Understanding intraocular lymphomas

Abstract

The purpose of this review is to describe the clinical features, pathology and molecular biology of intraocular lymphomas, which represent a heterogenous group of malignant neoplasms; to propose an anatomical classification of these tumours according to whether they occur in the retina or uvea; and to overview laboratory investigations and highlight factors required for successful biopsy. Recent findings show that retinal lymphomas are high-grade (i.e. aggressive), B-cell malignancies and are associated with a poor prognosis, with most patients dying of central nervous system disease. Immunophenotyping and somatic mutation analyses indicate that these lymphomas are probably derived from early post-germinal centre cells. Primary choroidal lymphomas are typically low-grade (i.e. indolent), B-cell tumours with morphological, immunophenotypical and genotypic features similar to extranodal marginal zone B-cell lymphomas (EMZL) elsewhere in the body. The putative cell of origin is the post-germinal centre (memory) B cell. Primary iridal lymphomas are very rare, with an equal distribution of B- and T-cell types and with a variable clinical course, most patients succumbing to their disease as a result of systemic dissemination. Primary lymphomas limited to the ciliary body are exceptionally rare. Secondary uveal lymphomas/leukaemias occur in patients with advanced systemic lymphoma or leukaemia, respectively. In summary, the term 'primary intraocular lymphoma (PIOL)' is imprecise. It would be preferable to refer to the various forms of intraocular lymphoma according to whether they are retinal, choroidal, ciliary or iridal and whether they are primary or secondary in these locations.

Molecular pathology of lymphoma

“…41 DLBCL is remarkably diverse in both clinical presentation and outcome, likely reflecting both its pathogenetic and biological heterogeneity. DLBCL is the most frequent lymphoma subtype arising in the eye as VRL (see below), 3 and the second most common lymphoma subtype occurring in the ocular adnexa. 6,42,43 Molecular genetic subtyping of DLBCL Over the past decade, the use of genome-wide expression profiling (GEP) has not only allowed a better understanding of the molecular mechanisms underlying the development of this disease, but also revealed a number of features associated with an unfavourable clinical outcome.…”

“…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.…”

“…[5][6][7][8][9] Interestingly, the EMZL is also the most common primary lymphoma occurring in the choroid. 3 In the following review, the molecular pathologies of only DLBCL and EMZL will be discussed. Concerning the other lymphoma subtypes occurring in the ocular adnexa and in the other intraocular tissues (eg the choroid), the reader is referred to recent reviews.…”

“…Intraocular lymphomas are rare with the most common type being the vitreoretinal lymphoma (VRL; previously called 'primary intraocular lymphoma'), which is usually a diffuse large B-cell lymphoma (DLBCL) occurring in the vitreous and retina, and with frequent involvement of the central nervous system (CNS). [2][3][4] Lymphomas of the ocular adnexa are relatively uncommon, accounting for B8% of all extranodal malignant lymphomas. Most are primary tumours and are usually NHL of B-cell type: the most common primary lymphoma subtype occurring in the ocular adnexa is the low-grade malignant extranodal marginal zone B-cell lymphoma (EMZL), accounting for approximately two thirds of all ocular adnexal lymphomas.…”

Combined therapy associating systemic platinum-based chemotherapy and local radiotherapy into the treatment of primary intraocular lymphoma

“…PIOL is considered to be a rare subtype of central nervous system lymphoma with a high risk of relapse that is characterised by either intraocular relapse or metastasis into the central nervous system (1,7). This type of lymphoma is mainly found in elderly and immunocompromised patients and rarely in young patients (2,3).…”