Atypical Mononuclear Cells

Atypical mononuclear cells (from Greek a- — negation, typos — model, monos — one, and Latin nucleus — nucleus) are large, round or irregularly shaped, morphologically altered white blood cells (activated T lymphocytes) that appear in large numbers in the peripheral bloodstream in response to infection.

The presence of atypical mononuclear cells is the most common diagnostic criterion for infectious mononucleosis caused by the Epstein–Barr virus. However, they may also occur in other viral diseases and occasionally in bacterial or parasitic infections; therefore, they are not a specific sign of infectious mononucleosis.

Etiology and pathophysiology

The pathogenesis underlying the appearance of these cells reflects a large-scale war within the immune system. When the Epstein–Barr virus enters the body, it predominantly infects B lymphocytes.

In response, the healthy component of the immune system deploys an army of cytotoxic T lymphocytes (CD8+ cells) to combat the infected cells.

During this acute reaction, T lymphocytes become hyperactivated. They undergo physical transformation:

• they increase significantly in size;
• their cytoplasm becomes abundant;
• the nucleus becomes loose, folded, or bean-shaped.

Under the microscope, these activated killer cells lose the classic appearance of a normal lymphocyte, which is why hematologists termed them atypical.

Clinical Significance

Detection of atypical mononuclear cells is a rapid and inexpensive method for diagnosing infectious mononucleosis. A laboratory medicine physician visually counts them during examination of a complete blood count (in the white blood cell differential).

In a healthy person, such cells are virtually absent from the blood. If the proportion of atypical mononuclear cells in the blood increases in the presence of fever, sore throat, and enlarged lymph nodes, a diagnosis of infectious mononucleosis may be suspected.

As recovery progresses and infected B lymphocytes are destroyed, T-cell hyperactivity decreases, and atypical mononuclear cells disappear from the bloodstream.