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

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

OBJECTIVETo study the clinicopathological characteristics of papillary cystadenoma of the epididymis.

METHODSUsing routine pathology and immunohistochemistry, we observed the surgically obtained samples from 2 cases of papillary cystadenoma of the epididymis, analyzed their pathological features and clinical presentations, and reviewed the related literature.

RESULTSThe 2 patients were both adult males. The tumors typically manifested as painless swelling in the epididymis, with occasionally dull pain and tenesmus in 1 of the cases. Pathologically, the lesions exhibited three morphological features, i. e., dilated ducts and small cysts surrounded by fibrous connective tissue, adenoid papillary hyperplasia into the cysts embraced by fibrovascular stroma, and acidophil substance present in the cysts. Immunohistochemistry showed that the tumors were strongly positive for CK8/18, CK7, and EMA, but negative for CK20, CEA, MC, Calretenin, P53, P63, SMA, VHL, and CD10, with the positive rate of Ki-67 <1%. Follow-up visits revealed good prognosis in both cases.

CONCLUSIONPapillary cystadenoma of the epididymis is a rare benign tumor in the male urogenital system, which may be accompanied by the VHL syndrome. Surgery is the first choice for its treatment.

Adult ; Cystadenoma, Papillary ; chemistry ; pathology ; Epididymis ; Genital Neoplasms, Male ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Male ; von Hippel-Lindau Disease

Humans ; von Hippel-Lindau Disease ; pathology

PURPOSE: Standard treatment of asymptomatic spinal cord hemangioblastoma in von Hippel-Lindau (VHL) disease has yet to be established. The purpose of this study was to propose guidelines for the treatment of asymptomatic spinal cord hemangioblastomas in VHL disease. MATERIALS AND METHODS: VHL disease patients treated for spinal cord hemangioblastomas between 1999 and 2009 were included. All spinal cord hemangioblastomas were divided into three groups: Group 1, asymptomatic tumors at initial diagnosis followed with serial imaging studies; Group 2, asymptomatic tumors at initial diagnosis that were subsequently resected; and Group 3, symptomatic tumors at initial diagnosis, all of which were resected. RESULTS: We identified 24 spinal cord hemangioblastomas in 12 patients. Groups 1, 2 and 3 comprised 13, 4 and 7 tumors, respectively. Group 1 exhibited a smaller tumor volume (257.1 mm3) and syrinx size (0.8 vertebral columns) than those of Group 2 (1304.5 mm3, 3.3 vertebral columns) and Group 3 (1787.4 mm3, 6.1 vertebral columns). No difference in tumor volume or syrinx size was observed between Groups 2 and 3. Five tumors in Group 1 were resected during follow-up because symptoms had developed or the tumor had significantly grown. Finally, among 17 asymptomatic tumors at the initial diagnosis, nine tumors were resected. Only one tumor of these nine tumors resulted in neurological deficits, while five of seven symptomatic tumors caused neurological deficits. CONCLUSION: Selective resection of asymptomatic tumors before they cause neurological deficits might bring about better outcomes.
Adult ; Aged ; Aged, 80 and over ; Female ; Hemangioblastoma/etiology/*pathology/*surgery ; Humans ; Male ; Middle Aged ; Treatment Outcome ; von Hippel-Lindau Disease/*complications

Cerebellum ; surgery ; Cystadenoma, Papillary ; complications ; pathology ; surgery ; Epididymis ; pathology ; surgery ; Follow-Up Studies ; Genital Neoplasms, Male ; complications ; pathology ; surgery ; Humans ; Keratin-7 ; metabolism ; Kidney ; surgery ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Vimentin ; metabolism ; von Hippel-Lindau Disease ; complications ; metabolism ; pathology ; surgery

OBJECTIVETo study the clinical characteristics and summary diagnostic and therapeutical experience of von Hippel-Lindau syndrome.

METHODSvon Hippel-Lindau syndrome genealogy and clinical characteristics was investigated. Then a dendrogram was drawn and a genetic analysis was performed. Last the diagnostic and therapeutical experience of von Hippel-Lindau syndrome was investigated according to literatures.

RESULTSThere are 6 members attacked by the von Hippel-Lindau syndrome of 5 generations which includes 42 members. Three patients underwent operation. Two of the three patients who suffered operation had been removed of right lobe of liver tumor and one cerebellar hemangioblastomas independently. The third patient sustained three operations for removal of three cerebellar hemangioblastomas and left renal clear cell carcinoma. Three patients died of this syndrome.

CONCLUSIONSThe characteristic of this kindred is according with that of autosomal dominant inheritance disease. Until now, von Hippel-Lindau syndrome involves in multisystem, the prognosis of this syndrome is not very well. However, patients and their family members may get much benefit from genetic testing, periodic surveillance, early diagnosis and prompt treatment.

Adult ; Child ; Female ; Humans ; Inheritance Patterns ; Male ; Middle Aged ; Pedigree ; Prognosis ; von Hippel-Lindau Disease ; genetics ; pathology ; surgery

OBJECTIVETo investigate the clinicopathologic features of epididymal cyst in von Hippel-Lindau (VHL) syndrome.

METHODSWe reviewed the clinical data of 3 epididymal cyst patients treated by surgery, and detected the expressions of HIF-1alpha, VEGF, alpha-SMA and CD34 in the epididymal tissue samples by the immunohistochemistry SP method.

RESULTSAll the 3 patients underwent surgical removal of the epididymal cyst. Immunohistochemistry of the epididymal tissues showed HIF-1alpha, VEGF, alpha-SMA and CD34 to be positive. All the 3 cases were confirmed to be VHL syndrome, 1 right after surgery, and the other 2 within 8 years postoperatively.

CONCLUSIONEpididymal cyst is a usual benign disease, which may occur independently of or be complicated by VHL syndrome. If immunohistochemistry of epididymal tissues shows HIF-1alpha, VEGF, alpha-SMA and CD34 to be positive, VHL syndrome should be considered, and further clinical examinations and post-operation follow-up are necessitated.

Actins ; metabolism ; Adult ; Epididymis ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Middle Aged ; Spermatocele ; etiology ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; von Hippel-Lindau Disease ; complications ; metabolism ; pathology

INTRODUCTIONGenetic predisposition to clear cell renal cell carcinoma (ccRCC) has been linked to disorders such as von Hippel-Lindau (VHL) syndrome. While twin research is a classic approach for elucidating genetic and environmental contributions to disease, no monozygotic twin-pair concordant for ccRCC in the absence of VHL syndrome has been previously reported in the literature or in major twin registries.

CLINICAL PICTUREWe describe a unique monozygotic twin-pair concordant for ccRCC, with discordant but early ages of onset of 25 and 38 respectively. Cytogenetic studies and direct sequencing for VHL gene mutations in the second twin proved unremarkable.

CONCLUSIONSThis is the fi rst reported case of monozygotic twins concordant for ccRCC in the absence of VHL gene mutation. The early yet discordant, age of onset of disease in both twins suggests both genetic and environmental contributions to ccRCC.

Adult ; Carcinoma, Renal Cell ; genetics ; pathology ; Diseases in Twins ; genetics ; pathology ; Humans ; Kidney Neoplasms ; genetics ; pathology ; Male ; Twins, Monozygotic ; von Hippel-Lindau Disease ; genetics

Antigens, CD34 ; metabolism ; Carcinoma, Renal Cell ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; surgery ; ultrastructure ; Diagnosis, Differential ; Ependymoma ; metabolism ; pathology ; Hemangioblastoma ; metabolism ; pathology ; surgery ; ultrastructure ; Humans ; Meningeal Neoplasms ; metabolism ; pathology ; Meningioma ; metabolism ; pathology ; Mutation ; Neoplasm Recurrence, Local ; Prognosis ; Receptor, Epidermal Growth Factor ; metabolism ; Vimentin ; metabolism ; von Hippel-Lindau Disease ; genetics ; metabolism ; pathology ; surgery