HAIRY CELL LEUKEMIA
Hairy cell leukemia (HCL) is a chronic B-lineage lymphoproliferative disorder that was initially described by Bouroncle and coworkers in 1958 (1). It accounts for only 2 % of all leukemias, occurring most frequently in men, throughout adult life (2). The normal cellular counterpart of the hairy cell has not been identified, but immunologic (3), molecular genetics (4) and chromosomal studies (5) show that it is of B-cell origin. Patients present with abdominal discomfort, which is related to splenomegaly, or - as in this patient - with fatigue, easy bruising and infection, which is related to anemia, thrombocytopenia, neutropenia, and monocytopenia. Sometimes HCL is found incidentally during investigation of an unrelated medical problem. Most patients are pancytopenic at the time of the diagnosis (6). Clinical manifestations secondary to various autoimmune disorders are being recognized with increasing frequency in patients with HCL (7). More unusual clinical manifestations are peripheral lymphadenopathy, lytic bone lesions, skin involvement, splenic rupture, and other organ involvement (8).
The most characteristic laboratory finding is pancytopenia - as seen in this patient - which is followed by isolated neutropenia, thrombocytopenia, anemia, or monocytopenia. Leucocytosis can also occur, but rarely. Hairy cells are present in the bone marrow and often in the peripheral blood (9). The characteristic morphologic appearance of hairy cells on a Wright's stained peripheral blood smear is the single most important diagnostic finding. The cells are mononuclear with relatively abundant cytoplasm and a cell diameter in the range of 10 to 25 micrometers. The cytoplasm is pale, blue-gray, and agranular, with variable numbers of elongated (hairy) projections. The nuclei are either round, oval, reniform, or dumbbell-shaped, with a nuclear chromatin pattern that is homogenous and less clumped, and lighter staining than that of mature lymphocytes and those seen in classic chronic lymphocytic leukemia and prolymphocytic leukemia. A prominent nucleolus is rarely seen. A useful diagnostic test is the tartrate resistant acid phosphatase activity (TRAP). Such activity is rare, but not unknown in other lymphoproliferative disorders. The bone marrow is usually difficult to aspirate as a consequence of fibrosis (10), as was the case with this patient. When it can be aspirated hairy cells are relatively more numerous than in the blood. The bone marrow biopsy shows infiltration that may be interstitial in a hypocellular marrow - as in our case - focal or diffuse with a highly characteristic pattern of infiltration. The characteristic delicate chromatin pattern, and indented or lobulated nuclei are usually readily apparent. Reticulin is usually increased (10).
Immunophenotyping has proved very useful in the diagnosis of HCL and in differentiating it from variants and other B-cell malignancies (11). Hairy cells have the immunophenotype of a relatively mature B-cell. B-lineage associated antigens CD19, CD20, CD22, and CD79a are expressed. The expression of CD22 is strong. Surface immunoglobulin, and in some cases cytoplasmic immunoglobulins are also expressed. CD10 and CD23 are negative. FMC7 is positive, as is CD25, which represents the Interleukin 2 receptor and is a marker for activated T and B-cells. CD11c is usually positive. In addition to the B-lineage associated immunophenotypic markers there are also markers with specificity for hairy cells: they include HC2, CD103 and DBA-44. CD-103 is an integrin, which is also known as mucosal lymphocyte antigen (MLA). TRAP activity can also be detected immunologically by using a specific antibody. Immunophenotypic studies performed on our case revealed a monoclonal lambda B-cell population, with strong CD22 and 11c expression, as well as CD25 expression. This population was also positive for the specific CD103 marker.
Cytogenetic abnormalities described include translocations with a 14q32 breakpoint, del(6)q, monosomy 10, trisomy 5 and monosomy 12 (12).
Splenectomy has been the traditional treatment for HCL but is seldom performed anymore. Splenectomy and alpha-interferon may be still used for HCL under specific circumstances. However, the standard therapy consists now of the nucleoside analogs 2'-deoxycoformycin (dCF) or 2-chlorodeoxyadenosine (CdA), which produce complete and durable remission in the majority of patients (13). The prognosis of the disease has improved dramatically since the development of the new nucleoside analogs.
Contributed by Octavia Graur, MD, PhD