543
Review
www.expert-reviews.com ISSN 1746-9899 © 2008 Expert Reviews Ltd 10.1586/17469899.3.5.543
To understand the histiogenesis of lympho-
mas and to define distinct lymphoma entities,
the current WHO classification emphasizes
an approach whereby the clinical characteris-
tics are correlated with distinct morphological,
immunophenotypical, and genotypical features
of each neoplasm [1] . For each lymphoma entity,
a putative cell of origin is postulated.
Intraocular lymphomas are heterogeneous
and have been subsumed for many years under
the vague title ‘primary intraocular lymphoma’
(PIOL). In fact, intraocular lymphomas repre-
sent several distinct entities, arising in different
structures of the eye and have differing clinical
courses; therefore, more specific terminology
is warranted (BOX 1 & TABLE 1) . In this review, the
pathology and molecular biology of the main
types of intraocular lymphoma are summarized.
Where possible, the cell from which the neoplas-
tic population has arisen will be proposed for the
main intraocular lymphoma entities.
Retinal lymphoma
Most intraocular lymphomas occur in the
retina, usually with vitreous involvement [2] .
Occasionally, retinal lymphoma occurs without
visible vitreous opacities and, less commonly,
lymphomatous vitreous infiltrates are seen in the
absence of any obvious retinal disease. For ease
of reference, the three different clinical variants
of retinal and vitreal lymphoma will be described
here under the term ‘retinal’ lymphoma (BOX 1).
Clinical features
Retinal lymphoma is a high-grade malignancy
that is often associated with cerebral disease. It
may be primary or secondary to CNS disease
or may present simultaneously [3–5] . Retinal
lymphoma most often affects elderly patients;
however, it is also seen in younger individuals,
particularly those who are immunocompromised
following HIV infection or organ transplantation.
Inexplicably, the incidence of retinal lymphoma
is increasing worldwide, even in immunocom-
petent patients [6] . Retinal lymphoma is usually
bilateral (60–90% of patients) but is often very
asymmetrical and apparently unilateral at initial
presentation [2] .
Approximately 80% of patients with reti-
nal lymphoma subsequently develop CNS
Sarah E Coupland
†
and
Bertil E Damato
†
Author for correspondence
Department of Cellular and
Molecular Pathology, University
of Liverpool, Duncan Building,
Daulby Street, Liverpool,
L69 3GA, UK
Tel.: +44 151 706 5885
Fax: +44 151 706 5859
s.e.coupland@liverpool.ac.uk
This article describes recent advances in the understanding of the molecular genetics of intraocular
lymphomas. These comprise vitreoretinal lymphoma, primary choroidal lymphoma, primary iris
lymphoma and secondary choroidal lymphomas. Following WHO principles, their classification
is now based on morphological, immunophenotypical and genotypical features. Retinal lymphoma
is a high-grade lymphoma, usually of B-cell type, and is associated with a poor prognosis because
of CNS involvement. Immunophenotyping and somatic mutation analysis suggest derivation
from early postgerminal center B cells. Chromosomal translocation data suggest that some arise
from germinal center B cells, which may have a better prognosis. Primary choroidal lymphoma
is a low-grade B-cell lymphoma similar to nonocular, extranodal marginal zone B-cell lymphomas
(EMZL). The putative cell of origin is a postgerminal center (memory) B cell. Primary iridal
lymphomas are rare, with an equal distribution of B- and T-cell types and with a variable clinical
course, most patients succumbing to systemic dissemination. Only one case of primary ciliary
body lymphoma has been reported. Secondary choroidal lymphomas/leukemias tend to represent
advanced systemic disease. Progress has been made in understanding the histiogenesis of
intraocular lymphoma. Further investigations, such as gene expression profiling, are required to
identify oncogenic pathways, to enhance prognostication and improve therapy.
KEYWORDS:choroidallymphoma•ciliarybodylymphoma•DLBCL•EMZL•intraocularlymphoma•irislymphoma
•retinallymphoma•vitreallymphoma•vitreoretinallymphoma•uveallymphoma
Molecular pathology of
intraocular lymphomas
Expert Rev. Ophthamol. 3(5), 543–551 (2008)
For reprint orders, please contact reprints@expert-reviews.com