A 10-year retrospective study of hemangioblastomas of the central nervous system with reference to von Hippel-Lindau (VHL) disease

We aimed to analyze the clinical, radiological, surgicopathological and clinical outcome data of patients who underwent surgery for central nervous system (CNS) hemangioblastoma (HBL) with or without von Hippel-Lindau (VHL) disease. The clinico pathological and radiological findings, management and clinical outcome of patients with CNS HBL (operated between 2000 and 2009) were analyzed retrospectively. The differences between sporadic and VHL-associated HBL were analyzed. Forty-nine patients (28 male, 21 female) underwent surgery for CNS hemangioblastoma. Thirty-nine patients (80%) harbored sporadic HBL whereas 10 (20%) had VHL disease. The mean age at diagnosis for VHL-associated HBL was 32 years when compared to 40 years in sporadic HBL. The lesions were solitary in 41 patients and multiple in eight. The cerebellum was the most common site of HBL (35/49, 71%). Six patients with sporadic and two with VHL disease had spinal lesions. On imaging (available in 43/49 patients), a cyst with a mural nodule was the most common finding, seen in 16 patients (37.2%) whereas nine patients (21%) had solid and cystic lesions. Clinical presentation, radiological features, and histomorphology of HBL with or without VHL disease were similar. Multiple cysts in the pancreas, kidney, broad ligament, epididymis, clear cell renal cell carcinoma, phaeochromocytoma and retinal angiomas were the visceral manifestations seen in patients with VHL disease. Of all patients with VHL disease, three required multiple surgeries for new lesions and one died of renal failure and sepsis. Among the patients with sporadic disease (31/39), two died of surgical complications, one died of postoperative sepsis, three were lost to follow-up and the remainder had resolution of symptoms at 1 year following surgery. We concluded that the diagnosis of VHL disease is important as management is more difficult and lifelong follow-up and counseling are required in these patients and for their at-risk relatives.     

Hippel-Lindau disease]

Hippel-Lindau disease is one of inherited tumour susceptibility syndromes. The most common lesions are located in central nervous system, retina and visceral organs. In Poland the disease was rarely diagnosed although the prevalence is much higher than it was supposed and is estimated as 1: 30-50,000. It is inherited in an autosomal dominant manner with age related penetrance reaching almost 98% penetrance at the age of 60 and variable expression. The VHL gene is located near the tip of the short arm of chromosome 3 (3p25-26). Classical lesions in VHL patients are: haemangioblastomas of CNS, retina, cysts and clear cell carcinoma of kidney, cysts and tumours of pancreas, phaeochromocytoma and paraganglioma, papillary cystadenoma of epididymis and endolymphatic sac tumours. Multifocal, often bilateral lesions in form of benign cysts, vascular tumours or carcinomas occur. Management of the lesions often differs from that in sporadic cases of the tumours. Non-symptomatic lesions of CNS need no treatment, neither do non-symptomatic tumours of epididymis and some of phaeochromocytomas. Kidney carcinoma is treated when it reaches a certain size preferably by nephron-sparing surgery. Special care should be provided to pregnant VHL patients. Available DNA testing enables to identify VHL carriers. Although the mean age of death in VHL patients is 41 at the moment a proper prophylactic, diagnostic and treatment management can probably prolong survival of the patients and limit complications of the disease. The coordination between genetic consultants and clinicians is crucial in the management of the patients. The authors coordinate work of Polish VHL Registry and Polish VHL Association.     

Spinal Cord Hemangioblastoma : Diagnosis and Clinical Outcome after Surgical Treatment

Objective

Spinal cord hemangioblastoma is an uncommon vascular neoplasm with a benign nature and is associated with von Hippel-Lindau (VHL) disease in 20-30% of patients. Total removal of these tumors without significant neurological deficit remains a great challenge. The purpose of this study was to investigate the efficacy of VHL mutation analysis and to evaluate surgical outcome of patients with spinal cord hemangioblastomas.

Methods

This study included nine patients treated for spinal cord hemangioblastomas at our institute between December 1994 and March 2006. There were four male and five female patients. Mean age was 37.8 years. The mean follow-up period was 22.4 months. Magnetic resonance imaging (MRI) of the complete neuraxis was done in all cases and VHL mutation analysis was performed in three cases for a definite diagnosis.

Results

Six patients had intramedullary tumor, and the remaining patients had intradural extramedullary lesions. Five patients were associated with VHL disease. The von Hippel-Lindau mutation analysis was done in three patients and two of them showed VHL gene abnormality. Tumors were located in the cervical cord in five cases and in the thoracic cord in four cases. All patients underwent surgical intervention, and total removal was achieved in six cases. All patients showed improvement or, at least, clinically stationary state. Surgical complications did not develop in any cases.

Conclusion

Spinal hemangioblastoma in this series has been safely and effectively removed via a posterior approach. Postoperatively, clinical outcome was excellent in the majority of cases. The VHL mutation analysis was useful in patients with family history and in those with multiple hemangioblastomas.     

家族性中枢神经系统血管母细胞瘤VHL基因突变与临床预后分析

目的 探讨汉族人家族性中枢神经系统血管母细胞瘤（HB）的临床特点及家系表现和VHL基因突变的关系.方法 回顾性分析9个家族15例经手术和病理证实的HB患者进行临床分析.对长期随访的7个家族中的12例患者和15例相关家族成员抽取外周血进行VHL基因测序.对于测序阴性的患者,对其DNA进行三个外显子实时定量PCR测定.结果 本组15例HBs中,多发性肿瘤10例,共34个肿瘤.进行开颅和脊髓手术17次,共切除HB22个.基因测序发现在4种点突变.通过实时定量PCR发现2个家族外显子1大片段缺失.在未发病家族成员中检出携带者3例.随访期间发现2例复发和3例新生的HB,主要集中在移码突变和拼接错误的家族中.通过再次手术和对脑干HB进行γ刀治疗,效果较好.结论 VHL相关的HB易复发,并不断有新生HB出现.基因测序和实时定量PCR联合应用可以提高VHL基因突变的检出率.基因突变分析可有助于未发病基因突变携带者确诊,基因突变的分型有助于对患者的预后进行判断.     

VHL相关性和散发性中枢神经系统血管母细胞瘤

目的 探讨VHL病相关性和散发性中枢神经系统(CNS)血管母细胞瘤(HB)临床、处理及预后特征。方法 回顾性分析连续20年中我科收治的66例CNS-HB病人资料。对近期病例作了VHL基因突变和VEGF表达检测。结果 66例HB病人中,散发性58例,VHL相关性8例,共79处病变,7例为多发病变。全组62例共施行了70次手术治疗,其中5例进行了多次手术。8例VHL相关病人中有3例多次手术。64次全切,6次大部分切除。大部分切除的病人有4例复发。手术死亡3人。70次手术中手术效果良好者46次,病情改善者18次,稳定者3次。57例平均随访6.7年(1～16年),41例恢复工作,5例生活自理,部分自理和完全不能自理各1例,9例死亡。VEGF基因突变率为75％(18/24),HB中均见VEGF过度表达。结论 CNS-HB病人的手术治疗结果良好,VHL相关病人的远期愈后较差。     

散发性与VHL相关性颅内血管母细胞瘤的MRI与病理相关性研究

目的 探讨散发性与Von Hippel-Lindau(VHL)病相关性颅内血管母细胞瘤的MRI表现类型及其病理基础.方法 2002年至2009年经手术病理证实的颅内血管母细胞瘤患者29例,将肿瘤MRI影像表现特点与手术病理结果做对照分析.结果 29例颅内血管母细胞瘤患者,散发性17例(59%),VHL病12例(41%),共计66个血管母细胞瘤,MRI表现为实性小结节型(28个)、实性肿块型(18个)及囊结节型(20个),病理光镜下表现为网状型、细胞型及混合型.结论 血管母细胞瘤的MRI表现类型与其病理基础密切相关.对VHL病患者颅内无症状的实性小结节型血管母细胞瘤应长期追踪观察.     

Central nervous system involvement in Von Hippel-Lindau disease

Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency and distribution of CNS lesions. The associated clinical features were also reviewed. Thirty-six (72%) of the 50 had 1 or more CNS tumors. The most frequently affected sites in the CNS excluding the retina were the cerebellum (52%), spinal cord (44%), and brainstem (18%). New regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study. Forty-one percent of all VHL patients with CNS tumors were neurologically asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem tumors (44%) were often without clinical signs or symptoms. Multiple lesions were common. The mean age of all VHL patients (34.5 years) was similar to the mean age of all CNS VHL patients (34.4 years), suggesting a lack of age association. CNS lesions commonly occurred in the 2nd decade of life. All patients at risk for VHL should be evaluated using gadolinium-enhanced MRI after 10 years of age, although ophthalmic examination should be initiated within the 1st 2 years of life. Enhanced MRI is particularly useful in the detection of CNS tumors in patients with the VHL gene.     

The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system

OBJECTIVES: Haemangioblastoma of the CNS occurs as a sporadic entity and as a manifestation of the autosomal dominant von Hippel-Lindau disease with the major additional components retinal angioma, renal cancer, and pheochromocytoma. Genetic testing for germline mutations predisposing to von Hippel-Lindau disease has been available since identification of the VHL tumour suppressor gene. The impact of this testing was evaluated in patients with haemangioblastomas seen in this centre. METHODS: A register and database of patients with symptomatic haemangioblastomas for the last 15 years was evaluated. The VHL gene was analysed by the SSCP method for all exons and Southern blotting for mutations and deletions of the gene. RESULTS: 141 patients with haemangioblastoma of the CNS were registered. In 81 patients (57%) there was a disease predisposing germline mutation including eight novel mutations. Population related calculation of patients from the administrative district of Freiburg disclosed VHL germline mutations in 22% of the patients with haemangioblastoma. Analysis of mutation carriers for clinical information suggestive of the syndrome showed (1) a positive family history of a brain tumour in 50%, (2) a history for the patient of extracranial manifestations in 36% (retinal angioma 30%, pheochromocytoma 6%), and (3) 19% presenting with multiple brain tumours when first admitted. By genetic testing of haemangioblastoma patients without any indications of von Hippel-Lindau disease mutation carriers were identified in 14%. Sensitivity of VHL germline testing was 86%. CONCLUSIONS: DNA analysis for VHL germline mutations is clearly superior to clinical information in the diagnosis of von Hippel-Lindau disease. Although the percentage of von Hippel-Lindau disease associated haemangioblastoma decreases after the fourth decade of life and is infrequent in patients without other symptomatic lesions and a negative family history, it is recommended that every patient with CNS haemangioblastoma should be screened for von Hippel-Lindau disease germline mutations. This provides the key information and enables screening for extraneurological tumours of the patients and investigations of the patient's family to ameliorate management of von Hippel-Lindau disease.     

Surgical treatment of hemangioblastomas of the central nervous system in pediatric patients

Objective Hemangioblastomas are histologically benign lesions that occur sporadically or as a manifestation of von Hippel–Lindau disease (VHL). The treatment strategy of these neoplasms is complicated by their unpredictable growth patterns and the often irreversible neurological deficits they may cause. This study aims to outline the neurosurgical treatment options and to address the ongoing debate of surgical timing in pediatric patients with VHL.Patients and methods Thirteen consecutive pediatric patients (mean age 15.1 years) who were surgically treated for intracranial (n=8) or spinal hemangioblastomas (n=5) were included in this study (range of clinical follow up 12–86 months). Ten patients were affected by von Hippel–Lindau and three were with sporadic tumors. Serial examinations, preoperative MRI studies, and operative findings were reviewed.Results Patients with cerebellar and intramedullary hemangioblastomas did not develop additional neurological deficits postoperatively. Two patients with brainstem tumors exhibited transient hemiparesis and caudal nerve palsy, respectively. Both patients recovered completely from their postoperative deficits. Preoperatively symptomatic patients with spinal tumors did not deteriorate nor improve after surgery. During the observed follow-up periods, no tumor recurrences were observed.Conclusion Central nervous system (CNS) hemangioblastomas in pediatric patients can be surgically treated with low morbidity. Based on our experience, we recommend considering also the surgical removal of asymptomatic hemangioblastomas with proven radiological progression to prevent the development of permanent neurological deficits. Molecular screening of every pediatric patient and family is mandatory to enable the detection of extraneurological tumors and the development of an efficient therapeutic strategy.     

Von Hippel-Lindau病相关性中枢神经系统血管母细胞瘤

目的探讨yon Hippel—Lindau病相关性中枢神经系统血管母细胞瘤的临床特点、治疗原则及预后。方法对2000年1月-2005年1月收治的18例von Hippel—Lindau病相关性中枢神经系统血管母细胞瘤患者的临床资料进行回顾分析，并与同期收治的散发性中枢神经系统血管母细胞瘤患者比较，对其中1例资料完整者的家系进行详细调查。结果18例患者平均年龄37．60岁，其中有明确家族遗传史者7例，伴肾囊肿10例，伴胰腺囊肿5例，伴视网膜血管瘤3例，伴肾癌1例，伴肾上腺嗜铬细胞瘤1例。与散发性中枢神经系统血管母细胞瘤相比，von Hippel—Lindau病相关性中枢神经系统血管母细胞瘤患者更容易出现多发性血管母细胞瘤，手术前平均外周血红蛋白水平多〉160g／L。18例中无一例手术死亡，手术后全部获得平均42个月的随访，Kamofsky预后评分〉80分者12例〈66．67％），死亡2例（分别死于脑干血管母细胞瘤复发和肾癌多发转移）。家系调查显示．家系成员发病以血管母细胞瘤多见（10／12），且2例为多发性血管母细胞瘤，遗传可能来自母系，外显率为12／31（38．71％）。结论对于多发性血管母细胞瘤或手术前平均外周血红蛋白水平〉160g／L的血管母细胞瘤患者应高度怀疑von Hippel-Lindau病，须施行严格的眼底镜检查或眼底荧光造影、腹部B超、CT检查，以排除von Hippel-Lindau病。一旦明确诊断则建议患者出院后定期进行上述检查，以便早期发现新的病灶，及时治疗。     

Stereotactic linac radiosurgery for arteriovenous malformations.

Stereotactic linear accelerator (linac) radiosurgery has been in operation in the West Midlands since 1987, the first of its kind in the United Kingdom. Forty two patients with high-flow cerebral arteriovenous malformations have been treated, 26 of whom have been followed up. Angiography one year after treatment showed that five lesions were obliterated, 11 were reduced in size and/or flow rate and 10 were unchanged. Overall results show that nine out of 10 patients reviewed at 24 months had total obliteration. Three patients had complications; one has fully recovered, one died of an unrelated cause at 36 months and the other died from recurrent haemorrhage at nine months. Two patients had recurrent non-fatal haemorrhage within 24 months of treatment; both recovered without further deficit. All patients are fit to work but eight are unemployed. Although the follow up period is short, the early results indicate a success rate similar to those published by others using linac radiosurgery.     

Épidémiologie,traitement et suivi des hémangioblastomes du système nerveux central dans le cadre de la maladie de von Hippel-Lindau

Introduction

Central nervous system (CNS) hemangioblastomas (HGB) are rare vascular tumors. The goal of this study was to analyze their epidemiology, treatment and prognosis in association with von Hippel-Lindau (VHL) disease.

Methods

We retrospectively reviewed a series of patients treated in our department for a CNS HGB with VHL disease between 1996 and 2008. We analyzed pre- and postoperative clinical and radiological characteristics, number of visceral lesions (fundoscopy, abdomino-pelvian CT, metanephrines), clinical course (modified Rankin Scale and McCormick scale) and late prognosis (Kaplan-Meier survival curves).

Results

We studied 19 cases (sex-ratio 0.9, mean age 36). The mean time to diagnosis was 61 days. The main symptom was intracranial hypertension for cerebellar lesions (7/15) and a sensitive-motor deficit for medulla oblongata (2/5) or spinal lesions (5/11). Preferred locations were cerebellum (15/31), often nodulo-cystic appearance, followed by spinal cord (11/31), frequently coming with adjacent syringomyelia. Multiple locations and visceral lesions were found in two-third of the cases. Surgical removal was complete in more than three-quarter of the cases. Mean follow-up duration was 9 years. Postoperative mortality rate was 16%. In cerebellar and medulla oblongata locations together, final mRS was ≤ 1 in 17 of the 20 cases. In spinal cord locations, final McCormick score was ≤ 2 in all the cases. After delayed follow-up, about two-third of patients experienced recurrence or new progressive CNS lesions.

Conclusion

HGB are rare CNS tumors. VHL disease should be considered when an HGB is diagnosed before 30, is located at the spinal cord, comes with multiple other CNS lesions or with typical peripheral lesions. Microsurgical removal is the gold standard treatment and can offer good functional results.     

Late effects on the hypothalamo-pituitary function after the treatment of parasellar tumors]

Long term follow-up of patients submitted to treatment of parasellar tumours region is important for the detection of late therapeutic complications. In this study the authors conducted an evaluation of six patients with craniopharyngioma, one with germinoma, one with meningioma, and one epidermoid cyst. All above tumours were localized at parasellar region. Six out of nine patients had been treated both by surgery and by radiotherapy and the other three surgically only, on an average 3.8 +/- 3.2 years before this observation was carried out. Five patients were female with their ages average 24.3 +/- 18.8 years old. Evaluation consisted: in the first place, an intravenous infusion of thyrotropin-releasing hormone (TRH, 200 micrograms), gonadotropin-releasing hormone (GnRH, 100 micrograms), and insulin tolerance test (0.1 IU/Kg, regular insulin); and secondly, in measurements of pituitary hormones secretion at different time points--0, 20, 40, 60 and 80 minutes. We found both diminished response of growth hormone and cortisol in all the patients. Seven out of nine patients did not have adequate response to follicle-stimulating hormone. Three out of nine responded unsatisfactory to luteinizing hormone. Four out of nine showed inadequate responses to prolactin as well as, two out of eight to thyrotropin. We concluded that: (a) growth hormone and cortisol deficiency are the most frequent finding in these patients; (b) post-radiotherapy lesions can be located in the hypothalamus or pituitary, or even in both; (c) hypophysial and hypothalamic cells sensitivity to irradiation is different, according to their respective hormones; and (d) it is necessary a frequent endocrinologic follow-up of patients to detect late hormonal deficiencies.     

Low frequency of VHL germline mutations in Norwegian patients presenting with isolated central nervous system hemangioblastomas – a population‐based study

Rønning P, Andresen PA, Hald JK, Heimdal K, Scheie D, Schreiner T, Helseth E. Low frequency of VHL germline mutations in Norwegian patients presenting with isolated central nervous system hemangioblastomas – a population‐based study.
Acta Neurol Scand: 2010: 122: 124–131.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Explore the genetic and clinical incidence of von Hippel–Lindau disease in patients presenting with isolated central nervous system hemangioblastomas. Results – We report a 3.2% (1/31) and 25% (8/32) incidence of genetic and clinical VHL, respectively. One patient tested positive for a VHL mutation that has not previously been reported. This genotype phenotypically predicts VHL type 2B. We had seven patients with renal cysts. In a total follow‐up of 33 person years, none of these cysts progressed to renal cell carcinoma. Conclusion – von Hippel‐Lindau disease anchored in germline mutations of the VHL gene is rare in the Norwegian population as opposed to clinical VHL disease, which appears to be relatively common in patients with apparently sporadic hemangioblastomas. There exists insufficient data regarding the natural history of patients with renal cysts, which makes it difficult to include or disregard these lesions as an entity of VHL disease.     

Neuro-ophthalmology of von Hippel-Lindau

von Hippel-Lindau (VHL) disease is a multisystem inherited cancer syndrome with characteristic tumors and a known genetic basis. Patients with VHL develop, among other tumors, retinal capillary hemangiomas, central nervous system hemangioblastomas, renal clear cell carcinomas, and pheochromocytomas. Nearly all patients can be shown to have a mutation in the VHL gene, which is located on chromosome 3p25. Genetic abnormalities result in abnormal levels of pVHL, which in turn lead to the different tumors. Four distinct phenotypes of VHL disease have been identified based on the relative frequency of and propensity for the development of different VHL tumors. Aggressive screening of patients with VHL disease can prevent morbidity and mortality from these tumors. Although these tumors typically have been treated with observation or surgery, trials of newer medical therapies that target some of the cellular dysregulation caused by mutation in pVHL are ongoing. Even though these trials have not been wholly successful, they present an exciting direction for future research. This article presents a summary of new developments in VHL disease with a focus on ophthalmic and neuro-ophthalmic practice.     

Stereotactic biopsy for multifocal, diffuse, and deep-seated brain tumors using Leksell's system.

Using the Leksell stereotactic system, we selectively performed 91 biopsies for surgically inaccessible brain lesions. There were 25 multiple (27.5%), 15 diffuse (16.5%), and 51 (56.0%) deep-seated lesions. However, we avoided subjecting the patients with lesions adjacent to major vascular trunks or complex vascular structures such as the cavernous sinus, peri-insular regions and the pineal regions to stereotactic biopsy. The diagnosis was histologically confirmed in 84 cases (92.3%). Sixty-nine (75.8%) lesions were primary tumors; 44 (48.4%) were malignant gliomas, 18 (19.8%) malignant lymphomas, and five (5.5%) low-grade gliomas. Thirteen (14.3%) cases had previously undergone radiation and/or chemotherapy for brain tumors, seven had recurrent glioma (five with malignant transformation) and six manifested radiation necrosis. None of the patients died due to the stereotactic procedure; one (1.1%) exhibited morbidity due to complicated hemorrhage. We found asymptomatic minor bleeding occurred in nine (9.9%) patients; the rate of hemorrhage was significantly higher in patients with preoperative angiographic evidence of tumor stain. Two patients (2.2%) suffered seizures, in one case seizure was induced by electric stimulation test at the target site. All five patients younger than 15 years underwent the procedure without complications. The Leksell stereotactic system is useful for diagnostic tissue sampling and contributes effectively to the selection of appropriate therapy in patients with malignant brain tumors. While it carries a low morbidity rate without mortality in our series, care must be taken for selected target sites in highly vascularized lesions exhibiting positive tumor stains.     

Developmental effects of von Hippel-Lindau gene deficiency

The histogenetic origin and the basis of the distribution of central nervous system (CNS) hemangioblastomas in the von Hippel-Lindau (VHL) tumor suppressor gene syndrome, VHL disease, are unknown. To better understand hemangioblastoma histogenesis, we analyzed postmortem CNS tissues from four patients with well-established diagnosis of VHL disease including development of characteristic tumors and positive family history. Numerous angiomesenchymal tumorlets, which resembled hemangioblastoma, but which also consistently showed distinct histological features, were distributed in the nerve roots, spinal cord, and cerebellum. Genetic analysis consistently showed deletion of the wild-type VHL allele in these tumorlets. Most angiomesenchymal tumorlets were in the dorsal nerve roots; the anterior roots and cerebellum were less frequently affected. Tumorlet distribution was highly consistent in the four cases. In analogy to the wide morphological spectrum of lesions known to exist in VHL kidneys, nerve roots appear to harbor more wide-spread and morphologically heterogeneous changes than previously appreciated. The abundance of tumorlets, associated with highly consistent morphology and topography, suggests a developmental origin of hemangioblastoma. Therefore, in VHL disease, inactivation of the VHL wild-type allele appears necessary, but not sufficient, for the formation of tumor that produces symptoms and neurological disability.     

显微手术治疗中枢神经系统血管母细胞瘤的临床疗效

目的观察显微手术治疗中枢神经系统血管母细胞瘤(HB)的临床疗效。方法回顾性分析昆明医科大学第一附属医院神经外科2016年1月至2020年1月采用显微手术治疗的41例HB患者的临床资料。其中3例合并Von Hippel-Lindau(VHL)综合征。肿瘤切除术前,2例行脑室-腹腔分流术,1例行第三脑室底脚间池造瘘术,3例行部分供血动脉栓塞术。术中患者均行冲经电生理监测,2例联合应用术中B超与术前MRI融合技术,2例辅助神经内镜技术。术后3个月采用Karnofsky功能状态评分(KPS)评估临床疗效,影像学观察肿瘤复发情况。结果41例患者中,肿瘤全切除40例(97.6%),部分切除1例(2.4%)。术后1例(2.4%)患者死于颅内感染,2例(4.9%)出现严重的肺部感染。术后3个月随访,40例患者中,症状改善者30例(75.0%),较术前尤明显变化者10例(25.0%);KPS为(79.8±15.3)分,与术前的(70.2±14.9)分比较,差异有统计学意义(P=0.011)。MRI检查显示4例(10.0%)出现原位复发或远隔部位新发病灶,其中3例为合并VHL的患者;4例均给予放射治疗,随访MRI证实肿瘤均缩小。结论在多种技术联合下,中枢神经系统的手术全切除率高、并发症的发生率低。合并VHL综合征者术后肿瘤可能更易复发。     

Surgical management of large solid hemangioblastomas of the posterior fossa

From January 2000 to January 2009, 15 patients presented with large solid hemangioblastomas of the posterior fossa; eight of these patients were also diagnosed with von Hippel-Lindau (VHL) disease. Diagnostic imaging showed large vascular lesions. All 15 patients underwent surgery through a suboccipital ipsilateral, modified far-lateral, suboccipital midline or suboccipital supracerebellar approach. Preoperative embolization was attempted in seven patients. Complete removal of the tumor was performed in all patients. An overall neurological improvement was observed in 11 of the 15 patients, corresponding to 61.5%. During follow-up, six patients, all with VHL disease, developed recurrence. Two patients died of renal cell carcinoma after 1 year. Our favorable outcomes suggest that surgical resection is the optimal treatment for patients with large solid hemangioblastomas of the posterior fossa. With improved microsurgical techniques and a better understanding of the vascular pattern of this type of tumor, total microsurgical removal can be performed with low mortality.     

Management of von Hippel-Lindau disease-associated CNS lesions

Patients with von Hippel-Lindau disease (VHL) often harbor significant disease burden within the CNS, specifically craniospinal-axis hemangioblastomas and endolymphatic sac tumors (ELSTs). The majority (60-80%) of patients with VHL harbor hemangioblastomas, and 10-15% will develop ELSTs. Advances in the understanding of the natural history and outcomes associated with the surgical management of VHL-associated tumors have led to improved management of patients with VHL. Optimizing indications for surgical intervention and refining of surgical techniques for these lesions can reduce patient morbidity associated with the management of this syndrome. In this article, we review the various aspects of perioperative management of patients with VHL, surgical indications and general operative principles for the management of hemangioblastomas and ELSTs, and outcomes associated with the surgical treatment of these tumors.