Infectious mononucleosis. The spectrum of morphologic changes simulating lymphoma in lymph nodes and tonsils

Lymph-node and tonsillar biopsies occasionally are obtained from patients with the infectious mononucleosis syndrome secondary to Epstein-Barr viral infection, particularly if the clinical presentation is atypical and a viral etiology is not suspected. The presence of Reed-Sternberg-like cells in infectious mononucleosis resulting in confusion with Hodgkin's disease is well-known; however, similar difficulty in excluding a non-Hodgkin's lymphoma can be encountered. Eleven cases of reactive lymphoid hyperplasia with the morphologic features of infectious mononucleosis are reported, nine of which had documented Epstein-Barr viral infection. The spectrum of morphologic changes associated with Epstein-Barr viral infection is discussed, with emphasis on the features that permit their distinction from non-Hodgkin's lymphoma. Morphologic features mimicking lymphoma included extensive immunoblastic proliferations in sheets and nodules and marked cytologic atypia. Hodgkin's disease was simulated by the tendency in some cases for the atypical Reed-Sternberg-like cells to cluster about necrotic foci and to show pronounced cytologic atypia. Features permitting the distinction from non-Hodgkin' lymphoma included persistent reactive foci with the classic features of infectious mononucleosis, a polymorphous background of transformed lymphocytes rather than irregular or twisted lymphoid cells as seen in non-Hodgkin's lymphoma, and preservation of underlying reticulin architecture rather than destruction, even in cases with extensive immunoblastic proliferation. Hodgkin's disease was excluded by requiring strict criteria for Reed-Sternberg cells and noting the reactive background as inconsistent with Hodgkin's disease. Immunoperoxidase staining of seven of the cases with anti-Leu-M1 failed to demonstrate immunoreactivity of the Reed-Sternberg-like cells with this monoclonal antibody.