Humans ; Neuroendocrine Tumors/pathology* ; Pancreatic Neoplasms/pathology* ; Neoplasms, Second Primary ; von Hippel-Lindau Disease/pathology*

Hemangioblastoma (HBL) in the suprasellar region is very rare and a few cases have been reported. Suprasellar HBL without von Hippel-Lindau disease is much rarer. A 76-year old male patient presented progressively deteriorating visual disturbance. MRI demonstrated solid suprasellar mass of 20 mm in diameter, broadly based to planum sphenoidale and diaphragm sella and dural tail sign after the administration of gadolinium diethylene triamine penta-acetic acid (Gd-DTPA). Preoperative diagnosis was meningioma. Total resection of the tumor was not accomplished because of massive hemorrhage, and the histopathologic examination revealed the tumor to be HBL. The visual disturbance of the patient was not improved. The authors reviewed the literature and considered a differential diagnosis of suprasellar tumors and treatment of suprasellar HBL.
Diagnosis ; Diagnosis, Differential ; Diaphragm ; Gadolinium ; Hemangioblastoma ; Hemorrhage ; Humans ; Magnetic Resonance Imaging ; Male ; Meningioma ; Tail ; Temazepam ; von Hippel-Lindau Disease

Objective To analyze the clinical features of Von-Hippel-Lindau(VHL)syndrome and explore the diagnostic value of abdominal ultrasound for this disease.Methods The clinical features including age at first diagnosis,symptoms,signs,affected organs,number of operations,and diagnostic examinations of 35 patients with VHL syndrome admitted to our center from January 1994 to December 2017 were retrospectively analyzed.The diagnostic value of abdominal ultrasound for VHL syndrome was analyzed.Results Pheochromocytoma(=14)and nervous system hemangioblastoma(=13)were the common firstly-identified tumors.Nervous system hemangioblastoma(=21),pheochromocytoma(=19),renal carcinoma(=17),and pancreatic mass(=15)were common tumors.The main surgical reasons were nervous system hemangioblastoma(=22),pheochromocytoma(=23)and renal carcinoma(=13).Abdominal organ involvements were found in 33 patients,which were first detected by abdominal ultrasound in 20 patients and were found accidently during routine health checkups in 6 patients.The ultrasound results were accurate in 27 of 33 adrenal gland scans,13 of 16 pancreas scans,and 8 of 19 kidney scans.Conclusions When multiple tumors are detected in the kidney,adrenal gland,and pancreas by ultrasound,the possibility of VHL syndrome should be considered.When the clinical findings suggest the possibility of VHL syndrome,ultrasound can discover and diagnose the abdominal tumors and can also be used for the long-term follow-up of the tumors.Therefore,ultrasound is an important method in the screening and follow-up of patients with VHL syndrome.
Abdomen ; diagnostic imaging ; Adrenal Gland Neoplasms ; diagnostic imaging ; Hemangioblastoma ; diagnostic imaging ; Humans ; Pheochromocytoma ; diagnostic imaging ; Retrospective Studies ; Ultrasonography ; von Hippel-Lindau Disease ; complications ; diagnostic imaging

OBJECTIVE: To detect VHL gene mutation in a pedigree affected with von Hippel-Lindau syndrome (VHL). METHODS: Clinical data of the pedigree was reviewed. Patients were subjected to Sanger sequencing to detect mutation of the VHL gene. Structure of pVHL was predicted by 3D modeling using the swiss-model. RESULTS: A novel c.426delT(p.V142fs) [NM_000551] mutation was found in exon 2 of the VHL gene. 3D modeling suggested that the alpha-structure of pVHL is completely absent. CONCLUSION The novel c.426delT(p.V142fs) mutation probably underlies the VHL in this pedigree.
DNA Mutational Analysis ; Exons ; Humans ; Mutation ; Pedigree ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

STUDY DESIGN: Retrospective cohort study. PURPOSE: To examine the clinical profile and surgical complications in patients with spinal hemangioblastomas and to evaluate the long-term outcome in them. OVERVIEW OF LITERATURE: Although considered to be histologically benign, hemangioblastomas may cause significant neurological deficits. The proportion of spinal hemangioblastomas associated with von Hippel–Lindau (VHL) disease has been estimated be 13%–59%. Preoperative neurological function correlates with postoperative neurological status. Studies have shown no difference in outcomes between sporadic and VHL-associated spinal hemangioblastomas. METHODS: This retrospective study included 14 consecutive patients treated for spinal hemangioblastomas at our institute between January 2000 and June 2013. The mean follow-up period was 5 years. Magnetic resonance imaging of the complete neuraxis was performed in all cases, and preoperative embolization was performed in two cases. RESULTS: In total, 14 patients underwent 18 surgeries, of which 15 were for spinal hemangioblastomas. Of all the patients, 86% had motor weakness and 79% presented with sensory disturbances. Preoperative McCormick functional grades were grade I in 7 (50%), grade II in 3 (21%), and grade III in 4 (29%) patients; 50% patients were diagnosed with VHL disease. All patients underwent complete resection of the tumor. Eight patients experienced deterioration in their neurological status in the immediate postoperative period; among them, five had gradual improvement. At 5-year follow-up, 11 (78.57%) patients showed good functional outcomes. CONCLUSIONS: Microsurgical excision of spinal hemangioblastomas can cause postoperative morbidity, mainly in the form of neurological deterioration. Almost half of our patients had deterioration in the McCormick grade in the immediate postoperative period. However, a complete microsurgical excision can result in good long-term functional outcomes, as most of the immediate postoperative neurological deterioration in our patients was reversible. There was no difference in the long-term functional outcomes between sporadic and VHL-associated spinal hemangioblastomas.
Cohort Studies ; Follow-Up Studies ; Hemangioblastoma* ; Humans ; Magnetic Resonance Imaging ; Microsurgery ; Postoperative Period ; Retrospective Studies ; Spinal Cord ; Spinal Cord Neoplasms ; von Hippel-Lindau Disease*

von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with mutations of the VHL tumor suppressor gene located on chromosome 3p25. The loss of functional VHL protein contributes to tumorigenesis. This condition is characterized by development of benign and malignant tumors in the central nervous system (CNS) and the internal organs, including kidney, adrenal gland, and pancreas. We herein describe the case of a 74-year-old man carrying the VHL gene mutation who was affected by simultaneous colorectal adenocarcinoma, renal clear cell carcinoma, and hemangioblastomas of CNS.
Adenocarcinoma* ; Adrenal Glands ; Aged ; Carcinogenesis ; Carcinoma, Renal Cell* ; Central Nervous System ; Colorectal Neoplasms ; Genes, Tumor Suppressor ; Hemangioblastoma* ; Humans ; Kidney ; Pancreas ; von Hippel-Lindau Disease*

von Hippel-Lindau (VHL) disease is an inherited syndrome manifesting with benign and malignant tumors. Deficiency of carnitine palmitoyltransferase type II (CPT2) is a disorder of lipid metabolism that, in the muscle form, manifests with recurrent attacks of myalgias often associated with myoglobinuria. Rhabdomyolytic episodes may be complicated by life-threatening events, including acute renal failure (ARF). We report on a male patient who was tested, at 10 years of age, for VHL disease because of family history of VHL. He was diagnosed with VHL but without VHL-related manifestation at the time of diagnosis. During childhood, the patient was hospitalized several times for diffuse muscular pain, muscle weakness, and dark urine. These recurrent attacks of rhabdomyolysis were never accompanied by ARF. The patient was found to be homozygous for the mutation p.S113L of the CPT2 gene. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations.
Acute Kidney Injury ; Carnitine O-Palmitoyltransferase ; Diagnosis ; Humans ; Lipid Metabolism ; Male ; Models, Animal ; Myalgia ; Myoglobinuria ; Rhabdomyolysis ; von Hippel-Lindau Disease

A 21-year-old Chinese gentleman with no known medical illness, presented with a history of right painless blurring of vision with central scotoma of two weeks duration. He also had a history of multiple episodes of seizures prior to presentation. Visual acuity was 1/60 with unremarkable anterior segment findings and no relative afferent pupillary defect. Fundus examination of the right eye revealed dilated and tortuous retinal veins with multiple retinal capillary hemangiomas and sub retinal hard exudates at the macula with edema. A diagnosis of Von Hippel Lindau disease was made when a posterior fossa mass suggestive of hemangioblastoma with obstructive hydrocephalus was seen on computed tomography of the brain. Craniotomy with nodule excision was performed. The retinal capillary hemangiomas were treated with the combination of laser photocoagulation and intravitreal Ranibizumab injections. Visual acuity subsequently improved to 6/36.
Hemangioblastoma ; von Hippel-Lindau Disease

BACKGROUNDVon Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.

METHODSAn epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.

RESULTSA five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167 th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.

CONCLUSIONSThe results supported the notion that the genomic sequence that corresponds to the 167 th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.

Adolescent ; Adult ; Asian Continental Ancestry Group ; China ; Female ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Retrospective Studies ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; Young Adult ; von Hippel-Lindau Disease ; diagnosis ; genetics

BACKGROUNDVascular endothelial growth factor-targeted agents are standard treatments in advanced clear-cell renal cell carcinoma (ccRCC), but biomarkers of activity are lacking. The aim of this study was to investigate the association of Von Hippel-Lindau (VHL) gene status, vascular endothelial growth factor receptor (VEGFR) or stem cell factor receptor (KIT) expression, and their relationships with characteristics and clinical outcome of advanced ccRCC.

METHODSA total of 59 patients who received targeted treatment with sunitinib or pazopanib were evaluated for determination at Cancer Hospital and Institute, Chinese Academy of Medical Sciences between January 2010 and November 2012. Paraffin-embedded tumor samples were collected and status of the VHL gene and expression of VEGFR and KIT were determined by VHL sequence analysis and immunohistochemistry. Clinical-pathological features were collected and efficacy such as response rate and Median progression-free survival (PFS) and overall survival (OS) were calculated and then compared based on expression status. The Chi-square test, the Kaplan-Meier method, and the Lon-rank test were used for statistical analyses.

RESULTSOf 59 patients, objective responses were observed in 28 patients (47.5%). The median PFS was 13.8 months and median OS was 39.9 months. There was an improved PFS in patients with the following clinical features: Male gender, number of metastatic sites 2 or less, VEGFR-2 positive or KIT positive. Eleven patients (18.6%) had evidence of VHL mutation, with an objective response rate of 45.5%, which showed no difference with patients with no VHL mutation (47.9%). VHL mutation status did not correlate with either overall response rate (P = 0.938) or PFS (P = 0.277). The PFS was 17.6 months and 22.2 months in VEGFR-2 positive patients and KIT positive patients, respectively, which was significantly longer than that of VEGFR-2 or KIT negative patients (P = 0.026 and P = 0.043).

CONCLUSIONVHL mutation status could not predict the efficacy of sunitinib or pazopanib. Further investigation of VHL/VEGFR pathway components is needed.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Renal Cell ; genetics ; mortality ; pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Indoles ; therapeutic use ; Kidney Neoplasms ; genetics ; mortality ; pathology ; Male ; Middle Aged ; Prognosis ; Pyrimidines ; therapeutic use ; Pyrroles ; therapeutic use ; Sulfonamides ; therapeutic use ; Vascular Endothelial Growth Factor A ; genetics ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; Young Adult