70 Infectious Mononucleosis/Reactive Lymphocytes

Michelle To and Valentin Villatoro

Images of peripheral blood smears with heterogeneous reactive lymphocytes with prominent basophilic skirting of the cytoplasm. From MLS Collection, University of Alberta.

Image 1: 50x oil immersion. https://doi.org/10.7939/R3G44J57B

Image 2: 50x oil immersion. https://doi.org/10.7939/R34M91R9B

Image 3: 60 x oil immersion. https://doi.org/10.7939/R3GQ6RH6F


Cell Features:1-3

Large reactive (atypical) lymphocytes that represent activated T cells. The cytoplasm shows characteristic basophilic skirting in areas where there is contact with red blood cells. Red blood cells look as if they are creating indents in the cytoplasm. The population of reactive lymphocytes is heterogeneous with diverse shapes and sizes in cytoplasm and nuclear shapes.



Epstein-Barr Virus (EBV) infection that is usually acute, benign, and self-limiting.


Age group affected:1,3,5

Young adults (approx. 15-25 years of age)


Common Clinical Symptoms:1,4

Classic Triad: Pharyngitis, fever, lymphadenopathy.


Laboratory Features:1,3,5



Absolute lymphocytosis


Reactive lymphocytes


Other Tests:1,3,5

Positive heterophile antibody*

Positive EBV specific antigen and antibody (ELISA)*

Elevated C-reactive protein (CRP)

Viral cultures

Flow cytometry (to rule out malignancies with similar cell morphologies)


*Positivity for antigen or antibody varies depending on the date of testing. Some antigen or antibodies may appear only after a few weeks of infection.


Immunologic Markers:2

CD3, CD4 or CD8


1. Marionneaux S. Nonmalignant leukocyte disorders. In: Rodak’s hematology clinical applications and principles. 5th ed. St. Louis, Missouri: Saunders; 2015. p. 475-97.

2. Holmer LD, Bueso-Ramos CE. Chronic lymphocytic leukemia and related lymphoproliferative disorders. In: Clinical hematology and fundamentals of hemostasis. 5th ed. Philadelphia: F.A. Davis Company; 2009. p. 440-65.

3. Beglinger SS. Nonmalignant lymphocyte disorders. In: Clinical laboratory hematology. 3rd ed. New Jersey: Pearson; 2015. p. 409-24.

4. Turgeon ML. Leukocytes: nonmalignant lymphocytic disorders. In: Clinical hematology: theory and procedures. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. p. 229-43.

5. Harmening DM, Marty J, Strauss RG. Cell biology, disorders of neutrophils, infectious mononucleosis, and reactive lymphocytosis. In: Clinical hematology and fundamentals of hemostasis. 5th ed. Philadelphia: F.A. Davis Company; 2009. p. 305-30.


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Infectious Mononucleosis/Reactive Lymphocytes Copyright © 2019 by Michelle To and Valentin Villatoro is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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