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”.