Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium

Abstract

Primary vitreoretinal lymphoma (PVRL), also known as primary intraocular lymphoma, is a rare malignancy typically classified as a diffuse large B-cell lymphoma and most frequently develops in elderly populations. PVRL commonly masquerades as posterior uveitis and has a unique tropism for the retina and central nervous system (CNS). Over 15% of primary CNS lymphoma patients develop intraocular lymphoma, usually occurring in the retina and/or vitreous. Conversely, 65%-90% of PVRL patients develop CNS lymphoma. Consequently, PVRL is often fatal because of ultimate CNS association. Current PVRL animal models are limited and require further development. Typical clinical findings include vitreous cellular infiltration (lymphoma and inflammatory cells) and subretinal tumor infiltration as determined using dilated fundoscopy, fluorescent angiography, and optical coherent tomography. Currently, PVRL is most often diagnosed using both histology to identify lymphoma cells in the vitreous or retina and immunohistochemistry to indicate monoclonality. Additional adjuncts in diagnosing PVRL exist, including elevation of interleukin-10 levels in ocular fluids and detection of Ig(H) or T-cell receptor gene rearrangements in malignant cells. The optimal therapy for PVRL is not defined and requires the combined effort of oncologists and ophthalmologists. PVRL is sensitive to radiation therapy and exhibits high responsiveness to intravitreal methotrexate or rituximab. Although systemic chemotherapy alone can result in high response rates in patients with PVRL, there is a high relapse rate. Because of the disease rarity, international, multicenter, collaborative efforts are required to better understand the biology and pathogenesis of PVRL as well as to define both diagnostic markers and optimal therapies.

Figure 1.

Slit-lamp biomicroscopy of a patient with primary vitreoretinal lymphoma. Binocular slit-lamp examination reveals numerous infiltrating cells (arrows) behind the lens in the vitreous.

Figure 2.

Optical coherent tomography (OCT) of the patient in Figure 1. (A): Cross-sectional images of the retina through several bright lesions are examined. (B): OCT shows nodular hyperreflective lesions (arrows) at the retinal pigment epithelium (RPE) level and sub-RPE space.

Figure 3.

Fundoscopy of the patient in Figure 1. There are many small, round, yellow-orange lesions (arrows) at the retinal pigment epithelium level in the deep retina.

Figure 4.

Fluorescein angiography and autofluorescence image of the patient in Figure 1. (A): There are small, round, hyperflorescent spots (arrows) corresponding to the lesions seen in Figure 3. (B): Fundus autofluorescence (fluorescence from the eye occurs without injection of dye) image shows small, round, hypofluorescent spots (arrows) reflecting lymphoma cells at the retinal pigment epithelium level.

Figure 5.

Cytology of primary vitreoretinal lymphoma. (A): Typical lymphoma cells are characterized by large nuclei, prominent nucleoli, and scanty basophilic cytoplasm (Giemsa stain; original magnification, ×640). (B): Immunohistochemistry illustrates CD20⁺ cells that are brown in color (avidin-biotin-complex immunoperoxidase; original magnification, ×400).