This disease has now been classified as a B-lymphocyte disorder. A few variant patients, such as rare patients with T-cell characteristics, have been reported. A few cases have been reported in association with retrovirus HTLV-II infection. Hairy cell leukemia was originally called leukemic reticuloendotheliosis. It affects primarily men (male/female ratio 4:1) between ages 40 and 60 (range, 24-80) years. The clinical course if untreated is usually described as chronic but progressive (mean 4 years, range <1 to >20 years). The most common cause of death is infection (55%-65% of patients). There is splenomegaly in 80%-90% of cases; about 20% have spleens with enlargement to palpation of less than 5 cm, whereas about 15% are more than 15 cm. In the typical patient there is splenomegaly without lymphadenopathy; lymphadenopathy actually does occur in approximately 30% of cases but is usually not prominent. Mild hepatomegaly is found in approximately 20%.

Laboratory picture.— Cytopenia in one or more peripheral blood elements is present in 87%-100% of patients. Normocytic-normochromic anemia is found in 80%-84%; thrombocytopenia in 60%-70% (range, 50%-87%); leukopenia in 50%-60% (range, 48%-66%); normal WBC count in 20% (range, 15%-24%); leukocytosis in 10%-15%; and pancytopenia in about 60% (range, 35%-90%). A relative lymphocytosis is frequently present. Serum alkaline phosphatase levels are elevated in about 20% of cases. Hairy cells are present in the peripheral blood in approximately 90% of patients, although the number of such cells varies considerably. In most cases there are relatively few hairy cells; in 10% of cases more than one half of all leukocytes are hairy cells. Hairy cells are present in the bone marrow and spleen as well as the peripheral blood. The hairy cell is similar to a lymphocyte in appearance but the cytoplasm appears frayed or has irregular, narrow, hairlike projections. The hairy cytoplasm appearance is not specific; it may occasionally be seen in a few persons with other conditions or as an artifact (usually only a few cells are affected).

Bone marrow aspiration is diagnostic in 70%-80% of cases in which marrow is obtained; no marrow can be aspirated in 30%-50% of patients, and a bone biopsy is then necessary. Some investigators believe that bone marrow is nearly always diagnostic if the correct specimen in sufficient quantity is obtained and adequate testing is done. Clot sections as well as smears should be prepared if marrow is aspirated, and slide imprints should be made if a bone biopsy is performed. The bone marrow is usually hypercellular but occasionally may be normocellular or even hypocellular. Some patients develop varying degrees of marrow fibrosis, which could lead to a misdiagnosis of myeloid metaplasia. Marrow infiltration by hairy cells begins in small patches that eventually become confluent and finally become generalized. Spleen sections typically show involvement of the red pulp rather than the malpighian corpuscles, and spleen sections may contain diagnostic pseudosinuses lined by hairy cells.

Acid phosphatase stain.— Hairy cells typically demonstrate a positive cytoplasmic acid phosphatase cytochemical reaction, which is resistant to tartrate. This reaction was originally thought to be specific for hairy cells but has since been found (more often with weak reactivity) in some patients with B-cell or T-cell CLL, prolymphocytic leukemia, adult T-cell leukemia, Sйzary syndrome, and occasionally in acute myeloblastic leukemia and acute monoblastic leukemia. On the other hand, the number of hairy cells that exhibit a positive tartrate-resistant acid phosphatase reaction is variable (5%-95% of the hairy cells), and in about 5% (range, 5%-10%) of patients all peripheral blood and bone marrow cells may be normal. A few patients become diagnostic problems, and electron microscopy (ribosomallamellar complex in 60%) or testing for certain antigens (e.g., HLA-DR) may be helpful.