Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (556 page)

VON HIPPEL-LINDAU DISEASE

   Definition

Von Hippel-Lindau disease (VHLD) is a rare genetic disorder inherited in an autosomal dominant manner and caused by mutations of the von Hippel-Lindau tumor suppressor gene on the short arm of chromosome 3. Approximately 20% of VHLD patients have a de novo mutation and do not have a family history of the disease.

   Who Should Be Suspected?

   Clinical hallmarks are the development of retinal and central CNS hemangioblastomas, pheochromocytomas, multiple visceral cysts in the pancreas and kidneys, and an increased risk for malignant transformation of renal cysts into renal cell carcinoma, which is the leading cause of death in VHLD patients.

   Classified in two types, depending on the likelihood of developing pheochromocytoma:

   Type 1: results from deletion or nonsense mutations. Patients mainly have hemangioblastomas; renal cell carcinoma and pheochromocytoma are rare.

   Type 2: results from missense mutations and subdivided into 2A, 2B, and 2C. Patients with this type are at high risk of developing pheochromocytoma. Type 2A patients are at risk of hemangioblastomas and pheochromocytomas, but not renal cell carcinomas; type 2B patients are at risk of all three tumors with a high risk of renal cell carcinoma; type 2C patients are at risk for only pheochromocytoma.

   Laboratory Findings

   Complete blood count (CBC) to look for evidence of polycythemia vera due to increased erythropoietin production.

   Urinalysis: to detect hematuria. Analysis of catecholamine metabolites in the urine (metanephrine, normetanephrine, dopamine, and vanillylmandelic acid) may aid to detect pheochromocytoma. Urine cytology may detect renal cell carcinoma.

   Diagnosis is also based on family history, imaging studies, and genetic testing.

Suggested Reading

Maher ER, Neumann HP, Richard S. von Hippel-Lindau disease: a clinical and scientific review.
Eur J Hum Genet.
2011;19(6):617–623.

   
KIDNEY TUMORS

JUXTAGLOMERULAR CELL TUMOR

   Definition