Clinical imaging features and prognosis of von Hippel-Lindau syndrome associated with pancreatic lesions / 中华消化外科杂志

Objective:To investigate the clinical imaging features and prognosis of von Hippel-Lindau (VHL) syndrome associated with pancreatic lesions.Method:The retrospective case-control study was conducted. The clinicopathological data of 161 patients with VHL syndrome who were admitted to Peking University First Hospital from September 2010 to August 2022 were collected. There were 83 males and 78 females, with age of onset as 27.0(range, 8.0-66.0)years. Observation indicators: (1) imaging results of VHL syndrome associated with pancreatic lesions; (2) clinical characteristics of VHL syndrome associated with pancreatic lesions; (3) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions; (4) comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic neuroendocrine neoplasms (pNENs). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Results:(1) Imaging results of VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, there were 151 patients associated with pancreatic lesions and 10 patients not associated with pancreatic lesions. Of the 151 patients with VHL syndrome associated with pancreatic lesions, there were 136 patient with pancreatic cystic lesions and 34 patients with pNENs, 22 patients with both pNENs and pancreatic cystic lesions, and the type of pancreatic lesions could not be accurately determined in 3 cases. (2) Clinical characteristics of VHL syndrome associated with pancreatic lesions. The age of onset in 151 patients with VHL syndrome associated with pancreatic lesions was 33.0(range, 14.0-68.0)years. Cases with gene site mutation of exon 1, exon 2, exon 3 and other types of gene site was 51, 16, 43 and 41, respectively. There were 116 patients of VHL type 1 and 35 patients of VHL type 2. There were 92 patients with family history of VHL syndrome and 59 patients without family history of VHL syndrome. There were 127 patients combined with renal cell carcinoma, 112 patients combined with central nervous system lesions, 46 patients combined with retinal hemangioblastoma. Patients may combined with multiple lesions. (3) Comparison of clinicopathological factors in patients with VHL syndrome associated with pancreatic cystic lesions. The age of onset, VHL syndrome type (VHL1 type, VHL2 type) and cases combined with renal cell carcinoma were 32.5(range, 14.0-68.0)years, 110, 26 and 115 in 136 patients with VHL syndrome associated with pancreatic cystic lesions, versus 22.0(range, 8.0-64.0)years, 13, 12 and 14 in 25 patients with VHL syndrome not associated with pancreatic cystic lesions, showing significant differences in the above indicators between them ( Z=-3.384, χ2=9.770, 10.815, P<0.05). (4) Comparison of clinicopathological factors in patients with VHL syndrome associated with pNENs. The age of onset, gene mutation sites (exon 1, exon 2, exon 3, other types of gene site) and VHL syndrome type (VHL1 type, VHL2 type) were 33.5(range, 14.0-64.0)years, 12, 5, 14, 3 and 18, 16 in 34 patients with VHL syndrome associated with pNENs, versus 27.0(range, 9.0-66.0)years, 41, 12, 32, 42 and 105, 22 in 127 patients with VHL syndrome not associated with pNENs, showing significant differences in the above indicators between them ( Z=-4.030, χ2=8.814, 13.152, P<0.05). (5) Treatment and prognosis of patients with VHL syndrome associated with pancreatic lesions. Of the 161 patients with VHL syndrome, 3 patients underwent surgical treatment, and the remaining patients were followed up. All 161 patients with VHL syndrome were followed up for 6 (range, 1-12)years, in which 15 patients died and 146 patients alive during the follow-up. The follow-up time of 3 patients undergoing surgical treatment was 4, 14, 9 years, respectively, and all of them were alive. Conclusions:The clinical imaging features of pancreatic lesions related to VHL syndrome are cystic lesions and pNENs, which with the characteristics of multiple lesions and benign tumors. Such patients usually do not requiring surgical treatment and have good prognosis.

Manifestaciones endocrinológicas en la enfermedad de Von Hippel-Lindau: revisión narrativa

La enfermedad de Von Hippel-Lindau es un síndrome neoplásico, autosómico dominante, caracterizado por una mutación germinal del gen VHL que codifica para la proteína VHL en el cromosoma 3. Esta mutación predispone al desarrollo de tumores benignos y malignos que afectan diferentes órganos, a causa de una ausencia de la inhibición de la vía de la tumo-rigénesis mediada por el factor inducible por hipoxia. La prevalencia de esta enfermedad es de 2 a 3 por 100 000 personas y las neoplasias se localizan con mayor frecuencia en retina, sistema nervioso central, cabeza y cuello, páncreas, riñón, glándula suprarrenal y órgano reproductor. Se clasifica en 2 tipos dependiendo de la presencia o ausencia de feocromocitoma. El feocromocitoma y las neoplasias pancreáticas constituyen las manifestaciones endocrinas más frecuentes. El feocromocitoma se presenta entre el 10-30% de los casos. Puede cursar desde una entidad asintomática hasta una sintomatología variable que incluye la triada clásica de cefalea, palpitaciones y diaforesis. El diagnóstico se realiza mediante pruebas bioquímicas o sus metabolitos que confirman niveles elevados de catecolaminas, y estudios imagenológicos. Las lesiones pancreáticas son con frecuencia asintomáticas y se detectan de forma incidental en estudios de imagen realizados en los pacientes con VHL. Aunque las características clínicas y bioquímicas de estas neoplasias no son patognomóni-cas, pueden ser útiles para sugerir la enfermedad VHL como la etiología subyacente.

Von Hippel-Lindau disease is an autosomal dominant neoplastic syndrome characterized by a germline mutation of the VHL gene encoding the VHL protein on chromosome 3. This mutation predisposes to the development of benign and malignant tumors that affect different organs, due to an absence of inhibition of the hypoxia-inducible factor-mediated tumorigenesis pathway. The prevalence of this disease is 2 to 3 per 100,000 people, and neoplasms are most frequently located in the retina, central nervous system, head and neck, pancreas, kidney, adrenal gland, and the organ. It is classified into 2 types depending on the presence or absence of pheochromocytoma. Pheochromocytoma and pancreatic neoplasms are the most frequent endocrine manifestations. Pheochromocytoma occurs in 1030% of cases. It can range from an asymptomatic entity to a variable symptomatology that includes the classic triad of headache, palpitations and diaphoresis. The diagnosis is made through biochemical tests that confirm high levels of catecholamines and imaging studies. Pancreatic lesions are frequently asymptomatic and are detected incidentally in imaging studies performed in VHL patients. Although the clinical and biochemical characteristics of these malignancies are not pathognomonic, they may be useful in suggesting VHL disease as the underlying etiology.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on abdominal manifestations / Manifestações de imagem da doença de von Hippel-Lindau: um guia ilustrado das manifestações abdominais

Abstract Von Hippel-Lindau (VHL) disease is a monogenic autosomal dominant disorder with germline mutations of the VHL anti-oncogene on the short arm of chromosome 3 (3p25-26). It affects 1:36,000-50,000 individuals, with a penetrance greater than 90% at 65 years of age. Although of variable onset and presentation, with pleiotropism even among members of the same family who share a specific mutation, VHL disease usually manifests initially in young adults. It predisposes to the development of benign and malignant tumors of the central nervous system (CNS) and visceral organs. The clinical diagnosis of VHL disease can be made in the following circumstances: a) in patients with a family history of the disease and at least one of the tumors characteristic of it (e.g., retinal or CNS hemangioblastomas, clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, and endolymphatic sac tumors); b) in patients with two or more CNS hemangioblastomas; c) or in patients with a retinal or CNS hemangioblastoma plus at least one visceral tumor characteristic of the disease, excluding renal and epididymal cysts. Imaging plays an important role in the diagnosis and follow-up of patients with VHL disease. This pictorial essay presents characteristic images of abdominal manifestations of VHL disease-related tumors that all radiologists should be aware of.

Resumo A doença de von Hippel-Lindau (VHL) é uma desordem autossômica dominante monogênica com mutações na linha germinativa do antioncogene VHL, no braço curto do cromossomo três (3p25-26). Afeta 1:36.000-50.000 indivíduos, com penetrância superior a 90% aos 65 anos de idade. Embora tenha início e apresentação variáveis, com pleiotropismo mesmo entre membros da mesma família que partilham uma mutação específica, usualmente manifesta-se de início em adultos jovens e predispõe ao desenvolvimento de tumores benignos e malignos no sistema nervoso central (SNC) e órgãos viscerais. Clinicamente, o diagnóstico pode ser realizado em uma das seguintes circunstâncias: a) em pacientes com história familiar de doença de VHL e pelo menos um dos tumores característicos relacionados à síndrome (como hemangioblastomas retinianos ou do SNC, carcinoma de células renais de células claras, tumores neuroendócrinos pancreáticos e tumores do saco endolinfático); b) dois ou mais hemangioblastomas do SNC; c) um hemangioblastoma retiniano ou do SNC mais pelo menos um tumor característico visceral relacionado à síndrome, excluindo-se cistos renais e epididimários. Nesse contexto, a imagem ocupa importante papel no diagnóstico e acompanhamento desses pacientes. Este ensaio iconográfico apresenta imagens características de manifestações abdominais de tumores relacionados à doença de VHL que todos os radiologistas devem conhecer.

Manifestações de imagem da doença de von Hippel-Lindau: um guia ilustrado com foco no sistema nervoso central / Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on the central nervous system

Abstract A doença de von Hippel-Lindau (VHL) é uma síndrome hereditária autossômica dominante rara que afeta a linha germinativa do gene VHL, um gene supressor tumoral. A doença de VHL é caracterizada pelo desenvolvimento multissistêmico de uma variedade de tumores benignos e malignos, especialmente no sistema nervoso central (SNC). Dentre eles, destacam-se hemangioblastomas retinianos e do SNC, e o tumor do saco endolinfático. Os diferentes locais dos tumores justificam a diversidade de sinais e sintomas relacionados à doença, que usualmente se manifestam com a idade média de 33 anos. Apesar dos avanços da medicina, a expectativa de vida média desses pacientes é de 49 anos. Exames de imagem têm papel fundamental no diagnóstico e são essenciais no seguimento dos pacientes com doença de VHL. Este ensaio iconográfico descreve as manifestações características dos tumores do SNC relacionados à doença de VHL que todos os residentes de radiologia devem saber.

Abstract Von Hippel-Lindau (VHL) disease is a rare, autosomal dominant inherited syndrome that affects the germline of the VHL gene, a tumor suppressor gene. VHL disease is characterized by the multisystemic development of a variety of benign and malignant tumors, especially in the central nervous system (CNS). Such tumors include retinal and CNS hemangioblastomas, as well as endolymphatic sac tumors. The various tumor sites are responsible for the diversity of signs and symptoms related to the disease. The mean age at symptom onset is 33 years. Despite medical advances, the average life expectancy of patients with VHL disease is 49 years. Imaging plays a pivotal role in the clinical diagnosis and is essential to the follow-up of patients with VHL disease. This pictorial essay describes characteristic CNS manifestations of VHL disease-related tumors that all radiology residents should be aware of.

Pancreatoduodenectomy in patient with von hippel-lindau disease: a literature review / Pancreaticoduodenectomia em paciente com doença de von hippel-lindau - revisão da literatura

ABSTRACT BACKGROUND: The von Hippel-Lindau disease is a highly penetrant autosomal dominant syndrome characterized by tumor predisposition in different organs. AIM: This study aimed to describe a case of a pancreatoduodenectomy for a 30-year-old male patient with von Hippel-Lindau disease. METHODS: We present a case study and the literature review aiming at the state-of-the-art management of a patient with pheochromocytoma, capillary hemangioblastoma in the peripheral retina, and two neuroendocrine tumors in the pancreas. RESULTS: A larger pancreatic lesion was located in the uncinate process, measuring 31 mm. The smaller lesion was located in the proximal pancreas and was detected only on the positron emission tomography-computed tomography scan with DOTATOC-68Ga. Genetic investigation revealed a mutation in the locus NM_000551.3 c.482G>A (p.Arg161Gln) of the Von Hippel-Lindau Human Suppressor gene. The uncinate process tumor was larger than 30 mm and the patient had a mutation on exon 3; therefore, we indicated a pancreatoduodenectomy involving the proximal pancreas to resect both tumors en bloc. During the postoperative period, the patient presented a peripancreatic fluid collection, which was treated as a grade B pancreatic fistula with clinical resolution of the complication. On postoperative day 21, he was discharged home. CONCLUSION: The management of patients with von Hippel-Lindau disease and pancreatic neuroendocrine tumors is complex and must be centered on tertiary institutions with a large volume of pancreatic surgery. Although the current literature assists in decision-making in most situations, each step of the treatment requires analysis and discussion between different medical specialties, including surgeons, clinicians, radiologists, and anesthesiologists.

RESUMO RACIONAL: A doença de von Hippel Lindau é uma síndrome autossômica dominante que se caracteriza por maior incidência de tumores em diferentes órgãos. OBJETIVO: Descrever um caso de pancreatoduodenectomia em paciente do sexo masculino de 30 anos com von Hippel Lindau. MÉTODO: Apresentamos o caso e a revisão da literatura realizada para otimizar o manejo do paciente, que apresentava feocromocitoma, hemangioblastoma capilar na retina periférica e dois tumores neuroendócrinos no pâncreas. RESULTADOS: O maior tumor pancreático localizava-se no processo uncinado medindo 31 mm. A lesão menor estava localizada no corpo proximal do pâncreas e foi detectada apenas na tomografia computadorizada por emissão de pósitrons com DOTATOC-68Ga. A investigação genética revelou uma mutação no locus NM_000551.3 c.482G>A (p.Arg161Gln) do gene supressor humano de Von Hippel-Lindau. O tumor no processo era maior que 30mm e o paciente apresentava mutação no exon 3. Indicamos pancreatoduodenectomia envolvendo o corpo proximal do pâncreas para ressecar em bloco ambos os tumores. No pós-operatório o paciente apresentou coleção líquida peripancreática que foi tratada como fístula pancreática grau B, com resolução clínica da complicação. Ele recebeu alta hospitalar no vigésimo primeiro dia pós-operatório. CONCLUSÕES: o manejo de pacientes com doença de von Hippel Lindau e tumores neuroendócrinos pancreáticos é complexo e deve ser centrado em instituições terciárias com grande volume de cirurgia pancreática. Embora a literatura atual auxilie na tomada de decisão na maioria das situações, cada etapa do tratamento requer análise e discussão entre diferentes especialidades médicas, incluindo cirurgiões, clínicos, radiologistas e anestesiologistas.

Papillary cystadenoma of the epididymis

ABSTRACT Background Papillary cystadenoma is a rare benign neoplasm of the epididymis. It may occur sporadically or in association with von Hippel-Lindau disease (VHLD). Papillary cystadenoma of the epididymis (PCE) is a benign mimic of metastatic clear cell renal cell carcinoma (CCRCC) given their histologic similarities. Case presentation Herein, we present the case of a 40-year-old man with a four-year history of microhematuria and a recently detected right paratesticular mass. A testicular sonogram revealed a hypoechoic, hypervascular solid mass in the right epididymal head treated by surgical excision. Histopathological examination demonstrated a 1.1 cm papillary cystadenoma of the epididymis. Genetic testing performed later showed no signs of VHLD. However, heterozygous mutations in three genes - CASR, POT1, and RAD51D - were found which have never been reported in PCE before. Conclusions Papillary cystadenoma of the epididymis should always be considered in the differential diagnosis of epididymal lesions, especially those that are cystic. The mainstay of treatment remains surgical excision, which provides an excellent prognosis.

Familial erythrocytosis 2 and von Hippel-Lindau disease in the same pediatric patient / Eritrocitosis familiar 2 y enfermedad de von Hippel-Lindau en el mismo paciente

Abstract Background: Patients with familial erythrocytosis type 2 have no increased risk of von Hippel-Lindau-associated tumors, although mutations in the VHL gene cause both pathologies. Case report: We present a case of a compound heterozygote patient with von Hippel-Lindau disease and familial erythrocytosis type 2. One of the mutations found in our patient, c.416C>G (p.Ser139Cys) of the VHL gene, has not been previously reported. This case is the second one reported where von Hippel-Lindau disease and familial erythrocytosis type 2 coexist in the same individual. Conclusions: Despite the low frequency of familial erythrocytosis type 2 in patients with von Hippel-Lindau disease, the possibility of this diagnosis should be considered to avoid unnecessary invasive studies to explain the polyglobulia in these patients and guarantee an adequate follow-up and vigilance of both diseases.

Resumen Introducción: Los pacientes con eritrocitosis familiar tipo 2 no muestran un riesgo incrementado de desarrollar tumores asociados con la enfermedad de von Hippel-Lindau, a pesar de que ambas afecciones están causadas por variantes patogénicas en el gen VHL. Caso clínico: Se presenta el caso de un paciente heterocigoto compuesto con enfermedad de von Hippel-Lindau y eritrocitosis familiar tipo 2. Una de las variantes patogénicas en el paciente, VHL c.416C>G (p.Ser139Cys), no ha sido previamente reportada. Este es el segundo reporte de caso en que la enfermedad de von Hippel-Lindau y la eritrocitosis familiar tipo 2 coexisten en el mismo individuo. Conclusiones: A pesar de la baja frecuencia de la eritrocitosis familiar tipo 2 en pacientes con enfermedad de von Hippel-Lindau, la posibilidad del diagnóstico debe considerarse con el fin de evitar estudios invasivos innecesarios para explicar la presencia de poliglobulia en estos pacientes y para garantizar un adecuado seguimiento y una correcta vigilancia de ambas enfermedades.

Insights into retinal hemangioblastoma using ultra widefield imaging

Purpose: Retinal hemangioblastomas (RHs) are characteristic of von Hippel-Lindau (VHL) disease. Early diagnosis of retinal lesions may aid in systemic diagnosis. Early identification of VHL is life-saving and also prevents vision loss. Fundus fluorescein angiography (FFA) is a useful tool in the diagnosis and management of RHs. The aim of this study is to report FFA features of RH using ultra-widefield (UWF) imaging. Methods: A retrospective cross-sectional study of consecutive patients of RH who underwent UWF FFA at a tertiary eye care center. Images were analyzed and assessed by authors. The main outcome measures were (a) the number and size of RH in each eye and (b) vascular characteristics of the retina. UWF-FFA characteristics in each eye were tabulated. The number of clock hours involved by these characteristics and their correlation with the number and size of RH were analyzed. Results: The study evaluated 24 eyes of 13 patients. The mean age was 28.4 years. The median number of RHs in an eye was 3.5 (range 1�16), and the size of RHs varied from 0.1 to 4 disc diameters. Novel UWF-FFA findings noted in this study were the presence of abnormal capillary network in 22 of 24 eyes (91.7%), capillary leakage in 15 of 24 eyes (62.5%), and capillary telangiectasia in 7 of 24 eyes (29.2%). In addition, feeder arterioles and venules showed bulbous projections in 8 of 24 eyes (33.3%). Conclusion: The UWF-FFA characteristics of RH, which have not been described before, were identified. These add to our understanding of the pathogenesis of the disease and may pave the way for future therapeutic targets.

“Endolymphatic sac tumour”: A case report with review of literature

Endolymphatic sac tumour (ELST) is a non-metastasizing low grade adenocarcinoma of endolymphatic sac origin. It is also known as Heffner tumour, low grade adenocarcinoma of endolymphatic sac origin and aggressive papillary middle ear tumour. These tumours are closely associated with Von Hippel Lindau (VHL) disease. Here we report a case of Endolymphatic sac tumour in a 63 yr old lady who presented with left sided facial palsy. Since the tumour was highly vascular and required preoperative embolization, initial clinicoradiological diagnosis was Jugulotymphanic paraganglioma. Histopathology showed features of Endolymphatic sac tumour, which was confirmed by immunohistochemistry. Since this tumour is locally aggressive low grade adenocarcinoma, the diagnosis is difficult in advanced cases where there is erosion of petrous temporal bone or the lesion shows extension into cerebellopontine angle as in our case. Since the association of this tumour with VHL disease is well established, it is important to screen all the patients of VHL disease for this lesion and also all the patients of ELST should be screened for other lesions of VHL disease to aid in early diagnosis and treatment. The case is presented here for its rarity and difficulty in initial diagnosis.

Analysis of characteristics of pedigrees with von Hippel-Lindau disease / 中华泌尿外科杂志

Objective To discuss the clinical characteristics of yon Hippel-Lindau (VHL)syndrome and the significance of genetic test for this disease.Methods Patients with VHL disease from 3 different families were reviewed from August 1985 to October 2017.The study was including clinical family survey and VHL-gene test on phylogenetic level.Totally 21 family members from 3 families were investigated,consisting of 14 males and 7 females with average age of 48.6 (5-70)years when analyzed.There were 8 patients with VHL disease comprising 5 males and 3 females with average onset age of 31.5 (9-67) years.Results The proband of pedigree one (VHL-Ⅱ C) was diagnosed as pheochromocytoma (PHEO) of right adrenal gland at 18 years old and underwent adrenalectomy,and her son was diagnosed with PHEO of bilateral adrenal glands with diagnostic age of 9 years old and received bilateral adrenalectomy sequentially.Her niece was diagnosed as PHEO of bilateral adrenal glands at 28 years old and received bilateral adrenal-sparing surgery simultaneously.Genetic analysis revealed a heterozygous mutation located at the third exon of the VHL gene (c.482G ＞ A).The proband of pedigree two (VHL-Ⅱ B) was diagnosed as right PHEO,bilateral multiple renal clear cell carcinoma (RCC),multiple pancreatic cysts and bilateral epididymal cystadenoma,and he received right adrenalectomy,right partial nephrectomy at 25 years old and delayed eystadenoma excision.His younger brother was also diagnosed as bilateral,pancreatic multiple cysts and bilateral epididymal nodules at 27 years old,and underwent right radical nephrectomy.Genetic analysis revealed a heterozygous mutation located at the first exon of the VHL gene (c.233A ＞ G).The proband of pedigree three (VHL-Ⅱ B) was diagnosed with central nerve system hemangioblastomas (CNS-HB) at 35 years old and received external beam radiotherapy.His elder sister was diagnosed as CNS-HB at 43 years old and received surgery.His father was diagnosed as right PHEO,bilateral RCC,bilateral multiple renal and pancreatic cysts and pancreatic neuroendocrine tumors at 67 years old.He received right adrenalectomy and partial nephrectomy.Genetic analysis showed a heterozygous mutation located at the third exon of the VHL gene(c.500G ＞ A).In addition,two cases (F2-Ⅲ 1 and F3-ⅣV1) were found to be asymptomatic VHL gene carriers by genetic screening.8 patients were followed up for an average of 9.8 (2-32) years.The symptoms were stable and no local recurrence or distant metastasis was found after operation.In this study,no CNS-HB was found in patients within family 1 and family 2,and RCC in 3 patients within family 2 and family 3 were low grade.Conclusions The clinical manifestations of VHL disease are diverse.RCC and CNS-HB are not present in all patients with the disease.PHEO is the only manifestation in patients with VHL-ⅡC.It is necessary to inform the members of VHL syndrome family for genetic test.Genetic test combined with clinical screening can facilitate differential diagnosis for VHL syndrome and other hereditary urological diseases.

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.

Von Hippel–Lindau disease

Von Hippel–Lindau (VHL) disease is a rare autosomal dominantly inherited multisystem disorder characterised by the development of a variety of benign and malignant tumours. We report a case of VHL disease that was inherited by a daughter from her father, who both presented at a young age with progressive headache and were found to have a posterior fossa haemangioblastoma (HB) on magnetic resonance imaging (MRI). Multiple benign pancreatic and renal cysts were also noted in both patients.

Pancreatic lesions in 3 patients with Von Hippel-Lindau disease / 中华胰腺病杂志

Objective To investigate the clinical features, diagnosis and management of pancreatic lesions in patients with von Hippel-Lindau (VHL) disease, and improve the current understanding on pancreatic lesions in VHL disease.Methods The clinical data of three VHL disease patients with pancreatic lesions were analyzed retrospectively, including clinical features, laboratory findings, imaging, pathological features, operation method and follow-up.Results Two patients had a family history of hemangioblastoma in central neural system, and 1 patient had retinal multiple angioma and angioma in central neural system, who were diagnosed as VHL.One patient with pancreatic portal hypertension had splenectomy and biopsy of left renal tumor.During the surgery, pancreatic cystic lesions were observed and the transparent cysts were diffusively distributed on the surface.The other 2 patients were diagnosed as pancreatic multiple cysts and non functional pNETs, and pancreatic multiple cysts, respectively, based on the imaging.All the three patients had stable disease status, and followed up by outpatient visits.Conclusions VHL disease can manifest as simple pancreatic cyst, pancreatic serous cystadenoma and pNETs.The optimal individualized treatment should be determined by Multidisciplinary team (MDT) according to the general condition of patient.

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.

CT and MRI Manifestations of Von Hippel-Lindau Syndrome / 中国医学影像学杂志

PurposeVon Hippel-Lindau (VHL) syndrome is a rare autosomal dominant diseases involved multiple organs. This paper aims to explore the clinical and imaging features of VHL syndrome for the improvement of early diagnosis and treatment of this disease.Materials and Methods The clinical and imaging data, as well as their history of 5 patients with VHL syndrome were retrospectively studied. Follow-up was performed and the related literature was also reviewed.Results Among the 5 patients, 4 were found with angioreticulomas. One out of four patients simultaneously suffered from multiple angioreticulomas in brainstem, and another one had multiple cervical cord angioreticulomas. The typical MRI showed multiple cystic and solid mass with mixed intense signals, and the enhanced MRI displayed obvious enhancement in the solid part of the mass. Three patients were diagnosed with renal clear cell carcinomas. The typical CT scan showed equidensity or slightly low density signals, and the enhanced CT scan noted heterogeneous enhancement. Besides, bilateral epididymis cystadenoma occurred in one case. The ultrasonography presented heterogeneous echo and rich blood vessels. The follow-ups had been conducted till January 2015. According to the Glasgow outcome scale, three patients were in good conditions, while the other two died from renal clear cell carcinomas.Conclusion Patients with VHL syndrome usually have an unsatisfactory prognosis and most may die from renal carcinoma. Genetic test and investigation of family history should be performed as early as possible on patients with highly suspected or confirmed VHL Early treatment, life-long follow-up and periodic imaging examinations may be helpful in the prognosis.

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.