A 36-year-old man presented to the emergency room with fever and fatigue for two weeks. Analytically showed: hemoglobin 143 g/L, platelet count 218 × 109/L, leukocytosis 17.5 × 109/L with lymphocytosis (81%), alanine aminotransferase 3.22 µkat/L, aspartate aminotransferase 2.13 µkat/L, lactate dehydrogenase 7.15 µkat/L, serologic testing for hepatitis B, C and HIV negative. Monospot test was positive.

The peripheral blood film (PBF) showed atypical lymphocytes (21% of leukocytes): (a) large lymphocytes with abundant and indented cytoplasm that surrounds red blood cells, with large nucleus some having central nucleoli; (b) sometimes with an apparent double cytoplasmic membrane; (c) large lymphocytes with a diffuse and reticular chromatin pattern and diffuse reticular cytoplasm; (d) large lymphocytes with strongly basophilic cytoplasm (plasmacytoid lymphocytes); (e) large to medium lymphocytes with large, medium and small uropods (thick and thin), some presenting microspikes or detached cytoplasm (hand-mirror cells); (f) medium to small lymphocytes with lobulated nucleus, sometimes occasionally resembling a cloverleaf; (g) large to medium granular lymphocytes; (h) apoptotic lymphocytes with regular vacuolated nucleus, and (i) band forms or hyposegmented neutrophils (pseudo-Pelger-Huët) with toxic granulations (Figure 1, Wright-Giemsa stain, × 100 objective).

Figure 1.

Peripheral blood film in infectious mononucleosis by Epstein-Barr virus.

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Infectious mononucleosis (IM) is associated with primary infection by Epstein–Barr virus (EBV), a gamma herpesvirus. The incubation period is about 30–50 days. 1

Atypical lymphocytes are activated T lymphocytes produced as part of the immunological response to EBV infected B lymphocytes. The presence of (a) ≥50 % lymphocytes in total leukocytes, and (b) ≥10 % atypical lymphocytes on PBF (sensitivity 75 %; specificity 92 %) are strongly suggestive of IM. 1,2

A positive heterophile antibody test (monospot) has a sensitivity of 85 % and a specificity 94 %. 1

Aminotransferase levels may be elevated in adults. 1

The diagnosis of IM can be done by clinical presentation, the presence of atypical lymphocytes on a PBF, and a positive monospot. 1

If the diagnosis is unclear, EBV-specific serologic testing (testing for specific IgM and IgG antibodies against viral capsid antigens, early antigens, and EBV nuclear antigen proteins) can be used to a final diagnose. 1

Treatment is supportive. Antiviral therapy is not recommended, and corticosteroids are only recommended for complicated cases. 1