Disseminated cerebellar hemangioblastoma in two patients without von Hippel-Lindau disease

Abstract

Background:Two patients who had received a total resection of cerebellar hemangioblastoma developed cerebrospinal fluid dissemination during a long-term follow-up period. We present this rare disease with discussion based on the literature.Case Description:The patients were two women aged 45 and 57 years. In the cerebellar hemisphere, one patient had cystic hemangioblastoma of mural nodule type and the other had solid type. Both the patients successfully underwent total resection by craniotomy. They presented no mutations in the von Hippel-Lindau disease (VHL) gene or lesions in the other organs. One patient developed local recurrence 38 months after the initial surgery, and received stereotactic radiosurgery. Three spinal cord tumors developed 91 months later, and the tumors were disseminated to the entire cerebrospinal cavity 107 months later. The other patient developed hydrocephalus 53 months after the initial surgery with tumor tissues disseminated in the intracranial subarachnoid space. The conditions of the two patients gradually aggravated despite treatment with ventriculo-peritoneal shunt and irradiation to the whole brain and whole spinal cord.Conclusion:Cerebrospinal fluid dissemination of cerebellar hemangioblastoma was found dominantly in non-VHL patients. The diagnosis was made 10 years after the initial surgery. Irradiation therapy was performed, but the patients died about 2 years after the diagnosis was given. Molecular targeted therapies including vascular proliferation suppression have been attempted lately, but no effective therapy has been established. Early diagnosis of dissemination as well as combination of aggressive excision and stereotactic radiosurgery are considered to be appropriate for current interventions.

Hemangioblastomas with leptomeningeal dissemination: case series and review of the literature

“…Indeed, none of our patients developed disseminated HB in the absence of previous surgery. An assessment of the tumor cell burden required for dissemination found that a smaller, rather than a larger, number of tumor cells implant at some locations, resulting in subsequent proliferation and the formation of extensive foci [1]. However, we do not know the reason why there was no local recurrence during a relatively short period in any of the presented sporadic HBs patients in our literature, but only distant leptomeningeal seeding.…”

“…The most common cause of death in patients with CNS hemangioblastomatosis is respiratory failure, caused by pontomedullary or cervical cord compression [1,18]. Most patients died within 6 years.…”

“…Moreover, the incidence of seeding and the relationship of dissemination with VHL disease have not been completely determined. The postoperative prognosis of patients with disseminating HB in the CNS is very poor compared with the prognosis in patients with non-seeding HB [1,18,21]. This multicenter case series describes hemangioblastomatosis in seven patients who underwent gross total removal of CNS HBs and compares these findings with those in previously described patients with sporadic and VHL-associated HBs.…”

CNS hemangioblastomatosis in a patient without von Hippel–Lindau disease

“…Fewer than 20 individual cases of disseminated disease are reported in the literature [4-6, [13][14][15][16][17][18][19][20][21]. The most typical scenario entails discovery of a relatively small number of tumor deposits along the brain stem and spinal cord, generally years after initial diagnosis and/or treatment of a cerebellar hemangioblastoma.…”

Surgical treatment of cerebellar hemangioblastomas

“…Mechanisms underlying tumor spread suggests a small number of cells implant at distant sites giving rise to new tumor lesions. [ 1 ] Craniospinal radiation is recommended for cases of CSF dissemination combined with ventriculoperitoneal shunt depending on other symptoms. Time elapsed between initial surgery and detection of tumor spread was on average 10 years.…”