● highly vascular well-circumscribed benign solid or cystic neoplasm of CNS or retina
● may occur sporadically or as part of von Hippel-Lindau disease
● on imaging, may be solid, or cystic with enhancing mural nodule
Hemangioblastomas are WHO Grade I neoplasm that consists of neoplastic vacuolated stromal cells and highly developed capillary blood vessels.
They originate from the vascular system.
Clinical presentation typically occurs in the fifth decade for sporadic cases and as early as the third decade for patients with a diagnosis of von Hippel-Lindau (VHL) disease
They may be associated with other diseases such as polycythemia (increased blood cell count), pancreatic cysts and Von Hippel-Lindau syndrome (VHL syndrome). Hemangioblastomas are most commonly composed of stromal cells in small blood vessels and usually occur in the cerebellum, brain stem or spinal cord.
Although they can occur in any section of the central nervous system, they usually occur in either side of the cerebellum, the brain stem or the spinal cord.
These tumors are almost exclusively found in the central nervous system, but in extremely rare cases, it can arise in peripheral nerves.
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.
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).
S/S of cerebellar HGB are usually those of any p-fossa mass—H/A, N/V, cerebellar findings…; see Posterior fossa tumors — and obstructive hydrocephalus may occur. HGB is rarely documented as a cause of apoplexy due to intracerebral hemorrhage (ICH) (lobar or cerebellar); however, some studies indicate that if cases of ICH are carefully examined, abnormal vessels consistent with HGB (and occasionally misidentified as AVM) may be found with surprising frequency (in spite of negative CT and/or angiography).
Retinal HGBs tend to be located peripherally and may hemorrhage and cause retinal detachment. Erythrocytosis may be due to erythropoietin liberated by the tumor.
The treatment for hemangioblastoma is surgical excision of the tumour that can be complicated by preoperative hemorrhage.
Successful resection of hemangioblastoma depends on preoperative assessment of the precise locations of feeding arteries and draining veins.
Although usually straightforward to carry out, recurrence of the tumor or more tumors at a different site develop in approximately 20% of patients.
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.
Hemangioblastomas can cause polycythemia due to ectopic production of erythropoietin as a paraneoplastic syndrome.
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 1).