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Overview

Lymphocytes tend to be small leukocytes with a large nucleus, though may be larger with a lower nuclear:cytoplasmic ratio if reactive. These cells play several key roles in the adaptive immune response.

Lymphocytosis

Lymphocytosis refers to an increase in circulating lymphocytes. These cells may be small mature lymphocytes, reactive lymphocytes or atypical lymphocytes and therefore it is important to assess the morphology of these cells histologically.
  • Causes of Lymphocytosis

  • Relative Lymphocytosis

  • Acute viral infection
  • Autoimmune disease
  • Thyrotoxicosis
  • Adrenocortical insufficiency
  • Hyposplenism
  • Absolute Lymphocytosis

  • Acute viral infection - EBV, CMV, viral hepatitis
  • Chronic infection - TB, brucellosis
  • Mature lymphocytic leukaemias - CLL, hairy cell leukaemia, T-LGL
  • Leukaemic phase of lymphomas - follicular, mantle cell, SMZL, DLBCL, burkitt

Lymphopaenia

Lymphopaenia is a reduction in circulating lymphocytes. This may be reactive, reflect immunodeficiency or occur secondary to drugs.
  • Causes of Lymphopaenia

  • Primary immunodeficiency disorders - e.g. severe combined immunodeficiency, Wiskott-Aldrich syndrome
  • Infection - viral (especially HIV), bacterial, TB, malaria, fungal
  • Medications - corticosteroids, cytotoxic chemotherapy, methotrexate, azathioprine, rituximab
  • Dietary deficiency - severe malnutrition, alcohol abuse, zinc deficiency
  • Autoimmune disease (especially SLE)
  • Sarcoidosis
  • Hodgkin lymphoma
  • Aplastic anaemia
  • Radiotherapy
  • Post surgery

Small Mature Lymphocytes

Mature lymphocytes are small cells with high nuclear : cytoplasmic ratio (i.e. a very small amount of cytoplasm). These cells are normally seen in peripheral blood however if present in a large number then they may suggest chronic lymphocytic leukaemia.
  • Small Mature Lymphocytes
     
  • Causes of Small Mature Lymphocytosis

  • Chronic lymphocytic leukaemia
  • Monoclonal B lymphocytosis (pre-CLL)
  • Certain infections
  • Hyposplenism

Reactive Lymphocytes

Reactive lymphocytes are medium to large cells with mature chromatin abundant cytoplasm 
  • Features of Reactive Lymphocytes

  • Medium to large cells
  • Mature nuclear chromatin - coarse, clumped nuclear material
  • Abundant basophilic cytoplasm
  • Scalloping / invagination - the cells appear to invade around neighbouring red cells
  • Causes of Reactive Lymphocytes

  • Viral infections - EBV, CMV, HIV, COVID
  • Other infections - e.g. toxoplasmosis, bordatella pertussis
  • Certain autoimmune disorders
  • Example

  • A reactive lymphocyte in a patient with acute mononucleosis.
  • A reactive lymphocyte in a patient with acute mononucleosis.
     

Plasmacytoid Lymphocytes

Plasmacytoid lymphocytes, or Türk cells, are an intermediate stage between a B lymphocyte and a plasma cell.
  • Plasmacytoid Lymphocytes
     
The presence of Türk cells in peripheral blood is usually reactive, however they may be present in patients with Waldenstrom's macroglobulinaemia.

Atypical Lymphocytes

The term atypical lymphocyte is used to refer to any abnormal lymphocyte that does not appear reactive. The presence of such cells in the peripheral blood suggests a neoplastic process, such as a lymphoid leukaemia or the leukaemic phase of lymphoma. These cells may be difficult to distinguish on morphological examination.
  • Causes of Atypical Lymphocytes

  • Mature B cell leukaemias - CLL, B cell prolymphocytic leukaemia, hairy cell leukaemia, hairy cell leukaemia variant
  • Leukaemic phase of B cell lymphomas - follicular lymphoma, mantle cell lymphoma, splenic marginal zone lymphoma, diffuse large B cell lymphoma, burkitt lymphoma
  • Mature T cell neoplasms - T cell prolymphocytic leukaemia, T cell large granular lymphocytic leukaemia, adult T cell leukaemia / lymphoma, Sezary syndrome, anaplastic large cell lymphoma
  • Interpretation

  • Chronic lymphocytic leukaemia - large numbers of small mature lymphocyes with smudge cells
  • Hairy cell leukaemia - medium-sized cells with 'hairy' projections
  • Follicular lymphoma - small cells with deeply clefted nuclei
  • Splenic marginal zone lymphoma - 'polar' projections from two ends of the cell
  • Diffuse large B cell lymphoma - large cells with cytoplasmic vacuoles
  • Burkitt lymphoma - deeply basophilic cytoplasm with vacuoles
  • T large granular lymphocytic leukaemia - medium-sized cells with the nucleus to one side of the cell, and azurophilic granules
  • Sezary syndrome - 'cerebriform' nucleus (looks like a brain)
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