Síndrome de von Hippel-Lindau em um Serviço Privado de Câncer em São Paulo: Relato de Caso / Síndrome de von Hippel-Lindau en un Servicio Privado de Cáncer en São Paulo: Informe de Caso / Von Hippel-Lindau Syndrome in a Private Cancer Service in São Paulo: Case Report

Introdução: A síndrome de von Hippel-Lindau (VHL) é uma patologia hereditária autossômica dominante que envolve o crescimento de tumores em diversas regiões do corpo humano em razão da mutação no gene VHL. Relato do caso: Paciente, sexo masculino, 38 anos, há três anos queixava-se de cefaleia recorrente, com piora progressiva. Foi diagnosticado com uma lesão em cerebelo cuja ressonância magnética cerebral encontrou uma formação expansiva na porção posteroinferior do hemisfério cerebelar esquerdo. Foi realizada tomografia multislice de abdome, que evidenciou formação nodular esplênica com realce marginal. A imagem da coluna cervical demonstrou pequeno nódulo localizado na medula cervical (intramedular) adjacente à vértebra cervical 3 (C3). Diante dos achados, o paciente foi submetido à ressecção macroscópica total da lesão do cerebelo, com laudo anatomopatológico de hemangioblastoma cerebelar grau 1, de acordo com a classificação da Organização Mundial da Saúde (OMS), que é um tumor benigno com baixa agressividade e recorrência. O teste imuno-histoquímico mostrou cluster of differentiation 34 (CD 34) positivo, índice de proliferação celular (Ki67) positivo (<5%), alfa inibina positiva e epithelial membrane antigen (EMA) negativo. Como o paciente não tinha história familiar de câncer, em função dos achados radiológicos, foi realizado sequenciamento de nova geração identificando a variante patogênica VHL c.292T>C, constatado em linhagem germinativa que, apesar do desconhecimento de história familiar positiva para a síndrome, confirmou o diagnóstico do paciente.

Introduction: Von Hippel-Lindau (VHL) syndrome is an autosomal dominant hereditary pathology that involves the growth of tumors in different regions of the human body due to mutation of the VHL gene. Case report: Male patient, 38 years old, complained of recurrent headache for 3 years, with progressive worsening. A lesion in the cerebellum was diagnosed, whose magnetic resonance imaging found an expansive formation in the posteroinferior portion of the left cerebellar hemisphere. Multislice tomography of the abdomen was performed, showing splenic nodular formation with marginal enhancement. Cervical spine imaging demonstrated a small nodule located in the cervical (intramedullary) cord adjacent to cervical vertebra 3 (C3). In view of the findings, the patient underwent total macroscopic resection of the cerebellar lesion, with an anatomopathological report of World Health Organization (WHO) grade 1 cerebellar hemangioblastoma, which is a benign tumor with lower risk of aggressiveness and recurrence. Immunohistochemical test showed positive cluster of differentiation 34 (CD34), cell proliferation index positive (Ki67) (<5%), positive alpha inhibin and epithelial membrane antigen (EMA) negative. As the patient had no family history of cancer, a new generation sequencing was performed due to the radiological findings, which identified the pathogenic variant VHL c.292T>C found in germ lineage; although the family was unaware of any past family history of the syndrome, the patient's diagnosis was confirmed.

Introducción: El síndrome de von Hippel-Lindau (VHL) es una patología hereditaria autosómica dominante que consiste en el crecimiento de tumores en diferentes regiones del cuerpo humano debido a una mutación en el gen VHL. Informe del caso: Paciente, masculino, 38 años, consulta por cefalea recurrente desde hace 3 años, con empeoramiento progresivo. Se diagnosticó lesión en cerebelo, cuya resonancia magnética encontró una formación expansiva en la porción posteroinferior del hemisferio cerebeloso izquierdo. Se realizó tomografía multicorte de abdomen, que mostró formación nodular esplénica con realce marginal. Las imágenes de la columna cervical demostraron un pequeño nódulo ubicado en el cordón cervical (intramedular) adyacente a vértebra cervical 3 (C3). Ante los hallazgos se procedió a la resección macroscópica total de la lesión cerebelosa, con informe anatomopatológico de hemangioblastoma cerebeloso grado 1, de acuerdo con la clasificación de la Organización Mundial de Salud (OMS) que es un tumor benigno con baja agresividad y recurrencia. La prueba inmunohistoquímica mostró cluster of differentiation 34 (CD34) positivo, índice de proliferación celular (Ki67) positivo (<5%), alfa inhibina positivo y epithelial membrane antigen (EMA) negativo. Como el paciente no tenía antecedentes familiares de cáncer, debido a los hallazgos radiológicos, se realizó una secuenciación de nueva generación identificando la variante patogénica VHL c.292T>C, encontrada en el linaje germinal, que, a pesar del desconocimiento de antecedentes familiares positivos para el síndrome, confirmó el diagnóstico del paciente. Conclusión: El conjunto de hallazgos clínicos y la variante en el gen VHL confirman el diagnóstico del síndrome.

Endolymphatic Sac Tumour: A Case Report and Review of the Literature

Introduction Endolymphatic sac tumor (ELST) is a slow-growing, low-grade, locallyinfiltrative tumor arising from the endolymphatic sac/duct, which is located in the posterior part of the petrous temporal bone. It may be sporadic in origin, or may be associated with Von-Hippel Lindau (VHL) syndrome. Case description A 40-year-old female patient with an ELST without VHL syndrome who was treated successfully by microsurgical extirpation of the tumor. Discussion We discuss the radiological features and the histopathology of this rare tumor and review the relevant literature. Conclusion The case herein reported adds to the previously-reported cases of this rare tumor.

Co-Occurrence of Pineal-Region and Pituitary-Stalk Hemangioblastomas in a Patient Presenting with Von Hippel-Lindau Disease ­ A Case Report

Introduction Hemangioblastomas of the pineal region or pituitary stalk are extremely rare. Only two cases of hemangioblastomas involving the pineal region have been reported, and four involving the pituitary stalk. The purpose of the present manuscript is to describe an unusual case of supposed hemangioblastoma found concomitantly in the pineal region and pituitary stalk of a patient diagnosed with Von Hippel-Lindau (VHL) disease. Case Report A 35-year-old female patient with a previous diagnosis of VHL complaining of occipital headaches and balance disturbances for three weeks, who previously had a cerebellar hemangioblastoma resected. The visual characteristics of the tumor suggested a friable vascular lesion with a reddish-brown surface, and an incisional biopsy was performed. The tumor consisted of a dense vascular network surrounded by fibrous stroma abundant in reticulin and composed by both fusiform and dispersed xanthomatous cells; the immunohistochemistry was immunopositive for neuronspecific enolase and immunonegative for epithelial membranous antigen. The patient has been monitored closely for 2 years, and the supratentorial masses have not presented any volume alteration. Conclusion This rare association must be taken into account in patients with VHL disease, or at least be suspected in patients who present a thickening of the pituitary stalk and a pineal-region mass. We believe a biopsy of our asymptomatic patient could have been dangerous due to inherent complications like intraoperative bleeding. We recommend close observation of asymptomatic lesions with MRIs every six months or until the lesions become symptomatic. If the pineal-region tumor does become symptomatic, gross resection via a transcallosal approach would be ideal.

Jugular Foramen's Paraganglioma in a Patient with Von Hippel-Lindau Disease: Case Report

Glomus jugular tumors, also known as paragangliomas (PGLs), are rare and related to several clinical syndromes described. These are located in the carotid body, the jugular glomus, the tympanic glomus and the vagal glomus. The symptoms are directly related to the site of involvement and infiltration. These lesions have slow growth, are generally benign and hypervascularized, have a peak incidence between the age of 30 to 50 years old; however, when associated with hereditary syndromes, they tend to occur a decade earlier. Several familial hereditary syndromes are associated with PGLs, including Von Hippel- Lindau disease (VHL) in< 10% of the cases. The diagnosis and staging of PGLs are based on imaging and functional exams (bone window computed tomography [CT] with a "ground moth" pattern and magnetic resonance imaging (MRI) with a "salt and pepper" pattern). The cerebral angiography is a prerequisite in patients with extremely vascularized lesions, whose preoperative embolization is necessary. The histopathological finding of cell clusters called "Zellballen" is a characteristic of PGLs. Regarding the jugular foramen, the combination of two or three surgical approaches may be necessary: (1) lateral group, approaches through themastoid; (2) posterior group, through the retrosigmoid access and its variants; and (3) anterior group, centered on the tympanic and petrous bone. In the present paper, we report a case of PGL of the jugular foramen operated on a young female patientwho underwent a surgery with a diagnosis ofVonHippel-Lindau Disease (VHL) at the Neurosurgery Service of the Hospital Heliópolis, São Paulo, state of São Paulo, Brazil in 2018, by the lateral and posterior combined route.

Síndromes neurocutáneos y leucemia linfoide aguda: a propósito de un caso / Neurocutaneous syndromes and acute lymphoid leukemia: a case report

Introducción: Los síndromes neurocutáneos comprenden un grupo heterogéneo de trastornos hereditarios que comprometen principalmente la piel y el sistema nervioso central. Dentro de estos se incluye la neurofibromatosis, la esclerosis tuberosa y la enfermedad de Von-Hippel Lindau. Se caracterizan por presencia de displasia en distintos tejidos y formación de tumores en diversos órganos. Se ha descrito también un riesgo relativo aumentado para leucemia linfoblástica aguda, leucemia mielomonocítica crónica y linfoma no Hodgkin. Objetivo: Describir caso de paciente con diagnóstico de síndrome neurocutáneo (esclerosis tuberosa) que desarrolló a los 6 años una leucemia linfoide aguda. Caso clínico: Paciente femenina, seis años de edad, con antecedentes de síndrome neurocutáneo tipo esclerosis tuberosa diagnosticado a los dos años de edad- Comenzó con síndrome febril, adenopatías cervicales y hepatoesplenomegalia. El hemograma mostró anemia, trombocitopenia grave y leucocitosis con presencia de blastos. En el medulograma se observó una infiltración de 90 por ciento de blastos linfoides, por lo que se diagnosticó como una leucemia linfoide aguda. Conclusiones: La coexistencia de síndromes neurocutáneos y leucemia linfoide aguda no es frecuente. Se describe una paciente con ambas enfermedades, que fallece a pesar del tratamiento(AU)

Introduction: Neurocutaneous syndromes comprise a heterogeneous set of hereditary disorders mainly affecting the skin and the central nervous system. Among the conditions included are neurofibromatosis, tuberous sclerosis and von Hippel-Lindau disease, characterized by dysplasia in various tissues and the formation of tumors in various organs. Increased relative risk has also been described for acute lymphoblastic leukemia, chronic myelomonocytic leukemia and non-Hodgkin lymphoma. Objective: Describe the case of a patient diagnosed with neurocutaneous syndrome (tuberous sclerosis) who developed acute lymphoid leukemia at age six. Clinical case: A case is presented of a female six-year-old patient with a history of neurocutaneous syndrome, tuberous sclerosis type, diagnosed at age two. The patient started with febrile syndrome, cervical adenopathies and hepatosplenomegaly. The blood count revealed anemia, severe thrombocytopenia and leukocytosis with the presence of blasts, whereas the medullogram showed 90 percent infiltration by lymphoid blasts, leading to the diagnosis of acute lymphoid leukemia. Conclusions: Coexistence of neurocutaneous syndromes and acute lymphoid leukemia is not frequent. A case is described of a patient with both conditions who died despite the treatment indicated(AU)

Mecanismo sensor y de adaptación a los niveles de oxígeno y su implicancia en las enfermedades cardiovasculares: a propósito del Premio Nobel de Fisiología-Medicina 2019 / Role of hypoxia-inducible factor-1 (HIF-1) in the adaptacion to oxygen levels: Nobel Prize in physiology-medicine 2019

RESUMEN: El Premio Nobel 2019 en Fisiología-Medicina se confirió a los Profesores Gregg Semenza, William Kaelin y Sir Peter Ratcliffe por sus investigaciones en la maquinaria molecular que regula la expresión de genes sensibles a los cambios en los niveles de oxígeno. La síntesis de eritropoyetina inducida por la disminución de los niveles sanguíneos de oxígeno condujo al estudio del gen de la eritropoyetina y descubrimiento de los elementos de respuesta a hipoxia (HRE) en la región promotora y posteriormente al factor transcripcional inducible por hipoxia tipo 1 (HIF-1). Este factor consta de dos subunidades: HIF-1α, sensible al oxígeno, y HIF-1β, expresada constitutivamente. HIF1 activa la transcripción de genes que codifican enzimas, transportadores y proteínas mitocondriales que disminuyen la utilización de oxígeno al cambiar el metabolismo oxidativo al metabolismo glicolítico y además aquellos involucrados en la angiogénesis y diferenciación celular. Las investigaciones paralelas en la enfermedad von Hippel-Lindau (VHL), un desorden autosómico dominante, permitieron descubrir el mecanismo de degradación de HIF1 en condiciones de normoxia y como se estabiliza bajo hipoxia. El impacto de HIF en clínica radica en el establecimiento de nuevas dianas terapéuticas para combatir la anemia y diversas enfermedades cardiovasculares. HIF promueve la angiogénesis a través de la expresión del factor de crecimiento vascular endotelial (VEGF), agente cardioprotector con potencial para tratar la isquemia/reperfusión, hipertrofia patológica e insuficiencia cardíaca.

ABSTRACT: The Nobel Prize in Physiology-Medicine was awarded to Drs. Gregg Semenza, William Kaelin and Sir Peter Ratcliffe for their research in the molecular machinery that regulates the expression of genes sensitive to the change in oxygen levels. The synthesis of erythropoietin induced by the decrease levels of oxygen in the blood led to investigate the promoter of the erythropoietin gene where the so-called hypoxia response elements (HRE) were described. Semenza et al. described a protein that binds to HREs and called it hypoxia-inducible transcriptional factor (HIF) that regulates gene expression among those involved in angiogenesis, cell differentiation and glycolytic enzymes. HIF presents two oxygen-sensitive subunits HIF-1α and HIF-1β constitutively expressed. In parallel, Kaelin et al. investigated von Hippel-Lindau disease (VHL), an autosomal dominant disorder, discovering a mutation of this protein generated a behavior similar to hypoxia. The impact of HIF-1α lies in the search for new strategies such as hydrolase inhibitors to combat prevalent diseases, including anemia and cardiovascular diseases These compounds promote the expression of vascular endothelial growth factor (VEGF), a cardioprotective agent with potential use in pre- and post-conditioning therapy, cardiac hypertrophy and heart failure.

Multiple renal tumorectomy in a Von Hipple Lindau patient. Combined retro/transperitoneal approach with intracorporeal hypotermia

ABSTRACT Objective & Introduction: To show the feasibility of a combined transperitoneal (TP) and retroperitoneal (RP) laparoscopic approach in a Von Hipple-Lindau (VHL) patient with multiple kidney tumors. VHL is an autosomal dominant inherited syndrome characterized by a high incidence of benign and malignant tumors and cysts in many organs. Renal cell carcinoma is one of the most common and a leading cause of mortality (1). Surgical approach is usually complex because of its multiplicity and the need of maximum kidney function preservation due to the risk of future recurrences (2, 3). Intracorporeal renal hypothermia may be useful in these cases to prevent permanent renal function loss (4). Materials and Methods: A 40 years old male was being monitored for multiple bilateral renal masses. Family history included a VHL syndrome affecting his mother and sister. Past medical history included a VHL syndrome with multiple cerebellar and medular hemangioblastomas, a pancreatic cystoadenoma and bilateral kidney tumors which had significantly grown up during follow-up. The patient was scheduled for laparoscopic multiple partial nephrectomy. A combined TP and RP approach with intracorporeal hypothermia was chosen. Results: A total of six right kidney tumors were removed. Operative time was 240 min. Cold ischemia time was 50 min. Average kidney temperature was 23.7°C. Blood losses were negligible. The patient was discharged after 72 hours. No major changes in serum creatinine were found during the follow-up. Final pathology revealed a clear cell renal cell carcinoma, pT1a, ISUP grade 2 in most of the tumors but one ISUP grade 3. Surgical margins were negative. Conclusions: Combined TP and RP is a feasible alternative for the treatment of multiple renal tumors. It's safe and effective, allowing the use of intracorporeal hypothermia which may improve postoperative renal function. Consistent experience is needed before embarking on this surgery.

Clinical Features of Von-Hippel-Lindau Syndrome and Its Ultrasonographic Diagnosis of Abdominal Mass / 中国医学科学院学报

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.

A Case of Sporadic Suprasellar Hemangioblastoma Mimicking Meningioma

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.

Mutation analysis for a family affected with von Hippel-Lindau syndrome / 中华医学遗传学杂志

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.

Carcinomas renales múltiples como manifestación inicial del Síndrome de Von Hippel Lindau. Presentación de caso / Multiple renal carcinoma as a clinical manifestation of Von Hippel Lindau Syndrome. Case presentation

Introducción: El Síndrome de Von Hippel Lindau es una afección neoplásica multisistémica, heredada de manera autosómica dominante y con alta penetrancia. Su expresividad clínica es muy diversa,oscilando la incidencia entre 1/35000 y 1/36000 nacidos vivos. Esta enfermedad usualmente se diagnostica entre los 20 y 30 años, pero los síntomas pueden aparecer en la infancia. La lesión clínica inicial más común y precoz es el hemangioblastoma de la retina y/o del sistema nervioso central. Objetivo: Presentar un caso de un paciente con carcinomas renales múltiples como manifestación inicial de un Síndrome de Von Hippel Lindau. Presentación del Caso: Paciente masculino de 59 años, con antecedentes de salud, quien acude a urgencias por cuadro febril de 3 días de evolución, que fue interpretado como Dengue; se le realizó, dentro de los complementarios, ultrasonido abdominal, donde se descubrió masa sólida a nivel del polo superior del riñón derecho, asociado a existencia de otra en polo inferior de este mismo riñón, así como de 2 más en el contralateral. Además, se encontraron varios quistes pancreáticos y 2 renales izquierdos corticales. El paciente fue intervenido quirúrgicamente; se corroboró el diagnóstico de carcinomas renales de células claras. El examen oftalmológico reveló la presencia de un hemangioblastoma retiniano derecho; en tanto la tomografía computarizada simple de cráneo y la resonancia magnética espinal no mostraron alteraciones. Conclusiones: Este síndrome es una rara, pero grave afección genética, caracterizada por un alto riesgo de desarrollar enfermedades neoplásicas, lo que hace que sea aún más importante conocerlo, para poder identificar y tratar a tiempo sus temidas complicaciones(AU)

Introduction: Von Hippel Lindau Syndrome is a multisystem neoplastic affection, which is inherited as an autosomal dominant trait, with high penetrance. Its clinical expressivity is very diverse, ranging its incidence between 1/35000 and 1/36000 born alive. This disease is usually diagnosed between the 20 and 30 years of age, but its symptoms can appear in childhood. The most common and early initial clinical lesion is the hemangioblastoma of the retina and/or central nervous system. Objective:To present a case of a patient with multiple renal carcinoma as initial manifestation of Von Hippel Lindau Syndrome. Case presentation: 59 years old male patient with a history of good health who comes to the Emergency Room because of febrile clinical state of 3 days´ evolution, that was interpreted as dengue. Abdominal ultrasound was included in the complementary studies, in which a solid mass at level of upper pole of right kidney was observed, associated with the existence of another one in lower pole of the same kidney, as well as two others in contralateral. Also, multiple pancreatic cysts and two left cortical renal ones were found. The patient underwent surgery, and the diagnosis of clear cells renal carcinoma was corroborated. The ophthalmological exam revealed the presence of a right retinal hemangioblastoma whereas the plain skull CT-scan, and the magnetic resonance imaging of the lumbar spine did not show any alterations. Conclusions:This syndrome is a rare, but a serious genetic affection, characterized by a high risk to develop neoplastic diseases; that´s one reason why it is very important to know about it in order to identify, and treat its feared complications in time(AU)

Microsurgical Treatment of Sporadic and von Hippel-Lindau Disease Associated Spinal Hemangioblastomas: A Single-Institution Experience

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.

Hemangioblastoma in the Setting of Von Hippel Lindau Disease: A Case Report

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.

Coexistence of VHL Disease and CPT2 Deficiency: A Case Report / Journal of the Korean Cancer Association, 대한암학회지

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.

A Case of von Hippel-Lindau Disease with Colorectal Adenocarcinoma, Renal Cell Carcinoma and Hemangioblastomas / Journal of the Korean Cancer Association, 대한암학회지

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.

Hemangioblastoma cereberoloso en el síndrome de von Hippel-Lindau, como causa de muerte: reporte de un caso / Case report: cereberoloso in Von Hippel-Lindau disease, hemangioblastoma cause of death

El síndrome de von Hippel-Lindau es una enfermedad caracterizada por el desarrollo de tumores como hemangioblastomas del sistema nervioso central y de la retina, quistes renales, hepáticos y pancreáticos; carcinoma renal de células claras, feocromocitoma, así como adenomas en el oído interno, la nariz y la laringe. En la mayoría de los casos hay un antecedente familiar positivo del síndrome 8. A continuación se presenta el caso de una femenina de 35 años de edad, sin antecedentes personales patológicos conocidos, con antecedente familiar positivo por la enfermedad de von Hippel-Lindau. Según la historia de sus familiares, la mujer presentaba “ataques de rigidez” de dos semanas de evolución, posterior a uno de estos ataques fue atendida por paramédicos quienes la declararon fallecida. Según la autopsia médico legal se diagnosticó una hidrocefalia obstructiva secundaria a hemangioma cerebeloso y hallazgos compatibles con el Síndrome de von Hippel-Lindau. El objetivo de este artículo es resaltar los hallazgos postmortem de esta entidad y su relación con la causa de la muerte.

Von Hippel-Lindau syndrome is characterized by tumors as central nervous system and retinal hemangioblastomas; renal, liver and pancreas cysts; clear cells renal carcinoma, pheochromocytoma and adenomas of the ear, nose and larynx. In most cases there is a positive family history of the syndrome 8. The follow case is about a female how was 35 years old without known medical history. She had a positive family history of von Hippel-Lindau, and her family told us about she had “stiffness attacks” and two weeks later had another stiffness attack so it was treated by paramedics who declared her dead. In agreement with the forensic autopsy findings the diagnosis was hydrocephalus induced by brain stem hemangioma and the findings were compatible with von Hippel-Lindau. The aim of this article is to highlight the most important postmortem findings of this syndrome and its relation to the cause of death.

Estudio de tiempo de progresión y sobrevida global en pacientes con cáncer renal de células claras metastásico tratados con Sunitinib en el servicio de Oncología del Hospital Carlos Andrade Marín en el período comprendido entre enero de 2010 a diciembre de 2012 / Progression and global survival times study in patients with clear-cell terminal kidney cancer treated with Sunitinib in the Carlos Andrade Marin Hospital Oncolgy department during the January 2010 ­ December 2012 period

Introducción: el carcinoma renal de células claras (CRCC) es el más común de los cánceres del riñón, al tiempo del diagnóstico un 30% de pacientes presenta metástasis y un 40% se encuentra en recurrencia de la enfermedad. Es altamente resistente al tratamiento de quimioterapia y se ha evidenciado pobres respuestas con las interleuquinas e interferón antes utilizados, por lo que actualmente la terapia blanco con inhibidores de la tirosina quinasa son utilizados. Este estudio tiene como objetivo establecer la sobrevida global y el tiempo de progresión en pacientes con CRCC metastásico tratados con Sunitinib. Materiales y métodos: estudio clínico de cohorte analítico retrospectivo, con análisis de supervivencia mediante la técnica de Kaplan Meier. Se revisan las historias clínicas de 42 pacientes con diagnóstico de cáncer renal de células claras (CRCC) metastásico tratados con el inhibidor de tirosin quinasa Sunitinib en el servicio de Oncología del Hospital Carlos Andrade Marín durante el período comprendido entre el primero de enero de 2010 y 31 de diciembre de 2012 para obtener variables clínicas y realizar análisis de supervivencia. Resultados: 42 pacientes analizados con cáncer renal metastásico de células claras, 22 de ellos recibieron tratamiento con Sunitinib y 20 no recibieron este tratamiento, encontrando que la mediana de sobrevida para el grupo de pacientes tratados con Sunitinib fue de 16 meses versus 4,5 meses para los pacientes que no recibieron. La mediana del tiempo de progresión en el grupo de Sunitinib fue de 6 meses. Conclusiones: los resultados del análisis de tiempo de progresión en los pacientes tratados con Sunitinib fue similar a los estudios de referencia y guías de manejo oncológicos internacionales. En términos de sobrevida se obtuvo un resultado favorable sin embargo, los resultados aún no son concluyentes.

Introduction: the clear cell renal cell carcinoma (CRCC) is the most common cancer of the kidney, at the time of diagnosis 30% of patients have metastases and 40% are in disease recurrence. It is highly resistant to chemotherapy and poor responses were evidenced with the interleukins and interferon before use, so that the current target therapy with tyrosine kinase inhibitors were used. The objective of this study is to determine the survival and time to progression in patients with metastatic CRCC treated with Sunitinib. Materials and methods: retrospective study by Kaplan Meier technique, using the statistical package Epi Info 3.5, in patients with metastatic CRCC evaluated in the oncology department in the period between january 2010 and december 2012. Results: 42 patients with CRCC clear cell were analyzed, 22 of them were treated with Sunitinib and 20 did not receive this treatment. Findings show that the median survival for the group of patients treated with Sunitinib was 16 months versus 4.5 months for patients who did not. The median time to progression in the Sunitinib was 6 months. Conclusions: the results of the analysis of time of progression in patients treated with Sunitinib were similar at baseline and according to international oncology management guidelines. Favorable results were obtained in terms of survival; however results still are inconclusive.

Pheochromocytoma associated with von Hippel-Lindau disease in a Pakistani family

The aim was to study the presentation, disease characteristics, operative outcome, and prognosis in patients with familial Pheochromocytoma associated with von Hippel-Lindau [VHL] disease. There were six patients belonging to two generations of a single family who developed features of VHL over a period of 13 years and were treated at our institute. Patients' characteristics, that is, age, gender, presenting complaints and clinical signs, laboratory and biochemical evaluation, and the presence of associated conditions was gathered from medical records. The preoperative and postoperative radiological imaging and histopathological results were also collected. Out of six cases, five were male, and one was female. The mean age at first presentation was 25 years [16-40]. All patients presented with uncontrolled hypertension and were found to have Pheochromocytoma on workup. Three patients had unilateral adrenal tumor, and three had bilateral disease. None of the patients had extra-adrenal Pheochromocytoma. All patients were managed with adrenalectomy and had benign pathology. Two patients subsequently had craniotomy for excision of cerebellar hemangioma, and one patient had bilateral partial nephrectomy at the time of adrenalectomy. There was no peri- post-operative mortality and all patients are being followed by the surgeon[s] and endocrinologist. Pheochromocytoma can be a part of familial conditions including VHL. Other associated features should be suspected, investigated, and treated in these patients that can influence patients' clinical course and prognosis. Family members should also be screened to achieve early diagnosis

Papillary cystadenoma of the epididymis: a report of 2 cases and review of the literature / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the clinicopathological characteristics of papillary cystadenoma of the epididymis.</p><p><b>METHODS</b>Using 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>Papillary 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.</p>

Hemangioma of Endolymphatic Sac in Von Hippel-Lindau Patient / 대한이비인후과학회지

The present study reports a rare case of capillary hemangioma of endolymphatic sac. A 23-year-old male who underwent von Hippel-Lindau disease presented with recurrent sudden sensorineural hearing loss. Magnetic resonance imaging revealed a heterogenous enhanced mass in the right endolymphatic sac, which was hyperintense on the enhanced T1-weighted images and inhomogenous on the T2-weighted images. Pre-operatively, this tumor was believed to be an endolymphatic sac tumor because of the history of von Hippel-Lindau disease. During the surgery, vascular tumor was removed by transmastoid approach. A histopathological examination indicated that the tumor was a capillary hemangioma. To the best of our knowledge, the present study is the second case of hemangioma in the endolymphatic sac and first case of von Hippel-Lindau disease.