasgow Outcome Scale (GOS) showed 5 patients with good recovery, 6 with moderate disability, and 3 with severe disability. Major complications occurred in 1% (95% CI: 0% to 3%), and minor complications occurred in 1% (95% CI: 0% to 4%). Intraoperative blood loss during resection was estimated at 464.29 ml (95% CI: 350.63 ml to 614.80 ml). CONCLUSION: Preoperative embolization holds promise in reducing intraoperative bleeding risk in neurosurgical intracranial HB treatment, primarily due to its low complication rates. Nonetheless, additional research and larger-scale studies are essential to establish its long-term efficacy and safety. These findings highlight preoperative embolization as a valuable tool for HB management, potentially enhancing future patient outcomes.

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Background: Spinal cord hemangioblastomas (HBs) account for 2-15% of all spinal cord neoplasms. They are the third most common primary intramedullary tumor (1-5%). Here, 72-year-old female presented with a thoracic intramedullary spinal HB that responded well to surgery. Case Description: A 72-year-old female presented with a 3-4 years of progressive paresthesias and paraparesis. On examination, she exhibited diffuse distal weakness of the lower extremities. The magnetic resonance scan showed an intramedullary expansive lesion at the T1-T2 level that markedly enhanced with contrast with both proximal and distal hydromyelia. Surgery included a C7 partial and T1-T2 total laminectomies performed under microscope visualization with intraoperative monitoring. At surgery, there was a well-documented cleavage plane between the tumor and the cord; excision was facilitated using the cavitron ultrasonic surgical aspirator device. Conclusion: Surgery is the gold standard treatment for treating/resecting HBs and should include utilization of an operating microscope and intraoperative monitoring.

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Background: Intramedullary spinal cord metastasis is uncommon and represents only 0.6% of all spinal tumors. Renal cell carcinoma is even less frequent in this group than in lung and breast cancer. Patients with Von Hippel- Lindau disease (VHLd) present spinal hemangioblastoma more frequently. Case Description: A 59-year-old female patient presented with medullary syndrome. There was a previous history of VHLd, with a cerebellar hemangioblastoma resection years ago. The radiological investigation showed a cervical intramedullary solid-cystic lesion. The patient has submitted a tumor resection, and a pathological and immunohistochemistry study confirmed clear cell renal carcinoma metastasis. Conclusion: In patients with VHLd, the presence of an intramedullary solid-cystic lesion may not represent always a hemangioblastoma. Other diagnostic possibilities must be evaluated, despite being epidemiologically less frequent. Inside the group of patients with VHLd, only a previous case of intramedullary spinal cord renal cell carcinoma was reported in the literature.

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Purpose: To describe a successful surgical approach to macula-off retinal detachment in von Hippel-Lindau disease. Observations: A 28-year-old male with a history of von Hippel-Lindau disease presented to us with significant worsening of vision in his single functional eye after undergoing a cryotherapy and laser session for multiple retinal capillary hemangioblastomas. Given a tractional and exudative retinal detachment involving macula, we performed a vitrectomy, epiretinal membrane peeling, internal limiting membrane peeling, endophotocoagulation of all hemangioblastomas, and fluid-air exchange. Over 30 days, there was total resolution of retinal detachment and improvement of his vision. At 13-month follow-up, the patient exhibited anatomical and functional stability. Conclusions and Importance: Double peeling and endolaser ablation may be an alternative treatment approach for patients with tractional and exudative retinal detachment in von-Hippel-Lindau disease.

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Background: Hemangioblastomas (HBs) typically present with benign behavior and are most commonly found in the posterior fossa. Multiple central nervous system (CNS) HBs are usually associated with von Hippel-Lindau disease, and leptomeningeal dissemination of sporadic HBs is extremely rare. A review of the literature identified 30 cases of leptomeningeal dissemination of sporadic HBs previously published in the literature. Case Description: We report the case of a patient who was diagnosed with multiple CNS HBs with aggressive progression 6 years after resection of a posterior fossa HB. He underwent multiple surgeries and died 4 years after the diagnosis of the first spinal dissemination. Conclusion: Dissemination of sporadic HBs is rare and aggressive disease evolution is usually observed. Further studies are necessary to determine the optimal therapeutic options.

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We report a patient with Von Hippel-Lindau disease who presented with an intradural extramedullary hemangioblastoma as a primary manifestation.

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Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant inherited syndrome that affects the germline of the VHL gene, a tumor suppressor gene. VHL disease is characterized by the multisystemic development of a variety of benign and malignant tumors, especially in the central nervous system (CNS). Such tumors include retinal and CNS hemangioblastomas, as well as endolymphatic sac tumors. The various tumor sites are responsible for the diversity of signs and symptoms related to the disease. The mean age at symptom onset is 33 years. Despite medical advances, the average life expectancy of patients with VHL disease is 49 years. Imaging plays a pivotal role in the clinical diagnosis and is essential to the follow-up of patients with VHL disease. This pictorial essay describes characteristic CNS manifestations of VHL disease-related tumors that all radiology residents should be aware of.

A doença de von Hippel-Lindau (VHL) é uma síndrome hereditária autossômica dominante rara que afeta a linha germinativa do gene VHL, um gene supressor tumoral. A doença de VHL é caracterizada pelo desenvolvimento multissistêmico de uma variedade de tumores benignos e malignos, especialmente no sistema nervoso central (SNC). Dentre eles, destacam-se hemangioblastomas retinianos e do SNC, e o tumor do saco endolinfático. Os diferentes locais dos tumores justificam a diversidade de sinais e sintomas relacionados à doença, que usualmente se manifestam com a idade média de 33 anos. Apesar dos avanços da medicina, a expectativa de vida média desses pacientes é de 49 anos. Exames de imagem têm papel fundamental no diagnóstico e são essenciais no seguimento dos pacientes com doença de VHL. Este ensaio iconográfico descreve as manifestações características dos tumores do SNC relacionados à doença de VHL que todos os residentes de radiologia devem saber.

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Background: Hemangioblastomas are benign tumors that develop in the central nervous system. They represent 1.5-2.5% of all intracranial tumors, and about 2-15% of all spinal cord tumors. They are highly associated with von Hippel-Lindau disease. Case Description: A 36-year-old female presented with a 4-year history of progressive right upper extremity distal weakness and cervical pain. The magnetic resonance imaging demonstrated a homogeneously, contrast enhancing intradural/intramedullary tumor at C6-C7 with perilesional edema and a syrinx accompanied by a cerebellar cyst with a mural nodule. Surgery included excision of the spinal lesion and decompression and excision of the cerebellar cyst and mural nodule (i.e., median suboccipital craniectomy and cervical C5-C7 laminectomy). Conclusion: Surgery is the gold standard treatment for symptomatic hemangioblastomas, and surgical approaches should minimize risk.

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Abstract A doença de von Hippel-Lindau (VHL) é uma síndrome hereditária autossômica dominante rara que afeta a linha germinativa do gene VHL, um gene supressor tumoral. A doença de VHL é caracterizada pelo desenvolvimento multissistêmico de uma variedade de tumores benignos e malignos, especialmente no sistema nervoso central (SNC). Dentre eles, destacam-se hemangioblastomas retinianos e do SNC, e o tumor do saco endolinfático. Os diferentes locais dos tumores justificam a diversidade de sinais e sintomas relacionados à doença, que usualmente se manifestam com a idade média de 33 anos. Apesar dos avanços da medicina, a expectativa de vida média desses pacientes é de 49 anos. Exames de imagem têm papel fundamental no diagnóstico e são essenciais no seguimento dos pacientes com doença de VHL. Este ensaio iconográfico descreve as manifestações características dos tumores do SNC relacionados à doença de VHL que todos os residentes de radiologia devem saber.

Abstract Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant inherited syndrome that affects the germline of the VHL gene, a tumor suppressor gene. VHL disease is characterized by the multisystemic development of a variety of benign and malignant tumors, especially in the central nervous system (CNS). Such tumors include retinal and CNS hemangioblastomas, as well as endolymphatic sac tumors. The various tumor sites are responsible for the diversity of signs and symptoms related to the disease. The mean age at symptom onset is 33 years. Despite medical advances, the average life expectancy of patients with VHL disease is 49 years. Imaging plays a pivotal role in the clinical diagnosis and is essential to the follow-up of patients with VHL disease. This pictorial essay describes characteristic CNS manifestations of VHL disease-related tumors that all radiology residents should be aware of.

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A 6-year-old girl with visual impairment in the right eye (OD) was referred for an eye evaluation. The fundus of the OD showed a fibrotic orange endophytic lesion located adjacent to the optic disc. In retinal optical coherence tomography, a local tractional retinal detachment and choroidal neovascular membrane were observed together also with the presence of subretinal fluid. Due to the vision of the OD evolved to nonlight perception in the following exam, enucleation was performed. The pathology report was correlated with hemangioblastoma. Herein, we describe a case of a young girl with a retinal hemangioblastoma with quick evolution and without prior systemic diagnosis.

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A series is presented of sixteen cases of retinal capillary haemangioma (RCH) from consecutive patients at an ophthalmology teaching hospital in Mexico City. There were seven primary haemangioblastomas, and nine due to von Hippel-Lindau disease (VHL). All cases associated with VHL already had systemic manifestations, such as, cerebellar, medullary and renal tumours. Treatment of capillary haemangiomas must be individualised, based on several factors, including the number of lesions, exudation, or presence of retinal detachment. A multidisciplinary approach is essential.

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Introduction Hemangioblastomas of the pineal region or pituitary stalk are extremely rare. Only two cases of hemangioblastomas involving the pineal region have been reported, and four involving the pituitary stalk. The purpose of the present manuscript is to describe an unusual case of supposed hemangioblastoma found concomitantly in the pineal region and pituitary stalk of a patient diagnosed with Von Hippel-Lindau (VHL) disease. Case Report A 35-year-old female patient with a previous diagnosis of VHL complaining of occipital headaches and balance disturbances for three weeks, who previously had a cerebellar hemangioblastoma resected. The visual characteristics of the tumor suggested a friable vascular lesion with a reddish-brown surface, and an incisional biopsy was performed. The tumor consisted of a dense vascular network surrounded by fibrous stroma abundant in reticulin and composed by both fusiform and dispersed xanthomatous cells; the immunohistochemistry was immunopositive for neuronspecific enolase and immunonegative for epithelial membranous antigen. The patient has been monitored closely for 2 years, and the supratentorial masses have not presented any volume alteration. Conclusion This rare association must be taken into account in patients with VHL disease, or at least be suspected in patients who present a thickening of the pituitary stalk and a pineal-region mass. We believe a biopsy of our asymptomatic patient could have been dangerous due to inherent complications like intraoperative bleeding. We recommend close observation of asymptomatic lesions with MRIs every six months or until the lesions become symptomatic. If the pineal-region tumor does become symptomatic, gross resection via a transcallosal approach would be ideal.

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ABSTRACT Purpose: The aim of this study was to present our own experience with the use of thermography as a complementary method for the initial diagnosis and differentiation of intraocular tumors, as well as for the evaluation of the efficacy of treatment of intraocular melanomas. Methods: The study group comprised 37 patients with intraocular tumors, including 9 with uveal melanoma, 8 with uveal melanoma after I125 brachytherapy, 12 with a focal metastasis to the uvea, and 8 with retinal capillary hemangioblastoma. A FLIR T640 camera was used to capture images in the central point of the cornea, eye area, and orbital cavity area. Results: Eyes with uveal melanoma had higher temperature compared with the fellow normal eye of the patient in the range of all measured parameters in the regions of interest. In the group of patients with melanoma after unsuccessful brachytherapy, higher temperature was observed at the central point of the cornea. In patients with tumor regression, all measured parameters were lower in the affected eye. We observed lower tempe­ratures in the range of all tested parameters and areas in eyes with choroidal metastases. Eyes with diagnosed intraocular hemangioblastoma were characterized by higher parameters for the regions of interest versus eyes without this pathology. Conclusions: A thermographic examination of the eye can be used as an additional first-line diagnostic tool for the differentiation of intraocular tumors. Thermography can be a helpful tool in monitoring the treatment outcome in patients with intraocular melanoma.

RESUMO Objetivo: O objetivo deste estudo foi de apresentar a nossa experiência no uso da termografia como método complementar para o diagnóstico inicial e a diferenciação de tumores intraoculares, bem como para a avaliação da eficácia do tratamento de melanomas intraoculares. Métodos: O grupo estudado compunha-se de 37 pacientes com tumores intraoculares, sendo 9 com melanoma uveal, 8 com melanoma uveal após braquiterapia com I125, 12 com metástases focais na úvea e 8 com hemangioblastoma capilar retiniano. As imagens do ponto central da córnea, da área do olho e da área da cavidade orbital foram obtidas com uma câmera FLIR T640. Resultados: Os olhos dos pacientes com melanoma uveal tinham temperaturas mais elevadas do que as dos olhos normais dos mesmos, em toda a faixa dos parâmetros medidos nas regiões de interesse. No grupo de pacientes com melanoma após braquiterapia mal sucedida, encontrámos temperaturas maiores no ponto central da córnea. Nos pacientes com regressão do tumor, todos os parâmetros medidos foram menores no olho acometido. Encontrámos temperaturas mais baixas em toda a faixa dos parâmetros testados e das áreas medidas nos olhos com metástases na coroide. Os olhos com hemangioblastoma intraocular diagnosticado caracterizaram-se por parâmetros mais elevados nas regiões de interesse, em comparação com olhos sem essa patologia. Conclusões: O exame termográfico do olho pode usar-se como ferramenta de diagnóstico adicional de triagem na diferenciação de tumores intraoculares. A termografia pode ser uma ferramenta útil no acompanhamento do des­fe­cho do tratamento em pacientes com melanoma intraocular.

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Hemangioblastomas (HBs) of the brain may present without neurological symptoms over a long period of time due to their benignity and slow growth. We herein present the case of a female patient who developed a HB of the fourth ventricle presenting only with severe weight loss and anorexia. The patient was screened for mutations in all 3 exons of the VHL gene using Sanger sequencing, and was found to have a nonsense mutation in the VHL gene (single-nucleotide change causing a premature stop codon: c.481C>T; p.Arg161*), causing formation of a truncated protein, consistent with von Hippel-Lindau syndrome (VHLs). The patient was first misdiagnosed with anorexia nervosa (AN) due to the lack of other symptoms. Molecular diagnosis allows further investigation of other VHLs-related tumors and timely, appropriate treatment. However, misdiagnosing anorexia nervosa may lead to poor prognosis and even death; thus, differential diagnosis is crucial in all such cases. The present case report provides evidence that fourth ventricular lesions may affect food intake control and satiety, and highlights the importance of accurate molecular diagnosis.

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von Hippel-Lindau syndrome (VHLS) is a rare, autosomal dominant genetic disease with high penetrance and variable phenotypic expression caused by variants in the VHL gene. VHLS is associated with the presence of vascular tumors, often hemangioblastoma of the central nervous system, retina, or spinal cord and, less frequently, pancreatic cystic neoplasm, pancreatic neuroendocrine tumor, clear cell carcinoma of the kidney, endolymphatic sac tumor, pheochromocytoma, and paraganglioma. The authors report a case of a patient with VHLS with a rare pathogenic variant in the VHL gene and with an optic nerve hemangioblastoma, a rare phenotypic expression. Case report: A 49-year-old woman was diagnosed with cystic neoplasm of the pancreas, renal cell carcinoma of the right kidney, and hemangioblastoma of the left optic nerve. The patient's family history revealed siblings with VHLS manifestations. The index case was her mother who died at age 63 of clear cell renal carcinoma. The information was obtained by consulting the patient's medical register and by interviews with the patient and her relatives. The presence of left optic nerve hemangioblastoma was suggested by CT scan of the skull and orbit. The sequencing of the VHL gene was performed in the peripheral blood by the polymerase chain reaction (PCR) technique, and the duplication and deletion research was performed using the multiplex ligation-dependent probe amplification (MPLA) technique. The presence of a rare pathogenic variant c.263G> A (p.Trp88Ter) was observed in heterozygosity in the VHL gene that determined a premature stop codon. CT scan of the skull and orbits suggested the presence of HB in the optic nerve of the left eye. The results of the CT scan of the skull and orbits show thickening with tortuosity of the left optic nerve, with a small area of nodular enhancement. The right optic nerve had a conserved aspect. Conclusion: This is the fourth case described of this rare pathogenic variant of the VHL gene, according to the Human Gene Mutation Database and VHLdb database records and with an optic nerve hemangioblastoma of the optic nerve, a very rare phenotypic expression of the VHLS.

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This case report aims to describe the diagnosis, treatment, and evolution of bilateral, asymmetrical retinal capillary hemangioblastomas treated with argon laser and intravitreal anti-vascular endothelial growth factor and also reports the results of an online survey of treatment preferences among retina and vitreous specialists. A previously healthy 23-year-old female presented to our Retina Department complaining of progressive visual loss in her right eye. Visual acuity at admission was 20/300 in her right eye and 20/20 in her left eye. Anterior segment findings were unremarkable and fundoscopy revealed the presence of retinal capillary hemangioblastomas in both eyes. In the right eye, the hemangioblastoma was associated with pronounced exudation and macular edema; in the left eye, the lesion was quiescent. After a complete anamnesis and genetic counseling, Von Hippel-Lindau disease was diagnosed. Treatment with laser photocoagulation was performed on both eyes. One dose of 0.5 mg intravitreal ranibizumab was applied to the right eye. Two months after treatment, the right eye demonstrated improved visual acuity (20/100). Moreover, an important decrease in tumor dimensions and a reduction of vessel tortuosity was seen in both eyes. At 18 months of follow-up, the patient maintains a good visual acuity without recurrence of the treated tumors. Laser treatment should be considered as the primary treatment option for patients with capillary hemangioblastomas with and without exudation and can be combined with intravitreal antiangiogenics if exudation is significant. Inactive smaller lesions without exudation are likely to have an excellent response to laser treatment alone. Management should be individualized since no consensus between experts has been reached.

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BACKGROUND: This is a case of a man aged 40 years with a past medical history of smoking, hypertension, polycythemia vera, intellectual disability, and schizophrenia who presented with generalized headaches, progressive loss of balance, and visual disturbance for 1 month. CASE DESCRIPTION: Head computed tomography and magnetic resonance imaging revealed a right cerebellar hematoma associated to heterogenous lesion with cystic components and flow-voids in the right cerebellar hemisphere. A ventriculoperitoneal shunt was placed with partial improvement of symptoms. Further vascular studies confirmed presence of a vascular nidus with significant arteriovenous shunting. The patient later required intervention for cerebellar arteriovenous malformation (AVM) removal. Microscopic evaluation of the lesion showed the AVM nidus, as well as large, vacuolated stromal cells and numerous thin-walled vessels. Immunostaining with inhibin and S-100 highlighted the stromal cells with numerous lipid-containing vacuoles. The earlier mentioned findings were consistent with the diagnosis of an AVM with coexistent hemangioblastoma of the right cerebellar hemisphere. CONCLUSIONS: Coexistence of hemangioblastomas and AVMs are extremely rare, and only 3 cases have been reported previously in the literature.

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La población pediátrica es, de lejos, la más afectada por las lesiones del cuarto (IV) ventrículo. La gran mayoría presentan un patrón radiológico similar; actualmente, con las secuencias de difusión, espectroscopia y mapas de ADC, se puede inferir la compatibilidad de los hallazgos visualizados con alguna de las patologías que se revisarán en el presente trabajo

The pediatric population is by far the most affected by lesions of the fourth (IV) ventricle. The vast majority present a similar radiological pattern, for which today, with the diffusion sequences, spectroscopy and ADC maps, it can be inferred that the visualized findings are more likely compatible with some of the pathologies that we will review later

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