Spotlight Case: Do I Have Cancer?
A 20-year-old woman from Honduras presented with decreased vision in the left eye over the past 2 months. She reported transient episodes of complete bilateral visual blackout, as well as intermittent headaches for 12 months prior to examination. She also stated that she had fainted 3 times in the past week.
Her medical history was significant for mild sensorineural hearing loss, for which she was evaluated 3 years prior. Studies at the time were inconclusive. Family history was significant for a maternal uncle with liver cancer and a maternal grandmother with breast cancer.
The patient informed us that she was seeking treatment because of an urgent referral from her physician in Honduras. She nervously asked us, “Do I have cancer?”
Visual acuity was 20/20 in the right eye and 20/400 in the left eye. A relative afferent pupillary defect was present in the left eye. Fundus photos, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) images are shown in Figures 1-5.
Figure 1: Color fundus photo of the right eye demonstrated blurred disc margins.
Figure 2: Color fundus photo of the left eye demonstrated blurred disc margins and a prominent vitreous ring overlying the nerve and nasal macula. Additionally there was abnormal vascularity in the retina adjacent to the fovea.
What’s your diagnosis?
This patient was diagnosed with Von Hippel-Lindau (VHL) syndrome based on the presence of retinal capillary hemangiomas in both eyes, as well as central nervous system (CNS) hemangiomas.
The presence of papilledema and cerebellar hemangiomas prompted urgent neurosurgical intervention, and a posterior fossa craniotomy with preoperative embolization for the 2 lesions was performed. The patient subsequently developed a pseudomeningocele, for which a ventriculoperitoneal shunt was created.
Argon laser photocoagulation was applied to the peripheral retinal hemangiomas in the right eye, but treatment was withheld for the left eye due to the juxtapapillary location of the hemangioma.
CT scan of the abdomen was normal, as were blood pressure and urinalysis.
She has been stable for 7 months following initial presentation. The peripheral retinal capillary hemangiomas in the right eye were treated with laser photocoagulation a second time, with good control. Following the neurosurgical procedures alone, the juxtapapillary lesion in the left eye appeared smaller in size and the tractional retinal detachment was improved, which is a common occurrence in vitreoretinal traction associated with VHL.
Visual acuity has remained at 20/20 in the right eye and improved to 20/70 in the left. Follow-up photos, OCT, and wide-field fluorescein angiography (FA) are shown in Figures 6-9.
Figure 9: Wide-field FA easily demonstrates small new retinal capillary hemangiomas in the left eye.
VHL comprises retinal and CNS hemangiomas, pheochromocytoma, hypernephroma, pancreatic cysts, pancreatic neuroendocrine tumors, endolymphatic sac tumors, and renal cell carcinomas, among other lesions.[1,2]
The incidence of VHL is approximately 1/36,000 live births, and a patient is considered to have the condition when either a retinal or CNS hemangioma occurs with 1 or more visceral cysts or tumors, or when a single lesion is found in an at-risk relative.
The most common findings are retinal and cerebellar hemangiomas, which are found in approximately 55% of cases. Renal cell carcinoma (RCC) occurs in approximately 25% of cases, while pheochromocytomas may occur in close to 20%. The genotypic variations between families result in significant heterogeneity in the presentations of the various tumors.
While most cases are inherited in an autosomal dominant fashion, a new germline mutation occurs in 20% of cases. As in retinoblastoma, the emergence of tumors follows inactivation of the wild-type allele of the VHL gene (Knudson’s 2-hit hypothesis).
As a tumor-suppressor gene, VHL has been studied as a model of tumor angiogenesis. VHL is the primary cause of inherited RCC, and interestingly, somatic VHL inactivation is a hallmark of most cases of sporadic RCC.
Retinal capillary hemangiomas have been treated in several ways:[3-6]
- Argon and diode laser therapy is highly effective in small tumors. Treatments are often performed over several sessions. We generally treat the tumor itself without targeting the adjacent feeder vessels, which may bleed or lead to inflammation, choroidal neovascularization, or tractional detachments if treated too aggressively.
- Cryotherapy and brachytherapy have been successfully employed for larger lesions.
- En bloc surgical resections and vitrectomies have also been performed successfully for larger lesions that were refractory to other therapies.
- Recently, anti-VEGF intravitreal injections have been employed with mixed results.
Prognosis is variable and depends largely on tumor location. Life expectancy is shortened at 50 years, with mortality primarily due to RCC, pheochromocytomas, and CNS lesions.[1-4] Fortunately, the prevalence of severe bilateral vision loss is low, at approximately 5%.
- Our patient was relieved to find out that she did not have cancer; however, VHL is a serious condition that can lead to tumors in multiple organs in the body. Mutations in the gene may also cause renal cell carcinoma.
- If a patient presents with a solitary retinal capillary hemangioma, a systemic workup must be performed that includes:
- Blood pressure monitoring and urinalysis to evaluate for pheochromocytoma
- Brain and spinal cord MRI
- Abdominal imaging with ultrasonography, CT, or MRI
In a patient newly diagnosed with VHL, genetic testing should be offered to family members, as current methods are both highly sensitive and specific for VHL mutations.
Retinal capillary hemangiomas are generally well controlled with laser photocoagulation if treated early. Wide-field FA is an excellent tool to search for lesions that may be difficult to detect with biomicroscopy.
- Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel–Lindau disease. Q J Med. 1990;77(283):1151-1163.
- Lonser RR, Glenn GM, Walther M, et al. von Hippel–Lindau disease. Lancet. 2003;361(9374):2059-2067.
- Richard S, Gardie B, Couve S, Gad S. Von Hippel-Lindau: how a rare disease illuminates cancer biology [published online May 30, 2012]. Semin Cancer Biol. 2013;23(1):26-37. doi:10.1016/j.semcancer.2012.05.005.
- Singh AD, Shields CL, Shields JA. von Hippel-Lindau disease. Surv Ophthalmol. 2001;46(2):117-142.
- Wong WT, Liang KJ, Hammel K, Coleman HR, Chew EY. Intravitreal ranibizumab therapy for retinal capillary hemangioblastoma related to von Hippel-Lindau disease [published online September 11, 2008]. Ophthalmol. 2008;115(11):1957-1964. doi:10.1016/j.ophtha.2008.04.033.
- Singh AD, Agarwal A. Retinal Capillary Hemangioma. In: Agarwal A. Gass’ Atlas of Macular Diseases. 5th ed. New York, NY: Elsevier; 2012:1128-1137.
Dr. Chen - None.
Dr. Harbour - CASTLE BIOSCIENCES INC: Intellectual Property Rights.
Dr. Berrocal - THROMBOGENICS, INC: Advisory Board, Honoraria; GENENTECH, INC: Advisory Board, Honoraria; ALCON: Speaker, Honoraria.
Dr. Hau - SEQUENOM: Speaker, Honoraria; THROMBOGENICS, INC: Other, Honoraria.
Dr. Choudhry - None.