A 58 years old female presents with a history of fatigue, easy bruising and recurrent infection. She is found to have gross splenomegaly. A full blood count is performed and the following results noted:
Hb 143 g/L, WBC 45.0 x 109/L and platelet count 91 x 109/L.
The peripheral blood film showed 84% abnormal lymphocytes with irregular cytoplasmic projections and 16% neutrophils. A diagnosis of the variant form of hairy cell leukaemia (HCL-V) is made.
Hairy cell leukaemia is an indolent malignant lymphoproliferative disease of B-cell origin. It occurs more often in men than in women (ratio 4:1). The classical form presents with pancytopenia, including neutropenia, and a mean white cell count of less than 4 x 10/L. In 15%-20% of cases, there is a variant or leukaemic form with a mean white cell count of 88 x 10/L. The variant form is not neutropenic.
The hairy cells on the peripheral blood film in the classical form vary in size from 10-20 µm in diameter. The cell cytoplasm stains a pale blue-grey colour with many fine hair-like projections around the entire circumference of the cell. This is in contrast to the projections found on the cells of splenic marginal zone lymphoma which are thin and short and unevenly distributed, often concentrated towards one pole of the cell. In classical hairy cell leukaemia, the nucleus is often eccentric and is round to oval in shape. The hairy cells in the variant form are smaller with a diameter of 10-15 µm. The nuclei are generally placed centrally rather than eccentrically. In both forms, there may be few recognisable hairy cells in the peripheral blood and diagnosis relies on a bone marrow study. The marrow trephine shows a patchy or diffuse interstitial infiltrate characterized by a halo of pale-staining cytoplasm surrounding a sea of round to oval hairy cell nuclei.
Flow cytometry performed on hairy cell leukaemia shows expression of pan-B-cell antigens CD19, CD20 and CD22 but are negative for CD5 and CD23 (both being positive in B-CLL). Almost all cases of classical hairy cell leukaemia also express CD103, CD11c and CD25. In the variant form of hairy cell leukaemia, the cells are negative for CD25 (a pre B antigen) and positive/negative for CD103.
Cytochemistry can be used to demonstrate the hairy cells on a blood film. In 95% of cases of classical hairy cell leukaemia, the cells show strong tartrate-resistant acid phosphatase (TRAP) activity whereas in the variant form, only 60% show TRAP activity and it is only weak. Thus TRAP activity studies are not really useful to confirm a diagnosis of hairy cell leukaemia.
There are no specific cytogenetic changes in hairy cell leukaemia – add(14)(q32) occurs in 20% of cases, del(6)(q23) occurs in 10% of cases and del(14)(q22;q32) occurs in 10% of cases.
Patients with the variant form of hairy cell leukaemia have a median survival of 5 years. Those with the classical form have a longer survival. Some patients with mild disease do not require treatment and have a prolonged survival. Complications in hairy cell leukaemia include infection due to neutropenia and immune dysfunction, anaemia due to bone marrow infiltration and bleeding due to thrombocytopenia.