Olfactory Neuroblastoma: An Unusual Ocular Presentation

ABSTRACT

We report a case of 51–year–old medically healthy male who presented with gradual painless diminution of vision in both eyes for 3 months. His visual acuity was hand movement perception in the right eye, and no light perception in the left eye. The intraocular pressure, external eye examination, ocular motility and anterior segment examinations were normal. Fundus examination revealed severe bilateral papilloedema and engorged tortuous veins in both eyes. Imaging exhibited a large intracranial tumour causing raised intracranial pressure. This was debulked by neurosurgery and histological examination revealed that the tumour was an olfactory neuroblastoma (ONB). This case is noteworthy since ONBs rarely present with isolated papilloedema without any accompanying ophthalmoplegia, proptosis, epistaxis, nasal, or neurological symptoms.

Introduction

Olfactory neuroblastoma (ONB) is a rare malignant neuroepithelial tumour that originates from the olfactory sensory epithelium in the upper nasal fossa at the level of the cribriform plate.^1,2 It has bimodal peaks in incidence in the second and sixth decades of life. This rapidly growing tumour can be asymptomatic until it occupies the nasal cavity and causes obstruction and/or epistaxis. It can spread into adjacent tissues including the cranium, orbit, and paranasal sinuses.² Orbital invasion can lead to proptosis, ophthalmoplegia and compressive optic neuropathy leading to vision loss.¹

There is a relative paucity of reports in the literature on ophthalmological presentations of olfactory neuroblastoma. We present a case of a patient who presented with bilateral painless insidious vision loss due to severe papilloedema secondary to an ONB.

Case report

A 51–year–old otherwise healthy male presented to the emergency room of our institution with a history of bilateral painless insidious vision loss for 3 months. There was no history of medication use, substance abuse, methanol intake, weight loss, night sweats, anorexia, loss of smell, nasal bleeding or discharge, sinus pain, or headache. His visual acuity was hand motion in the right eye (OD) and no light perception in the left eye (OS). The intraocular pressure was normal. His pupillary reactions to light were reduced bilaterally with a + 1 relative afferent pupillary defect OS. External eye, motility, and slit lamp examination were normal. Fundus examination revealed bilateral grade 5 optic disc oedema (Figure 1). The systemic examination was unremarkable and he had no lymphadenopathy was noted. At presentation, all waves in the electroretinogram were normal however the visual evoked potentials were absent in both eyes. Blood workup, including inflammatory and infectious markers, were normal.

Figure 1.

Ultra-wide field pseudocolour fundus images of the left (a) and right (b) eyes showing bilateral grade 5 optic disc oedema with total obscuration of the major retinal vessels, peripapillary haemorrhages, congested tortuous retinal veins, flame-shaped haemorrhages in all four quadrants of the retina, and horizontal chorioretinal folds within the macula. Spectral-domain optical coherence tomography of the left (c) and right (d) eyes, vertical cut, demonstrating chorioretinal folds at the macular area, more prominent in the left eye.

Imaging revealed a large lesion in the left nasal cavity, ethmoidal air cells and maxillary sinus and extending into the anterior, middle cranial fossa along with sphenoid fossa. (Figure 2). He was urgently referred to neurosurgery and underwent bilateral frontal craniotomy, intracranial lesion excision and skull base reconstruction. Histological examination showed the lesion was an ONB with divergent epithelial differentiation (Figure 3). The primitive component of the biopsy contained lobules of high-grade tumour with true rosette formation, frequent mitoses and apoptosis. Furthermore, immunohistochemistry revealed primitive component positive for synaptophysin, S100 and CD99, epithelial glandular component positive for CK7 and EMA, and squamous component positive for CK5/6. INI-1 showed retained nuclear positivity.

Figure 2.

(a) Coronal computed tomography of the paranasal sinuses in bone algorithms demonstrating a mass filling the left nasal cavity that erodes the floor of the anterior cranial fossa and extends intracranially (white arrow). (b) Coronal and (c) sagittal contrast-enhanced magnetic resonance image showing an avidly enhancing nasal vault mass that fills the left olfactory groove and extends intracranially, with a peri-tumoural cyst (white arrow). (d) Apparent diffusion coefficient map showing a clear distinction between the restricted weighted image mass (black arrow) and high intensity trapped secretions in the adjacent sinuses (thick white arrow).

Figure 3.

(a) Haematoxylin and eosin-stained slide (10X): Olfactory neuroblastoma with divergent epithelial differentiation; biphasic tumour with primitive neuronal and epithelial components. (b) Haematoxylin and eosin-stained slide (20X): The primitive component with lobules of high-grade tumour and true rosette formation. (c) Synaptophysin immunohistochemistry (20X): Positive in the primitive component. (d) CD99 immunohistochemistry (20X): Positive in the primitive component. (e) CK7 immunohistochemistry (10X): Positive in the glandular component. (f) CK5/6 immunohistochemistry (10X): Positive in the squamous component.

He continued to follow-up with oncology and neurology services in a monthly manner and he received postoperative radiotherapy of 54 Gy in 28 fractions. Eight months later, visual acuity in both eyes was at the level of no light perception. He was wheelchair bound but was generally alert. No signs of recurrent lesions or metastasis were present.

Discussion

The most common manifestations of ONB are mainly due to nasal and sinus involvement. Patients usually develop epistaxis, anosmia, and nasal obstruction. As the lesion grows, it compresses orbit and brain tissue causing headaches, optic neuropathy, and/or neurological dysfunction.² A cornerstone in differentiating this tumour from others is histopathology. ONBs show neuroepithelial cells arranged in pseudorosette and rosette shapes. They also exhibit intracellular fibrillar background with pronounced vascularity.^3,4

Previous reports have indicated that they can present with unilateral vision loss, proptosis or proceeded by nasal symptoms such as epistaxis or discharge.^2,4–6 Rakes et al. reported a large series of 38 cases, in which 53% presented with orbital or ocular symptoms. The most frequent symptoms were periorbital pain and lacrimation⁵. Moreover, diplopia was the first presenting ocular sign in 8% of the patients secondary to cranial nerve palsies.¹ Lee and Tang also reported third cranial nerve palsy with pupil involvement due to mass extension to the cavernous sinus, without orbital involvement.⁷ Our patient presented with bilateral gradual vision loss without proptosis, ophthalmoplegia, proceeding nasal, sinuses, or neurological symptoms. The only evident finding was bilateral papilloedema secondary to raised intracranial pressure without optic nerve invasion along with central retinal vein occlusion in both eyes.

The established approach to treatment is en bloc tumour excision to debulk the tumour combined with radiation. This method has been proven to have excellent prognosis except in females, metastatic lesions, or those aged over 50 years.^8,9 In these, ONB can have an aggressive and lethal nature. The most common site of metastasis in ONB patients is the cervical lymph nodes, observed in 20–25% of patients.¹ Neck metastases are identified in 5–8% of patients at time of diagnosis.¹ However, no evidence of metastasis has been found in our patient. ONB has a low survival rate of 50% or less over 5 years.¹⁰ Recurrences occur in about 30% of patients (range 15–70%), mostly within the first 2 years after initial management.¹¹

In brief, ONB is a fast-growing tumour, but rarely initially presents to an ophthalmologist with mere vision in the absence of proptosis or ophthalmoplegia. Early diagnosis, urgent referral and a multi-disciplinary approach can be lifesaving.