Sandbox: patho3

# Overview
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. The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations. On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include a small cells with "Fried egg"-like appearance, well-demarcated fuzzy borders, and a clear cytoplasm.

# 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  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 .
- 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)
- Illustrated below is a series of microscopic images observed in hairy cell leukemia:
- Hairy cell leukemia illustrated on a blood film
- Hairy cell leukemia illustrated on high magnification
- Hairy cell leukemia illustrated on very high magnification
-  Jump up to: 1.0 1.1 Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.
-  Jump up to: 2.0 2.1 What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) / Accessed on October, 19 2015
-  Jump up to: 3.0 3.1 3.2 3.3  Hairy cell leukemia. Wikipedia (2015) #Pathophysiology Accessed on Ocotber, 19 2015
-  Jump up to: 4.0 4.1 4.2 4.3 4.4 Small cell lymphoma. Libre Pathology (2015) #Hairy_cell_leukemia Accessed on October, 8 2015
-  Jump up to: 5.0 5.1 Tiacci E, Liso A, Piris M, Falini B (2006). "Evolving concepts in the pathogenesis of hairy-cell leukaemia". Nat Rev Cancer. 6 (6): 43748. doi:10.1038/nrc1888. PMID 16723990.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}