Grouped as a hereditary phakomatosis,
von Hipple-Lindau (VHL) disease is a rare inherited,
autosomal dominant syndrome with high penetrance (80-100%) but variable expression that manifests as a multisystem disorder.
The prevalence of the VHL gene abnormality (inactivation of a tumor suppression gene located in chromosome 3p25.5) stands between 1 in 31,000 and 1 in 53,000 individuals.
Sex distributions are equal.
The mean age at initial presentation is 26 years and the median life expectancy is 49 years.
Genetic abnormalities are believed to induce the development of a wide range of benign and malignant tumors affecting different organs.
Abdominal manifestations of this disease are protean and tend to be asymptomatic at the onset,
being frequently diagnosed later than other manifestations.
The most common abdominal lesions in decreasing order of frequency are: pancreatic cysts,
renal cysts,
renal cell carcinomas (RCC),
pheochromocytomas and neuroendocrine tumors (NET) of the pancreas.
Pancreatic cysts are extremely rare in the general population but constitute the most common lesion in VHL patients (50-91%).
These lesions are benign and generally asymptomatic or associated with mild symptoms (related to mass effect).
They may precede other manifestations by some years facilitating earlier diagnosis of VHL disease,
when detected in screening.
Serous cystadenomas are other cystic pancreatic lesions that occur associated with VHL disease (12% of patients).
Renal cysts tend to be bilateral and multiple.
They occur in 50–75% of patients with VHL disease.
Cysts can be simple or complex (with malignant potential),
the latter being a precursor of RCC and requiring follow-up or surgery.
Renal cell carcinoma is the abdominal lesion responsible for the highest mortality rate and occurs in 24-45% of patients with VHL disease.
Tumors usually appear at a younger age (mean,
30-36 years) than the sporadic forms of RCC.
Pheochromocytomas develop in less than 30% of patients with VHL disease.
These lesions develop at a younger age,
are often bilateral (50-80%) and usually benign.
15-18% are extraadrenal (paragangliomas).
Neuroendocrine tumors of the pancreas occur in 5–17% of patients with VHL disease.
Most tumors are slow growing,
nonfunctional and asymptomatic.
NETs are often multiple and have no particular pancreatic location.
The frequency of malignancy and metastases in these tumors is lower than in the general population (only 10%),
thus they may be observed rather than immediately removed.
Molecular genetic testing allows confirmation of the diagnosis in most patients with VHL disease.
These tests permit identification of mutation carriers among asymptomatic family members.
The high-risk gene carriers must undergo regular surveillance both clinically and radiologically.
Screening is important because the lesions in VHL disease are treatable.
Early detection enables more conservative therapy to be performed and may enhance the patient’s length and quality of life.
Those family members who did not inherit the mutation do not require regular monitoring.
Genetic counseling is essential both before and after molecular testing.