von Hippel-Lindau Disease-Associated Pheochromocytoma: Epidemiology, Clinical Characteristics, and Screening and Surveillance Protocols in Japan - Abstract
von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited syndrome characterized by a predisposition to various neoplastic lesions. To clarify the epidemiology and clinical characteristics of VHL-associated pheochromocytoma (PHEO) in Japan, we have summarized VHL-PHEO characteristics from a nationwide cross-sectional survey for VHL disease on the basis of the epidemiological study program for incurable disease by the Japanese Ministry of Health, Labour and Welfare. The details of the survey included age of onset, sex, living area, treatment modalities, and patient outcome. The incidence rate of PHEO in VHL disease was 15% (62/409). Males and females were equally affected. The mean and median ages of onset were 29.7 and 31.5 years, respectively. The age of onset was distributed between 10 and 75 years and presented two peaks between 15-20 and 35-40 years. Twenty-six (42%) bilateral cases, 8 (13%) extra-adrenal paragangliomas, and 4 (6.4%) malignant cases were observed. Forty-one (65%) patients underwent surgical resection once and 13 (19%) underwent 2 or 3 surgeries, whereas six (10%) were surveyed without surgical treatment. Fourteen of 26 bilateral PHEOs (56%) received steroid replacement therapy following bilateral adrenal surgeries. Four cases died from metastatic PHEOs and one from a severe infection during steroid replacement therapy. None of the patients died of cardiovascular complications due to PHEO crisis. From the current survey results, it is concluded that VHL-PHEO characteristics in Japan are similar to those in Western countries. Based on the above, we propose a screening and surveillance protocol for VHL-PHEO in Japan. Due to its rare incidence and unique characteristics, the continuous survey and registration of VHL-PHEO will remain important to understanding the disease’s nature.