White Blood Cell Neoplasia Summary

White Blood Cell Neoplasia

Normal Development of WBCs

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

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

  • Discrete structures surrounded by a connective tissue capsule.
    • Periphery: B-cells in lymphoid follicles (primary vs. secondary/germinal follicles).
    • Parafollicular Area: T-cells.
    • Center (Medullary Cords): Plasma cells and macrophages.

WBC Disorders

  • Leukopenia
  • Leukocytosis
  • Leukemia
  • Lymphoma

Leukopenia

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

Leukocytosis

  • Increased circulating number of mature, non-neoplastic WBCs.
  • May be confused with 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.
  • Lymphadenitis is almost always seen with lymphadenopathy.
  • Lymphadenopathy can occur independently of lymphadenitis.

Leukemias

  • Definition: Neoplastic disorders characterized by uncontrolled proliferation of hematopoietic stem cells, leading to replacement of bone marrow with malignant cells.
  • Leukemic cells "spill" into the blood and may infiltrate visceral organs.

Classification of Leukemias

  • Based on cell type 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”.
  • Based on state of maturity of cell/clinical presentation:
    • Acute Leukemias
    • Chronic Leukemias

Acute Leukemias

  • Histology: Immature neoplastic cells (“leukemic blasts”) due to a block in differentiation of stem cell precursors.
  • Neoplastic cells may be of lymphocytic or myelogenous stem cell origin, classified as ALL or AML respectively.
  • 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 symptomatology: anemia, fatigue & weakness, weight loss, organomegaly.

Specific Leukemia Types

  • Acute Lymphoblastic Leukemia (ALL):
    • 90% of all childhood leukemias.
    • Transformed B-lymphocytes are myeloperoxidase negative.
    • Three subdivisions (FAB system): L1-L3.
    • CNS involvement.
    • Dramatic advances in treatment.
  • Acute Myeloid Leukemia (AML):
    • 90% of adult acute leukemias (15-40 years old).
    • Heterogeneous group due to complexity of myeloid stem cell maturation.
    • Auer Rod positive, Myeloperoxidase positive.
    • Difficult to treat; relapses are frequent.
    • Gene fusion yields abnormal retinoic acid receptor, which blocks differentiation; role of vitamin A therapy.
  • Chronic Lymphocytic Leukemia (CLL):
    • 25% of all leukemias, more common in older males.
    • Mature lymphocytes (B-cell).
    • The leukemic counterpart of SLL.
    • Asymptomatic or vague symptoms: infection, fatigue, organomegaly.
    • Difficult to treat.
  • Chronic Myeloid Leukemia (CML):
    • 15-20% of all leukemias.
    • Most often fairly mature granulocytes.
    • Philadelphia (Ph) chromosome = translocation resulting in bcr-c-abl gene.
    • Non-specific symptomology (see CLL).
    • Difficult to treat: 50% progress to “Blast crisis”.