Sandbox:patho3

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.
• Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.
• 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.
• 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.
• Structural genomic aberrations involved in the pathogenesis of chronic lymphocytic leukemia include:

• 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:

• 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:

• 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:

• CD5 +ve
• CD 19 +ve
• CD20 +ve
• CD23 +ve/-ve
• CD43 +ve
• Cyclin D1 -ve
• CD38 -ve/+ve

• Shown below is a series of microscopic images seen in multiple myeloma:

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  Chronic lymphocytic leukemia demonstrated on low magnification

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  Chronic lymphocytic leukemia demonstrated on intermediate magnification

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  Chronic lymphocytic leukemia demonstrated on high magnification

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  Chronic lymphocytic leukemia demonstrated on very high magnification