Fibrous meningioma in a patient with von Hippel—Lindau disease: a genetic analysis

2001 ◽  
Vol 95 (6) ◽  
pp. 1045-1049 ◽  
Author(s):  
Lance S. Governale ◽  
Alexander O. Vortmeyer ◽  
Zhengping Zhuang ◽  
Edward H. Oldfield
Keyword(s):  
Gene Locus ◽  
Neurofibromatosis Type ◽  
Magnetic Resonance Images ◽  
Polymorphism Analysis ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Single Stranded Conformational Polymorphism ◽  
Von Hippel Lindau Disease ◽  
Unaffected Parent ◽  
Vhl Disease

✓ Meningioma has been included in the constellation of tumors associated with von Hippel—Lindau (VHL) disease in previously published reports. It is unclear whether these tumors are an uncommon component of VHL disease or are more readily detected in these patients because of the frequency with which they undergo central nervous system imaging as part of the routine management of VHL disease. The authors report the case of a patient with VHL disease in whom a progressively enlarging supratentorial mass developed and was diagnosed as a hemangioblastoma because of its appearance on serial magnetic resonance images. At surgery the tumor displayed the typical features of a meningioma and was given the histological diagnosis of fibrous meningioma. Single-stranded conformational polymorphism analysis of the tumor DNA revealed a loss of heterozygosity at the neurofibromatosis Type 2 gene locus, known to be associated with sporadically occurring meningiomas. Despite this finding, the VHL gene locus on the allele from the patient's unaffected parent was normal. Thus it is unlikely that the occurrence of this patient's fibrous meningioma was associated with underlying VHL disease. Given the high frequency of neuroimaging sessions in patients with VHL disease, some supratentorial lesions that have been given radiological diagnoses of hemangioblastomas may be incidental meningiomas.

Endolymphatic sac tumors in von Hippel—Lindau disease

2004 ◽  
Vol 100 (3) ◽  
pp. 480-487 ◽  
Author(s):  
Daniel Choo ◽  
Lawrence Shotland ◽  
Maryann Mastroianni ◽  
Gladys Glenn ◽  
Carter van Waes ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Family Members ◽  
Magnetic Resonance Images ◽  
Endolymphatic Sac ◽  
Specific Gene ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Vhl Disease ◽  
Fine Print

Object. Von Hippel—Lindau (VHL) disease is a hereditary multiple-neoplasia syndrome mapping to chromosome 3p25–26. Endolymphatic sac (ELS) tumors have been identified as a neoplastic manifestation of VHL disease. The purpose of this study was to evaluate comprehensively the natural history of inner ear disease in a large population of patients with confirmed or suspected VHL disease and to correlate the clinical features with the VHL genotype. Methods. The authors collated and analyzed clinical and genotypic data obtained in patients enrolled in an Institutional Review Board—approved protocol in which families and individuals affected by VHL disease were studied. These data included results from multidisciplinary history workups and physical examinations, imaging studies, and a battery of audiological tests. One hundred seventy-five patients were enrolled in the study, 129 with confirmed VHL disease and 46 of their family members in whom test results for VHL disease were negative and who served as controls. Twenty-one patients had ELS tumors that were evident on magnetic resonance images; three of them had bilateral ELS lesions. Hearing loss, often sudden in onset and severe to profound in nature, vestibulopathy, aural fullness, and tinnitus represented the primary symptoms of ELS tumor. Distinct patterns of auditory and vestibular dysfunction occurred at different stages of the disease. Phenotypic data showed that 17 of 21 patients with ELS tumors did not have pheochromocytomas, whereas all had VHL disease affecting the kidney, all but two had VHL disease affecting the central nervous system, and all but one had disease affecting the pancreas. Genotyping revealed 10 rearrangements (partial deletions), eight single bp substitutions, and one 3-bp insertion. Although there was no difference in the incidence of hearing loss between populations, symptoms of imbalance and aural fullness were more common in patients with VHL disease but without imaging evidence of ELS tumor than they were in family members who did not have VHL disease (p < 0.01). Conclusions. Endolymphatic sac tumors are frequently associated with VHL disease. Symptoms of disequilibrium or aural fullness in patients with VHL disease may be an early indication of endolymphatic dysfunction. Patients with VHL disease provide a unique opportunity to examine the effects of specific gene mutations and a discrete neoplastic process on the human inner ear. The study of ELS tumors in this group also provides a pathological model of ELS function and supplies evidence for a role of the ELS in clinical Ménière-like disease(s).

Surgical management of brainstem hemangioblastomas in patients with von Hippel—Lindau disease

2003 ◽  
Vol 98 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Robert J. Weil ◽  
Russell R. Lonser ◽  
Hetty L. Devroom ◽  
John E. Wanebo ◽  
Edward H. Oldfield
Keyword(s):  
Magnetic Resonance ◽  
Preoperative Evaluation ◽  
Magnetic Resonance Images ◽  
Long Term Outcome ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Vhl Disease ◽  
Fine Print

Object. Hemangioblastomas of the brainstem constitute 5 to 10% of central nervous system (CNS) tumors in patients with von Hippel—Lindau (VHL) disease. At present, optimal management of brainstem hemangioblastomas associated with VHL disease is incompletely defined. In an attempt to clarify some of the uncertainty about the operative treatment of these lesions and its outcome, the authors reviewed all cases of VHL disease in which resection of brainstem hemangioblastomas was performed at the National Institutes of Health during a 10-year period. Methods. Twelve consecutive patients with VHL disease (six male and six female patients [mean age 31.7 ± 9 years; range 15–46 years]) who underwent 13 operations to remove 17 brainstem hemangioblastomas were included in this study (mean follow-up period, 88.4 ± 37.4 months; range 37–144 months). Serial examinations, hospital charts, magnetic resonance images, and operative records were reviewed. To evaluate clinical course, clinical grades were assigned to each patient before and after surgery. Preoperative neurological function was the best predictor of long-term outcome. In addition, patients who underwent CNS surgeries for hemangioblastomas were more likely to improve or to remain neurologically stable. Tumor or cyst size, the presence of a cyst, or the location of the tumor (intramedullary, extramedullary, or mixed; posterior medullary, obex, or lateral) did not affect outcome. No patient was neurologically worse after brainstem surgery. At long-term follow-up review (mean 88.4 months), only one patient had declined neurologically and this was due to the cumulative neurological effects caused by eight additional hemangioblastomas of the spinal cord and their surgical treatment. Conclusions. Brainstem hemangioblastomas in patients with VHL disease can be removed safely; they generally should be resected when they become symptomatic or when the tumor has reached a size such that further growth will increase the risks associated with surgery, or in the presence of an enlarging cyst. Magnetic resonance imaging is usually sufficient for preoperative evaluation and presurgical embolization is unnecessary. The goal of surgery is complete resection of the lesion before the patient experiences a disabling neurological deficit.

Gamma knife radiosurgery in 11 hemangioblastomas

1996 ◽  
Vol 85 (4) ◽  
pp. 591-596 ◽  
Author(s):  
Mika Niemelä ◽  
Young Jin Lim ◽  
Michael Söderman ◽  
Juha Jääskeläinen ◽  
Christer Lindquist
Keyword(s):  
Gamma Knife ◽  
De Novo ◽  
Gamma Knife Radiosurgery ◽  
Corticosteroid Treatment ◽  
Magnetic Resonance Images ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Solid Part

✓ One suprasellar, one mesencephalic, and nine cerebellar hemangioblastomas were treated with the gamma knife in 10 patients (median age 48 years) in Stockholm between 1978 and 1993. Four patients had von Hippel—Lindau disease, a dominant inherited trait predisposing to multiple hemangioblastomas. Six hemangioblastomas were treated with radiotherapy at a median margin dose of 25 Gy (20–35 Gy) before 1990 and the next five with a median of 10 Gy (5–19 Gy). Computerized tomography or magnetic resonance images were available for 10 of the 11 hemangioblastomas at a median follow-up time of 26 months (4–68 months) after radiosurgery. The solid part of six hemangioblastomas shrank in a median of 30 months, whereas four hemangioblastomas were unchanged at a median of 14 months. Five hemangioblastomas had an adjoining cyst and three of these cysts had to be evacuated after radiosurgery. One solitary hemangioblastoma later developed a de novo cyst that also needed evacuation. One patient with two cerebellar hemangioblastomas (margin dose 25 Gy each) developed edema at 6 months and required a shunt and prolonged corticosteroid treatment. The combined follow-up data of the 23 hemangioblastomas in 15 patients from previous literature and the present series indicate that, first, a solitary small- or medium-sized hemangioblastoma usually shrinks or stops growing after radiosurgery. The recommended margin dose is 10 to 15 Gy. Second, the adjoining cyst often does not respond to radiosurgery but requires later, sometimes repeated evacuation.

scholarly journals Inactivation of the Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Suppresses von Hippel-Lindau Disease-Associated Vascular Tumors in Mice

2005 ◽  
Vol 25 (8) ◽  
pp. 3163-3172 ◽  
Author(s):  
Erinn B. Rankin ◽  
Debra F. Higgins ◽  
Jacqueline A. Walisser ◽  
Randall S. Johnson ◽  
Christopher A. Bradfield ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Germ Line ◽  
Hypoxia Inducible Factor ◽  
Suppressor Gene ◽  
Vascular Tumors ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Arylhydrocarbon Receptor ◽  
Vhl Disease ◽  
Endothelial Growth Factor

ABSTRACT Patients with germ line mutations in the VHL tumor suppressor gene are predisposed to the development of highly vascularized tumors within multiple tissues. Loss of pVHL results in constitutive activation of the transcription factors HIF-1 and HIF-2, whose relative contributions to the pathogenesis of the VHL phenotype have yet to be defined. In order to examine the role of HIF in von Hippel-Lindau (VHL)-associated vascular tumorigenesis, we utilized Cre-loxP-mediated recombination to inactivate hypoxia-inducible factor-1α (Hif-1α) and arylhydrocarbon receptor nuclear translocator (Arnt) genes in a VHL mouse model of cavernous liver hemangiomas and polycythemia. Deletion of Hif-1α did not affect the development of vascular tumors and polycythemia, nor did it suppress the increased expression of vascular endothelial growth factor (Vegf) and erythropoietin (Epo). In contrast, phosphoglycerokinase (Pgk) expression was substantially decreased, providing evidence for target gene-dependent functional redundancy between different Hif transcription factors. Inactivation of Arnt completely suppressed the development of hemangiomas, polycythemia, and Hif-induced gene expression. Here, we demonstrate genetically that the development of VHL-associated vascular tumors in the liver depends on functional ARNT. Furthermore, we provide evidence that individual HIF transcription factors may play distinct roles in the development of specific VHL disease manifestations.

scholarly journals Adrenal Cortex-Sparing Surgery for Bilateral Multiple Pheochromocytomas in a Patient with Von Hippel-Lindau Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Tarık Esen ◽  
Ömer Acar ◽  
Ahmet Tefekli ◽  
Ahmet Musaoğlu ◽  
İzzet Rozanes ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Adrenocortical Function ◽  
Renal Masses ◽  
Von Hippel Lindau ◽  
Pancreatic Masses ◽  
Adrenal Pheochromocytoma ◽  
Von Hippel Lindau Disease ◽  
Vhl Disease

Pheochromocytomas can be a part of familial neoplastic syndromes, in which case they tend to be multiple and involve both adrenal glands. Therefore, sparing adrenocortical function represents a major concern while dealing with these hereditary lesions. Herein, we describe the clinical characteristics and the management strategy of a patient with von Hippel-Lindau (VHL) disease who had multiple, bilateral pheochromocytomas as well as bilateral renal masses, pancreatic masses, and a paracaval mass. Only a portion of the left adrenal gland has remained in situ after two consecutive open surgeries and a percutaneous radiofrequency ablation which have been performed to treat the various components of this syndrome. No adrenal or extra-adrenal pheochromocytoma recurrences have been detected during a follow-up period of more than 2 years. Pancreatic and adrenal functions were normal throughout the postoperative period and never necessitated any replacement therapy. Adrenal cortex-sparing surgery is a valid option for VHL disease patients who present with synchronous bilateral adrenal pheochromocytomas.

Surgical management of spinal cord hemangioblastomas in patients with von Hippel—Lindau disease

2003 ◽  
Vol 98 (1) ◽  
pp. 106-116 ◽  
Author(s):  
Russell R. Lonser ◽  
Robert J. Weil ◽  
John E. Wanebo ◽  
Hetty L. Devroom ◽  
Edward H. Oldfield
Keyword(s):  
Spinal Cord ◽  
Surgical Management ◽  
Postoperative Outcome ◽  
Tumor Location ◽  
Neurological Dysfunction ◽  
Autosomal Dominant Disorder ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Vhl Disease ◽  
Fine Print

Object. Von Hippel—Lindau (VHL) disease is an autosomal-dominant disorder frequently associated with hemangioblastomas of the spinal cord. Because of the slow progression, protean nature, and high frequency of multiple spinal hemangioblastomas associated with VHL disease, the surgical management of these lesions is complex. Because prior reports have not identified the factors that predict which patients with spinal cord hemangioblastomas need surgery or what outcomes of this procedure should be expected, the authors have reviewed a series of patients with VHL disease who underwent resection of spinal hemangioblastomas at a single institution to identify features that might guide surgical management of these patients. Methods. Forty-four consecutive patients with VHL disease (26 men and 18 women) who underwent 55 operations with resection of 86 spinal cord hemangioblastomas (mean age at surgery 34 years; range 20–58 years) at the National Institutes of Health were included in this study (mean clinical follow up 44 months). Patient examination, review of hospital charts, operative findings, and magnetic resonance imaging studies were used to analyze surgical management and its outcome. To evaluate the clinical course, clinical grades were assigned to patients before and after surgery. Preoperative neurological status, tumor size, and tumor location were predictive of postoperative outcome. Patients with no or minimal preoperative neurological dysfunction, with lesions smaller than 500 mm3, and with dorsal lesions were more likely to have no or minimal neurological impairment. Syrinx resolution was the result of tumor removal and was not influenced by whether the syrinx cavity was entered. Conclusions. Spinal cord hemangioblastomas can be safely removed in the majority of patients with VHL disease. Generally in these patients, hemangioblastomas of the spinal cord should be removed when they produce symptoms or signs.

Intraorbital optic nerve hemangioblastoma with von Hippel-Lindau disease

1982 ◽  
Vol 56 (3) ◽  
pp. 426-429 ◽  
Author(s):  
Seiich In ◽  
Jun Miyagi ◽  
Nobuto Kojho ◽  
Shinken Kuramoto ◽  
Masaki Uehara
Keyword(s):  
Optic Nerve ◽  
Content Type ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Dural Attachment ◽  
Microscopic Findings ◽  
Fine Print

✓ An intraorbital hemangioblastoma of the optic nerve is reported in a 23-year-old woman with von Hippel-Lindau disease. The absence of dural attachment and the microscopic findings were characteristic of hemangioblastoma. Four years later the patient developed a cystic hemangioblastoma in the left cerebellum which was successfully treated.

von Hippel–Lindau disease and succinate dehydrogenase subunit (SDHB, SDHC, and SDHD) genes

2011 ◽  
pp. 954-959
Author(s):  
Eamonn R. Maher
Keyword(s):  
Succinate Dehydrogenase ◽  
Von Hippel Lindau ◽  
Clinical Phenotypes ◽  
Molecular Features ◽  
Von Hippel Lindau Disease ◽  
Vhl Disease

This chapter considers the clinical and molecular features of von Hippel–Lindau (VHL) disease (OMIM 193300) and mutations in succinate dehydrogenase subunit genes (SDHB (OMIM 115310), SDHC (OMIM 605373), and SDHD (OMIM 168000)). Both disorders are important causes of phaeochromocytoma and, in addition to having overlapping clinical phenotypes, also share some similarities in mechanisms of tumourigenesis.

Endocrine Manifestations of von Hippel–Lindau Disease

2015 ◽  
Vol 139 (2) ◽  
pp. 263-268 ◽  
Author(s):  
Clarissa Cassol ◽  
Ozgur Mete
Keyword(s):  
Neuroendocrine Tumors ◽  
Autosomal Dominant ◽  
Suppressor Gene ◽  
Autosomal Dominant Disorder ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Sporadic Cases ◽  
Vhl Disease

von Hippel–Lindau (VHL) disease is an autosomal dominant disorder caused by heterozygous mutations in the VHL tumor suppressor gene that is characterized by the occurrence of multiple endocrine and nonendocrine lesions. This review focuses on the endocrine manifestations of VHL disease. Pancreatic neuroendocrine proliferations (ductuloinsular complexes, islet dysplasia, endocrine microadenoma, and neuroendocrine tumors), pheochromocytomas, and extra-adrenal paragangliomas are important endocrine manifestations of VHL disease. They frequently display characteristic clinical, biochemical, and histopathologic features that, although not pathognomonic, can be helpful in suggesting VHL disease as the underlying etiology and distinguishing these tumors from sporadic cases. Recent improvements in treatment and outcomes of renal cell carcinomas have allowed pancreatic neuroendocrine tumors to emerge as a significant source of metastatic disease, making the accurate recognition and classification of these neoplasms by the pathologist of utmost importance to determine prognosis, treatment, and follow-up strategies for affected patients.

scholarly journals Novel genotype–phenotype correlations in five Chinese families with Von Hippel–Lindau disease

2018 ◽  
Vol 7 (7) ◽  
pp. 870-878 ◽  
Author(s):  
Qiuli Liu ◽  
Gang Yuan ◽  
Dali Tong ◽  
Gaolei Liu ◽  
Yuting Yi ◽  
...  
Keyword(s):  
Malignant Neoplasms ◽  
Missense Mutations ◽  
Chinese Families ◽  
Von Hippel Lindau ◽  
Disease Phenotypes ◽  
Mri Scans ◽  
Von Hippel Lindau Disease ◽  
Vhl Disease

Context Von Hippel–Lindau (VHL) disease manifests as a variety of benign and malignant neoplasms. Previous studies of VHL disease have documented several genotype–phenotype correlations; however, many such correlations are still unknown. Increased identification of new mutations and patients with previously described mutations will allow us to better understand how VHL mutations influence disease phenotypes. Patients and design A total of 45 individuals from five unrelated families were evaluated, of which 21 patients were either diagnosed with VHL disease or showed strong evidence related to this disease. We compared the patients’ gene sequencing results with their medical records including CT or MRI scans, eye examinations and laboratory/pathological examinations. Patients were also interviewed to obtain information regarding their family history. Results We identified four missense mutations: c.239G>T (p.Ser80Ile), linked with VHL Type 2B, was associated with renal cell carcinoma, pheochromocytoma and hemangioma in the cerebellum; c.232A>T (p.Asn78Tyr) manifested as RCC alone and likely caused VHL Type 1; c.500G>A (p.Arg167Gln) mutation was more likely to cause VHL Type 2 than Type 1 as it preferentially induced Pheo and HB in the retina, cerebellum and spinal cord; c.293A>G (p.Try98Cys) was associated with Pheo and thus likely induced VHL Type 2. Conclusions Characterizing VHL disease genotype–phenotype correlations can enhance the ability to predict the risk of individual patients developing different VHL-related phenotypes. Ultimately, such insight will improve the diagnostics, surveillance and treatment of VHL patients. Precis Four missense mutations in VHL have been identified in 21 individuals when five unrelated Chinese families with VHL disease were analyzed; VHL mutations are highly associated with unique disease phenotypes.

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