Hemangioblastoma

Key concepts

● highly vascular well-circumscribed benign solid or cystic neoplasm of CNS or retina

● the most common primary intra-axial tumor in the adult posterior fossa

● may occur sporadically or as part of von Hippel-Lindau disease

● on imaging, may be solid, or cystic with enhancing mural nodule

● ✔ Complete blood count (CBC): may be associated with erythrocytosis (polycythemia).

Definition

Hemangioblastomas (HGB) are histologically benign slow-growing tumors with neoplastic stromal cells and copious small vessels.

Epidemiology

Hemangioblastoma Epidemiology.

Classification

Hemangioblastoma Classification.

Etiology

Hemangioblastoma Etiology.

Pathogenesis

Hemangioblastomas are composed of endothelial cells, pericytes and stromal cells. In VHL syndrome the von Hippel-Lindau protein (pVHL) is dysfunctional, usually due to mutation and/or gene silencing. In normal circumstances, pVHL is involved in the inhibition of hypoxia-inducible factor 1 α (HIF-1α) by ubiquitin mediated proteosomal degradation. In these dysfunctional cells pVHL cannot degrade HIF-1α, causing it to accumulate. HIF-1α causes the production of vascular endothelial growth factor, platelet derived growth factor B, erythropoietin and transforming growth factor alpha, which act to stimulate growth of cells within the tumour.

Pathology

Hemangioblastomas (HGB) are histologically benign slow-growing tumors with neoplastic stromal cells and copious small vessels. Intracranially, they occur almost exclusively in the p-fossa (hemangioblastomas are the most common primary intra-axial p-fossa tumor in adults). May occur in the cerebellar hemisphere, vermis, or brainstem. May also occur in the spinal cord (1.5–2.5% of spinal cord tumors). Also difficult to distinguish histologically from a renal cell carcinoma (which is common in VHL adds to the difficulty of this differential).

Diagnosis

see Hemangioblastoma diagnosis.

Differential diagnosis

Differentiation between hemangioblastoma and brain metastases remains a challenge in neuroradiology using conventional MRI. Amide proton transfer imaging can provide unique molecular information. A study by Kamimura et al. from Kagoshima aimed to evaluate the usefulness of APT imaging in differentiating hemangioblastomas from brain metastases and compare APT imaging with diffusion-weighted imaging and dynamic susceptibility contrast perfusion-weighted imaging.

This retrospective study included 11 patients with hemangioblastoma and 20 patients with brain metastases. Region-of-interest analyses were employed to obtain the mean, minimum, and maximum values of APT signal intensity, apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV), and these indices were compared between hemangioblastomas and brain metastases using the unpaired t-test and Mann-Whitney U test. Their diagnostic performances were evaluated using receiver operating characteristic (ROC) analysis and area under the ROC curve (AUC). AUCs were compared using DeLong’s method.

All MRI-derived indices were significantly higher in hemangioblastoma than in brain metastasis. ROC analysis revealed the best performance with APT-related indices (AUC = 1.000), although pairwise comparisons showed no significant difference between the mean ADC and mean rCBV.

APT imaging is a useful and robust imaging tool for differentiating hemangioblastoma from metastases ¹⁾

Treatment

see Hemangioblastoma treatment.

Outcome

The outcome for hemangioblastoma is very good, if surgical extraction of the tumor can be achieved; excision is possible in most cases and permanent neurologic deficit is uncommon and can be avoided altogether if the tumor is diagnosed and treated early. Persons with VHL syndrome have a bleaker prognosis than those who have sporadic tumors since those with VHL syndrome usually have more than one lesion.

Complications

Hemangioblastomas can cause polycythemia due to the ectopic production of erythropoietin as a paraneoplastic syndrome.

Case series

Ten hemangioblastomas were investigated immunohistochemically. CD44, a mesenchymal stem cell marker, was detected in stromal cells of all cases, suggesting that stromal cells have mesenchymal stem cell-like properties. Neither CD31 nor α-SMA was expressed in stromal cells, suggesting that stromal cells have not acquired differentiated vascular cell properties. Both ephrin-B2 and EphB4, immature vascular cell markers, were detected in stromal cells of all cases. Jagged1, Notch1, and Hesr2/Hey2, which are known to be detected in both immature endothelial cells and mural cells, were expressed in stromal cells of all cases. Notch3, which is known to be detected in differentiating mural cells, was also expressed in all cases. These results suggest that stromal cells also have vascular progenitor cell properties. In conclusion, stromal cells of hemangioblastomas exhibit mesenchymal stem cell-derived vascular progenitor cell properties ²⁾.