Hairy cell leukemia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2], James Nasr[3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production. The most common gene involved in the pathogenesis of hairy cell leukemia is a BRAF V600E mutation. On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include small cells with “fried egg”-like appearance, well-demarcated thread-like cytoplasmic extensions, and a clear cytoplasm. Hairy cell leukemia is found to approximately comprise 1.4% of all lymphomas. The incidence of hairy cell leukemia is approximately 2.8-3.0 per 1,000,000 individuals in the United States. The incidence of hairy cell leukemia increases with age; the median age at diagnosis is 55-60 years. Males are more commonly affected with hairy cell leukemia than females. The male to female ratio is approximately 4 to 1. Studies have proposed a number of risk factors for the development of hairy cell leukemia such as certain chemicals exposure, radiation exposure, and UV light exposure. Symptoms of hairy cell leukemia include fever, night sweats, and weight loss. Physical examination of patients with hairy cell leukemia is usually remarkable for pallor, petechiae, and splenomegaly. Laboratory findings consistent with the diagnosis of hairy cell leukemia include abnormal complete blood count, immunohistochemistry, and flow cytometry. The presence of hairy cells with thread-like cytoplasmic extensions on blood smear is a key diagnostic feature among patients with hairy cell leukemia. Hairy cell leukemia is a chronic, highly treatable malignancy with prolonged remission achievable in most patients. The mainstay of therapy for hairy cell leukemia patients is chemotherapy. Pharmacological agents used for the treatment of hairy cell leukemia patients include cladribine, pentostatin, rituximab, and vemurafenib.

The term hairy cell leukemia was first used to describe the malignancy by Dr. R. Schrek and Dr. W. J. Donnelly, in 1966.

Hairy cell leukemia is a distinct indolent, small, mature B-cell neoplasm.

Hairy cell leukemia arises from  B cells that are normally involved in the process of human immunoglobulins production. It is thought to originate from a peripheral, antigen-experienced mature B cell with features resembling post–germinal center memory B cells. The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutation. On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include small cells with “fried egg” like appearance, well-demarcated thread-like cytoplasmic extensions, and a clear cytoplasm. Hairy cell leukemia is driven by constitutive activation of the RAF–MEK–ERK signalling pathway which inhibits apoptosis and drives survival.

Hairy cell leukemia may be caused by mutations in the BRAF gene.

Hairy cell leukemia is relatively rare, accounting for 1.4% of all lymphomas. The incidence of hairy cell leukemia is approximately 2.8-3.0 per 1,000,000 individuals in the United States. The incidence of hairy cell leukemia increases with age. The median age range at diagnosis of hairy cell leukemia is 55 to 60 years. Males are more commonly affected with hairy cell leukemia than females. The male to female ratio is approximately 4 to 1.

The most potent risk factor in the development of hairy cell leukemia is chemical exposure. Other risk factors include radiation exposure, and UV light exposure.

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for hairy cell leukemia.

Most patients with hairy cell leukemia are asymptomatic at the time of diagnosis. If left untreated, most of the patients with hairy cell leukemia will gradually develop anemia, recurrent infections, and recurrent bleeding. The complications of hairy cell leukemia are mainly due to bone marrow failure.

There is no established system for the staging of hairy cell leukemia.

A positive history of splenomegaly or cytopenias is suggestive of hairy cell leukemia. The most common symptoms of hairy cell leukemia include weakness, fatigue, gingival bleeding, epistaxisand menorrhagia.

Physical examination of patients with hairy cell leukemia is usually remarkable for pallor, petechiae, and splenomegaly.

Laboratory findings consistent with the diagnosis of hairy cell leukemia include abnormal complete blood count, immunohistochemistry, and flow cytometry. The presence of hairy cells with thread-like cytoplasmic extensions on blood smear is a key diagnostic feature among patients with hairy cell leukemia.

Abdominal CT scan may be helpful in the diagnosis of hairy cell leukemia. The presence of splenomegaly on CT scan is suggestive of hairy cell leukemia.

MRI of the femur may be helpful in the diagnosis of hairy cell leukemia. Diffuse hyper-intense lesions on T2-weighted MRI image is suggestive of bone marrow infiltration by malignant leukemic cells.

Hairy cell leukemia is a chronic, highly treatable malignancy with prolonged remission achievable in most patients. The mainstay of therapy for hairy cell leukemia patients is chemotherapy. Pharmacological agents used for the treatment of hairy cell leukemia patients include cladribine, pentostatin, rituximab, and vemurafenib.

The predominant therapy for hairy cell leukemia is chemotherapy. Surgical management, such as splenectomy, may be required in certain cases.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2], Vamsikrishna Gunnam M.B.B.S [3], James Nasr[4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

• The term hairy cell leukemia was first used to describe the malignancy by Dr. R. Schrek and Dr. W. J. Donnelly in 1966.

• Leukemic reticuloendotheliosis was first described in 1923 by Dr. O. Ewald, a German physician.
• Hairy cell leukemia was first recognised as a distinct clinicopathologic entity by Bouroncle in 1958.^[1]
• The term hairy cell leukemia was first used to describe the malignancy by Dr. R. Schrek and Dr. W. J. Donnelly in 1966.^[2]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2], Vamsikrishna Gunnam M.B.B.S [3], James Nasr[4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

• Hairy cell leukemia is a distinct, indolent, small, mature B-cell neoplasm. ^[1]

• Hairy cell leukemia is a distinct, indolent, small, mature B-cell neoplasm. ^[1]

• Several splenic B-cell neoplasms may mimic its clinical and morphologic features, including hairy cell leukemia variant, also referred to as splenic B-cell lymphoma or leukemia with prominent nucleoli.^[2]
• The chart below illustrates characteristic findings associated with hairy cell leukemia and splenic B-cell lymphoma:^{[3][4][5][6][7]}

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2], Haytham Allaham, M.D. [3], James Nasr[4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Hairy cell leukemia arises from B cells that are normally involved in the process of human immunoglobulins production. It is thought to originate from a peripheral, antigen-experienced mature B cell with features resembling post–germinal center memory B cells. The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutation. On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include small cells with “fried egg” like appearance, well-demarcated thread-like cytoplasmic extensions, and a clear cytoplasm. Hairy cell leukemia is driven by constitutive activation of the RAF–MEK–ERK signalling pathway which inhibits apoptosis and drives survival.

• Hairy cell leukemia arises from B cells, which are normally involved in the process of human immunoglobulins production.^[1]
• Hairy cell leukemia is thought to originate from a peripheral, antigen-experienced mature B cell with features resembling post–germinal center memory B cells.^[2]
• Bone marrow failure may develop among hairy cell leukemia patients due to:

• Malignant cells infiltration of the bone marrow, resulting in bone marrow failure or pancytopenia
• 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.
• Leukemic cells may also infiltrate both the spleen and liver and leads to organomegaly.
• Extravascular hemolysis may develop due to splenic sequestration of the circulating red blood cells.
• Lymph nodes involvement is unusual, and more often seen in relapse.^[3][4]
• Hairy cell leukemia is driven by constitutive activation of the RAF–MEK–ERK signalling pathway, most commonly due to the BRAF V600E mutation.^[5]
• Aberrant RAF–MEK–ERK signalling in hairy cell leukemia inhibits apoptosis, and BRAF inhibition can trim hairy projections and then induce apoptosis.^[6]
• In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple clonally-related IgG, IgA, and IgM isotypes.

• The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutation.^{[7][8][9][10][11]}
• The MEK-ERK cascade is activated which will amplify the cytoprotective survival pathways.^[12]

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

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

• Small cells with “fried egg” like appearance
• Well-demarcated thread-like cytoplasmic extensions
• Clear cytoplasm
• Round to oval nuclei with inconspicuous nucleoli
• Perinuclear clearing (“water-clear rim” appearance)

• A positive tartrate-resistant acid phosphatase (TRAP) stain is a key diagnostic feature for hairy cell leukemia.^[13]
• On immunohistochemistry, characteristic findings of hairy cell leukemia include:^[14][15]

• Annexin A1 +ve
• CD20 +ve
• CD25 +ve
• CD103 +ve
• Cyclin D1 +ve
• BRAF V600E +ve

• On flow cytometry, characteristic findings of hairy cell leukemia include:^[16]

• CD19 +ve
• CD20 +ve
• CD11c +ve
• CD25 +ve
• CD103 +ve
• CD123 +ve
• FMC7 +ve

• Illustrated below is a series of microscopic images observed in hairy cell leukemia:

• 
  Hairy cell leukemia illustrated on a blood film^[17]
• 
  Hairy cell leukemia illustrated on high magnification^[17]
• 
  Hairy cell leukemia illustrated on very high magnification^[17]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2], James Nasr[3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Hairy cell leukemia may be caused by mutations in the BRAF gene.

Causes of Hairy cell leukemia may include:

• Genetic mutations are the most common causes of hairy cell leukemia.

• Hairy cell leukemia is caused by a mutation in the BRAF V600E gene mutation.^[1][2]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2], James Nasr[3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Hairy cell leukemia must be differentiated from other diseases that cause weight loss, fatigue, splenomegaly, and fever, such as chronic lymphocytic leukaemia, splenic B-cell neoplasms, prolymphocytic leukaemia, follicular lymphoma, and mantle cell lymphoma.

• Hairy cell leukemia must be differentiated from other diseases that cause weight loss, fatigue, splenomegaly, and fever, such as chronic lymphocytic leukaemia, splenic B-cell neoplasms, prolymphocytic leukaemia, follicular lymphoma, and mantle cell lymphoma.^{[1][2][3][4][5]}

• Hairy cell leukemia must also be differentiated from other causes of fever, splenomegaly, and fatigue such as:^[6][7]

• Aplastic anemia
• Myelodysplastic syndrome
• Splenic marginal zone lymphoma
• B-cell pro-lymphocytic leukemia
• Idiopathic myelofibrosis

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2], James Nasr[3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Hairy cell leukemia is relatively rare, accounting for 1.4% of all lymphomas. The incidence of hairy cell leukemia is approximately 2.8-3.0 per 1,000,000 individuals in the United States. The incidence of hairy cell leukemia increases with age. The median age range at diagnosis of hairy cell leukemia is 55 to 60 years. Males are more commonly affected with hairy cell leukemia than females. The male to female ratio is approximately 4 to 1.

• Hairy cell leukemia is considered one of the least common types of leukemias in the United States.
• Hairy cell leukemia accounts for 1.4% of all lymphomas. ^[1]

• The incidence of hairy cell leukemia is approximately 2.8-3.0 per 1,000,000 individuals in the United States.^[1]
• For the past 30 years, the incidence of hairy cell leukemia has been relatively constant.

• The incidence of hairy cell leukemia increases with age.
• The median age range at diagnosis of hairy cell leukemia is 55 to 60 years.^[2]

• Males are more commonly affected with hairy cell leukemia than females.
• The male to female ratio is approximately 4 to 1.^[3]

• Hairy cell leukemia usually affects individuals of European Ancestry.
• Asian and African American individuals are less likely to develop hairy cell leukemia.^[4]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2], James Nasr[3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Hairy cell leukemia is relatively rare, accounting for 1.4% of all lymphomas. The incidence of hairy cell leukemia is approximately 2.8-3.0 per 1,000,000 individuals in the United States. The incidence of hairy cell leukemia increases with age. The median age range at diagnosis of hairy cell leukemia is 55 to 60 years. Males are more commonly affected with hairy cell leukemia than females. The male to female ratio is approximately 4 to 1.

• Hairy cell leukemia is considered one of the least common types of leukemias in the United States.
• Hairy cell leukemia accounts for 1.4% of all lymphomas. ^[1]

• The incidence of hairy cell leukemia is approximately 2.8-3.0 per 1,000,000 individuals in the United States.^[1]
• For the past 30 years, the incidence of hairy cell leukemia has been relatively constant.

• The incidence of hairy cell leukemia increases with age.
• The median age range at diagnosis of hairy cell leukemia is 55 to 60 years.^[2]

• Males are more commonly affected with hairy cell leukemia than females.
• The male to female ratio is approximately 4 to 1.^[3]

• Hairy cell leukemia usually affects individuals of European Ancestry.
• Asian and African American individuals are less likely to develop hairy cell leukemia.^[4]

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for hairy cell leukemia.

According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for hairy cell leukemia.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2], Vamsikrishna Gunnam M.B.B.S [3], James Nasr[4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Most patients with hairy cell leukemia are asymptomatic at the time of diagnosis. If left untreated, most of the patients with hairy cell leukemia will gradually develop anemia, recurrent infections, and bleeding. The complications of hairy cell leukemia are mainly due to bone marrow failure.

• Most patients with hairy cell leukemia are asymptomatic at the time of diagnosis.^[1]
• If left untreated, most of the patients with hairy cell leukemia will gradually develop the following:
  • Anemia
  • Recurrent infections
  • Bleeding

• Common complications of hairy cell leukemia include:^[2]
  • Anemia
  • Recurrent infections
  • Major recurrent bleeding
  • Massive splenomegaly which may rupture

• Prognosis is generally good, and the 5-year survival rate of patients with chronic lymphocytic leukemia is approximately 90%.^[3]
• Poor prognostic factors for hairy cell leukemia patients include hairy cell leukemia variant, VH4-34 rearrangement, TP53 mutations, large splenomegaly, leukocytosis, and high circulating hairy cell count. ^[4]
• The table below lists prognostic factors for hairy cell leukemia patients:^[5]

Template:WikiDoc Sources