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Hematology

Leukocytes

In the clinical hematology laboratory, the evaluation of leukocytes (white blood cells) is a critical diagnostic tool used to distinguish between the body’s normal immune response to stress and infection versus malignant transformations of the hematopoietic system. Leukocyte disorders are broadly categorized based on etiology (reactive vs. neoplastic), lineage (myeloid vs. lymphoid), and duration (acute vs. chronic). For the laboratory scientist, the primary objective involves accurately identifying morphological changes and quantifying cell populations to assist distinguishing benign, self-limiting conditions from life-threatening malignancies

Benign Disorders

Benign disorders are generally reactive processes, meaning the changes seen in the peripheral blood are secondary to an underlying condition such as infection, inflammation, or drug exposure. These conditions are typically non-clonal and resolve once the underlying stimulus is removed

  • Quantitative Changes: These involve fluctuations in cell counts. Examples include neutrophilia (bacterial infection), lymphocytosis (viral infection), and eosinophilia (parasitic infection or allergy). Conversely, conditions like neutropenia or lymphopenia indicate a suppression or destruction of these cell lines
  • Qualitative Changes: These are morphological alterations often visible on the peripheral blood smear. Key findings include toxic granulation, Döhle bodies, and cytoplasmic vacuolization, which signify activated neutrophils fighting infection. Reactive lymphocytes (atypical lymphocytes) are the hallmark of viral stimulation

Neoplastic Disorders

Neoplastic disorders represent clonal malignancies arising from hematopoietic stem cells or progenitor cells. These are characterized by uncontrolled proliferation and a disruption of normal hematopoiesis. The World Health Organization (WHO) classification system is the standard for categorizing these malignancies based on morphology, immunophenotyping, and genetics

  • Myeloid Neoplasia: These malignancies affect the granulocytic, monocytic, erythroid, or megakaryocytic lineages. They are generally grouped into three main categories:
    • Acute Myeloid Leukemia (AML): An aggressive malignancy defined by the accumulation of immature blasts (≥20%) in the bone marrow, leading to rapid marrow failure
    • Myelodysplastic Syndromes (MDS): Clonal disorders characterized by ineffective hematopoiesis and cytopenias. The hallmark feature is dysplasia (abnormal cell morphology) in one or more cell lines
    • Myeloproliferative Neoplasms (MPNs): Disorders characterized by the overproduction of mature blood cells. Common entities include Chronic Myeloid Leukemia (CML), Polycythemia Vera (PV), and Essential Thrombocythemia (ET)
  • Lymphoid Neoplasia: These disorders originate from B cells, T cells, or NK cells and are distinguished by the maturity of the cells involved:
    • Precursor Neoplasms: Involve immature lymphoblasts, such as in Acute Lymphoblastic Leukemia (ALL), which is common in children
    • Mature Neoplasms: Involve differentiated lymphocytes. This category includes Chronic Lymphocytic Leukemia (CLL), plasma cell dyscrasias like Multiple Myeloma, and various lymphomas (Hodgkin and Non-Hodgkin)

Hereditary Anomalies

Hereditary leukocyte disorders are rare, genetic defects that result in distinct morphological abnormalities. While often benign and asymptomatic, they are clinically significant because they can mimic signs of infection or leukemia

  • Diagnostic Challenges: The laboratory scientist must distinguish these inherited anomalies from pathological states. For example, the Pelger-Huët anomaly (hyposegmented neutrophils) must be differentiated from the “pseudo-Pelger-Huët” cells seen in myelodysplastic syndromes
  • Common Anomalies: These include May-Hegglin anomaly (associated with thrombocytopenia and giant platelets), Alder-Reilly anomaly (mimics toxic granulation), and Chédiak-Higashi syndrome (characterized by giant lysosomal granules and immune dysfunction)