Intraocular lymphoma: a clinical perspective

Abstract

Primary vitreoretinal lymphoma (PVRL) is a rare malignancy that is speculated to arise extraocularly, and preferentially invade and flourish in the ocular and CNS microenvironments. The eye is involved in about 20% of primary central nervous system lymphomas, but the brain is eventually involved in about 80% of PVRL. Most are B-cell lymphomas with small numbers of T-cell lymphomas metastatic to the vitreous and retina. Metastatic systemic B-cell lymphoma usually involves choroid. Primary choroidal lymphoma is rare. Intraocular lymphoma can usually be distinguished from uveitis clinically, although there are overlaps, which may be pronounced in eyes with a large component of reactive inflammation related to tumor surveillance and control. There are controversies in diagnosis and treatment. Diagnosis through examination of ocular fluid is technically difficult and can utilize cytology, immunohistochemistry, flow cytometry, molecular detection of gene rearrangements, and cytokine profiling. Treatment of intraocular lymphoma without detectable CNS disease could consist of a full course of systemic chemotherapy with ocular adjunctive treatment, or ocular treatment alone depending on the preference of the clinical center. In ocular only cases where the vitreous has been debulked to improve vision and there is no sight-threatening involvement of the RPE, orbital irradiation or intravitreal chemotherapy stabilizes the intraocular process but does not seem to modify the CNS component, which can present symptomatically in an advanced state. This is a highly malignant disease with a poor prognosis. Close collaboration with a pathologist and oncologist, and good communication with patients is essential.

Figure 1

Depiction of typical growth patterns for PVRL. Left, primarily vitreous infiltration. Vitreous haze was dense enough in some areas to completely obscure the fundus; the central clear zone permitted good vision of 20/30. Vitreous stranding and clumping typical of inflammatory disease is absent. Right, large deposit under the retinal pigment epithelium in an HIV-infected patient with PCNSL. The preretinal white patch on the dome of the lesion is lymphomatous proliferation into the vitreous. Note the vascular sheathing and the small clumps of RPE over the tumor mass.

Figure 2

Retinal lymphoma in a patient treated for PCNSL 5 years previously. Top left, right fundus photograph shows pale, round lesions. Top right, autofluorescent imaging shows the round lesions to be mainly hypofluorescent. The clustering of the lesions along retinal arterioles is better seen in the autofluorescent image and suggests entry into the eye via the retinal circulation. The optic nerve was normal. The diffuse hyperautofluorescence likely indicates RPE level infiltration. Bottom, video and spectral domain OCT through two of the round lesions confirms their intraretinal location. The lesion on the right has eroded through retina and is resting on the RPE.

Figure 3

RPE involvement in PVRL. Left, grayscale rendition of a color photograph. The pale lesions are lymphomatous deposits that appear yellow clinically. The larger round lesions are growing the RPE as evidenced by the clumps of pigment on their domes. The smaller punctate and spiculated deposits are also likely sub-RPE. Notice the hazy retinal infiltrates temporally in this right eye and the obscuration of the retinal vessels in this area either from sheathing or retinal infiltration. Right, early stage fluorescein angiogram of the same eye demonstrating classic leopard spot pigmentation. The hypofluorescent lesions are the deposits of lymphoma cells.

Figure 4

Autofluorescence and OCT imaging in PVRL. Left, the fundus is studded with multiple punctate hyperfluorescent dots. There is one placoid lesion in the inferior macula. The dark dots may represent areas of damage to the RPE or collections of lymphoma cells that have grown above the RPE and are blocking the native autofluorescence. Right, correlation with the OCT section through the fovea where the white dots are minimal nonetheless OCT shows multiple pre-Bruchs/sub-RPE deposits that protrude anteriorally to the outer retina.

Figure 5

Initial response to intravitreal methotrexate in a patient with PVRL who has not received prior treatment with corticosteroids, systemic chemotherapy, or ocular irradiation. Left, a large retinal infiltrate developed in a patient status post diagnostic vitrectomy showing B-cell predominance on flow cytometry but untreated by the hemato-oncologic consultant. Top right, spectral domain OCT through the infiltrated area on the day of injection (baseline). There are heavy deposits under the RPE and retina. The segmentation line is improperly drawn: Bruch's membrane corresponds to the smooth white line just anterior to the choroidal vessels. Bottom right, spectral domain OCT 2-weeks after intravitreal methotrexate injection 400 μg in 0.1 ml. There is dramatic resolution of the cellular deposits. The gray segmentation line is properly drawn along Bruch's membrane. Overall thickness is markedly reduced.