A fibrin ring granuloma may be present. Differential diagnosis
About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection. A differential diagnosis of acute infectious mononucleosis needs to take into consideration acute cytomegalovirus infection and Toxoplasma gondii infections. Because their management is much the same, it is not always helpful, or possible, to distinguish between Epstein–Barr-virus mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from toxoplasmosis is important, since it is associated with significant consequences for the fetus.Acute HIV infection can mimic signs similar to those of infectious mononucleosis, and tests should be performed for pregnant women for the same reason as toxoplasmosis.People with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the symptoms of fever, pharyngitis and adenopathy) and are given antibiotics such as ampicillin or amoxicillin as treatment.Other conditions from which to distinguish infectious mononucleosis include leukemia, tonsillitis, diphtheria, common cold and influenza (flu). Treatment
Infectious mononucleosis is generally self-limiting, so only symptomatic or supportive treatments are used. The need for rest and return to usual activities after the acute phase of the infection may reasonably be based on the persons general energy levels.
On the other hand, the absence of swollen cervical lymph nodes and fatigue are the most useful to dismiss the idea of infectious mononucleosis as the correct diagnosis. The insensitivity of the physical examination in detecting an enlarged spleen means it should not be used as evidence against infectious mononucleosis. A physical examination may also show petechiae in the palate. Heterophile antibody test
The heterophile antibody test, or monospot test, works by agglutination of red blood cells from guinea pigs, sheep and horses. This test is specific but not particularly sensitive (with a false-negative rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third). About 90% of diagnosed people have heterophile antibodies by week 3, disappearing in under a year. The antibodies involved in the test do not interact with the Epstein–Barr virus or any of its antigens.The monospot test is not recommended for general use by the CDC due to its poor accuracy. Serology
Serologic tests detect antibodies directed against the Epstein–Barr virus. Immunoglobulin G (IgG), when positive, mainly reflects a past infection, whereas immunoglobulin M (IgM) mainly reflects a current infection. EBV-targeting antibodies can also be classified according to which part of the virus they bind to:

Viral capsid antigen (VCA):Anti-VCA IgM appear early after infection, and usually, disappear within 4 to 6 weeks.