Outcome and prognostic factors in ocular adnexal lymphoma.

Aim: To classify ocular lymphomas in patients treated at the Zagreb University Hospital Center according to the new classification of the World Health Organization (WHO) and to determine factors with prognostic significance.

Methods: From 1986 to 2003, histological diagnosis of ocular lymphoma was made in 24 patients. The median age of patients was 62 years, with 2:1 female predominance. The patients underwent staging procedures and clinical evaluations prior to the date of the initial therapy. Histopathologic slides were reviewed and tumors were classified according to the new WHO classification. Additional immunohistochemical studies were performed on 35 available specimens. The antibodies used were CD3, CD5, CD10, CD20, CD43, and bcl-6; and in a few cases cyclin D1, bcl-2, CD23, CD79a, and CD138. The main outcome measures were development of distant recurrence after new presentation with solely ocular adnexal disease, and death attributable to widespread lymphoma.

Results: Ocular adnexal lymphomas were found in orbit in 20 patients, in eyelid in two, and conjunctiva in two patients. Twenty patients had lymphoma stage IE, one had IIE, and three had stage IV. Three patients had prior or concurrent systemic disease and 21 patients had primary lymphoma. The main subtypes of non-Hodgkin lymphoma according to the WHO classification were extranodal marginal zone B-cell lymphoma (n=20), diffuse large cell B-cell lymphoma (n=2), mantle cell lymphoma (n=1), and plasmacytoma (n=1). Six lymphomas were CD43 positive and five of them were extranodal marginal zone B-cell lymphomas. Radiotherapy was given to 11 patients, chemotherapy in 8 patients, whereas radiotherapy and chemotherapy were implemented in three patients. Two patients underwent only surgical excision of the tumor. Local relapse was found in three and distant recurrence in four patients. Distant recurrence was found in four patients with stage IE (two of them also had a local relapse). In the group of patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (B-EMZL), the estimated 5-year overall survival was 92.9+/-6.6% (mean+/-standard deviation) and the 5-year failure-free survival was 80.1+/-10.3%. Age, sex, side of involvement, anatomic localization of the lesion, clinical stage of disease, and mode of therapy did not have any prognostic significance during the follow-up period (median, 53; range, 9-131 months). Immunohistochemical marker CD43 was the only parameter of prognostic significance (p=0.035). Patients with B-EMZL had almost 14 times higher chance for an unfavorable outcome if the tumor cells expressed CD43 on their surface, than the CD43-negative cases.

Conclusion: Most ocular adnexal lymphomas usually have a B-cell immunophenotype, the morphologic and immunohistochemical features of extranodal marginal zone B-cell lymphoma, and a favorable prognosis. Our data suggest that CD43 could be useful to separate the group of patients with extranodal marginal zone B-cell lymphomas with unfavorable prognosis from those that have a good prognosis. CD43 positive ocular lymphomas are associated with a higher rate of subsequent distant recurrence and the rate of lymphoma-related death.