Perspective
Ocular Adnexal Lymphoid Tumors: Progress in Need of Clarification

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Purpose

To evaluate recent ophthalmic publications on ocular adnexal lymphomas (OALs) according to histopathologic and immunophenotypic criteria used in the diagnosis of systemic lymphomas (World Health Organization classification).

Design

Summary and critical analysis of recent clinical and pathologic studies.

Methods

Literature review and interpretation.

Results

In the largest study of 353 cases of OALs published in the pathology literature, extranodal marginal zone lymphoma (EMZL) constituted 52%, follicular lymphoma 23%, mantle cell lymphoma 5%, and small cell lymphocytic and chronic lymphocytic leukemia 4%—plus a residuum of arcane entities. In smaller series of less intensively studied OALs in the ophthalmic literature, EMZLs had a higher preponderance and also were associated with a favorable prognosis. Many EMZLs seemed to arise primarily in the ocular adnexa (mucosa-associated lymphoid tissue [MALT] lymphoma should be restricted for EMZLs involving epithelial tissues).

Conclusions

Rigorous diagnostic criteria and a proposal for a prospective multicenter study may bring further clarification to the emerging order in this set of tumors.

Section snippets

General Features and Anatomy

Among 1,269 autopsied cases of systemic lymphomas,4 0.24% patients initially sought treatment for an OAL; by the time of death, ocular adnexal involvement had developed in a total of 1.3%. Another series puts ocular adnexal involvement at 5% of non-Hodgkin systemic lymphomas.5 Of all tumors with a propensity for extranodal sites, 8% settle in the ocular adnexa.6

There are two fundamental ways of looking at OALs: from the perspective of putatively predictive features that may be distinctive to

Overview of Ocular Adnexal Lymphoid Tumors or Lymphomas

The following clinicopathologic and immunophenotypic generalizations about OALs continue to be valid, although they include occasional exceptions. While the most common orbital tumors of adults, they are extremely rare in children, in whom a leukemic infiltrate instead should be suspected. They are generally indolent clinically, painless, functionally well tolerated, and mold on imaging studies to adjacent structures like the sclera and tissue planes, usually without bone destruction (in

General Pathologic Background

The single most valuable study covering OALs over the past decade is that by Ferry and associates, which intensively analyzed a staggering 353 cases by means of a plethora of immunophenotypic markers in conjunction with the World Health Organization (WHO) morphologic classification of lymphopoietic and hematopoietic neoplasms.7, 30 It offers a wealth of clinical and anatomic correlations and a panoply of immunologic, genotypic, and cytogenetic findings. Because it was published in the pathology

Histopathologic Findings

Follicular architecture (Figure, Top) to various extents and at different levels of clear definition is seen in overt follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma, and small cell lymphoma or chronic lymphocytic leukemia (which have pseudofollicles or growth centers containing paraimmunoblasts).7, 30 Prominent marginal zones in nonneoplastic lymphoid tissue can be discerned in Waldeyer oropharyngeal tonsillar tissue, Peyer patches, and splenic follicles, but are less

Immunophenotypic Findings

The combination of meticulous architectural and cytologic evaluation with immunophenotypic profiling is a powerful approach because it tremendously reduces intraobserver and interobserver discordances of morphologic interpretations. As a shorthand, marginal zone lymphoma cells are B-antigen positive, cyclin D1 negative, and CD5 negative (also rarely CD5 positive, bcl-6 negative, and bcl-2 positive). The aberrant expression of a T-cell antigen (CD5, CD43) on a cell of B-lymphocytic lineage is

Clinical Correlations

The clinical implications of properly using the diagnosis of extranodal marginal zone lymphoma (EMZL) are apparent. At the time of diagnosis, OALs of EMZL type are the most likely to be restricted locally, and on follow-up the least likely to have spread7, 9, 25 (Ferry J. Unpublished Data from a Clinical Follow-up Paper in Preparation, personal communication, February 2008). Rosado and associates diagnosed 89% of EMZLs among 62 OALs (53% in orbit, 26% in conjunctiva, and 19% in lacrimal gland).9

Conclusions

Until we have the results of such a study, the best advice that can be offered at the moment is to become deeply familiar with the results of Ferry and associates' landmark article and to stage clinically all patients with OALs regardless of their diagnosis.7 Fifteen years ago, Knowles and associates established that there were no incontestable pathologic or immunophenotypic criteria for predicting the full extent of an OAL's spread and that clinical staging transcended tissue studies in this

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