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. 2000 Aug;84(8):907–913. doi: 10.1136/bjo.84.8.907

Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival

C Jenkins 1, G Rose 1, C Bunce 1, J Wright 1, I Cree 1, N Plowman 1, S Lightman 1, I Moseley 1, A Norton 1
PMCID: PMC1723589  PMID: 10906102

Abstract

BACKGROUND—The histological characteristics of ocular adnexal lymphomas have previously provided only a limited guide to clinical outcome for affected patients. This clinicopathological relation was re-examined using the Revised European American Lymphoma (REAL) system to classify the tumours in a large cohort of patients.
METHODS—The biopsies and clinical follow up data for 192 patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded in accordance with the REAL classification. For each of five histological groups, logistic regression analysis was used to determine the odds ratios (OR) for the presence of systemic disease at the time of orbital diagnosis and Cox regression analysis was used to assess the hazard ratios (HR) for disseminated disease and lymphoma related death. For 108 patients in whom extraorbital spread occurred, the histological category of lymphoma was compared with the sites of dissemination.
RESULTS—At presentation, the frequency of previous or concurrent extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma variants (OR 26.8). For all histological types, the estimated risk of extraorbital disease and lymphoma related death continued for many years and the proportion of patients with at least one extraorbital recurrence after 5 years was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other lymphoma variants. The corresponding estimated rates for 5 year lymphoma related mortality were 12%, 19%, 22%, 48%, and 53% respectively.
CONCLUSIONS—Patients with ocular adnexal lymphoma can be classified by REAL into five distinct groups, which show a progressive increase in the risks of extraorbital disease at diagnosis, of disease dissemination with time, and of tumour related death.



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Figure 1  .

Figure 1  

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Typical histomorphology for lymphomas of the ocular adnexa (haematoxylin and eosin staining, unless otherwise stated). (A) Centrocyte-like cells in marginal zone lymphoma; (B) lymphoplasmacytoid cells in marginal zone lymphoma; (C) trapped reactive follicle in marginal zone lymphoma; (D) follicular architecture in follicle centre lymphoma; (E) centrocytes and centroblasts in follicle centre lymphoma; (F) centroblasts in diffuse large B cell lymphoma; (G) centrocytes in mantle cell lymphoma; (H) Cyclin D-1 staining in mantle cell lymphoma.    

Figure 2  .

Figure 2  

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Cumulative proportion without extraorbital disease, based on 192 patients with ocular adnexal lymphoma: 82 marginal zone lymphomas (MZL), 44 lymphoplasmacytoid/lymphoplasmacytic lymphomas (LPL), 26 follicle centre lymphomas (FCL), 19 diffuse large B cell lymphomas (DLCL), and 21 other variants (H5). The data are censored for patients who, at time of last follow up, had not developed extraorbital disease. The figures refer, at a given time, to the number of survivors without recurrent extraorbital disease (classified by histopathological type).

Figure 3  .

Figure 3  

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Cumulative proportion without lymphoma related death, based on 192 patients with ocular adnexal lymphoma (abbreviations and numbers as Fig 2). The data were censored for patients in whom the last follow up was before the end of the 8 year study period, either because of incomplete follow up or where death was unrelated to lymphoma. The numerical data refer to the number of patients alive at a given time.

Figure 4  .

Figure 4  

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Cumulative proportion of patients, presenting with solely orbital disease, who remain without extraorbital spread—a comparison of marginal zone lymphoma (MZL; 67 cases) and lymphoplasmacytoid/lymphoplasmacytic lymphoma (LPL; 29 cases). The figures refer to the number of patients alive without recurrence at a given time.

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