Hemangioblastoma (HB) is a vascular tumor of the CNS.
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.
Hemangioblastoma are the rarest central nervous system tumours, accounting for less than 2% 1), and 7-12% of posterior fossa lesions in adult patients.
Hemangioblastomas usually occur in adults, yet tumors may appear in VHL syndrome at much younger ages. Men and women are approximately at the same risk.
About one-fourth of hemangioblastomas occur in patients with Von Hippel-Lindau disease (VHL); the remainders are sporadic. Although extremely rare, solid hemangioblastomas outside the CNS have been reported, involving peripheral nerve 5) retroperitoneum 6) , soft tissue and bone 7) 8) 9) and visceral organs including the pancreas 10) , adrenals 11) 12) , liver 13) , and lung 14) 15).
Most of the above cases of peripheral hemangioblastoma occurred in patients who also had CNS tumor with few exceptions 16).
Metastatic tumor involving the lung is exceedingly rare with only four cases previously reported
Two were autopsy studies in patients who died of complications of the CNS hemangioblastomas in 1943 and 1981, and the third was mentioned in a case report addendum providing follow-up information on hepatic hemangioblastoma in 1991.Lu et al. report a case of a 48-year-old man who presented with multiple lung nodules treated by surgical excision. Pathological study revealed features classic for hemangioblastoma. The patient had a remote history of hemangioblastomas having been excised from the posterior fossa 7 and 20 years previously. It is the first report on surgically resected hemangioblastomas from the lung of a living patient with histological and immunohistochemical characterization. 17).
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.
Contrast enhanced MRI of the conus medullaris and cauda equina of patient with VHL depicts a hemangioblastoma of the conus with extension into the nerve roots. The primary diagnosis is made with a computed tomography scan (CT scan). On a scan, hemangioblastoma shows as a well-defined, black region in the cerebellum with a white nodule on the wall. Sometimes multiple lesions are present.
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 18).