Lymphocytosis

Introduction:

• It is a condition in which absolute lymphocyte count is more than 4000/cmm
• In children this threshold is generally 8000/cmm

Causes

• Lymphoproliferative disorders.
  • Acute lymphoblastic leukemia.
  • Chronic lymphocytic leukemia
  • Monoclonal B cell lymphocytosis.
  • Prolymphocytic leukemia.
  • Hairy cell leukemia.
  • Adult T cell leukemia
  • Large granular lymphocytic leukemia
  • Splenic marginal zone lymphoma.
  • Lymphoplasmacytic leukemia.
  • Follicular lymphoma
  • Mantle cell lymphoma.
  • Sezary syndrome
  • Autoimmune lymphoproliferative syndrome.
• Reactive
  • Mononucleosis syndromes: EBV, CMV, HIV, HSV, Rubella, Toxoplasma, Adeno, Infections hepatitis, dengue, HHV6, HHV-8, VZV.
  • Bordetellapertussis
  • Chronic infections- TB,leprosy,leishmaniasis, strongyloides, brucellosis
  • Stress lymphocytosis- Cardiovascular collapse due to MI/Acute CCF, staphylococcal toxic shock syndrome, drug induced (anticonvulsants, sulphonamides), major surgeries, sickle cell crisis, status epilepticus, trauma, exercise
  • Hypersensitivity reactions- Insect bite, drugs.
  • Postsplenectomylymphocytosis.
• Others
  • Thymoma
  • NK cell lymphocytosis (May be secondary to exaggerated response to CMV, strongyloidiasis, use of dasatinib)
  • Persistent polyclonal B cell lymphocytosis
    • No evidence of infection or other conditions that can increase lymphocyte count. 
    • Peripheral blood shows unusual binucleated/ bilobed nuclear lymphocytes. 
    • These cells show low/expression of CD5/CD23, but express high levels of Ig D and CD27, a phenotype shared by memory B cells, 
    • Usually young to middle aged woman are affected. 
    • Usually associated with HLC-DR 7 
    • Presents with mild splenomegaly.
    • S. IgM is usually increased
    • No treatment is required

Investigations:

• Peripheral smear
  • Reactive lymphocytes: Infectious mononucleosis
  • Large granular lymphocytes- LGL leukemia
  • Smudge cells- CLL
  • Blasts- ALL
• Immunophenotyping by flow cytometry
  • Differentiates reactive from clonal proliferation
  • If clonal, helps in identifying type of leukemia
  • Panel depends on morphology of abnromal cells in peripheral smear
• Lymph node biopsy and IHC- If lymphadenopathy is present 

Lymphopenia

Introduction:

• It is a condition in which absolute lymphocyte count is less than 1200/cmm.
• Normally-80% are T cells out of which 66% are CD4 positive and 20% are B Cells

Causes:

• Congenital
  • Severe combined immunodeficiency
  • Common variable immunodeficiency
  • Congenital thymic aplasia
  • X-linked agammaglobulinemia
  • Wiskott -aldrich syndrome
  • Purine nucleoside phosphorylate deficiency
  • Ataxia telangiectasia
• Aplastic anemia
• Viral infection-HIV/AIDS, SARS, hepatitis, influenza, HSV-Hepatitis, HHV6, HHV8, measles, RSV, Parvovirus, dengue virus
• Bacterial infection-Tuberculosis, Rickettsiosis, typhoid, ehrlichiosis, sepsis, leptospirosis.
• Immunosuppressive agents-ATG, alemtuzumab, glucocorticoids.
• Psoralen with UV irradiation.
• Chemotherapy
• Radiation
• Renal/Hematopoietic stem cell transplantation
• Hemodialysis/end stage renal disease.
• Autoimmune disease-SLE, polyarteritis.
• Hodgkin’s lymphoma, DLBCL, 
• Carcinoma-Breast and colon, soft tissue sarcomas
• Sarcoidosis.
• Nutritional: Ethanol abuse, Zinc deficiency
• Thoracic duct obstruction, Intestinal lymphangiectasia
• Idiopathic CD 4+ T lymphocytopenia
  • CD4 count <300/cmm on 2 separate occasions without serology/ virology evidence of HIV infection
  • May have opportunistic infections
  • Incidence increases with age
  • CD4+ cell counts are stable for long periods
  • May have spontaneous complete/ partial recovery of counts

Investigations:

• HIV testing
• Lymphocyte subset analysis by flow cytometry
• ANA profile