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 IgH 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.

Molecular pathology of lymphoma

“…The clinical features and treatment of VRL will not be discussed here: the reader is referred to the accompanying manuscript of Dr Janet Davis in this edition of Eye, as well as to other recent reviews. 2,56,57 Histologically, VRL can be subtyped in most cases as DLBCL, 3 according to the latest WHO lymphoma classification. 1 Rare subtypes include T-cell-rich B-cell lymphoma 58 and T-cell lymphoma.…”

Primary Intraocular Lymphoma

“…The optimal treatment regimen for PIOL has yet to be established and requires a multidisciplinary approach between the ophthalmologist, radiologist, pathologist, and oncologist. 34,158 Even experts in the diagnosis and treatment of PIOL have contrasting views as to the use of systemic versus intravitreal chemotherapy and the role of irradiation. 205 Intravitreal chemotherapy with more than one agent may prove to be useful in ocular disease control.…”

Primary Intraocular Diffuse Large B-cell Lymphoma: Diagnostic Difficulties in Deep Retinal Infiltrations with Vitritis

“…According to the other data, the relapse of PIOL is frequent in the brain, spinal cord and the meningeal localization, and despite high doses of chemotherapy the course is often fatal. Follow-up periods range from 12 to 35 months, with mortality rates up to 81 % [7]. The optimal approach includes either systemic or intraocular chemotherapy, which delays the relapse and may influence the overall survival.…”