The great masquerader: primary vitreoretinal lymphoma presenting as white dot syndrome

Primary vitreoretinal lymphoma (PVRL) is a rare and aggressive subtype of intraocular lymphoma, most commonly associated with primary central nervous system lymphoma (PCNSL). It frequently mimics inflammatory retinal diseases and is therefore considered an important masquerade syndrome in ophthalmology. Early diagnosis remains challenging because clinical manifestations can resemble entities within the white dot syndromes (WDS) spectrum. We report a case initially diagnosed as white dot syndrome, followed by the diagnosis of PCNSL, in which later ocular progression led to the diagnosis of PVRL.

A 57-year-old male presented with painless, progressive visual loss in the left eye (LE) starting in July 2021. At that time, he was diagnosed at another center with multiple evanescent white dot syndrome (MEWDS) and treated with systemic corticosteroids, with subsequent improvement of visual symptoms after a single treatment course. His medical history was significant for COVID-19 infection in September 2021, followed one month later by neurological symptoms. Brain imaging revealed a left frontal tumor, and surgical resection established the diagnosis of PCNSL (non-Hodgkin B-cell lymphoma). The patient subsequently underwent systemic and intrathecal methotrexate (MTX) therapy combined with whole-brain radiotherapy. One year later, ophthalmologic reevaluation at our center revealed a best-corrected visual acuity (BCVA) of 20/20 in the right eye (RE) and motion in the left eye (LE). The LE showed a relative afferent pupillary defect (RAPD), vitreous cells, and multiple subretinal white-yellow lesions, including subfoveal involvement, associated with peripheral pigmentary changes. Given the patient's medical history, the findings raised suspicion for intraocular lymphoma. A diagnostic vitrectomy was subsequently performed, confirming PVRL. Intravitreal MTX therapy was initiated. Despite treatment, BCVA in the LE was counting fingers, and extensive chorioretinal atrophy was observed. Although subtle changes in the central outer retinal layers were observed in the RE, BCVA was 20/25. The patient subsequently underwent autologous stem cell transplantation. However, the clinical course was further complicated by a relapse of PCNSL and a severe Escherichia coli sepsis.

Primary vitreoretinal lymphoma is well known for its ability to masquerade as chronic posterior uveitis or inflammatory chorioretinal diseases, including WDS. The presence of vitritis combined with multifocal subretinal infiltrates should raise suspicion, particularly in patients with a history of PCNSL. Corticosteroid responsiveness may further obscure the diagnosis by temporarily improving inflammatory-like manifestations. Because up to 80% of patients with PVRL develop CNS involvement or present with CNS disease first, ophthalmologic surveillance is essential. Multimodal imaging and a high index of suspicion are critical for timely diagnosis.

Primary vitreoretinal lymphoma should be considered in the differential diagnosis of white dot-like retinal lesions, especially in patients with a history of CNS lymphoma. Recognition of this masquerade presentation is essential to avoid diagnostic delay and to ensure prompt multidisciplinary management.