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Lesson 10-1
Morphologic Disorders of the Leukocyte

INTRODUCTION

Some inherited morphologic changes are clinically insignificant and of interest only to morphologists, whereas others indicate a life-threatening disorder. Most acquired morphological changes to the granulocytic cells may be used as indicators of disease states in conjunction with their clinical description.


DISORDERS OF THE GRANULOCYTES (MORPHOLOGIC ABNORMALITIES- CYTOPLASMIC CHANGES)

Alder-Reilly Anomaly. This prevents normal breakdown of mucopolysaccharides. Mucopolysaccharides are deposited in the cytoplasm of neutrophils, monocytes, and lymphocytes. They appear as abnormally large azurophilic granules resembling severe toxic granulation and contain peroxidase-positive deposits.

Chediak-Higashi Syndrome. This occurs when large, fused lysosomes are produced and the cells cannot release their contents after bacterial digestion. They appear as large acidophilic granules in granulocytes. This condition leads to abnormal phagocyte function whereas, they do not move well in response to chemotactic stimuli (e.g., poor directional motility), as well as, recurrent infections, bleeding tendencies, hypopigmentation, anemia, neutropenia, thrombocytopenia, and abnormal platelet aggregation.

May-Hegglin Anomaly. This occurs when large, blue cytoplasmic inclusions resembling giant Dohle bodies in granulocytes and monocytes are present. These inclusions consist mainly of RNA. There is marked thrombocytopenia, instead large, bizarre-shaped platelets and variable neutropenia is observed. Many patients are asymptomatic, some may develop bleeding tendencies.

Pelger-Huet Anomaly. This is consistent with neutrophilic changes. The neutrophil nucleus fails to segment properly. All neutrophils have bi-lobed or non- segmented nuclei.


QUALITATIVE DISORDERS

Defective motility (e.g., Jobís syndrome, lazy leukocyte syndrome).

Defect in ability to kill microorganisms.

  • Chronic Granulomatous disease.
    • Neutrophils and monocytes ingest, but cannot kill, catalase-positive microorganisms due to a deficiency of membrane-bound oxidase or failure of the membrane surface to stimulate respiratory burst.
    • Bacteria multiply within the cell.
    • Recurrent, life-threatening infections and pneumonia common.
  • Myeloperoxidase deficiency.
    • Absence of myeloperoxidase enzyme from neutrophils and monocytes but not eosinophils - myeloperoxidase mediates oxidative destruction of microorganisms by H2O2.
    • Infections usually are not serious due to compensatory increase in respiratory burst activity - killing of bacteria is slowed but complete.
  • Monocyte-macrophage disorders.
    • Gaucherís disease. Problem in cellular lipid metabolism - deficiency of enzyme (e.g., beta-glucocerebrosidase) results in inability of monocyte to degrade glucocerebrosides. Cerebroside accumulates in macrophages - Gaucherís cells. Gaucherís cell typically is large with one to three eccentric nuclei and wrinkled cytoplasm. There is a decrease in production of RBCs and WBCs as these abnormal cells infiltrate into the bone marrow.
    • Niemann-Pick disease. Problem in cellular lipid metabolism - deficiency of enzyme (e.g., sphingomyelinase) that cleaves sphingomyelin. Sphingomyelin accumulates in macrophages - Niemann-Pick cells (large macrophages with foamy-looking cytoplasm; cytoplasm swollen by numerous small, uniform lipid droplets). This is the most prevalent form of disease develops in infancy and is fatal within the first few years of life.

NONMALIGNANT LYMPHOCYTIC DISORDERS

Infectious Mononucleosis. Contagious, viral disease that affects young adults and teenagers - symptoms include fever, sore throat, lymphadenopathy.

  • Epstein-Barr virus (EBV) infects B lymphocytes; T lymphocytes become activated and restrain viral replication in B lymphocytes.
  • Normal to slightly elevated WBC count; lymphocytosis common.
  • Variant (reactive or atypical) lymphocytes: greater than 20 percent (represent T lymphocytes responding to the infection).
  • Positive heterophile antibody test (e.g., Monospot) or EBV-specific serologic test.

Cytomegalovirus Infection. Closely resembles infectious mononucleosis but patients do not have sore throat or enlarged lymph nodes.

  • Reactive lymphocytosis is present; heterophile antibody is negative.
  • Increased cytomegalovirus titer.

Toxoplasmosis (Toxoplasma gondii infection). Disease resembles infectious mononucleosis. There is a relative increase in lymphocytes, reactive lymphocytes present on peripheral blood smear; heterophile antibody is negative and there is an elevation of Toxoplasma antibodies.

Differentiation between reactive and malignant lymphocytes.

  • Malignant cells are usually clonal and all abnormal cells appear very similar to one another.
  • Reactive lymphocytes are morphologically more variable - within a single specimen you have both large and small cells, basophilic and pale cells, cells with immature chromatin and cells with densely clumped chromatin.

 

David L. Heiserman, Editor

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Revised: June 06, 2015