Infectious Mononucleosis and Monoclonal B Lymphocytosis in an Elderly Man

Abstract

To the Editor: Infectious mononucleosis (IMN) is a clinical syndrome commonly associated with primary Epstein-Barr virus (EBV) infection. Primary EBV infection usually occurs in childhood or adolescence, and seroepidemiologic surveys indicate that more than 95% of adults worldwide are infected with EBV.1 Consequently, the diagnosis of IMN in older adults is uncommon and may be delayed. The case of an older adult hospitalized for an atypical presentation of IMN is reported. An 83-year-old white man was hospitalized for increasing fatigue, nighttime sweating, weight loss (5 kg), and blood abnormalities (Table 1) that had been progressing for a month. His medical history included cardiac arrhythmia, high blood pressure, and moderate kidney failure. Physical examination showed splenomegaly (3 cm under the costal margin) without peripheral lymphadenopathy, hepatic enlargement, pharyngitis, or skin rash. A computed tomography scan showed splenomegaly (17-cm axis), multiple abdominal lymphadenopathies (diameter between 1 and 2.5 cm), and mesenteric panniculitis. All clinical and laboratory abnormalities were compatible with two diagnoses: aggressive lymphoid proliferation and subacute viral disease. A lymphoma diagnosis procedure was implemented that consisted of blood smear, which indicated atypical lymphocytes compatible with a leukemic process; lymphocyte immunophenotyping, which revealed CD8 T-cell expansion without any abnormal population; and karyotyping of lymphoid cells, which showed chromosome 12 trisomy. The results of the viral disease diagnosis procedure indicated acute EBV infection. The tests for cytomegalovirus and human immunodeficiency virus were negative. Serological testing for toxoplasmosis indicated past infection. Infectious mononucleosis was thus diagnosed. Clinical and laboratory parameters improved, and the man was discharged on the fourth day. One month later, he reported complete recovery. Standard physical examination findings were normal, and laboratory results were subnormal (Table 1). Testing for antiviral capsid antigen immunoglobulin (Ig)G was positive; anti-Epstein Barr nuclear antigen IgG remained negative. Because of the abnormal lymphoid karyotype and IMN diagnosis, lymphocyte immunophenotyping was repeated 1 and 6 months after diagnosis. A ĸ monoclonal B-cell population was confirmed. All of the B-cells were included in that population, which accounted for 17% of the total lymphoid cell count and expressed CD5 and CD23 with weak CD20 and CD79b. Chronic lymphocytic leukemia-like monoclonal B lymphocytosis (CLL-like MBL) was thus diagnosed. This report highlights the potential difficulty in diagnosing IMN in older adults. Epidemiological data constitute the first obstacle. Three retrospective studies found a combined total of 107 cases of IMN in subjects aged 40 and older out of 11,112 positive sera.2-4 Because IMN is so rare in adults, it tends not to be considered, particularly in elderly adults. The clinical presentation in older adults may also be misleading because lymphadenopathy, pharyngitis, and splenomegaly are less common, unlike jaundice, which is more frequent.4-6 Atypical (pneumonia, abdominal pain, diarrhea, emesis, joint pain) or nonspecific (prolonged fever, weakness, nighttime sweating) symptoms frequently delay diagnosis, which is commonly misdirected to hepatitis, biliary obstruction, or hematological malignancy.4, 7-9 Some older adults may have a false-negative result for heterophile antibodies.4 All of the atypical symptoms may lead to inappropriate invasive diagnotic procedures such as bone marrow aspiration and hepatic or lymph node biopsies.4, 8 The case reported herein is highly informative. The nighttime sweating, weight loss, abdominal lymphadenopathy, mesenteric panniculitis, and splenomegaly suggested aggressive lymphoma or leukemia. The initial blood smear interpretation indicated atypical lymphocytes with immature chromatin, suggesting a leukemic phase of aggressive lymphoma. Subsequently, lymphocyte immunophenotyping and a repeat blood smear enabled rectification of the diagnosis. Serological testing for EBV and viral load determination both indicated acute EBV infection. The second interesting finding in this case is that the lymphoma diagnosis examination revealed CLL-like MBL. Like the monoclonal gammopathy of undetermined significance that precedes multiple myeloma, CLL-like MBL, which is a recently defined entity, precedes virtually all cases of CLL. The incidence of CLL-like MBL increases with age and is approximately 5% after age 60.10 The diagnostic criteria consist of the presence of a monoclonal B-cell population with specific immunophenotype, an absolute B-cell count of less than 5,000/μL, and the absence of other features of lymphoproliferative disorder or autoimmune disease. The risk of progression to CLL requiring treatment is approximately 1% to 2% per year and is associated with a high lymphocyte count and possibly the presence of trisomy 12.10 The case reported herein requires annual clinical follow-up with blood counts every 6 months. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: JVM: Physician in charge of the patient and manuscript preparation. FD: Physician in charge of the patient. JK: Helped write the manuscript. CS and TS: Helped in the diagnosis. TdR: Took part in the last reading of the manuscript. Sponsor's Role: No sponsor for this study.