In the currently published World Health Organization-Classification, the new entity of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly was introduced largely based on findings from East-Asian populations. Little is known about its frequency or characteristics in the West, especially in European populations. Using a tissue microarray approach, we identified 8 out of 258 diffuse large B-cell lymphoma cases fulfilling the World Health Organization criteria of an Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly, suggesting an incidence of 3.1% in a European population. The median patient age was 65 years. The highest diagnostic sensitivity was only achieved by EBER in situ hybridization. No correlation between Epstein-Barr virus status and outcome was noted except in latency type 3 lymphomas, which had a very poor survival. Sixty-seven percent of Epstein-Barr virus-positive cases showed the presence of necrosis and 50% expressed the activation marker CD30. However, no morphological or immunohistochemical features reliably distinguished all Epstein-Barr virus-positive diffuse large B-cell lymphoma cases. Thus, to identify these Epstein-Barr virus-positive diffuse large B-cell lymphoma in the elderly, EBER in situ hybridization of all de novo diffuse large B-cell lymphoma cases of patients older than 50 years should be considered. In summary, Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly is rare in Europeans older than 50 years. It can only be diagnosed by EBER-ISH, and its precise prognostic role is unclear. Whether routine testing of all diffuse large B-cell lymphoma patients older than 50 years can be recommended depends essentially on its clinical relevance. Future studies are needed to address this question.
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