Von Hippel-Lindau Syndrome

Implications for Nursing Care

Suzanne M. Mahon, RN, DNSc, AOCN®, APNG; Laura Waldman, MS, CGC


Oncol Nurs Forum. 2012;39(6):533-536. 

In This Article

Commentary on the Cases

Case 1 illustrates several red flags indicative of VHL. Hemangioblastomas are highly vascular, histologically benign tumors that occur in the cerebellum (80% of cases) and the spinal cord (20% of cases) (Farrell & Plotkin, 2007). In 50%–79% of patients with VHL, hemangioblastomas are the presenting symptom with an average age of onset of 30 years (Lindor et al., 2008). The presentation of two separate hemangioblastomas even in the absence of family history meets diagnostic criteria for VHL (see Figure 1). The fact that S.E.'s brother had a cerebellar hemangioblastoma also points toward VHL. In addition, the patient's father's history of high blood pressure and stroke may have been from an underlying pheochromocytoma estimated to occur in 3.5%–17% of patients with VHL. A pheochromocytoma is a tumor occurring in the adrenal gland tissue that results in the release of excessive epinephrine and norepinephrine causing an increase in heart rate, metabolism, and blood pressure. These pheochromocytomas rarely undergo malignant transformation (Lindor et al., 2008).

Figure 1.

Indications for Referral for von Hippel-Lindau (VHL) Genetic Testing
Note. Based on information from Frantzen et al., 2009; Lindor et al., 2008.

Clear cell renal carcinoma occurs in about 35%–75% of individuals with VHL (Lindor et al., 2008; Meister, Choyke, Anderson, & Patel, 2009). The clear cell renal cancers often are multiple and bilateral and may arise within complex cysts (Reed & Parekh, 2009). The mean age at diagnosis is 40 years. Early identification of renal cancers is critical because they account for 50% of the deaths in patients with VHL (Shehata et al., 2008).

Renal cancer treatment focuses on preserving renal function and limiting intervention until solid tumors reach 3 cm in diameter on imaging studies (Lindor et al., 2008; National Comprehensive Cancer Network, 2012). Larger tumors have a higher risk of invading and metastasizing, so they usually are surgically excised with a nephron-sparing nephrectomy aiming to preserve as much renal function as possible (García-Donas, Hernando, Romero, & Jara, 2011; Nguyen, Campbell, & Novick, 2008). Renal cysts also are commonly present, but the transition from a cyst to a solid lesion is thought to be relatively rare. Debate exists as to whether carcinoma in situ arises from the walls of complex cysts (Shehata et al., 2008). For that reason, cysts require careful follow-up and surgical management may be appropriate if a noted change in additional imaging is suggestive of cancer (Morrison, Donnelly, Atkinson, & Maxwell, 2010).Patients who have sporadic renal cell cancer (i.e., do not have an inherited VHL mutation) often have acquired VHL gene mutations, indicating that inactivation of the VHL gene plays a role in the pathogenesis of renal cell cancer. Because sunitinib often is used to treat patients with sporadic renal cell carcinoma, this agent also has been used to treat patients with VHL (Jonasch et al., 2011). In patients with VHL, a significant response to sunitinib therapy was observed in renal cell cancer, but not in hemangioblastomas (Jonasch et al., 2011).

Case 2 illustrates a scenario in which the patient initially presented without the traditional syndromic red flags for VHL. Pheochromocytoma is a tumor of the paraganglial system. About one in three patients with pheochromocytoma carry a cancer-predisposing germline mutation in one of six different genes. These gene mutations cause distinct clinical syndromes including VHL; multiple endocrine neoplasia type 2; paraganglioma syndromes type 1, type 3, and type 4; and neurofibromatosis type 1 (Erlic et al., 2009). Clinical features associated with the presence of a germline mutation include young age at diagnosis, multifocal or bilateral disease, and extra-adrenal location. When a tumor type, such as pheochromocytoma, can be attributed to a mutation in any one of several genes, assessment for specific syndromic features in the patient or their family members is essential for determining which gene to test first. In this case, eliciting the history of vision problems with subsequent confirmation of a retinal angioma served to determine the order of genetic testing. In some cases, the approach is not always as clear.

Retinal angiomas occur in about 70% of individuals with VHL. They are benign, slow-growing lesions capable, over time, of causing significant visual abnormalities (Wong & Chew, 2008). Treatment is accomplished by laser photocoagulation, cryotherapy, photodynamic therapy, radiation, or surgical excision. The efficacy and choice of treatment are influenced by location of the angioma.

Case 2 most likely represents a de novo (i.e., was not inherited from a parent) VHL gene mutation that occurred in the proband—the first person seeking genetic testing in this family—as no family members had VHL-related tumors. This was confirmed when P.L.'s parents tested negative for the VHL mutation. If neither parent has VHL, the chances of P.L.'s siblings having VHL is small but still somewhat increased because of the possibility of parental germline mosaicism. In other words, a parent can have a mixture (mosaic) of cells in which the majority of cells (blood or skin cells) have the normal VHL gene but some of the germ (sperm or egg) cells have a VHL mutation—that is why testing was offered to P.L.'s siblings. Because VHL tumors can manifest early, screening can begin as early as age 5 (Teplick, Kowalski, Biegel, & Nichols, 2011). For this reason, testing was offered to the offspring of those who tested positive so screening could be appropriately implemented.