Vitreoretinal lymphoma presenting as amaurosis fugax

Abstract

Purpose

To describe a case of vitreoretinal lymphoma with unilateral vascular involvement.

Observations

A 80-year-old male with recurrent amaurosis fugax (AF) in the left eye was seen in the ophthalmological department. During a period of seven months the patient developed central vein occlusion (CRVO) and later the panuveitis suspected to be acute retinal necrosis (ARN) before being diagnosed with vitreoretinal lymphoma (VRL). The patient preferred enucleation as treatment which allowed thorough histological examination revealing Epstein Barr virus-associated vitreoretinal lymphoma.

Conclusions and importance

Vascular involvement with AF and CRVO is yet to be described in relation to VRL. This case-study underlines the critical importance of considering VRL when the clinical course deviates from the expected.

1. Introduction

Vitreoretinal lymphoma (VRL) is a rare type of cancer with an estimated incidence of 380 cases per year in the US.¹ An increase in cases is globally recognized. The disease usually occurs between 50 and 70 years of age and earlier in immunosuppressed individuals.1, 2, 3

VRL may mimic other more common eye diseases and therefore often has a prolonged time to diagnosis. VRL presents most commonly with cells in the vitreous and/or sub-retinal infiltrates. It may, however, also present as anterior uveitis with hypopyon,⁴ keratic precipitates and/or posterior synechiae.⁵ It may also present with a primary affection of the retinal vessels mimicking infectious retinitis^6,7(6,7), occlusive retinal vasculitis,⁸ or frosted branch angiitis.⁹ Here, we present a case of Epstein-Barr virus-associated VRL presenting with amaurosis fugax (AF) and later complicated central retinal vein occlusion (CRVO) and acute retinal necrosis (ARN) with panuveitis.

2. Case report

A 80-year-old man was seen in the ophthalmological emergency room with two recurrent episodes of amaurosis fugax on the left eye. The first episode was sudden, painless, total vision loss with whiteout that lasted 20 minutes. The second episode occurred two days later and involved sudden blurry central vision that persisted for a couple of hours.

The patient was known with chronic anemia, chronic kidney failure, dry age-related macular degeneration (AMD) on both eyes and rheumatic polymyalgia (PMR), which simultaneously was flaring up with a C-reactive protein (CRP) of 41 mg/L. The underlying causes of the anemia and kidney failure were unknown. The patient, being a doctor himself, had initiated a dosage of 12.5 mg oral prednisolone prior to the ophthalmological encounter, which was the only immunosuppressive therapy he had received. No underlying infection including systemic EBV infection was evident at presentation.

On clinical examination Snellen visual acuity was 0.6 in the right eye and 1.0 in the left eye. There was no relative afferent pupillary defect (RAPD). Slit-lamp examination of the anterior segments was unremarkable. Ophthalmoscopy of the right eye showed epiretinal fibrosis and macular drusen. Ophthalmoscopy of the left eye showed disc hemorrhages, tortuous retinal veins and peripheral dot and blot hemorrhage in all quadrants (Fig. 1, a). Fluorescein angiography (FA) performed using an Optos ultra-widefield imaging system showed delayed choroidal and retinal filling. Diagnostic examinations measures including biopsy of the temporal artery, carotid ultrasound, CT, and MRI of the brain were unremarkable.

Fig. 1.

Progression of Vitreoretinal lymphoma in the left eye illustrated by widefield imaging (OPTOS) and optical coherence tomography (OCT). A) Disc hemorrhage, tortuous retinal veins and peripheral dot and blot hemorrhages in all quadrants at the first examination. B) Central retinal vein occlusion and flare bleeding in all quadrants, two months after debut. C) White-yellow creamy confluent lesions mimicking acute retinal necrosis (ARN) with panuveitis seven months after debut. The black line indicates location of OCT in picture D. D) Demonstrating granularity of the outer retina (blue arrows) and full-thickness necrosis/infiltration of the retina (white star). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

At one week follow-up CRP was normalized at <4 mg/L and visual acuity was 0.9 on the left eye but ophthalmoscopical examination showed impending central retinal vein occlusion with an increase in peripheral dot and blot hemorrhage. Two months later the patient was seen with a visual acuity of 0.05 and ischemic conversion of CRVO on the left eye with flare bleeding in all quadrants (Fig. 1, b). The patient received two ranibizumab intravitreal injections (0.5 mg) without effect.

At follow-up visit five months later, the left eye had poor VA, limited to light perception, but otherwise remained asymptomatic. Clinical examination revealed panuveitis with large keratic precipitates, multiple cells in the anterior chamber and vitreous body. Ophthalmoscopy and OCT showed large white-yellow infiltrates and necrosis (Fig. 1c and d). Acute retinal necrosis (ARN) was suspected, and a diagnostic vitrectomy was performed as well as systemic antiviral treatment was initiated. PCR from the vitreous biopsy was negative for VZV, HSV, CMV Examination of the vitreous aspirate with flow cytometry and cytology indicated diffuse large B-cell lymphoma with kappa light chain restriction. Polymerase chain reaction (PCR) for MYD88 was negative. MRI of the brain and lumbar puncture showed no sign of central nervous system (CNS) involvement. Whole body 18F-FDG PET/CT was without signs of systemic involvement. The patient was offered various treatment options but preferred enucleation of the left eye. Histological examination of the enucleated eye revealed dense retinal infiltration by atypical lymphocytes characterized by asymmetrically pleomorphic nuclei and granular cytoplasm. Additionally, the specimen tested positive for the B-cell marker CD79a and Epstein-Barr virus-encoded RNA (EBER), confirming the diagnosis of EBV associated vitreoretinal B-cell lymphoma (Fig. 2).

Fig. 2.

Histopathological features of a vitreoretinal lymphoma. A: A microscopic overview of the retina and choroid reveals dense retinal infiltration of atypical lymphocytes with increased basophilic/cytoplasm ratio (Hematoxylin & eosin stain, bar = 100μm). B: A large EBER positive lymphocyte (orange arrow) seen in the specimen with asymmetric pleonuclei and cytoplasm with granulation material (bar = 10μm). C: The B-cell marker CD79α demonstrating positive tumor cells (bar = 100μm). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

The patient died 34 months after PVRL diagnosis, with no CNS involvement noted on MRI or neurological examination during follow-up.

3. Discussion

The diagnostic delay in cases of vitreoretinal lymphoma is well known, as the disease can masquerade both common and rare ocular diseases.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 While amaurosis fugax previously have been described in relation to systemic lymphoma,¹³ it is an unusual manifestation in cases of VRL.

AF is a result of hypoperfusion of the retina or optic nerve due to arterial insufficiency. CRVO is a result of venous occlusion at an arteriovenous crossing posterior to the lamina cribrosa. In our case, the initial development of AF, followed by CRVO and later retinal infiltration with lymphoma cells indicates that the VRL is caused by hematogenous spread from a systemic focus. The hypothesis of the systemic spreading would be in an agreement with observations by others^8,14,15 and supports the notion that treatment of VRL should be systemic and not only ocular.

The enucleated left eye allowed a thorough examination which revealed EBV-associated VRL (Fig. 2). Interestingly, two cases with EBV-associated VRL, describe similar clinical course with a clinical diagnosis of ARN prior to VRL diagnosis. It is well known that EBV may induce VRL in immunosuppressed patients, but it is seldom in immunocompetent^1,3,16,17

This case study demonstrates that AF and CRVO can present as the initial symptoms in a patient with VRL. Furthermore, it highlights the prolonged latency until diagnosis due to the malignant masquerade syndrome, which in this case includes vascular, retinal, and inflammatory ocular diseases. This underlines the critical importance of considering VRL when the clinical course deviates from the expected.

CRediT authorship contribution statement

Andreas Arnold-Vangsted: Writing – original draft, Visualization, Formal analysis, Data curation, Conceptualization. Tomas Ilginis: Writing – review & editing, Supervision, Data curation. Jens Folke Kiilgaard: Writing – review & editing. Steffen Heegaard: Writing – review & editing, Visualization. Carsten Faber: Writing – review & editing, Validation, Supervision, Methodology.

Patient consent

Written informed consent was obtained from the patient for publication of this case including the accompanying images.

Authorship

All authors attest that they meet the current ICMJE criteria for Authorship.

Funding

No funding or grant support is obtained for this study.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.