The diagnosis of infectious mononucleosis associated with Epstein-Barr virus (EBV) is usually based on a constellation of clinical signs and symptoms and a correlation with laboratory findings. In classic cases, there is a triad that includes sore throat, fever, and cervical (or generalized) lymphadenopathy. In some cases, however, the only presenting features may be fever and malaise, with or without lymphadenopathy. Important laboratory findings include leukocytosis with circulating atypical lymphocytes, a positive Monospot test, and characteristic serologic antibodies that are subsequently produced as an immunologic response to the virus. A lymph node biopsy is usually not necessary to make the diagnosis of EBV-related infectious mononucleosis and is actually discouraged because the histologic features may be worrisome and may mimic a malignant lymphoma. In rare cases, however, especially those with atypical clinical presentations, an excisional lymph node biopsy is performed as part of the routine clinical workup. It is important to be familiar with the characteristic histologic features, including diffuse paracortical lymphoid hyperplasia, and to be aware of the differential diagnosis that includes reactive entities as well as malignant lymphomas. Important benign entities that characteristically show diffuse paracortical lymphoid hyperplasia include other viral lymphadenitides such as herpes simplex, cytomegalovirus, postvaccinial and measles lymphadenitis, and drug-related lymphadenopathy, especially Dilantin. Malignant neoplasms, such as diffuse large B-cell-, Hodgkin-, and CD30-positive anaplastic largecell lymphoma, are also in the differential diagnosis of EBVassociated lymphadenitis. (Pathology Case Reviews 2004;9: 192-198) T he usual patterns of reactive lymphoid hyperplasia include follicular (germinal center) hyperplasia, nodular and diffuse paracortical hyperplasia, and sinus hyperplasia, although many entities characteristically show mixed or overlapping patterns of reactivity. 1 Other nonspecific findings include necrosis, granulomas, and stromovascular hyperplasia. Familiarity with the histologic and immunophenotypic features of a reactive lymph node is important in the recognition of benign changes and the distinction from malignant processes. Some pathologic entities are associated with very characteristic architectural or cellular changes, while others show nonspecific histologic features.Diffuse paracortical hyperplasia is an important pattern of reactivity in a lymph node that affects the architectural and cellular compartments. It has many causes, including infection, especially viral, immunodeficiency, and drug-related conditions. The diagnosis of diffuse paracortical lymphoid hyperplasia can generally be made by histologic criteria alone. Some cases of diffuse paracortical hyperplasia, however, such as EBV-associated lymphadenitis with prominent immunoblastic hyperplasia, can be difficult to distinguish from malignant lymphoma, 2,3 especially in the absence of ancillary studies such ...
