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==Overview==
==Overview==
Hairy cell leukemia arises from  [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production.<ref name="m">Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.</ref> However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.<ref name="found">What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) https://www.hairycellleukemia.org/about-hcl/what-is-hairy-cell-leukemia/ Accessed on October, 19 2015</ref> The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref> 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.<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref>
==Pathogenesis==
==Pathogenesis==
* Hairy cell leukemia arises from  [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production.<ref name="m">Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.</ref>
* Hairy cell leukemia arises from  [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production.<ref name="m">Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.</ref>
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* Hairy cell leukemia has been found to be associated with Trisomy 5 in a number of cases.<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref>  
* Hairy cell leukemia has been found to be associated with Trisomy 5 in a number of cases.<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref>  
==Microscopic Pathology==
==Microscopic Pathology==
* On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include:<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref>
:* 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:
<gallery>
Image:
Hairy cell leukemia blood film.jpg|Hairy cell leukemia illustrated on a blood film<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref>
Image:
Hairy cell leukemia - high mag.jpg|Hairy cell leukemia illustrated on high magnification<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref>
Image:
800px-Hairy cell leukemia - very high mag.jpg| Hairy cell leukemia illustrated on very high magnification<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref>
</gallery>

Latest revision as of 20:22, 20 October 2015

Overview

Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production.[1] However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.[2] The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.[3] 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.[4]

Pathogenesis

  • Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production.[1]
  • However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.[2]
  • 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:[3]
  • The development of bone marrow failure interferes with the normal production of red blood cells and platelets among hairy cell leukemia patients.[5]
  • 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.[3]
  • 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:[5]
  • 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.[3]

Microscopic Pathology

  • On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include:[4]
  • 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[4]

    Hairy cell leukemia illustrated on a blood film[4]

  • Hairy cell leukemia illustrated on high magnification[4]

    Hairy cell leukemia illustrated on high magnification[4]

  • Hairy cell leukemia illustrated on very high magnification[4]

    Hairy cell leukemia illustrated on very high magnification[4]

  1. ↑ 1.0 1.1 Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.
  2. ↑ 2.0 2.1 What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) https://www.hairycellleukemia.org/about-hcl/what-is-hairy-cell-leukemia/ Accessed on October, 19 2015
  3. ↑ 3.0 3.1 3.2 3.3 Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015
  5. ↑ 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): 437–48. doi:10.1038/nrc1888. PMID 16723990.
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