Fatal infectious mononucleosis with evidence suggestive of the development of B cell lymphoma

A 4-year-old girl presented to a local hospital in August 1999 with fever and cervical lymphadenopathy. A diagnosis of Epstein-Barr virus (EBV) infection was made and the patient was treated with corticosteroids. One month later she developed dyspnea secondary to tonsilar swelling, and underwent tonsillectomy and adenoidectomy. Her dyspnea increased, however, and by mid September she required mechanical ventilation. Six weeks later, she was transferred to Chiba Children's Hospital (Chiba, Japan). Despite vigorous treatment, she died within four weeks of admission. At autopsy, microscopic examination revealed numerous histiocytes with frequent hemophagocytosis in her lungs, liver, spleen, thymus, and lymph nodes. The tentative diagnosis was EBV-associated hemophagocytic syndrome (EBVAHS). A proliferation of atypical lymphocytes was observed in the lymph nodes, the majority of which stained positive with CD79a antibody. A whitish nodule, 8 mm in diameter, was noted in her right ovary. It consisted of a proliferation of pleomorphic lymphoid cells expressing CD79a antigen. In situ hybridization detected EBV RNA within CD79a antigen-positive cells in the lungs, spleen, thymus, bone marrow, lymph nodes, and the right ovary. Polymerase chain reaction analysis of DNA from the ovarian nodule demonstrated a monoclonal rearrangement of the immunoglobulin heavy chain gene indicating that it consisted of a clone of B lymphocytes. We suggest that EBVAHS develops into polyclonal and monoclonal lymphoproliferative disorder in a short period, and that EBVAHS is a preneoplastic condition that may result in B cell lymphoma.