Polycythemia Secondary to Renal Hemangioblastoma: A Case Report and Literature Review.

Secondary polycythemia is a paraneoplastic syndrome observed in tumors with excessive erythropoietin (EPO) production. Renal cell carcinoma (RCC) and cerebellar hemangioblastoma are the 2 most well-known tumors to induce secondary polycythemia. Hemangioblastomas occurring in the kidney are rare. In this work we present a case of renal hemangioblastoma that caused erythrocytosis in a 19-year-old man. We demonstrated intratumoural EPO production by immunohistochemistry, and conducted whole-exome sequencing to evaluate possible genetic alterations that reported to induce tumor-related polycythemia. In spite of an indolent clinical behavior, renal hemangioblastoma is difficult to differentiate from RCC not only clinically, but also histopathologically. Given that RCC is the most well-known renal tumor to induce erythrocytosis, the uncommon manifestation of polycythemia in renal hemangioblastoma, as shown in our case, can cause further diagnostic challenges. Renal hemangioblastoma should be listed in the differential diagnoses of renal tumors presenting with erythrocytosis, apart from the most common RCC.

Hemangioblastomas of the cauda equina: Clinical features and long-term surgical outcomes.

BACKGROUND: Spinal hemangioblastomas (HBs) that involving cauda equina are rare. Data on clinical characteristics and long-term intervention outcomes of patients harboring cauda equina HBs remain lacking due to its scarcity. OBJECTIVE: This study aims to present the clinical-radiological features and treatment results of this rare pathology by using cases from a single center. METHODS: A review of demographic data and intervention outcomes of patients harboring cauda equina HBs in our department between 2009 and 2020 was retrospectively carried out. RESULTS: Ten consecutive adult patients were incorporated, with a slight female predominance (n = 6, 60%). The mean age was 39.9 ± 14.7 (range: 18-58) years. Six patients (60%) had von Hippel‒Lindau (VHL) syndrome and showed multiple symptoms and severe neurological deficits, while 4 (40%) were in the sporadic group and only presented pain symptoms. During follow-up, 3 patients (30%) experienced lesion relapse and underwent repeated surgery. Favorable outcomes were achieved in all patients. CONCLUSION: Cauda equina HBs are rare spinal vascular lesions that should be differentiated from other lumbar canal lesions. Total surgical resection is the main treatment modality and can benefit patients, even recurrent patients. The treatment outcome is usually satisfactory, especially in sporadic cases.

Surgical and visual outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma.

Purpose: We evaluated the anatomical and functional outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma (RCH). Methods: This was a retrospective case series of 15 patients (16 eyes) with tractional or combined retinal detachment (RD) managed with pars plana vitrectomy and tumor endoresection (ER) with/without feeder vessel ligation. Results: The mean age at the time of surgery was 30 years (range, 14-46 years). The most common tumor locations were inferotemporal (six eyes) and temporal (six eyes) quadrants. Indications for surgery included exudative RD with fibrovascular proliferation (eight eyes), combined RD (five eyes), vitreous hemorrhage (four eyes), and rhegmatogenous RD (two eyes). Tumor destruction was performed with laser and/or cryotherapy in nine eyes (57%) and ER in seven eyes (43%). Feeder vessel was ligated and cauterized in 10 (63%) and six eyes (37%), respectively. Anatomical success after initial surgery was 50% (eight eyes), which improved to 88% (14 eyes) after they underwent a repeat procedure for recurrent RD (eight eyes). At the last visit, visual acuity improved in seven eyes (44%), was stable in four eyes (25%), and worsened in five eyes (31%) with a mean follow-up of 29 months (6-79 months). Comparison between the ER group and the laser/cryotherapy group revealed no significant difference in final retinal reattachment rate (89% vs. 86%, P > 0.05), with better visual outcomes in laser/cryotherapy group (57% vs. 78%, P < 0.05). Conclusion: Pars plana vitrectomy with/without tumor endoresection can be a safe and effective treatment option for complex RCHs, achieving good tumor control and anatomical success with limited functional success.

Clear Cell Renal Cell Carcinoma with Hemangioblastoma-Like Features: A Case Report.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) constitutes the most frequently encountered sporadic class of kidney cancer in adults. Recently, a rare form of clear cell kidney cancer known as ccRCC with hemangioblastoma-like features was proposed, with unique immunological characteristics and a good prognosis. The tumor expressed alpha-inhibin and carbonic anhydrase Ⅸ (CA9) as examined by immunohistochemistry. METHODS: Herein, we report a clinical instance of ccRCC with hemangioblastoma-like features. A 49-year-old woman presenting with a chief complaint of hematuria underwent a comprehensive and meticulous assessment. Imaging findings indicated the presence of a mass in the right kidney. Subsequently, she underwent a partial nephrectomy. RESULTS: Histopathological analysis of the resected specimen confirmed the presence of ccRCC with hemangioblastoma-like features. The patient was discharged from the hospital six days post-surgery and could resume her daily activities. During a one-year follow-up after surgery, no signs of recurrence were detected. CONCLUSIONS: This case demonstrates the importance of including ccRCC with hemangioblastoma-like features in the differential diagnosis of renal masses in patients with hematuria, and suggests partial nephrectomy as an effective treatment modality for this rare subtype of renal cell carcinoma. However, because of the small number of reported cases and insufficient follow-up time, further investigation is necessary to determine the optimal therapeutic approach and to identify the molecular and genetic characteristics of this tumor.

Clinicopathological analysis of extraneural sporadic haemangioblastoma occurring in the tongue.

Haemangioblastoma is a morphologically distinctive tumour with uncertain histogenesis, typically occurring in the cerebellum, brain stem or spinal cord and less commonly in extraneural locations. Here, we present a case of haemangioblastoma occurring in the tongue, which is the first reported case in terms of the pathogenic site. The tumour was morphologically indistinguishable from central nervous system haemangioblastoma, that is, neoplastic stromal cells with cytoplasmic vacuolisation and abundant small vessels. Immunohistochemical studies revealed that the tumour cells were positive for S100, NSE, CD56, Syn, EMA, vimentin and α-inhibin, while negative for CK, SMA, factor Ⅷ, D2-40 and GFAP. Immunostainings for CD34 and CD31 outlined the rich and delicate vascular channels. Ki-67 expression was presented in approximately 3% of tumour cells. Primary haemangioblastoma has not been previously described at this site, and this case emphasises the need to consider haemangioblastoma in the differential diagnoses of neoplasms occurring in the tongue.

Novel Manifestation of Retinal Hemangioblastomas Detected by OCT Angiography in von Hippel-Lindau Disease.

PURPOSE: To elucidate the clinical characteristics of atypical retinal vascular proliferation in patients with von Hippel-Lindau (VHL) disease using OCT angiography (OCTA). DESIGN: Prospective, observational study. PARTICIPANTS: Fifty-seven consecutive patients with a diagnosis of VHL disease who visited Kyoto University Hospital between January 2019 and March 2022. METHODS: Retinal hemangioblastomas (RHs) were assessed using multimodal imaging including OCTA. Retinal hemangioblastomas were classified into 2 phenotypes: nodular and flat. Nodular RHs were defined as typical RHs that were globular, well-circumscribed tumors, often accompanied with dilated feeder arterioles and draining venules. Flat RHs lacked a protruded red or colored mass, had variable and indistinct borders, and were not accompanied with feeder and draining vessels. MAIN OUTCOME MEASURES: The prevalence, distribution, and description of atypical flat RHs. RESULTS: Among 57 consecutive patients with VHL disease, 37 patients (64.9%) showed RHs in at least 1 eye. Bilateral RHs were seen in 23 patients (62.2%). Among 58 eyes of 37 patients with RHs, typical nodular RHs were detected in 54 eyes. Nodular RHs were seen mainly in the peripheral retina and occasionally in the peripapillary region, and they showed exudative changes in some cases. Flat RHs were detected in 7 eyes (12.1%). Four eyes showed only flat RHs, and 3 eyes showed both types in the same eye. Most flat RHs appeared as retinal hemorrhages or faint flat abnormal retinal vessels in the inner retina on the fundus examination, often within the macula area or peripapillary. In all eyes with flat RHs, OCTA showed abundant blood flow in the lesions. OCT revealed that flat RHs were seen mainly between the retinal nerve fiber layer and the ganglion cell layer, and occasionally within the inner nuclear layer. During a mean follow-up period of 20.4 ± 15.0 months, no flat RHs accompanied exudative change, tractional retinal detachment, or progression in size. CONCLUSIONS: Patients with VHL disease can demonstrate 2 distinct types of RHs: the classic nodular type and an atypical flat type. OCT angiography can be useful in improving the detection of atypical flat RHs, which can be difficult to detect clinically. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

How 'eye' helped in von Hippel-Lindau syndrome.

BACKGROUND: Von Hippel-Lindau syndrome is a rare autosomal dominantly inherited multisystemic oncologic syndrome, presenting predominantly with angiomatosis in embryologically similar neurologic tissue such as retina, cerebellum and adrenals. Retinal hemangioblastomas are the hallmark ophthalmic finding. In this case report, we describe the importance of timely diagnosis, thorough systemic examination and treatment of bilaterally asymmetrical retinal hemangioblastomas in a young adult male. CASE PRESENTATION: A 31-year-old male presented with painless diminution of vision in both eyes, associated with eyestrain and headache. Multiple asymmetric retinal lesions and dilated feeder vessels were noted on ophthalmoscopic examination and confirmed by fluorescein angiography to be retinal hemangioblastomas. Comprehensive systemic examination revealed cerebellar hemangioblastomas and multiple pancreatic and renal cysts. Treatment of retinal lesions was done by combination therapy of argon laser photocoagulation and cryopexy, which lead to a good visual outcome. Subsequently, neurosurgical resection of cerebellar hemangioblastoma proved to be lifesaving for the patient. CONCLUSION: RHBs are the earliest, easiest and the most frequently detected manifestation of VHL. Identification of ocular manifestations play a pivotal role in early diagnosis and timely intervention in VHL syndrome, thereby significantly reducing associated morbidity and mortality. Therefore, an ophthalmologist's role is crucial in the management of these potentially deadly tumours.

Extraneuraxial Hemangioblastoma: An Unusual Soft Tissue Neoplasm that Mimics More Common Entities but Carries Distinct Clinical Implications.

Hemangioblastoma, one of the characteristic tumors associated with Von Hippel-Lindau (VHL) disease, most often presents in the central nervous system (CNS) but can uncommonly arise in extraneuraxial, or previously referred to as peripheral, locations. Without the clinical context of known VHL disease, hemangioblastoma may not enter the differential for a soft tissue mass outside the CNS. Here, we present two patients with diagnostically challenging extraneuraxial hemangioblastoma to highlight the importance of considering this entity within the differential diagnosis of soft tissue neoplasms containing clear cells and delicate vasculature. We review the relevant diagnostic features, including a suggested immunohistochemical panel, along with the potential associated clinical implications of making this diagnosis. It is recommended that affected patients be offered genetic counseling to assess for underlying VHL disease.

Hamartomas of the Retina and Optic Disc.

Hamartomas are local malformation of cells that demonstrate abnormal proliferation in the area where they are normally present. Retinal and optic disc hamartomas include astrocytic hamartoma, congenital hypertrophy of the retinal pigment epithelium (CHRPE), simple congenital hamartoma of the retinal pigment epithelium (CSHRPE), combined hamartoma of the retina and retinal pigment epithelium (CHRRPE), retinal hemangioblastoma (retinal capillary hemangioma), and retinal cavernous hemangioma. Retinal and optic disc hamartomas can be observed sporadically as well as with systemic associations. Astrocytic hamartoma usually appears as a flat, transparent yellowish lesion. CHRPE is a round, pigmented, and flat lesion. CSHRPE usually presents as a dark black macular tumor. CHRRPE consists of vascular, glial, and pigment epithelial components, which can demonstrate peripapillary, macular, and peripheral localization. Retinal hemangioblastoma is a vascular tumor, red-pink in color with tortuous and dilated afferent and efferent vessels, typically located in the peripheral retina or optic disc. Retinal cavernous hemangioma is characterized by the formation of thin-walled saccular angiomatous structures in the retina or optic nerve head resembling concord grapes. Ultrasonography, fundus autofluorescence, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography methods are used in the diagnosis of retinal and optic disc hamartomas. Some retinal and optic disc hamartomas do not require treatment. However, complications including vitreous hemorrhage, macular exudation, retinal detachment, macular hole, epiretinal membrane, and choroidal neovascularization require treatment.

Purely cystic meningioma: Case report and systematic review of the literature.

Meningiomas are the most common benign intracranial tumors. They are generally asymptomatic, and discovered incidentally during cerebral imaging. The vast majority of meningiomas are solid, highly cellular and well-vascularized neoplasms. However, in several cases, they can be partially or, even rarely, almost completely cystic making their differential diagnosis and management challenging. In this paper, we present the rare case of a 59-year-old female patient, presenting with persistent headaches, who was diagnosed with a left parieto-occipital purely cystic lesion. The patient underwent a complete resection of this cystic lesion because of increasing headaches and volumetric progression. Interestingly, the histological assessment confirmed a cystic WHO grade I meningioma. The evolution was favorable and there was no recurrence after 3 years of follow-up. We also perform a systematic review of the literature concerning purely cystic meningiomas and we discuss the particular histological features of cystic meningiomas as well as the possible pathogenesis. This challenging clinical entity can easily be misdiagnosed as hemangioblastoma or glial/metastatic tumor with cystic component.

Assessment of Retinal Changes Following Intravitreal Aflibercept in 2 Patients With Von Hippel-Lindau Disease-Related Retinal Capillary Hemangioblastoma.

This case report of 2 patients describes peripheral Von Hippel-Lindau disease associated with a series of aflibercept injections.

Clinical and Genetic Characteristics of Retinal Capillary Hemangioblastoma in Korean Patients.

PURPOSE: We investigated the clinical features of Korean patients with retinal capillary hemangioblastoma (RCH) and genetic variants of the von Hippel-Lindau (VHL) gene. METHODS: A retrospective analysis was performed on patients with RCH from 2003 to 2021 at Seoul National University Bundang Hospital. Sporadic and hereditary RCH associated with VHL disease were classified based on the specific tumors and family history. Clinical features, including the location and number of RCH and bilateral involvement, were investigated. Multiplex ligation-dependent probe amplification and direct sequencing targeting the VHL gene were performed for six RCH cases associated with VHL disease. RESULTS: A total of 18 patients (23 eyes) were enrolled in this study. The mean age at diagnosis was 37 ± 15 years. Twelve patients had hereditary RCH associated with VHL disease, and six patients had sporadic RCH. All five patients with bilateral RCH were clinically diagnosed with VHL disease, and 13 patients had unilateral RCH. Juxtapapillary RCH was only observed in patients with VHL. The most common complication of RCH was the epiretinal membrane, followed by the subretinal fluid. Pathogenic variants were identified in four patients. All three patients with type 1 VHL had the well-known missense mutation p.Glu70Lys, and one patient with type 2 VHL had the nonsense mutation p.Trp88Ter. CONCLUSIONS: In Korean patients with RCH, bilateral involvement and juxtapapillary RCH are highly likely to be associated with VHL disease. Because RCH may be the first clinical manifestation in patients with VHL, active genetic testing of the VHL gene and systemic evaluation are required.

Primary Optic Disc Tumors - Case Series and Literature Overview. / Primäre Papillentumoren ­ Fallserie und Literaturüberblick.

PURPOSE: Primary optic disc tumors are often a challenge for ophthalmologists. They have very different appearances, and many primary optic disc tumors are associated with syndromic diseases (especially phakomatoses). Because of the rarity of primary optic disc tumors, classification and assessment are often difficult. MATERIAL AND METHODS: A systematic search in the electronic patient files (period 01.01.2015 - 01.06.2022) of the Department of Ophthalmology of the University of Münster Medical Center for patients with primary optic disc tumors was performed. For each tumor entity, exemplary cases were selected, which are presented here in detail. The criteria for the exemplary case selection were a clear diagnosis, the presence of suitable image material and follow-up examinations in our clinic. RESULTS: The search yielded seven cases with three different primary tumor entities in the optic disc region (capillary hemangioblastoma, astrocytic hamartoma and melanocytoma). Four patients were selected as examples and are presented here: two cases for capillary hemangioblastoma (one isolated and the other in the context of Von-Hippel-Lindau syndrome) and one case each for astrocytic hamartoma and melanocytoma). We outline the further diagnosis and the course of the disease and we give an overview of the essential features of the underlying tumors in each case. CONCLUSION: The knowledge of the different primary tumors of the optic disc is necessary for a correct diagnosis and for the differentiation from malignant processes and optic disc anomalies. In many cases, further interdisciplinary diagnostics are necessary. Multimodal imaging is helpful and a referral to a center for ocular tumors is worth considering.

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. Online Video Link: https://youtu.be/CkoqWEnaPB8.

von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance.

von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families. This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations. RECOMMENDATIONS: vHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.

Combined therapy guided by multimodal imaging of fifteen retinal capillary hemangioblastomas in a monocular Von Hippel- Lindau syndrome case report.

BACKGROUND: To report the multimodal imaging and treatment of fifteen retinal capillary hemangioblastomas (RCHs) associated with Von Hippel-Lindau syndrome in a monocular patient during a long-term following-up, which supply high-resolution exquisite SS-OCTA images (VG200; SVision Imaging, Ltd., Luoyang, China) and management experience about multiple RCHs. CASE PRESENTATION: A 34-year-old monocular male patient complained decreased visual acuity (20/100) without pain and redness in the left eye five years ago. Von Hippel-Lindau syndrome were diagnosed with genetic testing. He, his son and daughter all carried a heterozygosity missense variant c.499C > T (p. Arg167Trp) in the Hg19 gene, a VHL gene located in Chr3:10,191,506. Fifteen RCHs were identified by the application of multimodal imaging, which including fundus photo, fundus autofluorescence (FAF), B-scan ultrasonography (US), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) and swept-source optical coherence tomography angiography (SS-OCTA). Transscleral cryotherapy and laser photocoagulation were performed to destroy the largest RCH with the size of 4 PD in diameter. Laser photocoagulation was conducted to seal the middle or tiny RCHs (< 1.5 PD) and their nourishing vessels. The retinal edema and exudative macular detachment were successfully relieved by intraocular injection of bevacizumab for 5 times. The RCHs in the left eye responded well to these treatments and best corrected visual acuity was 20/25 for three years. Three-month recall visits were recommended for him. CONCLUSION: For multiple retinal capillary hemangioblastomas in monocular patients, precise combined therapy guided by multimodal imaging has a profound impact on the management of new and recurrent RCHs.