WBC Neoplasia Notes

White Blood Cell Neoplasia

Normal Development of White Blood Cells

  • Liver: Primary site of blood cell formation until just before birth.
  • Bone Marrow: Becomes the hematopoietically active site at birth.
  • Pluripotent Stem Cell: All blood cells are derived from this stem cell.

Hematopoietic Stem Cell

  • Gives rise to:
    • Granulocytes
    • Agranulocytes

Lymphoreticular System

  • Lymphocytes and monocytes accumulate in organized masses within:
    • Lymph nodes
    • Thymus
    • Spleen
    • Tonsils
    • Adenoids
    • Peyer’s patches

Lymph Node Morphology

  • Structure: Discrete structures surrounded by a connective tissue (c.t.) capsule.
  • Periphery:
    • Contains B-cells in lymphoid follicles.
    • Primary vs. secondary/germinal follicles.
  • Parafollicular Area:
    • Contains T-cells.
  • Center:
    • Contains plasma cells and macrophages within medullary cords.

WBC Disorders

  • Leukopenia
  • Leukocytosis
  • Leukemia
  • Lymphoma

Leukopenia

  • Definition: Decreased circulating WBCs.
  • Causes: Reduced production or accelerated destruction of WBCs.
  • Most Common Cause: Chemotherapeutics (affects all cells, leading to aplastic anemia).
  • Association: Increased infections.
  • Symptoms: Malaise, chills, fever.

Leukocytosis

  • Definition: Increased circulating number of mature, non-neoplastic WBCs.
  • Differentiation: Must be differentiated from leukemias (leukemoid reaction).
  • Examples: Polymorphonucleocytosis, eosinophilic leukocytosis, monocytosis, lymphocytosis.

Lymphadenopathy vs. Lymphadenitis

  • Lymphadenitis: Inflammation of lymph nodes (acute or chronic).
  • Lymphadenopathy: Enlarged/swollen lymph nodes.
  • Relationship: Lymphadenitis almost always seen with lymphadenopathy, but lymphadenopathy can occur independently of lymphadenitis.

Leukemias: Definition

  • Neoplastic disorders involving uncontrolled proliferation of hematopoietic stem cells.
  • Characterized by replacement of bone marrow with malignant cells.
  • Leukemic cells can "spill" into the blood and infiltrate visceral organs.

Leukemias Classification (Cell Type)

  • Classified based on the type of cell involved:
    • Lymphocytic Leukemia: Derived from lymphoid stem cells (T cells and B cells).
    • Myelogenous Leukemia: Derived from myeloid stem cells (granulocytes, monocytes, megakaryocytes), also referred to as “non-lymphoblastic”.

Leukemias Classification (Maturity/Presentation)

  • Classified based on the state of maturity of the cell and clinical presentation:
    • Acute Leukemias
    • Chronic Leukemias

Acute Leukemias

  • Histology: Immature neoplastic cells (“leukemic blasts”) due to a block in differentiation of stem cell precursors.
  • Origin: Neoplastic cells may be of lymphocytic or myelogenous stem cell origin, leading to ALL or AML.
  • Clinical Features:
    • Abrupt, stormy onset, fulminant clinical course; fatal if untreated.
    • Symptoms related to depression of normal marrow function: fatigue, fever, bleeding (thrombocytopenia), bone pain, organomegaly, and CNS involvement.

Chronic Leukemias

  • Histology: More well-differentiated, mature leukocytes, predominantly granulocytes.
  • Clinical Presentation:
    • Insidious onset, rather slow, indolent clinical course (some chronic leukemias can become acute).
    • Elevated WBC count.
    • None or vague symptomology: anemia, fatigue & weakness, weight loss, organomegaly.

Acute Lymphoblastic Leukemia (ALL)

  • Prevalence: 90% of all childhood leukemias.
  • Cell Type: Transformed B-lymphocytes.
  • Myeloperoxidase: Negative.
  • Subdivisions: Three subdivisions (FAB system): L1-L3.
  • Common Features: CNS involvement.
  • Treatment: Dramatic advances in treatment.

Acute Myeloid Leukemia (AML)

  • Prevalence: 90% of adult acute leukemias (15-40 years).
  • Characteristics: Heterogeneous group due to the complexity of myeloid stem cell maturation.
  • Markers: Auer Rod +, Myeloperoxidase +.
  • Treatment: Difficult to treat; relapses are frequent.
  • Gene Fusion: Gene fusion yields abnormal retinoic acid receptor, which blocks differentiation; role of vitamin A therapy.

Chronic Lymphocytic Leukemia (CLL)

  • Prevalence: 25% of all leukemias, typically in older males.
  • Cell Type: Mature lymphocytes - B cell.
  • Relation: The leukemic counterpart of SLL.
  • Symptoms: Asymptomatic or vague symptoms; infection, fatigue, organomegaly.
  • Treatment: Difficult to treat.

Chronic Myeloid Leukemia (CML)

  • Prevalence: 15-20% of all leukemias.
  • Cell Type: Most often fairly mature granulocytes.
  • Philadelphia (Ph) Chromosome: Translocation resulting in bcr-c-abl gene.
  • Symptoms: Non-specific symptomology (similar to CLL).
  • Treatment: Difficult to treat; 50% progress to “Blast crisis”.