Infectious mononucleosis mimicking Epstein-Barr virus positive diffuse large B-cell lymphoma not otherwise specified

The Epstein-Barr virus (EBV) causes infectious mononucleosis (IM). In the case of atypical presentation, lymph node and tonsillar biopsies are required to rule out lymphoma. Here, we discuss an 83-year-old male who presented with findings suggestive of diffuse large B-cell lymphoma, which was later ruled out in favor of IM. The distinction between IM and lymphomas is quite challenging due to the extensive overlap between the two diseases. Various studies have demonstrated that EBV-positive diffuse large B-cell lymphoma mimics IM due to large B-cell proliferation in acute EBV infection. We suggest testing for acute EBV infection in addition to utilizing advanced testing to confirm IM in patients with atypical infection, to avoid misdiagnosis leading to inappropriate treatment.