Lymphocytosis



Lymphocytosis


Qian-Yun Zhang, MD, PhD





Key Facts


Etiology/Pathogenesis



  • Lymphocytosis in children most likely benign


  • Persistent lymphocytosis in adults warrants diligent work-up to exclude neoplastic process


  • More than 90% of humans are infected by EBV


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


  • Persistent polyclonal B-cell lymphocytosis may show underlying genetic abnormality


  • Transient stress lymphocytosis is likely induced by epinephrine released by body or administered iatrogenically


  • It is difficult to distinguish reactive from clonal lymphoproliferative disorders in large granular lymphocytosis


Clinical Issues



  • Flow cytometric studies should be performed on all persistent lymphocytosis in adults


  • Assessment of T-cell receptor gene rearrangement by PCR or Southern blot is helpful to assess clonality


Microscopic Pathology



  • PB of IM reveals Downey type II or III lymphocytes


  • Persistent polyclonal B-cell lymphocytosis shows mature nonreactive lymphocytes with frequent bilobed nuclei


  • Transient stress lymphocytosis shows mature nonreactive lymphocytes


  • Large granular lymphocytes have abundant pale cytoplasm and azurophilic granules






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.)


TERMINOLOGY


Synonyms



  • Reactive lymphocytosis


Definitions



  • Elevated blood lymphocyte count above age-defined normal range


ETIOLOGY/PATHOGENESIS


Etiology



  • 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


Pathogenesis



  • 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


CLINICAL ISSUES


Epidemiology and Clinical Presentation

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

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