Sandbox:patho3

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Pathogenesis

  • Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production.
  • Malignant lymphocytic cells infiltrate hematopoietic sites such as the bone marrow where they interfere with the production of normal blood cells.
  • Chronic lymphocytic leukemia may also infiltrate the lymph nodes, spleen, and liver.[1]
  • Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.[2]
  • Warm autoimmune hemolytic anemia may develop due to the production of IgA and IgG autoantibodies among certain cases of chronic lymphocytic anemia.
  • Richter's transformation may occur among 1-5% of chronic lymphocytic leukemia cases.[1]
  • Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing large B cell lymphoma.

Genetics

  • Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote leukemic proliferation and apoptotic resistance of mature B cells.[3]
  • Structural genomic aberrations involved in the pathogenesis of chronic lymphocytic leukemia include:[1][3]
  • Chromosome 13q deletion (most common genetic mutation)
  • Chromosome 17p deletion
  • Chromosome 11q deletion
  • Trisomy 12
  • Somatic gene mutations involved in the pathogenesis of chronic lymphocytic leukemia include:[3]
  • NOTCH1 gene located on chromosome 9
  • MYD88 gene located on chromosome 3
  • TP53 gene located on chromosome 7
  • ATM gene located on chromosome 11
  • SF3B1 gene located on chromosome 2
  • FBXW7 gene located on chromosome 4
  • CHD2 gene located on chromosome 15
  • Production of cytokines, angiogenic factors, and chemokines by the surrounding macrophages and T cells provide important stimuli for the malignant B cells proliferation in chronic lymphocytic leukemia.

Microscopic Pathology

  • On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include:[3][2]
  • Small lymphoid cells
  • Narrow cytoplasmic border
  • Dense nucleus
  • Lack of nucleoli
  • Clumped chromatin aggregates
  • Smudge cells
  • Gumprecht nuclear shadows
  • On Immunohistochemistry characteristic findings of chronic lymphocytic leukemia include:
  • CD20 +ve
  • CD5 +ve
  • CD23 +ve/-ve
  • CD43 +ve
  • Cyclin D1 -ve
  • CD38 -ve/+ve
  • Shown below is a series of microscopic images seen in multiple myeloma:
  1. 1.0 1.1 1.2 Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015
  2. 2.0 2.1 Nabhan C, Rosen ST (2014). "Chronic lymphocytic leukemia: a clinical review". JAMA. 312 (21): 2265–76. doi:10.1001/jama.2014.14553. PMID 25461996.
  3. 3.0 3.1 3.2 3.3 Hallek M (2015). "Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment". Am J Hematol. 90 (5): 446–60. doi:10.1002/ajh.23979. PMID 25908509.
  4. 4.0 4.1 Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015