Cancer genes, multiple primary cancer, and von Hippel-Lindau disease

Von Hippel-Lindau disease is inherited by an autosomal dominant gene that may show marked expressive variability of cancer phenotype in certain patients/families. We describe a patient with a strongly positive family history of this disease who, at age 28, underwent craniotomy with removal of a cystic cerebellar hemangioblastoma; at age 48, he developed syringomyelia of the spinal cord, became quadriplegic, and had a progressive downhill course. At autopsy, hemangioblastomas of the cerebellum and spinal cord were found, as well as a left renal cell carcinoma, an oat cell carcinoma of the lung, a hepatocellular carcinoma, and an atypical thyroid adenoma. This tumor spectrum appears to be unique, although chance cannot be excluded. It is possible, however, that these findings might represent an expression of the deleterious genotype that became evident because of this patient's prolonged survival from his initial cerebellar hemangioblastoma.