Sandbox: patho3

Pathogenesis

• Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production.
• However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.
• Hairy cell leukemia may also infiltrate the spleen and liver.
• Extravascular hemolysis may develop due to splenic sequestration of the circulating red blood cells.
• Hairy cell leukemia does not infiltrate peripheral lymph nodes.
• Bone marrow failure may develop among hairy cell leukemia patients due to:

• Malignant cells infiltration of the bone marrow
• Reticulin fibrosis of the bone marrow
• Dysregulated cytokine production

• The development of bone marrow failure interferes with the normal production of red blood cells and platelets among hairy cell leukemia patients.
• Production of cytokines, such as TNF α and IL-2R, provide important stimuli for malignant B cells proliferation in hairy cell leukemia.
• Leukemic cells demonstrate prolonged survival due to up-regulation of apoptosis inhibitors such as IAP1 and IAP2 by TNF α.
• In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.

Genetics

• The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.
• The BRAF V600E mutations is present among most of the patients with hairy cell leukemia (classic).
• The BRAF V600E mutations is absent among patients with hairy cell leukemia (variant).
• Molecular pathways involved in the pathogensis of hairy cell leukemia include:

• p38-MAPK-JNK molecular cascade is inhibited thus suppressing the apoptotic signaling pathways.
• MEK-ERK molecular cascade is activated thus amplifying the cytoprotective survival pathways.
• Phosphatidylinositol 3 kinase (PI3K)-AKT cascade is activated thus suppressing the apoptotic signaling pathways.

Associated Conditions

• Hairy cell leukemia has been found to be associated with Trisomy 5 in a number of cases.

Microscopic Pathology

• On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include:

• Small cells with "Fried egg"-like appearance
• Well-demarcated fuzzy cell borders
• Clear cytoplasm
• Central round nucleus
• Peri-nuclear clearing ("water-clear rim" appearance)