An important way to avoid this problem is to avoid the removal of enlarged lymph nodes in a patient with clinical features of infectious mononucleosis.
Reasons to suspect infectious mononucleosis rather than lymphoma:
(1) younger patient with no evidence of immunosuppression
(2) clinical features of infectious mononucleosis
(3) serologic evidence of Epstein-Barr virus
(4) atypical polymorphous reaction with plasma cells, histiocytes and “reactive-appearing” small lymphocytes
(5) presence of necrosis
(6) presence of ulceration in adjacent mucosa
(7) preservation of nodal architecture
(8) polyclonal kappa and lambda light chains
Immunoblastic cells in EBV infections are MUM1 positive, CD10 negative and bcl-6 negative.
Reed-Sternberg like cells in EBV infections are CD15 negative, BOB.1 positive and OCT-2 positive.
Reasons to suspect an EBV-related malignant lymphoma:
(1) immunosuppression, especially organ transplantation
(2) older age (diffuse large B-cell lymphoma of the elderly)