Sandbox:patho3

Overview

Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production. Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin cytoplasmic border, lack of nucleoli, and presence of smudge cells.

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 red 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 both malignant leukemic proliferation and apoptotic resistance of mature B cells.
• Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include:

• Chromosome 13 long arm deletion (most common genetic mutation)
• Chromosome 17 short arm deletion
• Chromosome 11 long arm 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
• Thin 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
• CD19 +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