Suprasellar paraganglioma in a clinical setting of von Hippel-Lindau syndrome

Abstract

A man in his 20s presented to the neurosurgery department 2 years ago with headache and blurred vision. He was diagnosed to have a suprasellar mass on neuroimaging. Best-corrected visual acuity in the right eye was 6/36 and that in the left eye was 6/60. Automated visual fields showed a temporal hemianopia in the right eye and an advanced field defect in the left eye. His hormonal profile was normal, and he underwent partial excision of suprasellar tumour, which was a histopathologically proven paraganglioma (PGL). Subsequently, the patient underwent radiotherapy and his vision and visual fields showed improvement. Follow-up examination 3 years later showed a left retinal capillary hemangioblastoma (RCH), which was treated with green laser photocoagulation, resulting in complete sclerosis. This case is unique because of the extremely rare coexistence of a sellar PGL and RCH, which to our knowledge has not been reported so far.

Background

Pheochromocytomas and paragangliomas (PGLs) are rare tumours arising from neuroendocrine cells. Pheochromocytomas are located in the adrenal glands and usually produce catecholamines, while PGLs are located at extra-adrenal sites and are of two types: sympathetic and parasympathetic.¹ Sympathetic PGLs are typically located in the chest and abdomen.¹ Parasympathetic lesions have been described in the head and neck region, and location in the sella is rare, with only 35 cases reported so far in literature.^{2 3} Though most PGLs are sporadic, associations with familial syndromes, particularly von Hippel-Lindau (VHL) syndrome, have been described. Scheithauer et al in 1996 mentioned for the first time that a sellar PGL was seen in a patient with a family history of VHL and proposed that it could be an association.⁴ We hereby report a case of sellar–suprasellar parasympathetic PGL in a patient with retinal capillary hemangioblastoma (RCH) and other known manifestations of VHL.

Case presentation

A healthy man in his 20s presented to the neurosurgery department 2 years ago with headache and defective vision in the left eye more than right eye of 6 months’ duration. He was referred for an ophthalmic evaluation. His best-corrected visual acuity (BCVA) in the right eye was 6/36 and that in the left eye was 6/60. Automated perimetry showed a temporal hemianopia in the right eye and an advanced visual field defect in the left eye. Anterior segment examination was unremarkable except for a relative afferent pupillary defect in the left eye. The fundus showed early disc oedema in both eyes. MRI of the brain showed a suprasellar lesion measuring 2.1×2.9×2.7 mm with contrast enhancement and flow voids within the lesion (figure 1). There was also a small homogeneously contrast-enhancing lesion noted at the foramen of Magendie. Clinical examination showed normal vital parameters including blood pressure with no history of episodes of palpitations, sweating or anxiety. His hormonal profile was within normal limits.

Figure 1.

MRI of the brain done in 2018 showing a suprasellar lesion measuring 2.1×2.9×2.7 mm with contrast enhancement and flow voids within the lesion.

He was scheduled for transcranial excision of the suprasellar tumour. However, intraoperatively, the lesion was noted to be a firm reddish one with very high vascularity. The tumour could not be excised due to excessive bleeding, and a biopsy of the tumour was taken. Histopathology of the suprasellar lesion depicted a zellballen pattern of tumour cells with large cell size, abundant cytoplasm and small round nuclei, which also showed cytoplasmic positivity for chromogranin and diffuse positivity for synaptophysin suggestive of a PGL (figure 2). Considering this rare location of PGL, this case was published in the World Neurosurgery journal.³

Figure 2.

Paraffin section demonstrating (A) typical zellballen pattern architecture of cell arrangement with thin sinusoidal vascular channels separating nests of cells; and (B) individual cell showing eosinophilic cytoplasm and fine nuclear chromatin. Tumour cells show immunopositivity for (A, inset) chromogranin and (B, inset) synaptophysin.

Digital subtraction angiography showed the tumour receiving multiple feeder vessels from bilateral internal carotid arteries and was not found amenable to embolisation. He then underwent 20 cycles of conventional radiotherapy with a total dose of 40 Gy for the tumour, after which there was marginal reduction in the size of the tumour with improvement in visual acuity and visual fields. Repeated hormonal workup was normal.

Three years later, he came for a follow-up. His BCVA now was 6/6 in both eyes, and visual fields showed bitemporal field defects with improvement in the central visual fields. MRI showed a minimal reduction in the size and significantly reduced contrast enhancement of the sellar mass. There was an increase in the posterior fossa lesion from 2 mm×2 mm to 8 mm×11 mm (figure 3). His optic discs showed minimal temporal pallor. However, on fundus examination, an RCH was detected incidentally, located 5 disc diameters from the optic disc in the inferonasal quadrant of the left eye measuring 1.5×1.5 disc diameter. There were no associated exudates or fluid surrounding the lesion. The feeder artery and draining vein were dilated and tortuous (figure 4). The feeder artery was identified on fundus fluorescein angiography (FFA), and the lesion showed a mulberry-like hyperflourescence starting from the arteriovenous phase. No other similar lesions were noted on FFA (figure 5).

Figure 3.

MRI of the brain showing the intensely enhancing posterior fossa lesion (yellow arrow) at the first visit (A). The lesion (yellow arrow) shows the increase in size after 3 years of follow-up (B).

Figure 4.

Colour fundus photograph showing the retinal capillary hemangioblastoma with the dilated feeder artery and draining vein in the inferonasal quadrant.

Figure 5.

Fundus fluorescein angiography identified the feeder vessel with hyperflourescence in the arterial phase. The tumour shows mulberry-like hyperflourescence. No similar lesions were noted in either eye.

In view of the RCH, we elicited a family history which was unremarkable for VHL or its manifestations.

Investigations

An abdominal ultrasound examination revealed a simple renal cyst measuring 1.44 cm×2.12 cm in size (figure 6). Hormonal profile showed normal levels of pituitary hormones.

Figure 6.

Ultrasonography of the abdomen showing a simple renal cyst.

Treatment

Since the sellar lesion was reducing in size and visual fields and visual acuity showed improvement, no further neurosurgical intervention was advised. It was decided to observe the posterior fossa lesion at this stage. For the RCH, green laser (532 nm) treatment was initiated along the feeder artery in order to occlude the lumen. Spot size of 100 microns and duration of 300–400 ms and power of 80–150 W were used, and multiple sessions were done along the feeder artery, which gradually closed completely. Laser was done on the tumour surface with confluent white burns and a spot size of 200 microns after the feeder artery was partially closed. The draining vein also decreased in size (figure 7).

Figure 7.

Serial colour fundus photographs showing progressive obliteration of the feeder vessel to the tumour (A-E). The tumour appears chalky white after complete obliteration of the feeder vessel (F).

A total of six laser sessions were done over 17 days, after which it was noted that the tumour was completely sclerosed and had become chalky white. There were overlying localised vitreous opacities and exudation around the lesion for which a posterior subtenon triamcinolone acetonide injection (40 mg in 1 mL) was given and the exudation resolved significantly on the fifth day after the injection.

Outcome and follow-up

The patient was counselled about the need for regular and close follow-up and the possible need for genetic studies in the future. Since he does not have any siblings, the need to evaluate his parents was stressed.

Discussion

We present a cluster of clinical findings such as a histologically confirmed suprasellar PGL, another slow-growing posterior fossa lesion in the brain, RCH and a simple renal cyst in a patient without a family history. According to the Danish criteria for the diagnosis of VHL, in the absence of family history, presence of one RCH and a PGL meets the diagnostic criteria for VHL.⁵ However, the international criteria for the diagnosis of VHL does not include PGL as a manifestation.⁶ The slow-growing, contrast-enhancing posterior fossa lesion in the brain clinically and radiologically is typical of a haemangioblastoma although not confirmed histologically. Hence, the presence of two haemangioblastomas fulfils the international criteria.

Regarding PGLs, majority of them are sporadic. Previous data suggest that 10% of PGLs and pheochromocytomas were associated with familial syndromes.⁷ However, recent data have suggested that between one-quarter and one-third of these tumours may be familial in nature.^8–10 Germline mutations in succinate dehydrogenase (SDH) gene have been associated with familial PGLs. VHL (caused by a mutation in the VHL gene), multiple endocrine neoplasia-2 and neurofibromatosis-1 have been associated with pheochromocytomas primarily but can also be associated with PGLs.¹¹ Another article published in 2009 by Gaal et al clearly mentioned that parasympathetic PGLs in VHL disease, although rare, are part of the syndrome and are related to VHL gene inactivation.² The presence of parasympathetic PGLs in patients with VHL disease is rare and reported as 0.005.²

Common parasympathetic PGL locations include the jugular bulb, the tympanic branch of the glossopharyngeal nerve, and the auricular branch of the vagus nerve.^{12 13} The sellar and parasellar regions are extremely rare cranial sites, with only 35 reported cases so far including this case.³ None of these cases have reported an associated RCH or VHL, although one case had only a family history of VHL.⁴ The others were most probably sporadic. There are various reports of PGLs in patients with known VHL disease or with a family history of VHL, the locations being the carotid body, retroperitonium, urinary bladder, mediastinum, vagal and spinal but none reported in the suprasellar location.^12–22

Our report highlights the rare occurrence of a sellar PGL in a clinical setting of VHL causing both papilloedema and compressive optic neuropathy. In contrast to pituitary adenomas which are smaller in size and generally present with compressive optic neuropathy, the tumour in our case was a large one causing raised intracranial tension and papilloedema as well.^{23 24} There are reports of papilloedema caused by pituitary tumours. Improvement of visual fields after surgery has been reported to occur in pituitary adenomas and was also seen in our case after reduction in tumour size following radiotherapy.²⁵

As of now, the RCH seems to have completely regressed. This is being followed up and further monitoring will be done according to the protocol guidelines.²⁶ The response of the capillary haemangioblastoma showing complete and sudden regression while laser was being done is also to be noted. We feel this could be due to the smaller size of the tumour and the good closure of the feeder artery.

Various ocular manifestations have been reported in patients with VHL.²⁷ These include retinal capillary haemangioblastoma and its effects on the retina such as macular oedema and exudates, exudative retinal detachment, neovascularisation, fibrovascular proliferation, tractional retinal detachment and also neovascular glaucoma. There are also reports of haemangioblastomas of the optic nerve and the anterior visual pathway extending upto the optic chiasm. Some of these have been reported to cause visual field defects, depending on their location in the optic nerve pathway.²⁷ This may be a first case of compressive optic neuropathy caused by a sellar PGL as an ophthalmic feature in VHL.

Various methods have been described for the treatment of RCH, including laser, which could be direct laser to the tumour and laser to close the feeder artery resulting in the reduction of size and sometimes complete closure of smaller tumours, photodynamic therapy to more posterior tumours and the ones close to the fovea and optic nerve, transpupillary thermotherapy, cryotherapy to the more anterior tumours and the use of anti-vascular endothelial growth factor as a supplement to any of the mentioned methods and radiation (including brachytherapy, external beam radiation and proton beam radiation).^27–29

Use of corticosteroids has also been described intravitreally to reduce the exudation after treatment of these tumours.²⁷ Use of anti-VEGF agents has been described to reduce the exudation and macular oedema caused by the tumour. Vitrectomy is advocated when there is vitreous haemorrhage or tractional retinal detachment. An online survey showed that most retina specialists believe in individualising the treatment for each patient.³⁰

Small case series have used anti-VEGF injections to treat lesions associated with exudation and lesions at locations not amenable to ablation such as juxtapapillary tumours.^{31 32} The retinal tumour in our case was a single lesion, away from the fovea, without exudation, and hence we chose to do laser and did not consider anti-VEGF. Literature search on laser for the CHB was done, and direct laser to the tumour in one case report showed bleeding and increase in exudation following which they tried the feeder vessel treatment with anti-VEGF supplementation.³³ Even in our experience starting with the feeder vessel occlusion, which reduces the blood supply to the tumour, and then treating the tumour directly has a benefit in avoiding bleeding, although the number of sessions of laser may be more and patients need to visit the clinic frequently. There is no literature available for the use of posterior subtenon injection of triamcinolone acetonide to reduce exudation. We considered this route in order to reduce the systemic side effects of steroids, though in this case the patient did not have a catecholamine-producing tumour.

Learning points.

• Rare sellar location of a paraganglioma (PGL).

• Association of a sellar PGL with a retinal capillary haemangioblastoma in a clinical setting of VHL.

• A unique response of retinal capillary haemangioblastoma to green laser photocoagulation.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).