Sporadic Intradural Extramedullary Hemangioblastoma Not Associated with von Hippel-Lindau Syndrome: A Case Report and Literature Review 폰 히펠린다우 증후군과 관련 없는 특발성 경막 내 수외 혈관모세포종: 증례 보고와 문헌고찰
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PROVIDER: S-EPMC9432444 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Project description:BackgroundRetinal hemangioblastoma (RH) is a rare benign tumor and a considerable number of which are caused by Von Hippel-Lindau disease (VHL). Herein, we described a case of VHL-associated RH with retinal detachment who underwent both laser photocoagulation and vitreoretinal surgery and received satisfactory visual recovery. In addition, we reviewed the current diagnosis, genotype-phenotype association, and treatment of VHL-associated RH.Case descriptionA 34-year-old woman presented with vision loss in the right eye at our hospital. Fundus photography and angiography showed retinal detachment and multiple large hemangiomas in the right eye. The visual acuity improved significantly after laser photocoagulation and vitreoretinal surgery. Genetic analyses showed a p.Asn78Ser (c.233A>G) heterozygous missense mutation in the VHL gene.ConclusionWe described a rare case of VHL-associated RH and may provide a new perspective towards diagnosis and treatment of this disease. RH is one of the most common manifestations of VHL and poses a serious threat to vision. Ophthalmic examination methods include fundus examination and fundus photography, etc. The management of the disease emphasizes timely follow-up, early detection of the lesion, and the decision of treatment options according to the size, location and complications of the lesion, including ablation therapy and vitreoretinal surgery. Clinicians should strengthen the understanding of this rare disease for early detection and treatment.
| S-EPMC9667117 | biostudies-literature
Project description:PurposeVon Hippel-Lindau (VHL) is a rare inherited disease mainly characterized by the growth of tumours, predominantly hemangioblastomas (Hbs) in the CNS and retina, and renal carcinomas. The natural history of VHL disease is variable, differing in the age of onset and its penetrance, even among relatives. Unfortunately, sometimes VHL shows more severe than average: the onset starts in adolescence, and surgeries are required almost every year. In these cases, the factor that triggers the appearance and growth of Hbs usually remains unknown, although additional mutations are suspected.MethodsWe present the case of a VHL patient whose first surgery was at 13 years of age. Then, along his next 8 years, he has undergone 5 surgeries for resection of 10 CNS Hbs. To clarify this severe VHL condition, DNA from a CNS Hb and white blood cells (WBC) was sequenced using next-generation sequencing technology.ResultsMassive DNA sequencing of the WBC (germ line) revealed a pathogenic mutation in CHEK2 and the complete loss of a VHL allele (both tumour suppressors). Moreover, in the tumour sample, several mutations, in BRAF1 and PTPN11 were found. Familiar segregation studies showed that CHEK2 mutation was in the maternal lineage, while VHL was inherited by paternal lineage.ConclusionsFinally, clinical history correlated to the different genotypes in the family, concluding that the severity of these VHL manifestations are due to both, VHL-and-CHEK2 mutations. This case report aims to notice the importance of deeper genetic analyses, in inherited rare diseases, to uncover non-expected mutations.
| S-EPMC10739370 | biostudies-literature
Project description:PurposeTo describe genetic analysis, treatment results, and complications of patients affected by retinal capillary hemangioblastoma (RCH) in von Hippel Lindau (VHL) syndrome.MethodsWe collected 17 patients with VHL syndrome, who underwent a molecular test and an ophthalmic evaluation at the Eye Clinic of the University Hospital of Florence from January 2005 to February 2020. We focused on eyes showing RCHs examined using color fundus photographs, fluorescein angiography, and optical coherence tomography.ResultsEight eyes of six patients (6/17; 35%) showed RCHs at the fundoscopic examination. All RCHs were treated with laser therapy. Three eyes underwent episcleral surgery, one eye showing vitreous hemorrhage received three intravitreal (IV) anti-VEGF injections and three cryotherapy procedures, and one eye underwent vitrectomy. In patients with RCHs, five were characterized by a truncating mutation of the VHL protein, and one patient showed a missense mutation. We have reported two VHL mutations not reported in literature.ConclusionsPatients with multiple RCHs, who developed RCH secondary effects, showed truncating mutations of the VHL protein. We recommend early screening and close monitoring, especially if RCHs are detected at presentation, for every patient with VHL syndrome independently of the results of the molecular test for a missense or a truncating mutation in VHL.
| S-EPMC8416136 | biostudies-literature
Project description:PurposeThis is the first single-institution study of its size to characterize the treatment impact and to address the question of whether hemangioblastoma treatment with Gamma Knife Stereotactic Radiosurgery (GKRS) in both sporadic and VHL patients changes the characteristic saltatory hemangioblastoma growth pattern.MethodsThe authors reviewed a single-institution tumor registry to identify patients who had received GKRS for hemangioblastomas between January 1st, 1999, and December 31st, 2017.Results15 patients with 101 lesions met search criteria with a median age of first GKRS of 39.2 years (interquartile range [IQR] of 25.7-57.4 years), including 96 VHL and 5 sporadic lesions. The median time from GKRS to last follow-up was 5.4 years (IQR 2.3-11.5 years). 4 lesions (4%) and 3 patients (20%) experienced a local failure. The 1-year, 3-year, and 5-year freedom from new hemangioblastoma formation rates were 97%, 80%, and 46% respectively. Multivariate analysis revealed a reduction in tumor volume after GKRS. Several variables associated with a greater percent reduction in volume from GKRS to last follow-up: non-cystic status (p = .01), no prior craniotomy (p = .04), and follow-up time from GKRS (p < .0001).ConclusionsGKRS is a successful long-term treatment option for hemangioblastomas changing the clinical course from saltatory growth to reduction in tumor volume. Non-cystic tumors and those without prior craniotomy were associated with a greater percent reduction in volume from GKRS at last follow-up.
| S-EPMC6805133 | biostudies-literature
Project description:IntroductionThe aim of this study was to determine the potential genetic cause of retinal capillary hemangioblastoma (RCH) with symptoms of Von Hippel-Lindau (VHL) disease.Case presentationsThree Iranian families (5 RCH patients) with novel variants are included in this study. The VHL variant analysis was performed by the Sanger sequencing technique. Molecular dynamics (MDs) simulations were conducted to analyze conformational changes resulting from variants in VHL protein structure and were compared with that of the native structure. Novel variant sites, including c.511A>C, c.511A>T, and c.514C>T in exon 3 of the VHL gene were identified. According to the American College of Medical Genetics (ACMG) classifications, c.514C>T (p.P172S) and c.511A>C (p.K171Q) are classified as variants of uncertain significance (VUS), and c.511A>T (p.K171*) is classified as a likely pathogenic variant. MD simulations demonstrated overall fluctuations of the proteins structure and a significantly lower degree of flexibility in the α-domain for the variant-encoded VHL protein structure compared to that of the native form.ConclusionThe structural information and computational analysis of the identified variants are predicted to induce conformational changes that limit the flexibility of protein VHL interaction interface with Elongin B/C, Elongin C/B, and Cullin-2, which are necessary for hypoxia-inducible factor 1-α binding. The genetic variants identified in Iranian patients with RCH may aid in the molecular confirmation of other patients diagnosed with VHL and their at-risk family members. These pioneering results that include detailed structural and functional analysis of a variant's effect on the VHL protein may serve as a model for future studies.
| S-EPMC11842073 | biostudies-literature
Project description:We present two cases of von Hippel-Lindau (VHL) disease-associated hemangioblastomas in the CNS treated with the newly approved HIF-2α inhibitor, belzutifan. The first case is a 31-year-old female with confirmed pathogenic germline VHL mutation who presented with multiple hemangioblastomas. The patient was started on belzutifan, and a brisk reduction in perilesional edema was observed after 2 months of treatment. The second patient is a 30-year-old male with familial VHL disease. Imaging revealed multiple cerebellar hemangioblastomas, and follow-up imaging after three cycles of belzutifan revealed a reduction in perilesional edema. Both patients tolerated belzutifan well, with only anemia and fatigue. We highlight our initial experience and early imaging findings associated with belzutifan in VHL disease-associated CNS hemangioblastomas.
| S-EPMC9280404 | biostudies-literature
Project description:Von Hippel-Lindau syndrome (VHL) is a familial neoplastic condition seen in approximately 1 in 36,000 live births. It is caused by germline mutations of the tumor suppressor gene VHL, located on the short arm of chromosome 3. While the majority of the affected individuals have a positive family history, up to 20% of cases arise from de novo mutations. VHL syndrome is characterized by the presence of benign and malignant tumors affecting the central nervous system, kidneys, adrenals, pancreas, and reproductive organs. Common manifestations include hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma and paraganglioma; renal cell carcinoma; pancreatic cysts and neuroendocrine tumors; and endolymphatic sac tumors. Diagnosis of VHL is prompted by clinical suspicion and confirmed by molecular testing. Management of VHL patients is complex and multidisciplinary. Routine genetic testing and surveillance using various diagnostic techniques are used to help monitor disease progression and implement treatment options. Despite recent advances in clinical diagnosis and management, life expectancy for VHL patients remains low at 40-52 years. This article provides an overview of the major clinical, histological, and radiological findings, as well as treatment modalities.
| S-EPMC5541202 | biostudies-other
Project description:PurposeTo better understand the histogenesis of ocular hemangioblastomas associated with von Hippel-Lindau (VHL) disease.MethodsWe found that co-expression of Epo and EpoR may mediate developmental stagnation and induce proliferation of hemangioblastoma. All lesions were frozen and/or fixed in formalin and embedded in paraffin. The specimens were sectioned and subjected to routine histology, immunohistochemistry and molecular analyses. Avidin-biotin-complex immunoperoxidase was used to evaluate the expression of erythropoietin (Epo), Epo receptor (EpoR), CD31, CD34, CD117, and CD133. Ocular hemangioblastoma cells were microdissected in order to determine expression of Epo and EpoR transcripts using reverse transcription-polymerase chain reaction.ResultsTumorlet-like cells were identified in retinal and optic nerve hemangioblastomas. Co-expression of Epo and EpoR at both protein and messenger levels was detected in many hemangioblastoma cells. In addition, ocular VHL lesions expressed several stem cell markers including CD133 to various degrees.ConclusionsThe data suggest that VHL disease-associated ocular hemangioblastomas are comprised of developmentally arrested stem cells including hemangioblasts, endothelial, and neuronal progenitor cells. We found that co-expression of Epo and EpoR may not only mediate developmental stagnation, but may also induce proliferation. Suppression of the growth of AC133/CD133 positive stem cells might be considered as one of the therapeutic targets for VHL-associated hemangioblastoma.
| S-EPMC1876780 | biostudies-literature
Project description:A germline mutation in the Von-Hippel Lindau (VHL) gene predisposes carriers to development of abundantly vascularised tumours in the retina, cerebellum, spine, kidney, adrenal gland and pancreas. Most VHL patients die from the consequences of cerebellar haemangioblastoma or renal cell carcinoma. The VHL gene is a tumour suppressor gene and is involved in angiogenesis by regulation of the activity of hypoxia-inducible factor 1-alpha (HIF1-alpha). Clinical diagnosis of VHL can be confirmed by molecular genetic analysis of the VHL gene, which is informative in virtually all VHL families. A patient with (suspicion for) VHL is an indication for genetic counselling and periodical examination.
| S-EPMC2837060 | biostudies-literature
Project description:Von Hippel-Lindau disease is an autosomal dominant syndrome which occurs secondary to germline mutations in the VHL tumor suppressor gene, located on chromosome 3. Clinically von Hippel-Lindau disease is characterized by an increased risk of developing simple visceral cysts, most commonly in the pancreas and kidneys, in addition to an increased risk of developing neoplasms, often with clear cell features, in a multitude of organ systems. The most common neoplasms are cerebellar and retinal hemangioblastomas, adrenal pheochromocytomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumors, pancreatic serous cystadenomas, and endolymphatic sac tumors. These lesions most commonly present during adulthood; however, screening and surveillance for the development of these lesions should begin in the pediatric years for patients with von Hippel-Lindau disease. In this review article, the genetics and most common neoplasms of von Hippel-Lindau disease are reviewed, with an eye towards implications for the pediatric patient.
| S-EPMC4918695 | biostudies-literature