Metastases to Hemangioblastomas in Von Hippel-Lindau Disease

Object: Patients with hereditary cancer syndromes may be at increased risk for the development of tumor-to-tumor metastases. To gain insight into the biological nature of these lesions in the central nervous system (CNS), to determine their prevalence in a familial neoplasia syndrome, and to better define their management, the authors retrospectively examined a series of cases in which metastatic lesions developed within hemangioblastomas in patients with von Hippel-Lindau (VHL) disease.

Methods: The study included all cases of VHL disease in which patients underwent resection of a CNS hemangioblastoma that contained a metastasis or were found at autopsy to have a metastasis to a hemangioblastoma between January 2002 and December 2005 at the National Institute of Neurological Disorders and Stroke (NINDS). Clinical, histopathological, imaging, and surgical and/or autopsy findings were analyzed. Metastasis to a CNS hemangioblastoma was found in six resected tumors (8% of all hemangioblastomas resected from patients with VHL disease at the NINDS during the study period) from six patients (five women, one man; mean age at surgery 42.5 years). The primary site of metastatic disease was the kidney in five patients (renal cell carcinoma) and the pancreas in one (a pancreatic neuroendocrine tumor). Only one patient had systemic metastases at the time of resection of the hemangioblastoma containing the metastasis. Neurologically, all patients had remained at baseline or were improved at last clinical follow-up examination (mean follow-up duration 16.5 months, range 3-40 months). In all cases, postoperative imaging revealed that the hemangioblastoma resection was complete, and there was no evidence of recurrence in any of the patients at the last follow up. Two patients (including one who was also in the surgical group) were found at autopsy to have CNS metastases exclusively to spinal hemangioblastomas.

Conclusions: Hemangioblastomas are an early and preferred site for metastasis in VHL disease. Emerging histopathological techniques may lead to recognition of an increasing number of cases of tumor-to-hemangioblastoma metastasis. Management of cases involving tumor-to-hemangioblastoma metastases in VHL disease should be based on the histological characteristics of the primary tumor, extent of the primary disease, and completeness of the resection.