Ocular adnexal lymphoma: Clinical behavior of distinct World Health Organization classification subtypes

Abstract

Purpose

To evaluate the clinical behavior and treatment outcome of ocular adnexal lymphomas classified by the World Health Organization system, with emphasis on marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT).

Methods and materials

The clinicopathologic materials from 98 consecutive patients treated for ocular adnexal lymphoma were reviewed. Fourteen patients had prior lymphoma and 84 patients had primary disease (75% Stage I, 6% Stage III, and 19% Stage IV). Radiation (photons/electrons) was administered to 102 eyes to a median dose of 30.6 Gy. The mean follow-up was 82 months.

Results

The most common subtypes among the primary patients were MALT (57%) and follicular (18%) lymphoma. The 5-year actuarial local control rate in 102 irradiated eyes was 98%. Among the low-grade lymphomas, the 5-year local control rate correlated with the radiation dose in the MALT lymphoma subgroup (n = 53): 81% for <30 Gy and 100% for ≥30 Gy (p <0.01). For the non–MALT low-grade lymphomas such as follicular lymphoma (n = 30), the local control rate was 100% regardless of dose. For 39 Stage I MALT lymphoma patients treated with radiation alone, the distant relapse-free survival rate was 75% at 5 years and 45% at 10 years. Distant relapses were generally isolated and successfully salvaged by local therapy. The overall survival for this subgroup was 81% at 10 years, with no deaths from lymphoma.

Conclusion

Dose–response data suggest that the optimal radiation dose for MALT lymphoma of the ocular adnexa is 30.6–32.4 Gy in 1.8-Gy fractions and follicular lymphoma is adequately controlled with doses in the mid-20 Gy range. The substantial risk of distant relapse in Stage I ocular adnexal MALT lymphoma underscores the importance of long-term follow-up for this disease and the need for additional comparative studies of MALT lymphoma of different anatomic sites.

Introduction

It is estimated that lymphoma of the ocular adnexa represents approximately 8% of extranodal non-Hodgkin's lymphomas (1). Although much has been written about the subject, the data are difficult to interpret because many of the published series grouped lymphomas of various histologic subtypes together in their analyses. The inclusion of benign lesions of lymphoid hyperplasia and the use of the now out-of-vogue term “pseudolymphoma” in certain studies further clouded the understanding of the malignant counterpart.

Although any of the many histologic subtypes of non-Hodgkin's lymphoma may be encountered in the ocular adnexa, the extranodal marginal zone lymphoma, mucosa-associated lymphoid tissue (MALT) type has been found to be an important subtype. Isaacson and Wright (2) first introduced the concept of MALT in the 1980s when they made the seminal observation that certain extranodal lymphomas were related to mucosa-associated lymphoid tissue rather than to nodal lymphoid tissue. Since then, MALT lymphoma has gained general acceptance as a distinct clinicopathologic entity and is included in the Revised European–American Lymphoma classification under the broader term of marginal zone B-cell lymphoma (3) and in the World Health Organization (WHO) classification as marginal zone B-cell lymphoma, MALT type (4).

This paper presents the Massachusetts General Hospital experience on a large cohort of consecutive patients with lymphoma of the ocular adnexa classified under the WHO classification scheme. Local control issues, as well as long-term clinical outcome, are discussed, with emphasis on the two most common histologic subtypes, marginal zone lymphoma/MALT type and follicular lymphoma.