The female has a history of bilateral retinal hemangioblastomas, is currently experiencing symptoms of a pheochromocytoma, and has a mutation on chromosome 3p suggesting a diagnosis of von Hippel-Lindau (VHL) disease. Patients with mutations in the VHL gene are at risk of developing clear cell renal cell carcinoma.
von Hippel-Lindau disease is a rare, autosomal dominant neurocutaneous disease that results in cavernous hemangiomas in the skin, mucosa, and viscera. It results from a mutated VHL gene on chromosome 3p, which normally acts as a tumor suppressor gene. VHL disease is associated with bilateral renal cell carcinomas, retinal and cranial/spinal hemangioblastomas, pheochromocytomas and cysts (pancreas, kidney, and reproductive tract). The hemangioblastomas are typically not cancerous, but they can compress the brain and spinal cord resulting in headaches, vomiting, paralysis, and ataxia.
Carlijn et al. review the diagnosis of VHL disease, which is usually suspected when an individual has lesions such as "hemangioblastomas, multiple renal cysts and renal cell carcinoma, pheochromocytoma, and endolymphatic sac tumors." Diagnosis is confirmed with genetic testing revealing mutations in the VHL gene.
Carlijn et al. review the management of VHL disease. Hemangioblastomas are removed surgically to prevent the symptoms of compression if the tumors become large. If the patient develops renal cell carcinoma, then nephron-sparing/partial nephrectomy surgery is performed if possible. Pheochromocytomas are typically removed, but partial adrenalectomy is preferable. Annual surveillance is recommended as early removal of tumors can spare the individual many of the complications of the disease.
Illustration A is a schematic diagram showing the various organs affected by VHL disease. Illustration B is an T2 weighted MRI showing a hemangioblastoma in the cerebellum (arrow). Illustration C is an H&E staining of a cerebellar hemangioblastoma. Notice the high vascularity and stromal cells (large and pale) with lipid-laden vacuoles.
Answer 2,3: Mutations in retinoblastoma 1 (RB1) increase the risk of developing retinoblastoma and osteosarcoma.
Answer 4,5: Mutations in breast cancer 1 (BRCA1) increase the risk of developing breast and ovarian cancer.
Frantzen C, Links TP, Giles RH. Von Hippel-Lindau Disease. 2000 May 17 [Updated 2012 Jun 21]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1463/
PMID:20301636 (Link to Abstract)