Qian-Yun Zhang, MD, PhD

PB smear is from a 20-year-old college student with fever, fatigue, and cervical lymphadenopathy for 2 weeks. The patient was diagnosed with infectious mononucleosis. Note Downey type II lymphocytes image.

PB smear is from a 34-year-old woman with persistent polyclonal B-cell lymphocytosis. Flow cytometric study reveals 2:1 κ/λ ratio. Note bilobed lymphocyte image. (Courtesy C.Y. Lee, MD.)



  • Reactive lymphocytosis


  • Elevated blood lymphocyte count above age-defined normal range



  • Lymphocytosis with reactive morphology

    • Viral infections, such as EBV, CMV, or other

  • Lymphocytosis with nonreactive morphology

    • Whooping cough (pertussis)

    • Transient stress lymphocytosis (TSL)

    • Persistent polyclonal B-cell lymphocytosis (PPBL)

  • Large granular lymphocytosis

    • T-cell large granular or chronic NK-cell lymphocytosis

  • Other causes of lymphocytosis

    • Neoplasia, postsplenectomy, or hypersensitive reactions


  • Infectious mononucleosis (IM)

    • EBV is DNA virus: Member of Herpesviridae family

    • EBV infects B lymphocytes and becomes latent; individual becomes lifelong EBV carrier

    • Acute infection induces cytotoxic T-cell response that eventually curbs viral proliferation and restrains immune response

    • Rarely chronic active EBV infection (CAEBV) develops; leads to progressive immunodeficiency

    • Hemophagocytic syndrome (HPS) and lymphoproliferative disorders can develop in CAEBV

    • In fatal IM, lymphocytes invade vital organs, cause HPS, massive marrow necrosis, and severe pancytopenia

    • Monoclonal or biclonal EBV and immunoglobulin heavy chain (IgH) or T-cell receptor (TCR) gene rearrangements are common in fatal IM

    • Nonfatal IM usually lacks monoclonal EBV, IgH@, or TRG@

    • Fatal IM patients are usually immunocompromised either by inherited immunodeficiency disorder, from immunosuppressants, or HIV infection

  • Persistent polyclonal B-cell lymphocytosis (PPBL)

    • Possible underlying genetic abnormality and familial occurrence

    • Association with HLA DR7 phenotype in some cases

    • Frequent detection of BCL2-IGH@ gene rearrangements and tri(3)(q10) in patients and first-degree relatives

    • Inhibition of apoptosis is proposed as cause for accumulation of peripheral blood lymphocytes

  • Transient stress lymphocytosis (TSL)

    • Associated with acute stressor, such as trauma, myocardial infarct, obstetric emergencies, sickle cell crisis, septic shock, status epilepticus

    • Likely induced by epinephrine released by body or administered iatrogenically

  • Large granular lymphocytosis

    • Difficult to distinguish reactive from clonal lymphoproliferative disorders

    • T-cell large granular lymphocytosis

      • Associated with solid tumor, lymphomas, viral infections, immune-mediated thrombocytopenia, or hemophagocytosis

      • Pathogenesis unclear; expansion in response to antigen stimulation possible

    • Chronic NK-cell lymphocytosis

      • Clonality assessment difficult

      • Often associated with cutaneous disorders, vascular diseases, or malignancy

      • Pathogenesis unclear; expansion in response to antigen stimulation possible


Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lymphocytosis
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