History Of Von Hippel-Lindau Disease Research Articles

Von Hippel-Lindau Disease Presenting With Cranial and Spinal Hemangioblastomas: MRI Findings

Hemangioblastoma (HB) is one of the most common primary neoplasms of the posterior fossa in adults. Although single tumors can be sporadic, multiple tumors are almost always associated with von Hippel-Lindau (VHL) disease. In our case report, we are describing a 39-year-old woman with complaints of severe headache, pain, and numbness in both arms. She had a history of VHL disease. We performed contrast-enhanced cranial and cervical spine magnetic resonance imaging (MRI) examinations. Given the patient’s history of VHL disease and characteristic MR imaging features of lesions, cranial and cervical HBs were considered for diagnosis. Surgical excision is the main treatment of these tumors and follow-up optimal imaging of these patients is crucial. In the screening of VHL patients, whole spinal axis imaging in conjunction with routine MRI studies must always be performed to rule out spinal HBs.

Von Hippel-Lindau Disease: Case Report of a Rare Condition

Introduction: Von Hippel-Lindau disease (VHL) also known as familial cerebello-retinal angiomatosis is an inherited disease caused by mutation of a gene, characterized by a variety of benign and malignant tumors in different parts of the body [1]. VHL disease is classified as: type 1 which is presented as hemangioblastoma at the level of the central nervous system (CNS), renal cancer and type 2, which is subdivided into A characterized by (retinal angioma, CNS hemangioma, renal cancer), B characterized by (hemangioblastoma, renal cancer, pheochromocytoma) and C characterized by isolated pheochromocytoma [2]. Clinical Case: A 32-year-old female patient of Jehovah's Witness religion with a clear family history of Von Hippel-Lindau disease, who at 28 years of age was admitted to the Neurosurgery Department with a severe headache; therefore, a basic cranial CT was performed with evidence of an infratentorial lesion in the left cerebellar hemisphere causing obstructive hydrocephalus due to compression of the fourth ventricle. It is complemented with brain MRI when there is evidence of an image compatible with hemangioblastoma that exerts mass effect. Through the Nephrology Service, renal ultrasound shows a non-vascularized mass; therefore, simple and contrast CT urogram is requested to rule out malignancy, nephroprotective scheme is placed to prevent CIN, Merhan Score of 2, low risk of 7.5%. In simple and contrast CT urogram, the findings described suggest left renal neoplasm, to be correlated with histopathological study, BOSNIAK type I renal cysts, right ovarian cyst. Conclusions: The treatment of Von Hippel-Lindau disease, due to all its clinical manifestations, is a challenge that should be approached in a multidisciplinary manner. Early detection of tumors means a more effective early management, also alerts family trees with high risk of suffering it.

Detection of retinal microvascular changes in von Hippel-Lindau disease using optical coherence tomography angiography.

PurposeVon Hippel-Lindau (VHL) disease is a hereditary disorder that can lead to ophthalmic manifestations, including retinal capillary hemangioma (RCH). The diagnosis of RCH is often guided by wide-field fluorescein angiography. In some cases, optical coherence tomography angiography (OCT-A) serves as a non-invasive alternative to FA. Herein, we used OCT-A to examine the macular microvasculature in patients with VHL disease.SubjectsSubjects were selected from patients with a diagnosis of VHL. The control group included eyes without retinal diagnosis from patients with an episode of unilateral retinal detachment or trauma and age ≤ 50 years old.MethodsSubjects were scanned on the Optovue RTVue-XR device to acquire 3mm x 3mm OCT-A images of the superficial (SCP) and deep capillary plexus (DCP). SCP and DCP vessel density (VD) were calculated after the images were binarized. Furthermore, for subjects with RCH, each OCT-A image was divided equally into four quadrants. SCP and DCP VD of quadrants with RCH were compared to those without RCH. T-tests were performed for statistical analysis.Results67 eyes with a history of VHL disease were included as study subjects, while 16 eyes were included as controls. Significant increases in VD were found in patients with VHL disease for both the SCP (p = 0.0441) and DCP (p = 0.0344). When comparing quadrants with associated RCH development to those without, we found no significant difference in SCP VD (p = 0.160) or DCP VD (p = 0.484).ConclusionsOCT-A can detect changes in the retinal microvasculature in the macula of patients with VHL disease. OCT-A imaging may be an additional tool for screening and early detection of patients at risk of developing ocular complications of VHL disease. Future studies should explore subtle progression on OCT-A associated with the pathogenesis and development of RCH, particularly with larger scan patterns.

Resection of a Thoracic Hemangioblastoma in a Patient With Von Hippel-Lindau: 3-Dimensional Operative Video.

This 3-dimensional operative video illustrates resection of a thoracic hemangioblastoma in a 30-year-old female with a history of Von Hippel-Lindau disease. The patient presented with right lower extremity numbness and flank pain. Magnetic resonance imaging (MRI) demonstrated an enhancing intradural intramedullary lesion at T 7 consistent with a hemangioblastoma. The patient underwent a thoracic laminectomy with a midline dural opening for tumor resection. This case demonstrates the principles of intradural intramedullary spinal cord tumor resection. In this particular case, internal debulking was untenable owing to the vascular nature of hemangioblastomas. The operative video demonstrates en bloc tumor removal. Postoperative MRI demonstrated gross total resection. The postoperative course was uneventful. The natural history of this disease, treatment options, and potential complications are discussed.

Short-Spindled Cell Haemangioblastoma with CD34 Expression: New Histopathological Variant or Just a Stochastic Cytological Singularity?

Haemangioblastomas are neoplasms of uncertain histogenesis with cellular and reticular variants advocated in current lore. Herein we describe an intriguing cerebellar specimen with unusual traits including spindle cell morphology and CD34 positivity. A thirty-nine-year old man had an infratentorial tumour discovered incidentally and resected three times. In all the instances, histopathological diagnosis was haemangioblastoma; nonetheless, he had neither physical stigmata nor family history of von Hippel-Lindau disease. By histology, the lesion was composed of areas of conventional stromal cells admixed with territories populated by short-spindled cells packed in lobules, sometimes giving the appearance of gomitoli. Immunoperoxidase-coupled reactions confirmed the expression of inhibin A, neuron-specific enolase (NSE), PS100, and CD57 but also revealed focal immunolabeling for CD34, CD99, and FXIIIa. This case highlights the potential phenotypical diversity that can be found within these neoplasms. Rather than uncertain histogenesis, it may in fact reflect multiple lines of differentiation—histomimesis—prone to adopt unusual morpho- and immunophenotypes in a subset of haemangioblastomas.

Imaging spectrum of von hippel–lindau disease

Von Hippel–Lindau (VHL) disease is a rare phakomatosis with autosomal dominant inheritance. It is the result of inactivation of tumor suppressor gene located on short arm of chromosome 3 and is characterized by the development of a variety of benign and malignant tumors of various organs. These include retinal and central nervous system hemangioblastomas, renal cysts and renal cell carcinoma, pheochromocytomas, pancreatic cysts and tumors, epididymal cystadenoma, and ductal ectasia of rete testis. Imaging plays a key role in the diagnosis of VHL disease. It is also useful for screening of patients with family history of VHL disease and in follow-up after treatment. This coupled with advanced surgical management helps in reducing the morbidity and mortality in VHL. The aim of this pictorial essay is to demonstrate the imaging spectrum of VHL disease.

Spinal Hemangioblastomas in Von Hippel-Lindau Disease Mimicking a Spinal Dural Arteriovenous Fistula

Introduction Spinal hemangioblastomas (HBs) are rare tumors that are closely associated with a diagnosis of Von Hippel-Lindau disease (VHL). A tissue diagnosis is needed to make the diagnosis of HB because many other entities can present similarly, which may require different management strategies. We present the first case in the literature of multiple intramedullary spinal HBs and VHL that mimicked a spinal dural arteriovenous fistula (dAVF) on radiological imaging. Material and Method Case illustration and literature review. Results A 60-year-old man was referred to our clinic for evaluation of progressive radiculomyelopathy and evidence of a T10 dAVF on MRI and MRA. MRI demonstrated perimedullar hypervascularity dorsal to the spinal cord from T10 to L1, and associated T2 signal change within the spinal cord. Prominent radicular arteries were identified at the exiting right T10 nerve root sleeve which was suspicious for the fistulous point. The patient underwent a T10-T12 laminoplasty for intradural exploration and possible ligation of the fistula; however, intraoperative findings included multiple small intra- and extramedullary vascular nodules along the spinal cord. Six lesions were biopsied, revealing a diagnosis of HB and VHL. Indocyanine green angiography (ICG) was used to rule out a concomitant dAVF. He is being managed expectantly and undergoing routine screening for VHL. He was discharged on postoperative day 3, and he reported symptom improvement at 2-week follow-up. Conclusion The present case is the first reported in the literature to describe multiple spinal HBs, in the setting of VHL, that appeared to be dAVF preoperatively. The patient's late clinical presentation, the greater degree of associated hypervascularity, and atypical vascular morphology were unique features, which highlight the diversity of this disease. Disclosure of Interest None declared References Wanebo JE, Lonser RR, Glenn GM, Oldfield EH. 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The cerebellar hemangioblastomas; review of fifty-three cases with special reference to cerebellar cysts and the association of polycythemia. AMA Arch Neurol Psychiatry 1952;67(2):237–252 Silver ML, Hennigar G. Cerebellar hemangioma (hemangioblastoma); a clinicopathological review of 40 cases. J Neurosurg 1952;9(5):484–494 Asthagiri AR, Mehta GU, Zach L, et al. Prospective evaluation of radiosurgery for hemangioblastomas in von Hippel-Lindau disease. Neuro-oncol 2010;12(1):80–86 Mehta GU, Asthagiri AR, Bakhtian KD, Auh S, Oldfield EH, Lonser RR. Functional outcome after resection of spinal cord hemangioblastomas associated with von Hippel-Lindau disease. J Neurosurg Spine 2010;12(3):233–242 Koch C. Spinal dural arteriovenous fistula. Curr Opin Neurol 2006;19(1):69–75 Jellema K, Canta LR, Tijssen CC, van Rooij WJ, Koudstaal PJ, van Gijn J. Spinal dural arteriovenous fistulas: clinical features in 80 patients. J Neurol Neurosurg Psychiatry 2003;74(10):1438–1440 Logue V. Angiomas of the spinal cord: review of the pathogenesis, clinical features, and results of surgery. J Neurol Neurosurg Psychiatry 1979;42(1):1–11 Steinmetz MP, Chow MM, Krishnaney AA, et al. Outcome after the treatment of spinal dural arteriovenous fistulae: a contemporary single-institution series and meta-analysis. Neurosurgery 2004;55(1):77–87, discussion 87–88 Conway JE, Chou D, Clatterbuck RE, Brem H, Long DM, Rigamonti D. Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery 2001;48(1):55-62, discussion 62–63 Wang C, Zhang J, Liu A, Sun B. Surgical management of medullary hemangioblastoma. Report of 47 cases. Surg Neurol 2001;56(4):218-226, discussion 226–227 Zhou LF, Du G, Mao Y, Zhang R. Diagnosis and surgical treatment of brainstem hemangioblastomas. Surg Neurol 2005;63(4):307-315, discussion 315–316

Low-Dose Quetiapine for the Treatment of Delusional Disorder in a Patient With Von Hippel-Lindau Disease

Low-Dose Quetiapine for the Treatment of Delusional Disorder in a Patient With Von Hippel-Lindau Disease

A Detailed Immunohistochemical Analysis of 2 Cases of Papillary Cystadenoma of the Broad Ligament

We report 2 cases of papillary cystadenoma, a rare neoplasm characteristic of patients with Von Hippel-Lindau (VHL) disease, involving the pelvic soft tissues of women and probably arising within the broad ligament. In only one of the women was there a history of VHL disease. The other woman was investigated for VHL disease after the diagnosis of papillary cystadenoma and all tests were negative. There has been debate as to whether papillary cystadenomas in women are of mesonephric (Wolffian) or of Mullerian origin and to investigate this we undertook a detailed immunohistochemical analysis. Both tumors were positive with AE1/3, Ber EP4, epithelial membrane antigen, CK7, CD10, CA125, CA19.9, calretinin, and vimentin. One exhibited focal nuclear staining with WT1 and PAX8. The tumors were negative with estrogen receptor, progesterone receptor, androgen receptor, CK20, CEA, TTF1, inhibin, RCC marker, and hepatocyte nuclear factor 1β. Although favoring a mesonephric origin, the immunohistochemical findings are essentially inconclusive and not definitive for either a mesonephric or a Mullerian origin. We believe that patients found to have papillary cystadenoma should be investigated for VHL disease if there is no history of this. This is the second reported example of papillary cystadenoma in a woman not known to have VHL disease and the first in which investigations have excluded this disease.

Incidence of Multiple Sporadic Renal Cell Carcinomas in Patients Referred for Renal Radiofrequency Ablation: Implications for Imaging Follow-Up

The objective of our study was to report the incidence of multiple sporadic primary renal cell carcinomas (RCCs) in patients referred for radiofrequency ablation (RFA). A retrospective search identified 162 patients (104 men and 58 women; mean age, 74 years) without a history of von Hippel-Lindau disease with a total of 175 tumors treated with RFA for biopsy-proven primary renal malignancies at our institution from 1998 to 2009. Three groups of patients with multiple RCCs were identified: patients with a history of nephrectomy for RCC who had been referred for RFA of a new renal tumor, patients who presented with multiple renal tumors at the time of referral for RFA, and patients who were shown to have developed a new renal tumor on follow-up imaging after RFA. Twenty-eight patients (17%) had multiple biopsy-proven RCCs. Eighteen patients (11%) had undergone prior nephrectomy for surgically proven RCC. The mean interval between prior nephrectomy and RFA referral was 122 months (range, 12-456 months). Seven patients (4%) without a history of nephrectomy presented with two biopsy-proven RCCs at RFA referral. Three patients (2%) who had not undergone nephrectomy and had a solitary RCC at the time of RFA had developed a new biopsy-proven RCC separate from the original treatment site on follow-up imaging after RFA. The mean time to diagnosis from the initial RFA treatment was 52 months (range, 25-89 months). Imaging surveillance of patients referred for renal RFA may be important not only to assess treatment success but also to detect new RCCs.

Abordaje multidisciplinar al tumor de saco endolinfático

Papilar adenocarcinoma of endolymphatic sac is related with Von Hippel Lindau disease at 15% of cases, has a slow growing with a high local aggressiveness, and doesn't metastasize. It causes symptoms of Meniere's syndrome due to the compression that produces at endolymphatic duct. When it presents with hearing loss is usually sudden and irreversible manner. The diagnostic is made with image tests and analysis of its structure with immunohistochemical tests. The elective treatment is surgical remove, and its main complication the perioperative bleeding it can be avoided with preoperative embolization or stereotactic radiation. A case of endolymphatic sac tumour is presented, in a 17-years-old male with unilateral deafness and crisis of rotate vertigo, with family history of Von Hippel-Lindau disease. Perceptive deafness and right vestibular arreflexia are detected at technical exploration. In a petrous bone computer tomography appears a mass at vestibular aqueduct. We performed a petrosectomy with presigmoidal approach and saving of inner ear. Pathological analysis revealed an endolymphatic sac tumour. In patients with a family history of Von Hippel Lindau disease and clinical symptoms of vertigo and normal hearing or with slight hearing loss we should suspect the presence of endolymphatic sac tumor. The clinical presentation of hearing loss can be sudden and irreversible even with negative or inconclusive images. Therefore, a quick action is important for the preservation of this function.

Oncological Outcomes of Partial Nephrectomy for Multifocal Renal Cell Carcinoma Greater Than 4 cm

Despite aggressive screening patients with hereditary renal cancers can present with large multifocal tumors. We present oncological outcomes in patients with hereditary renal cell carcinoma treated with partial nephrectomy for multifocal solid tumors with the largest lesion greater than 4 cm. Between 1995 and 2008 we identified 58 patients with hereditary renal cell carcinoma treated at our institution with partial nephrectomy for solid tumors greater than 4 cm. Data collected included demographic parameters, tumor size, pathological findings and laterality. Overall and metastasis-free survival was calculated based on information from the most recent followup evaluation and imaging. The cohort included 41 patients (71%) with von Hippel-Lindau disease, 10 (17%) with Birt-Hogg-Dubé syndrome and 7 (11%) with hereditary papillary renal carcinoma. Mean age was 43.7 years (range 18 to 63) and mean largest tumor size was 5.3 cm (range 4 to 13). A mean of 6.4 kidney tumors (range 1 to 44) was resected. There was a predominance of nuclear grade 2 tumors (51 cases or 85%) and clear cell histology (44 or 73%), followed by papillary type I histology (7 or 11.7%). Overall and metastasis-free survival rates were 93% and 96.5%, respectively, at a median followup of 45 months (range 2 to 163). Metastasis-free and overall survival of our patients is similar to that in the literature of those who undergo partial nephrectomy for T1B tumors in the sporadic population. Multifocality does not affect oncological outcomes at intermediate followup. Partial nephrectomy can be offered to patients with hereditary disease who present with multifocal tumors greater than 4 cm.

A 41‐YEAR‐OLD WOMAN WITH VON HIPPEL‐LINDAU AND A CEREBELLAR LESION

A 41-year-old woman with a 12-year history of von Hippel-Lindau disease presented with progressive quadriparesis and difficulty swallowing. MRI revealed a well-circumscribed, partially cystic cerebellar neoplasm, consistent with hemangioblastoma. The tumor was resected and the diagnosis of hemangioblastoma confirmed. Embedded within the hemangioblastoma was a small focus of metastatic renal cell carcinoma (RCC). RCC metastatic to a CNS hemangioblastoma is the second most common type of tumor-to-tumor metastasis, which may be due to a number of factors. Proper immunostaining panels are required to clearly identify these cases since both tumor may have similar histology.

Clear cell renal carcinoma presenting as a bleeding cyst in pregnancy: inaugural manifestation of a von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is a dominant autosomal disorder inducing the development of many tumors, such as hemangioblastomas in the central nervous system and retina, cysts or tumors (benign or malignant) in the kidneys and/or the pancreas. We report the case of a pregnant woman who presented with a voluminous hemorrhagic cyst of the right kidney with an exophytic lesion detected in the lower median part of the cyst wall. As an anamnestic inquiry resulted in a familial history of VHL disease, a screening imaging was performed and detected three medullary hemangioblastomas. Considering the active bleeding of the renal cyst and its potential malignancy, a unilateral nephrectomy was carried out after pregnancy interruption. Histological analysis confirmed a multilocular clear cell renal carcinoma. This case underlines the importance of screening procedures such as abdominal ultrasonography and medullary magnetic resonance imaging in all pregnant women with a familial history of VHL disease.

Angioma retiniano como síndrome mascarada de tumor del nervio óptico en la enfermedad de Von Hippel-Lindau

A 35-year-old man with a family history of von Hippel-Lindau disease was diagnosed to have two retinal hemangiomas in the right eye and another in the left eye. The hemangiomas were treated with cryotherapy and laser photocoagulation respectively. Despite apparent good resolution of the retinal lesions, progressive visual loss was observed. An MRI was then performed and showed bilateral tumoral lesions of the optic nerve compatible with a glioma, meningioma or hemangioblastoma. Currently the visual acuity in his right eye is hand movement, and is 0.6 in the left eye. The presence of the retinal hemangiomas delayed the diagnosis of an optic nerve tumor in this patient.

Capillary hemangioblastoma of soft tissue: report of a case and review of the literature

Capillary hemangioblastoma (CH) is a tumor of unknown histogenesis that arises primarily in the posterior cranial fossa, either as a sporadic event or in association with von Hippel-Lindau disease. To date, only 6 examples of a tumor with morphological features of CH arising in the somatic soft tissues have been documented in case reports and small series, and 3 of these tumors were associated with a peripheral nerve. Herein, we report a case of CH arising in the gastrocnemius muscle and not associated with a peripheral nerve in a 53-year-old woman with no clinical stigmata or family history of von Hippel-Lindau disease.

Laparoscopic Management of Extra-Adrenal Pheochromocytoma

Laparoscopic management of extra-adrenal pheochromocytoma presents a unique surgical challenge due to variable anatomical presentation and potential catecholamine surge during operative manipulation. We report our experience with laparoscopic removal of extra-adrenal pheochromocytomas. Between 1999 and 2002, 5 patients presented with retroperitoneal extra-adrenal pheochromocytomas. Of the patients 2 had a history of von Hippel-Lindau disease, and the remaining 3 patients were diagnosed with sporadic extra-adrenal pheochromocytoma during hypertension evaluation. Although 4 patients had a history of hypertension, only 2 reported symptoms (episodic flushing, headaches, blurred vision) associated with excess catecholamine production. All patients had markedly increased preoperative urinary and plasma normetanephrine and/or norepinephrine levels, and 3 had positive I131 metaiodobenzylguanidine scan. In each case tumor was accurately identified on computerized tomography before surgery. Laparoscopic resection of extra-adrenal pheochromocytoma was successful in 4 patients. Open conversion was required in 1 patient, who also had von Hippel-Lindau related bilateral adrenal pheochromocytomas due to significant adhesion of the extra-adrenal tumor to the aorta and renal hilum, and a concern for possible local invasion. Mean laparoscopic operative time and blood loss were 273 minutes (range 240 to 350) and 119 cc (range 75 to 200), respectively. Three 10 mm ports in a standard triangular fashion were used for the left side tumors, in which the tumors were found lateral to the aorta. For the right side tumors located either in the inter-aortacaval or para-caval region, a fourth port (10 mm) was inserted for liver retraction as needed. Laparoscopic ultrasound was used to localize the tumor and to assess the retroperitoneum for possible metastasis (none detected) in 3 cases. None of the patients had a hypertensive crisis intraoperatively, and all had unremarkable postoperative recovery with an average hospital stay of 3.8 days (range 3 to 4). Plasma and/or urinary norepinephrine and normetanephrine levels returned to normal range postoperatively in all cases. One patient was noted to have left lower extremity lymphedema and gluteal hematoma due to a positional injury related to prolonged pressure from the operating table and was treated conservatively. There has been no tumor recurrence at a median followup of 14 months (range 9 to 36). With careful surgical planning and appropriate preoperative pharmacological blockade, laparoscopic surgery can be safely performed in patients with extra-adrenal pheochromocytomas with minimal morbidity. Laparoscopic ultrasound may be helpful in precise localization and evaluation of tumor extension.

Imaging-guided radiofrequency ablation of solid renal tumors.

We performed a retrospective review of imaging-guided radiofrequency ablation of solid renal tumors. Since May 2000, 35 tumors in 20 patients have been treated with radiofrequency ablation. The size range of treated tumors was 0.9-3.6 cm (mean, 1.7 cm). Reasons for patient referrals were a prior partial or total nephrectomy (nine patients), a comorbidity excluding nephrectomy or partial nephrectomy (10 patients), or a treatment alterative to nephron-sparing surgery (one patient who refused surgery). Tumors were classified as exophytic, intraparenchymal, or central. Sixteen patients had 31 lesions that showed serial growth on CT or MR imaging. Of these 16 patients, four patients with 10 lesions had a history of renal cell carcinoma, and two patients with 11 lesions had a history of von Hippel-Lindau disease. Four patients had incidental solid masses, two of which were biopsied and shown to represent renal cell carcinoma, and the remaining two masses were presumed malignant on the basis of imaging features. Successful ablation was regarded as any lesion showing less than 10 H of contrast enhancement on CT or no qualitative evidence of enhancement after IV gadolinium contrast-enhanced MR imaging. Of the 35 tumors, 22 were exophytic and 13 were intraparenchymal. Twenty-seven of the 35 were treated percutaneously using either sonography (n = 22) or CT (n = 5). Two patients had eight tumors treated intraoperatively using sonography. Patients were followed up with contrast-enhanced CT (n = 18), MR imaging (n = 5), or both (n = 5) with a follow-up range of 1-23 months (mean, 9 months). No residual or recurrent tumor and no major side effects were seen. Preliminary results with radiofrequency ablation of exophytic and intraparenchymal renal tumors are promising. Radiofrequency ablation is not associated with significant side effects. Further follow-up is necessary to determine the long-term efficacy of radiofrequency ablation.

Molecular genetic alterations in adrenal and extra-adrenal pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas are neuroendocrine neoplasias of neural crest origin. Genetic mutations that are characterized in other human neoplasms are rarely seen in these tumors. About 10% of the patients with pheochromocytomas and paragangliomas present with a family history of von Hippel-Lindau disease (VHL), Multiple endocrine neoplasia type 2 (MEN2), one of the three familial paraganglioma syndromes (PGL; PGL1, PGL3, PGL4), or neurofibromatosis type 1 (NF1). In an even higher percentage, a genetic predisposition is involved in the development of these tumors. The genes of hereditary tumor syndromes such as the aforementioned ones are also ideal to study the molecular pathogenesis in the sporadic counterparts. Many studies have been undertaken to identify important secondary genetic events that contribute to the tumorigenesis of pheochromocytoma or paraganglioma, but a comprehensive review of these data is lacking. Recent findings of CGH and LOH studies provided new starting points to unravel the pathogenesis and progression of these tumors. This review presents an overview of our current understanding of the molecular pathogenesis of pheochromocytoma and paraganglioma.

Treatment of retinal capillary hemangioma

Objective To report on the methods of treatment and the visual outcome of eyes with retinal capillary hemangioma (RCH). Design Retrospective consecutive noncomparative case series. Participants Data on 68 patients with RCH were reviewed for the methods of treatment and visual outcome. Methods Statistical analysis using cumulative multinomial logistic regression (generalized estimating equations) was performed to determine significant predictors of visual outcome. Results Among 68 patients with RCH with von Hippel-Lindau disease (n = 31) and without von Hippel-Lindau disease (n = 37), we identified 174 RCH in 86 eyes. The overall median age at diagnosis of RCH was 30.8 years (range, 2.8–73.8 years). The RCH was bilateral in 18 cases (26%), and a family history of von Hippel-Lindau disease was positive in 19 cases (28%). Twenty-nine of the tumors (17%) touched the optic disc and were classified as juxtapapillary RCH, and the remaining 145 (83%) were extrapapillary in location. Ninety-nine (58%) RCH were 1.5 mm or smaller in size. The RCH were initially managed by observation (46%), laser photocoagulation (25%), or cryotherapy (23%). Small RCH (≤1.5 mm in size; 63 of 99; 64%) and those touching the optic disc (14 of 29; 48%) were more likely to be initially observed. Sixty-three (82%) of the 77 RCH that were initially observed remained stable for a median follow-up of 84 months. The remaining 14 progressed and were successfully controlled with laser photocoagulation or cryotherapy. Either laser photocoagulation or cryotherapy was effective as the sole method of treatment in controlling 74% (26 of 35) and 72% (28 of 39) of extrapapillary tumors, with a mean number of 1.2 and 1.1 sessions, respectively. In a multivariate model, the only variables that were significantly related to final vision of ≤ 20/400 were poor initial vision ( P = 0.01, odds ratio [OR], 8.5; 95% confidence interval [CI], 1.7,42) and the presence of retinal/vitreous hemorrhage ( P = 0.024, OR, 5.7; 95% CI, 1.3, 25.6). Conclusions RCH can be safely observed initially in selected cases. Laser photocoagulation and cryotherapy are the mainstays of treatment in most cases. Early detection of RCH and treatment before the onset of severe visual loss is recommended.