Hemangioblastoma is an uncommon benign tumor of central nervous system (CNS), accounting for 2% of all CNS tumors and 7%–12% of all posterior fossa tumors (1, 2). Composed of capillary vessels and stromal cells, it is classified as mesenchymal nonmeningothelial tumors of unknown origin and graded as WHO I. Generally, it occurs in the brain (90%) or spinal cord (10%). Among the intracranial cases, 95% locate in the posterior fossa. Hemangioblastoma at other locations are very rare especially the ones involving optic nerves and chiasm. Common clinical symptoms include headache, cerebellar ataxia, and dyskinesia, which are related to its anatomic locations. Hemangioblastoma can be sporadic (~75%) or von-Hippel Lindau (VHL) syndrome-associated (~25%) (3). VHL syndrome is an autosomal dominant disease characterized by multiple tumors such as hemangioblastoma, renal cell carcinoma, and pheochromocytoma (3). Based on the components, hemangioblastoma can be classified into four types, cystic with mural nodule (54.8%), solid (28.8%), cystic (12.5), and solid with cystic components (3.8%) (4).

Optic nerve hemangioblastoma (ONH) is a very rare subtype with only 39 cases reported. Unlike hemangioblastoma in cerebellum and other locations, most ONH (71%) were found to be associated with VHL syndrome. Visual defects and exophthalmos are the most common symptoms (5). However, these symptoms are unspecific and therefore have limited values in diagnosis. Though MRI with contrast is considered the optimal diagnostic tool by now, ONH is still often misdiagnosed or undiagnosed preoperatively due to its low prevalence and similar MRI patterns to glioma and meningioma. More neuroimaging clues are required to improve preoperative diagnosis.

Here, we employ advanced MR techniques including diffusion weighted imaging (DWI), apparent diffusion coefficient (ADC) maps and MR angiography (MRA) in an ONH case, expecting to offer more imaging information on the preoperative diagnosis. To our knowledge, it is the first reported ONH case characterized by these advanced MR techniques. Also, we have collected all other published ONH cases, summarized their neuroimaging findings, and compared them with other easily confused diseases of optic nerve such as optic pathway glioma and optic nerve sheath meningioma.

A 41-year-old male with a past history of cerebellar hemangioblastoma complained of vision loss in the left eye for 6 years, with reduced vision acuity in the right eye for 3 months. His vision acuity in the left eye started to deteriorate 6 years ago without other discomforts. CT scans at that time showed a mass at cerebellum. He underwent a resection surgery but the left eye still went blind several months later. Postoperative pathological examination confirmed the diagnosis of hemangioblastoma. Two years ago, MRI revealed a newly occurring mass adjacent to the left optic nerve which was asymptomatic. Unfortunately, the follow-up visits showed that it had been progressing gradually without treatment.

Three months ago, his right eye had a significant reduction in vision acuity from 20/20 to 20/25 and was referred to our hospital. The visual field test and fundoscopy revealed no abnormality in the right eye. MRI revealed a mass occupying from the left orbit apex to the anterior cranial fossa, with hypointensity on T1-weighted images and hyperintensity on T2-weighted images ( Figures 1A–C ). Apparent and homogenous enhancement of the mass was observed on the gadolinium-enhanced MRI scans ( Figure 1D ), while the surrounding area showed no enhancement. The mass showed evident hyperintensity compared to brain parenchyma on ADC maps ( Figure 1E ) but not on DWI ( Figure 1F ). The surrounding area along the left optic nerve was hyperintense on DWI ( Figure 1G ), and was considered severe peritumoral edema. Also, bilateral optic tracts were thickened on MRI due to swelling. MRA revealed no abnormity (Supplementary Material). Taken together, these imaging results highly suggested glioma. Hemangioblastoma was also suspected considering his past history. The latest MRI showed another mass in the left cerebellum, which was hyperintense on T2-weighted imaging (T2WI) and hypointense on T1-weighted imaging (T1WI) and DWI, with significant enhancement on contrast scans. These MRI findings and the location of posterior fossa strongly supported the possibility of hemangioblastoma. Combining these imaging clues and his past history, the recurrence of hemangioblastoma at both cerebellum and optic nerve was highly suspected.

The patient then received a left frontotemporal-approach craniotomy to resect the mass. At surgery, a reddish tumor adherent to the left optic nerve was observed. The attached tortuous vessels originated from ophthalmic artery indicated its rich blood supply. The tumor was excised and measured 1.5 × 0.8 × 0.8 cm. Postoperative MRI ( Figures 1H, I ) showed a complete excision of the mass. The edema has receded postsurgery but not completely. Changes in vision or visual fields have not been observed during the 2-week hospital admission after surgery.

Macroscopically, the mass was solid, soft, and had a taupe surface. Histopathological results revealed that the tumor consisted of vacuolated stromal cells and numerous capillary vessels. The stromal cells are NSE(+) and GFAP(+), and the vessels are CD34(+), CD31(+), and F8-R(+). Interspersed CD68(+) monocytes and macrophages were also observed. CgA and Syn were both negative among the whole tissue ( Figure 2 ). Therefore, the diagnosis of hemangioblastoma was confirmed by the typical pathological characteristics. Considering the frequent recurrence of hemangioblastoma in this patient, VHL syndrome was probably associated with his clinical manifestations. Unfortunately, the patient refused genetic testing.

We collected all 39 published ONH cases and reviewed their neuroimaging results.

Optic nerve hemangioblastoma is extremely rare. Including this case, 40 cases have been reported since 1940. Despite the fact that MRI is the major diagnostic tool of ONH, few of these case reports provided detailed descriptions of MRI results for reference in clinical practice. On the other hand, ONH has similar MRI performances to OPG and ONSM, making it highly challenging to accurately diagnose ONH. Therefore, more experience on MRI imaging is needed to improve the diagnosis. In this study, we reported a 41-year-old male with recurrent hemangioblastoma in both cerebellum and optic nerve. The manifestations on conventional MRI were described in detail. Moreover, advanced MR techniques were employed for the first time to explore for more diagnostic tools for ONH. The results revealed that the mass was evidently hyperintense on ADC maps but showed no abnormity on MRA, which was out of expectation.

We also reviewed all present case reports to summarize the MRI and angiography results of ONH and discussed the differential points between ONH and easily confused diseases. Similar to cerebellar hemangioblastoma, most ONH cases possess iso- or hypointensity on T1WI and hyperintensity on T2WI. The prominent enhancement and well-defined boundaries are prevalent. In addition, structural features including flow voids and extensive peritumoral edema are also widely accepted as suggestive evidences of ONH. The flow void effect has high specificity but is not sensitive enough. Larger masses seem to be more likely to cause the effect. Extensive peritumoral edema is a unique property of ONH absent in cerebellar hemangioblastoma. Optic pathway is often involved due to its low resistance environment and contralateral vision can be impaired consequently, indicating the necessity of timely and complete resection. It is also found that the solid-form hemangioblastoma accounts for the vast majority of ONH, instead of cystic form which typically presents in cerebellar hemangioblastoma. This possibly resulted from drainage of transudate through the extensive edema. Therefore, the absence of typical large cysts with mural nodules should not be recognized as a clue for excluding ONH during diagnostic process.

ONH is difficult to be distinguished from meningioma and glioma with simply conventional imaging approaches, especially when typical clinical features mentioned above are not observed. Though few studies and reports focus on applying advanced MRI techniques on ONH, experience from cerebellar hemangioblastoma can also be informative. It has been reported that ADC values in hemangioblastoma are distinctively higher when compared with most other posterior fossa tumors such as meningioma and metastases, indicating its potential diagnostic value in ONH. We here applied ADC on the evaluation of ONH for the first time and observed a hyperintense mass, similar to the manifestations of cerebellar hemangioblastoma.

In addition, high rCBV ratio on PWI can be another exclusive marker of hemangioblastoma. Cerebellar hemangioblastoma shows a remarkably higher rCBV ratio than metastases, meningioma, and both low-grade and high-grade gliomas, and thus can be easily distinguished. However, PWI results in ONH have not been reported yet.

Angiography used to be crucial for the diagnosis of ONH before MRI was advanced. Almost all cases performing angiogram revealed hypervascular masses originating from ophthalmic arteries. In contrast, MRA has not been frequently used in either optic nerve or cerebellar hemangioblastoma.

In conclusion, various MR modalities including DWI, ADC, and PWI provide new insights to the imaging manifestations of ONH. For diagnosed VHL patients, an optic nerve lesion is highly suspected to be hemangioblastoma. However, for patients who do not meet the clinical diagnosis criteria of VHL, any possibility of the lesion should be carefully evaluated. In such cases, preoperative diagnosis by advanced MRI techniques can be decisive for their following examinations, treatment, and prognosis. Though more ONH cases employing these advanced techniques are needed to systematically review their diagnostic performances, these tools are valuable auxiliary approaches that can prompt the differentiation of ONH in these situations.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

MD composed the manuscript and reviewed literature. LY provided figures and reviewed literature. JK and RW contributed to the organization and revision of the manuscript. HY reviewed the MRI images in case reports, analyzed the results, and edited the manuscript. MF selected and managed the patient case and edited the manuscript. All authors contributed to the article and approved the submitted version.

This work was supported by Chinese Academy of Medical Sciences / Peking Union Medical College Postgraduate Teaching Innovation Fund (No. 10023201900107).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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