● 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).

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

Hemangioblastoma Epidemiology.

Hemangioblastoma Classification.

Hemangioblastoma Etiology.

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).

see Hemangioblastoma diagnosis.

Differentiation between hemangioblastoma and brain metastases remains a challenge in neuroradiology using conventional MRIAmide 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)

see Hemangioblastoma treatment.

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 the 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 2).


Kamimura K, Nakajo M, Gohara M, Kawaji K, Bohara M, Fukukura Y, Uchida H, Tabata K, Iwanaga T, Akamine Y, Keupp J, Fukami T, Yoshiura T. Differentiation of hemangioblastoma from brain metastasis using MR amide proton transfer imaging. J Neuroimaging. 2022 Jun 22. doi: 10.1111/jon.13019. Epub ahead of print. PMID: 35731178.

Takada S, Hojo M, Takebe N, Tanigaki K, Miyamoto S. Stromal cells of hemangioblastomas exhibit mesenchymal stem cell-derived vascular progenitor cell properties. Brain Tumor Pathol. 2018 Jun 23. doi: 10.1007/s10014-018-0323-2. [Epub ahead of print] PubMed PMID: 29936560.

Cerebellar hemangioblastoma surgery

Cerebellar hemangioblastoma surgery

Preoperative embolization of cerebellar hemangioblastoma may help reduce the vascularity.

Solid HGBs tend to be more difficult to remove. They are treated like AVMs (avoid piecemeal removal), working along margin and devascularizing blood supply. A helpful technique is to shrink the tumor by laying a length of bipolar forceps along tumor surface and coagulating. HGBs with attachment to floor of 4th ventricle may be hazardous to remove (cardio-respiratory complications).

Multiple lesions: if ≥ 0.8–1 cm diameter: may treat as in solitary lesion. Smaller and deeper lesions may be difficult to locate at the time of surgery.

Surgical treatment of cerebellar hemangioblastoma is total resection, with the main goal being the preservation of surrounding neural tissue.

The tumors usually are well demarcated from the surrounding brain or spinal cord, but this border of separation does not contain any particular membrane or capsule.

Multiple feeding arteries are often present, as well as more than one abnormally thick draining vein, with large diameters and thick walls.

Simultaneous 3D visualization of feeding arteries, draining veins, and surrounding structures is needed.

The surgical approach must be wide enough to avoid compression of the healthy tissues during retraction. Thorough evaluation of preoperative imaging studies is the key to the safest possible exposure of the tumor.

A study evaluated the usefulness of high-resolution 3D multifusion medical imaging (hr-3DMMI) for preoperative planning of hemangioblastoma. The hr-3DMMI combined MRI, MR angiography, thin-slice CT, and 3D rotated angiography. Surface rendering was mainly used for the creation of hr-3DMMI using multiple thresholds to create 3D models, and processing took approximately 3-5 hours. This hr-3DMMI technique was used in 5 patients for preoperative planning and the imaging findings were compared with the operative findings. Hr-3DMMI could simulate the whole 3D tumor as a unique sphere and show the precise penetration points of both feeding arteries and draining veins with the same spatial relationships as the original tumor. All feeding arteries and draining veins were found intraoperatively at the same position as estimated preoperatively, and were occluded as planned preoperatively. This hr-3DMMI technique could demonstrate the precise locations of feeding arteries and draining veins preoperatively and estimate the appropriate route for resection of the tumor. Hr-3DMMI is expected to be a very useful support tool for surgery of hemangioblastoma 1).

Occasionally, a localized flow and rich blood supply within the tumor is observed and the color of intravenous blood is bright red 2).

The surface of the tumor may be coagulated with wide bipolar forceps; however, avoid penetration of the tumor itself because of its extreme vascularity and difficulties with hemostasis. Try to dissect the tumor circumferentially by careful coagulation and cutting the small feeding vessels and adhesions between the tumor and the surrounding parenchyma and by putting cottonoid strips into the developing plane to avoid direct pressure.

Once the feeding vessels are identified, they are coagulated and cut. Try to coagulate the arterial feeders prior to the draining veins, but this is not as crucial as it is in arteriovenous malformations. After the tumor is totally removed, the raw surface of the cerebellum remains relatively bloodless, and the oozing blood stops after a few minutes of gently packing the resection cavity with wet cotton balls, avoiding the need for additional coagulation.

Cerebrospinal fluid diversion is rarely necessary after complete tumor removal in patients with preoperative hydrocephalus.

Tumor recurrence is avoided by meticulous extracapsular resection 3).

If an associated hydrocephalus exists, it must be addressed separately, usually by means of external ventricular drainage (EVD) prior to tumor resection. After the tumor is removed, the need for permanent shunt placement may be determined by the patient’s response to EVD clamping.

Cystic cerebellar hemangioblastoma surgery

The tumor is usually easy to visualize because of its reddish-colored solid component and the yellow fluid inside the cyst.

Cystic HGBs require removal of the mural nodule (otherwise, the cyst will recur). The cyst wall is not removed unless there is evidence of tumor within the cyst wall on MRI (typically thick-walled cysts) or visually at the time of surgery.

5-ALA fluorescence may aid in the visual localization of small hemangioblastomas within the cyst wall.

Cystic brainstem HGB: the solid nodule of the tumor is removed under the microscope by bipolar- ing and cutting the gliotic adhesions to the parenchyma. Removal of the cyst wall is not necessary. There is often a cleavage between the tumor and the floor of the fourth ventricle which facilitates tumor removal. To reduce bleeding, avoid piecemeal removal. Preserve large draining veins until the arterial feeders to the mural nodule have been isolated and resected.

Surgical resection is the most effective treatment for cerebellar hemangioblastomas with an enhanced cystic wall 4). However, for this type of lesion, the tumor must not be punctured, biopsied or blocked via resection due to the rich blood supply. The enhanced tumor wall indicates that it contains partial tumor cells, therefore to avoid recurrence of the tumor, the wall and the solid part of the tumor require total resection 5).

If the cyst is present, it may be emptied by cutting the covering pial membrane or by aspirating the cystic contents using a syringe with a short small-caliber needle. Decompression of the cyst allows for improved delineation of the interface between the tumor.


Case reports

2 patients with von Hippel-Lindau disease-related hemangioblastomas successfully treated by a fully endoscopic transcranial approach via a short skin incision and a 2 cm × 2 cm small bony window. Before surgery, a three-dimensional virtual reality model was created to determine the ideal trajectory.

Patient 1 had 2 serial large cystic tumors that equally contributed to obstructive hydrocephalus and were resected sequentially via a single endoscopic trajectory. Patient 2 had a progressive large cystic tumor that was resected endoscopically. Complete resection of the tumors was achieved without any complications in either patient.

Small nodular tumors accompanying a large cyst are plausible candidates for endoscopic transcranial surgery. The spatial relationship of nodules, cyst, and cerebellar parenchyma is important to determine the applicability of the present technique. Preoperative three-dimensional virtual reality simulation helps assess the feasibility of this approach 6).

Krüger et al. presented the case of a minimally invasive removal of a superficial cerebellar hemangioblastoma with tumor-associated cyst and indicate the potential benefits and limitations of this technique 7).



Yoshino M, Nakatomi H, Kin T, Saito T, Shono N, Nomura S, Nakagawa D, Takayanagi S, Imai H, Oyama H, Saito N. Usefulness of high-resolution 3D multifusion medical imaging for preoperative planning in patients with posterior fossa hemangioblastoma: technical note. J Neurosurg. 2016 Aug 26:1-9. [Epub ahead of print] PubMed PMID: 27564468.
2) , 5)

Jito J, Nozaki K. Treatment strategies for cerebellar hemangioblastomas: simple or further studies? World Neurosurg. 2014 Nov;82(5):619-20. doi: 10.1016/j.wneu.2014.08.018. Epub 2014 Aug 20. PubMed PMID: 25151228.

Jagannathan J, Lonser RR, Smith R, DeVroom HL, Oldfield EH. Surgical management of cerebellar hemangioblastomas in patients with von Hippel-Lindau disease. J Neurosurg. 2008 Feb;108(2):210-22. doi: 10.3171/JNS/2008/108/2/0210. PubMed PMID: 18240914.

Neumann HP, Eggert HR, Weigel K, Friedburg H, Wiestler OD, Schollmeyer P. Hemangioblastomas of the central nervous system. A 10-year study with special reference to von Hippel-Lindau syndrome. J Neurosurg. 1989 Jan;70(1):24-30. PubMed PMID: 2909683.

Hasegawa H, Shin M, Kin T, Saito N. Fully Endoscopic Minimally Invasive Tumor Resection for Cystic Cerebellar Hemangioblastoma. World Neurosurg. 2019 Jun;126:484-490. doi: 10.1016/j.wneu.2019.03.158. Epub 2019 Mar 26. PubMed PMID: 30922906.

Krüger MT, Klingler JH. Resection of a cerebellar hemangioblastoma via a minimally invasive tubular approach. J Clin Neurosci. 2019 May;63:240-243. doi: 10.1016/j.jocn.2019.01.045. Epub 2019 Feb 4. PubMed PMID: 30732985.

Cerebellar hemangioblastoma

Cerebellar hemangioblastoma

Cerebellar hemangioblastoma is a vascular posterior fossa tumor with a clear border that develops intramedullary to extramedullary.


Histologically 1) and radiologically 2) , cerebellar HBs are traditionally described as four types:

Type 1 (5% of posterior fossa HBs) is a simple cyst without a macroscopic nodule.

Type 2 is a cyst with a mural nodule (60%).

Type 3, or solid tumors (26%).

Type 4, or solid tumors with small internal cysts (9%), are also seen in the cerebellum and predominate in the spinal cord.

Some authors have stated that type 1 is actually rare.

Clinical features


Differential diagnosis

Several primary pathologic entities in diverse anatomic locations have the potential to simulate metastatic neoplasms histologically. Their misinterpretation as such may result in needless and extensive clinical evaluations that are intended to detect a presumed malignancy at another site. More importantly, mistakes of this type can deprive patients of surgical excisions that could be curative 3).

In adults with only cerebellar masses, cerebellar hemangioblastoma and cerebellar metastases are the 2 most important differential diagnoses.

High b value DWI reflects diffusion more accurately than does regular b value. Results showed that ADC calculation by high b value (b = 4000) DWI at 3-T magnetic resonance imaging is clinically useful for differentiating hemangioblastomas from brain metastases 4).

Arterial spin labelled imaging can aid in distinguishing hemangioblastoma from metastasis in patients with only cerebellar masses 5).

Coexistence of hemangioblastomas and AVMs is extremely rare, and only 3 cases have been reported previously in the literature 6).


Radiation treatment

Effectiveness is dubious. May be useful to reduce tumor size or to retard growth, e.g. in patients who are not surgical candidates, for multiple small deep lesions, or for inoperable brainstem HGB. Does not prevent regrowth following subtotal excision.

Gamma Knife Radiosurgery as well as LINAC have also been employed to successfully treat recurrence and control tumor growth of cerebellar hemangioblastomas.

A retrospective chart review revealed 12 patients with a total of 20 intracranial hemangioblastomas treated with GKRS from May 1998 until December 2014. Kaplan-Meier plots were used to calculate the actuarial local tumor control rates and rate of recurrence following GKRS. Univariate analysis, including log rank test and Wilcoxon test were used on the Kaplan-Meier plots to evaluate the predictors of tumor progression. Two-tailed p value of <0.05 was considered as significant. Median follow-up was 64months (2-184). Median tumor volume pre-GKRS was 946mm3 (79-15970), while median tumor volume post-GKRS was 356mm3 (30-5404). Complications were seen in two patients. Tumor control rates were 100% at 1year, 90% at 3years, and 85% at 5years, using the Kaplan-Meier method. There were no statistically significant univariate predictors of progression identified, although there was a trend towards successful tumor control in solid tumors (p=0.07). GKRS is an effective and safe option for treating intracranial hemangioblastoma with favorable tumor control rates 7).

Suzuki et al. emphasize the usefulness of embolization with N-butyl cyanoacrylate for hemangioblastoma with ruptured feeder aneurysm, by which the aneurysm and the feeder could be simultaneously embolized 8).


Surgical treatment may be curative in cases of sporadic HGB, not in VHL.

Solitary hemangioblastomas are for the most part considered benign, curable by total resection, except in those cases associated with von Hippel Lindau disease.

Despite extensive literature describing the diagnosis, treatment, and prognosis of these lesions, 9) individual cases still present a surgical quandary given their frequently eloquent location and high degree of vascularity.

Case series

Bründl et al. retrospectively analyzed the clinical, radiological, surgical, and histopathologic records of 24 consecutive patients (11 men, 13 women; mean age 51.3 years) with HBL of the posterior cranial fossa, who had been treated between 2001 and 2012.

Mean time to diagnosis was 14 weeks. The extent of resection (EOR) was total in 20 and near total in 4 patients. Four patients required revision within 24 h because of relevant postoperative bleeding. One patient died within 14 days. One patient required permanent shunting. At discharge, 75% of patients [n = 18, modified Rankin scale (mRS) 0-1] showed no or at least resolved symptoms. Mean follow-up was 21 months. Two recurrences were detected during follow-up.

In comparison to other benign entities of the posterior fossa, time to diagnosis was significantly shorter for HBL. This finding indicates the rather aggressive biological behavior of these excessively vascularized tumors. In this series, however, the rate of complete resection was high, and morbidity and mortality rates were within the reported range 10).

Cerebrospinal fluid dissemination of cerebellar hemangioblastoma was found dominantly in non-Von Hippel Lindau disease 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 11).

Case reports

Cerebellar hemangioblastoma in von Hippel-Lindau disease



Richard S, Campello C, Taillandier L, Parker F, Resche F. Haemangioblastoma of the central nervous system in von Hippel-Lindau disease. French VHL Study Group. J Intern Med. 1998 Jun;243(6):547-53. Review. PubMed PMID: 9681857.

Lee SR, Sanches J, Mark AS, Dillon WP, Norman D, Newton TH. Posterior fossa hemangioblastomas: MR imaging. Radiology. 1989 May;171(2):463-8. PubMed PMID: 2704812.

Wick MR. Primary lesions that may imitate metastatic tumors histologically: A selective review. Semin Diagn Pathol. 2017 Nov 17. pii: S0740-2570(17)30137-5. doi: 10.1053/j.semdp.2017.11.010. [Epub ahead of print] Review. PubMed PMID: 29174934.

Onishi S, Hirose T, Takayasu T, Nosaka R, Kolakshyapati M, Saito T, Akiyama Y, Sugiyama K, Kurisu K, Yamasaki F. Advantage of High b Value Diffusion-Weighted Imaging for Differentiation of Hemangioblastoma from Brain Metastases in Posterior Fossa. World Neurosurg. 2017 May;101:643-650. doi: 10.1016/j.wneu.2017.01.100. Epub 2017 Feb 4. PubMed PMID: 28179177.

Kang KM, Sohn CH, You SH, Nam JG, Choi SH, Yun TJ, Yoo RE, Kim JH. Added Value of Arterial Spin-Labeling MR Imaging for the Differentiation of Cerebellar Hemangioblastoma from Metastasis. AJNR Am J Neuroradiol. 2017 Nov;38(11):2052-2058. doi: 10.3174/ajnr.A5363. Epub 2017 Sep 14. PubMed PMID: 28912280.

Monserrate Marrero JA, Monserrate Marrero AE, Pérez Berenguer JL, Álvarez EL, Corona JM, Feliciano C. Cerebellar Arteriovenous Malformation with Coexistent Hemangioblastoma. World Neurosurg. 2019 Nov 9;134:495-500. doi: 10.1016/j.wneu.2019.10.197. [Epub ahead of print] PubMed PMID: 31712111.

Silva D, Grabowski MM, Juthani R, Sharma M, Angelov L, Vogelbaum MA, Chao S, Suh J, Mohammadi A, Barnett GH. Gamma Knife radiosurgery for intracranial hemangioblastoma. J Clin Neurosci. 2016 Jul 12. pii: S0967-5868(16)30013-3. doi: 10.1016/j.jocn.2016.03.008. [Epub ahead of print] PubMed PMID: 27422585.

Suzuki M, Umeoka K, Kominami S, Morita A. Successful treatment of a ruptured flow-related aneurysm in a patient with hemangioblastoma: Case report and review of literature. Surg Neurol Int. 2014 Sep 26;5(Suppl 9):S430-3. doi: 10.4103/2152-7806.141887. eCollection 2014. PubMed PMID: 25324977; PubMed Central PMCID: PMC4199150.

Cushing H, Bailey P. Tumors arising from blood vessels in the brain: angiomatous malformations and hemangioblastomas. Springfield, IL: Charles C Thomas; 1928.

Bründl E, Schödel P, Ullrich OW, Brawanski A, Schebesch KM. Surgical resection of sporadic and hereditary hemangioblastoma: Our 10-year experience and a literature review. Surg Neurol Int. 2014 Sep 22;5:138. doi: 10.4103/2152-7806.141469. eCollection 2014. Review. PubMed PMID: 25317353; PubMed Central PMCID: PMC4192902.

Akimoto J, Fukuhara H, Suda T, Nagai K, Hashimoto R, Michihiro K. Disseminated cerebellar hemangioblastoma in two patients without von Hippel-Lindau disease. Surg Neurol Int. 2014 Oct 7;5:145. doi: 10.4103/2152-7806.142321. eCollection 2014. PubMed PMID: 25324974; PubMed Central PMCID: PMC4199185.
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