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Background: CD99 immunoreactivity has been documented in a variety of tumors, including lymphoid malignancies such as anaplastic large-cell lymphomas. However, few studies have investigated the prognostic impact of CD99 in diffuse large B-cell lymphoma (DLBCL). Methods: Using conventional paraffin embedding, immunoperoxidase staining and tissue microarrays, we retrospectively investigated CD99 expression in 155 DLBCL patients. Results: Of the 155 DLBCL patients, 60 (38.7%) were positive for CD99. CD99 positivity was significantly associated with advanced stage (p < 0.01), higher risk group according to the International Prognostic Index risk score (p < 0.01) and non-germinal center B cell-like type (p = 0.01). The difference in progression-free survival (PFS) between CD99+ and CD99- groups was statistically significant (p = 0.04), even though the difference in overall survival was not (p = 0.74). Multivariate analysis demonstrated that CD99 expression was marginally correlated with PFS. Conclusion: To the best of our knowledge, this is the first report on the clinicopathologic characteristics of CD99+ DLBCL, particularly unique clinicopathologic features. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]