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ESSENTIALS OF DIAGNOSIS

ESSENTIALS OF DIAGNOSIS

  • Pancytopenia.

  • Splenomegaly, often massive.

  • Hairy cells present on blood smear and especially in bone marrow biopsy.

GENERAL CONSIDERATIONS

Hairy cell leukemia is a rare malignancy of hematopoietic stem cells differentiated as mature B lymphocytes with hairy cytoplasmic projections. The V600E pathogenic variant in the BRAF gene is recognized as the causal genetic event of hairy cell leukemia since it is detectable in almost all cases at diagnosis and is present at relapse.

CLINICAL FINDINGS

A. Symptoms and Signs

The disease characteristically presents in middle-aged men. The median age at presentation is 55 years, and there is a striking 5:1 male predominance. Most patients present with gradual onset of fatigue, others complain of symptoms related to markedly enlarged spleen, and some come to attention because of infection.

Splenomegaly is almost invariably present and may be massive. The liver is enlarged in 50% of cases; lymphadenopathy is uncommon.

Hairy cell leukemia is usually an indolent disorder whose course is dominated by pancytopenia and recurrent infections, including mycobacterial infections.

B. Laboratory Findings

The hallmark of hairy cell leukemia is pancytopenia. Anemia is nearly universal, and 75% of patients have thrombocytopenia and neutropenia. The “hairy cells” are usually present in small numbers on the peripheral blood smear and have a characteristic appearance with numerous cytoplasmic projections. The bone marrow is usually inaspirable (dry tap), and the diagnosis is made by characteristic morphology on bone marrow biopsy (eFigure 13–32). The hairy cells have a characteristic histochemical staining pattern with tartrate-resistant acid phosphatase (TRAP). On immunophenotyping, the cells coexpress the antigens CD11c, CD20, CD22, CD25, CD103, and CD123. Pathologic examination of the spleen shows marked infiltration of the red pulp with hairy cells. This is in contrast to the usual predilection of lymphomas to involve the white pulp of the spleen.

eFigure 13–32.

Hairy cell leukemia, bone marrow aspirate. Five hairy cells have a characteristic appearance of a hyperchromatic nucleus surrounded by clear cytoplasm with projections giving "fried egg" appearance, leading to the "hairy cell" name. Note that there is slight variation in nuclear shape from circular to kidney-shaped in one cell. (Reproduced, with permission, from Lichtman MA, Shafer MS, Felgar RE, Wang N. Lichtman's Atlas of Hematology. McGraw-Hill, 2016.)

DIFFERENTIAL DIAGNOSIS

Hairy cell leukemia should be distinguished from other lymphoproliferative diseases that involve the bone marrow. It also may be confused with other causes of pancytopenia, including hypersplenism due to any cause, aplastic anemia, and paroxysmal nocturnal hemoglobinuria.

TREATMENT

Treatment is indicated for symptomatic disease, ie, splenic discomfort, recurrent infections, or significant cytopenias. The ...

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