The use of minimally-invasive cortical sparing adrenalectomy as an approach to bilateral adrenal masses in a patient with von Hippel Lindau Syndrome: Learnings from a lower middle-income country setting

@#von Hippel Lindau syndrome is a rare genetic disease which may present with bilateral adrenal masses requiring surgical intervention. Previous practice at UP-PGH was to perform outright total adrenalectomy on pathologic adrenal glands and rely on lifelong steroid replacement for patients who had both adrenals removed. Presented here is a case of a patient diagnosed with von Hippel Lindau syndrome with bilateral adrenal masses, surgically managed initially with open adrenalectomy on the right side, followed by the first ever performed minimally invasive cortical sparing adrenalectomy at UP-PGH on the left side.

A Case Report of Von Hippel-Lindau Syndrome with Hypertension and Diabetes as the First Manifestation / 罕见病研究

Von Hippel-Lindau (VHL) syndrome, also known as cerebral retinal angiomatosis, is a kind of neuroendocrine tumor. The incidence rate is high, and the heredity is very high, which can involve the retina, central nervous system, various organs and various tissue parts. This paper reports a case of VHL syndrome with hypertension and diabetes as the main manifestations, in order to improve the understanding of the disease and reduce misdiagnosis and missed diagnosis.

Surgical management of complicated retinal detachment in a case of retinal hemangioblastoma

Background: A 40-year-old male presented with a complaint of sudden onset diminution of vision in the left eye for 2 weeks. He was a follow-up case with retinal hemangioblastoma in both eyes. He underwent two sittings of fundus fluorescein angiography-guided trans-pupillary thermotherapy 2 years back. Since then, he was regularly followed up for 2 years with stable vision and stable retinal findings. At present, the best-corrected visual acuity (BCVA) in the right eye is 6/6, and in the left eye, it is counting fingers 2 meters. On fundus examination, he had one active hemangioblastoma in the right eye and total retinal detachment in the left eye with multiple active lesions. The right eye was treated with a single sitting of thermotherapy, and the left eye underwent pars plana vitrectomy and angioma excision, followed by silicone oil tamponade. The immediate and late post?operative periods were uneventful, with successful anatomical and functional outcomes. The left eye BCVA on late follow-up was 6/36, no further treatment was advised, and the patient was kept under follow-up and observed closely. Purpose: To educate regarding the systemic workup, diagnosis, and surgical management of complicated retinal detachment in retinal hemangioblastoma. Synopsis: Systemic workup, diagnosis, and surgical steps in the management of complicated retinal detachment in retinal hemangioblastoma were performed. Highlights: Close follow-up, keen observation, and prompt treatment in the early stages of the disease are indispensable to prevent untoward sequelae of retinal hemangioblastoma. A thorough systemic workup is necessary to diagnose the systemic involvements early. Surgery, if indicated for the retinal hemangioblastoma or its associated sequelae, should be performed diligently and with careful handling of blood vessels and anomalous tissues.

Manejo anestésico de feocromocitoma en paciente con enfermedad de Von Hippel-Lindau / Anesthesia for a patient with pheochromocytoma and Von Hippel-Lindau syndrome

Pheochromocytoma is a catecholamine-producing tumor that can occur sporadically or in association with other entities and syndromes. The anesthetic management of these patients must be very careful, focused mainly on avoiding hypertensive crises and therefore stimuli that can trigger them. The role of the anesthesiologist is very important in these cases, not only intraopera- tively but from the moment a pre-anesthetic assessment is made, since patients usually require drugs such as alpha-blockers to reach surgery in optimal conditions. We present the anesthetic management in a 54-year-old woman previously diagnosed with Von Hippel-Lindau syndrome in whom a pheochromocytoma was observed in the clinical follow-up and required to be scheduled for surgery.

El feocromocitoma es un tumor productor de catecolaminas que se puede presentar de forma esporádica o asociada a otras entidades y síndromes. El manejo anestésico de estos pacientes debe ser muy cuidadoso, enfocado principalmente a evitar crisis hipertensivas y por tanto estímulos que puedan desencadenarlas. El papel del anestesiólogo es muy importante en estos casos, no solo de manera intraoperatoria sino desde el momento en el que se hace una valoración preanestésica, ya que los pacientes suelen precisar fármacos como los alfabloqueantes para llegar en unas condiciones óptimas a la cirugía. Presentamos el manejo anestésico en una mujer de 54 años, diagnosticada previamente de síndrome de Von Hippel-Lindau, en la que se objetiva un feocromocitoma en el seguimiento clínico y requiere ser programada para cirugía.

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.

A case report of ⅡC type VHL syndrome / 中华泌尿外科杂志

On March 24, 2017, a patient with Von Hippel-Lindau syndrome (VHL) characterized by bilateral adrenal pheochromocytoma and pancreatic tumors was admitted to our hospital, who underwent simultaneous pancreatic body and tail tumor resection, bilateral adrenal tumor resection and Omentum transplantation of the right adrenal gland.Intraoperative hormone therapy was used. Part of the normal adrenal tissue was preserved and embedded in the omentum, but an adrenal crisis occurred on the first day after the operation.The hormone replacement was used. Postoperative hormone replacement therapy was performed for 6 months. After 4 years of follow-up, blood pressure was normal, no cortical dysfunction, no tumor recurrence or other related lesions appeared. The preserved part of adrenal tissue during simultaneous multi-organ tumor resection for such patients can reduce long-term hormone replacement after surgery and prevent late adrenal cortex dysfunction.

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.

Diagnosis and treatment of pancreatic neuroendocrine neoplasmas in Von Hippel-Lindau syndrome / 中华外科杂志

Von Hippel-Lindau(VHL) syndrome is a rare autosomal dominant hereditary disease, and pancreas is one of the frequently involved intra-abdominal organs, including simple pancreatic cysts, pancreatic serous cystadenomas and neuroendocrine neoplasmas. Most of the VHL-related pancreatic neuroendocrine neoplasmas (VHL-pNEN)were non-functional, but they still have a tendency to be malignant. Treatment options for VHL-pNEN include regular follow-up, surgical resection, and medication therapy. When compared with sporadic pNEN, the malignant degree of VHL-pNEN is lower, with a better prognosis, so the surgical treatment should be carefully considered. The indications of surgery for VHL-pNEN include big primary lesions (≥3 cm), fast tumor doubling time (<500 days), VHL gene mutation on exon 3, malignant manifestations on imaging findings, and functional pNEN lesions. The function-preserving approach should be performed to keep the functional pancreatic parenchyma as much as possible. Even for patients with a late stage malignancy that cannot be radically resected, active medication therapy may still lead to a long-term survival.

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)

Clinicopathological features of central nervous system hemangioblastoma in von Hippel-Lindau syndrom / 局解手术学杂志

Objective To investigate the clinicopathological features of central nervous system hemangioblastoma in von Hippel-Lindau syndrome.Methods The data of 10 patients with central nervous system hemangioblastoma in our hospital since 2013 were analyzed retro-spectively,and the clinicopathological features of central nervous system hemangioblastoma in von Hippel-Lindau syndrome were summarized. Results The macroexamination result showed that most tumor lesions were found in the cerebellum and medulla oblongata,with cystic chan-ges,size from 1 cm to 5 cm,the average size was (3.1 ±0.2)cm,clear boundary,intracapsular yellow cyst fluid.The microscopy result showed tumor foci with a rich blood supply,endothelial cell proliferation and hypertrophy in vascular,which arranged in nests or lobulated mesenchymal cells,the cytoplasm of stromal cells was abundant and lightly stained,a rich lipid was seen,with vesicular or foam.Conclusion The von Hippel-Lindau syndrome is usually cystic lesion,the microscopic examination shows tumor foci with rich blood supply,endothelial cell proliferation,hypertrophy and other changes in vascular.

Imaging features of Von Hippel-Lindau syndrome type Ⅰ / 实用放射学杂志

Objective To analyze the imaging characteristics of Von Hippel-Lindau Syndrome (VHL)typeⅠ.Methods 12 patients diag-nosed as VHL type Ⅰ were collected and all the patients had underwent 3.0T MRI and 64-slice spiral CT plain and enhanced scan. Imaging data was analyzed by two senior radiologists to summarize its imaging featueres.Results Multiple hemangioblastomas (HGBLs)in cerebellum,spinal cord or brainstem were seen in all the patients.Flow void effect with varied degree was seen in the lesions.Dilated feeding and drainage blood vessels around lesions was seen in 6 cases.Multiple kidney and pancreas cysts were seen in all the patients.There were 4 cases with syringomyelia,7 cases with ocular retinal angioma,5 cases with renal cell carcinoma,2 cases with ground-glass-like lesions and micronodulars in lung.Conclusion VHL type Ⅰ has complex imaging performance.Ima-ging examination is important for early detection of VHL disease.

Von Hippel-Lindau Syndrome: Demonstration of Entire Disease Spectrum with 68Ga-DOTANOC PET-CT

Von Hippel-Lindau (VHL) syndrome is a rare neoplastic disorder characterized by central nervous system (CNS) and visceral tumors. We here present 68Ga-labelled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-Nal3-Octreotide positron emission tomography computed tomography findings in a 52 year old female with VHL syndrome, demonstrating both CNS and visceral tumors.

Von Hippel-Lindau syndrome-2B accompanied with leukocytoclastic vasculitis: a case report and lirerature review / 中华泌尿外科杂志

Objective To explore clinicopathologic features,diagnosis,treatment and prognosis of von Hippel-Lindau (VHL) type 2B mixed cutaneous leukocytoclastic vasculitis. Methods A 22-Year-Old Man who presented with constitutional symptoms,severe hypertension,and purpuric lesions over the knees.Clinical features,histopathological,IHC and anti-angiogenesis therapy of this case with VHL syndrome-2B mixed cutaneous leukocytoclastic vasculitis was studied based on the available follow-up data.He underwent laparoscopic adrenalectomy and nephron sparing nephrectomy.Clinical evaluation included ophthalmologic examination as well as imaging exams and endocrinal hormone test for tumors markers ; molecular analysis consisted of PCR amplification of the complete VHL gene coding sequence (three exons) and automated nucleotide sequencing. Results 24 h urine Norepinephrine was 295.84 μg and octreotide scan was positive.The VHL-2B patient suffered from leukocytoclastic vasculitis,a retinal hole,pancroatic tumors (endocrine tumor and microcystic cystadenoma),bilateral pheochromocyoma,clear renal cell carcinoma,renal cysts,hepatic hemangioma and epididymal cyst.The patient developed 5 different tumors related to VHL within a period of 6 years.The cutaneous vasculitis persisted despite treatment with high-dose systemic corticosteroids,but rapidly resolved after treatment with phenoxybenzamine and removal of bilateral pheochromocytomas.Tumor cells of resected PHEO samples stained positive for CgA and S-100,but negative for Melan-A.,and with less than 1％ Ki-67. Conclusions Cutaneous leukocytoclastic vasculitis is one of paraneoplastic syndrome of pheochromocytoma.Because new lesions may develop during the patient's lifetime,regular clinical inspection is recommended in order to check up the development of any new lesions.

Surgical management of yon HippeI-Lindau disease(report of 4 cases) / 中华泌尿外科杂志

Objective To discuss the surgical management of von Hippel Lindau(VHL) syn drome.Methods The clinical data of four VHL patients who were clinically diagnosed from March1999 to October 2006 were reviewed.The first patient was a 56 year old man with the chief complaintof hypodynamia and low serum glucose as 2.37 mmol/L.CT scan showed three masses in the the leftkidney.He had a history of cerebral haemangioblastoma ten years before.The second case was a 57 year old woman with the chief complaint of lumbago in the left side.CT scan showed masses in theleft kidney,adrenal gland and panerease.The third case was a 39 year old woman with the chief com plaint of an accident mass in the left adrenal gland.She had the history of cerebellar hemangioblastoma9 years before,spinal hemangioblastoma resection 7 years before.The fourth case was a 41-year oldwoman,she was found brain tumors and cured by gamma radiation abalation.Bilateral renal masseswere found by B ultrasound one month later,CT scan showed four masses in the both kidneys,leftadrenal gland and pancreas.Results All 4 cases underwent surgical approach.The first case under went radical nephrectomy which pathological report was PEComa of kidney.The blood glucose wasnormal one week later.The second case underwent resection of the left adrenal gland,kidney,pancre atic body and tail and spleen.Pathological report was clear cell carcinoma,islet cell tumor and adrenal cyst.Three months later she was found spinal hemangioblastoma and refused treatment.The thirdcase underwent adrenalectomy in the left side and pathologieal report was adrenal pheoehromocytoma.There was not tumor reeurrenee during 2 years' follow up.The nephrectomy and adrenalectomy wasperformed for the last ease whose pathological report was clear celt carcinoma and pheochromoeytoma.Three weeks later,tumor enueleating of the right kidney was undertaken; the result was clear cellcancer.During the follow up for one year there was no relapse of tumor.Conclusions For VHL ac companied with multiple organ tumors,surgery resection is the proper approaeh when tumors of centralnervous system is large.Different approaches could be taken to deal with multiple tumors of VHL such aswatchful waiting,nephron sparing surgery.

Clear Cell Papillary Cystadenoma of the Epididymis Associated with Multiple Renal and Pancreatic Cysts / 대한남성과학회지

Papillary cystadenoma of the epididymis is a rare benign tumor that accounts for only 5% of all epididymal tumors. A case of epididymal cystadenoma was presented in a 25 year old man. The patient was hospitalized initially because of infertility and bilateral painless palpable scrotal masses. He had multiple renal cysts and pancreatic cysts. He had no renal, adrenal, cerebellar or retinal lesion as cardinal manifestation of the Von Hippel-Lindau Syndrome (VHL). The VHL gene mutation in this case was not identified. For evaluation and management, we planned left epididymovasostomy and left testicular biopsy. However, due to a cystic change on the left epididymis and left tunica albuginea, we instead performed a left partial epididymectomy for the cystic lesion, excision of the cystic mass from the left tunica albuginea, and diagnostic left testicular biopsy. The pathologic evaluation revealed a papillary cystadenoma of the epididymis and tunica albuginea, but with normal spermatogenesis.

Isolated Hemangioblastoma of the Filum Terminale

The filum terminale is an exceptional location for isolated hemangioblastoma, and most commonly hemangioblastomas are present in patients with von Hippel-Lindau(VHL) syndrome. We describe here a case of hemangioblastoma of filum terminale not associated with VHL, presenting with the history of progressive back pain, particularly severe in recumbent posture, and recurrent bilateral sciatica. MRI and spinal angiography revealed a well-vasculized mass lesion in filum terminale. The tumor was resected surgically. Histological examination confirmed the hemangioblastoma diagnosis. We recommended that, although rare, hemangiblastoma of the filum terminale be included in the differential diagnosis of a patient with low back pain.

Treatment of Retinal Detachment occurring in Two Cases of von Hippel-Lindau Syndrome

PURPOSE: To report two cases of retinal detachment associated with von Hippel-Lindau syndrome, one case of rhegmatogenous retinal detachment combined with mild proliferative vitreoretinopathy and a case of tractional retinal detachment. METHODS: Case reports. Pars plana vitrectomy with membrane peeling and silicone oil tamponade were performed in all cases. Lens aspiration was also performed in one case. RESULTS: Successful retinal reattachment was obtained in all cases. Case 2 developed cataract and secondary glaucoma and was treated with phacoemulsification with posterior chamber lens insertion and YAG laser iridotomy. CONCLUSIONS: In two patients with retinal detachment occurring in von Hippel-Lindau syndrome, we could obtain successful retinal reattachment with stabilized visual acuity after performing pars plana vitrectomy and silicone oil injection.

2 Cases of Multifocal and Recurrent Hemangioblastomas with Von Hippel-Lindau Syndrome: Case Report

Hemangioblastomas are benign tumors that most commonly occur in the posterior fossa around the 4th ventricle. Recurrent mutifocal hemangioblastomas are often found as a part of a systemic autosomal dominant disease, the Von Hippel-Lindau syndrome. Surgical removal of recurrent multifocal tumors are technically more difficult and challenging than solitary ones due to their proximity to critical structures, disturbed anatomical landmark and adehesion to the surrounding tissue, all of which may lead to high postoperative morbidity and mortality. Authors have experienced 2 cases of the multiple and recurrent hemangioblastomas with Von Hippel-Lindau syndrome. The patients of each of the cases underwent surgery for tumor removal at least 2 times. In the first patient, a 42-year-old male, a solitary cerebellar hemangioblastoma had been removed 6 years prior to recurrence. On followup MRI, more than three solid, homogenously enhanced nodules were found in the cerebellum. These tumors were operated on through the previous craniectomy site, but only two of them could be removed. This patient was discharged without additional neurologic deficit. The 2nd patient, a 40-year-old-male, had undergone three prior operations for cerebellar hemangioblastomas. On followup examination, he presented with progressive ataxia and confusion. Brain MRI showed multiple recurrent lesions of homogenously strongenhanced masses in the 4th ventricle and cerebellar vermis surrounded by cystic lesions, accompanied by obstructive hydrocephalus. No additional surgery of tumors were attempted, and only ventriculoperitoneal shunt was performed. He was discharged with improved neurological symtomes and sign.

Papillary Cystadenoma of the Epididymis: Component of von Hippel-Lindau Syndrome: A case report

Papillary cystadenoma of the epididymis is a rare benign tumor that represents the epididymal component of von Hippel-Lindau Syndrome. A case of epididymal papillary cystadenoma is presented in a 36 years old man. He also had pancreatic cysts, the pancreatic component of von Hippel-Lindau syndrome. His younger brother, who died of intracranial hemorrhage at age 27, revealed hemangioblastoma of the cerebellum, angioma of the retina and renal cell carcinoma on radiologic studies. These findings suggest familial occurrence of von Hippel-Lindau syndrome.