Hairy cell leukaemia

Definition

A neoplasm of small B lymphoid cells with oval nuclei and abundant cytoplasm with "hairy" projections, which diffusely infiltrates bone marrow and splenic red pulp and strongly expresses CD11c, CD22 and CD103.

Synonyms

Epidemiology

A rare disease, constituting 2% of lymphoid leukaemias. Patients are middle-aged to elderly.

Clinical features

Bone marrow and splenic involvement predominate, most patients presenting with splenomegaly and pancytopenia. There may also be infiltration of lymph nodes and live, occasionally of skin. Rarely there is marked abdominal lymphadenopathy due to infiltration by large hairy cells. Recurrent opportunistic infections, vasculitis and immune dysfunction are common.

Histopathology

Hairy cells are small to medium in size, with reniform nuclei. There is abundant pale blue cytoplasm. Occasionally the cytoplasm is vacuolated or contains rod-shaped inclusions. There is strong tartrate-resistant acid phosphatase (TRAP) positivity. Bone marrow involvement is by widely spaced nuclei surrounded by abundant cytoplasm with prominent cell borders, giving a "fried egg" appearance. Reticulin is increased and may result in a "dry tap" on aspiration. In some cases, the marrow is hypocellular, resembling an aplastic anaemia: a B cell marker will demonstrate the neoplastic infiltrate.

Splenic involvement is localised to the red pulp, with atrophy of the white pulp. Red blood cell lakes occur. The liver may show infiltration of sinusoids. Lymph node infiltration is predominantly paracortical.

Immunohistochemistry

CD5	negative
CD10	negative
CD11c†	positive (strong)
CD19†	positive
CD20	positive
CD22	positive
CD23†	negative
CD25	positive (strong)
CD68	positive
CD79a	positive
CD79b	negative
CD103	positive
SIg	+ (M+/D-, G or A)
FMC7	positive
DBA.44	positive
TIA-1	5/93
granzyme-B	0/93
perforin	0/93
CD11c (LeuM5)	8/93
CD25 (IL-2R)	7/93
FMC7	6/93

†: fresh frozen tissue only

Almost all cases are positive for tartrate-resistant acid phosphatase (TRAP), as are some other low-grade B cell lymphoproliferative disorders. DBA44 is very sensitive for hairy cell leukaemia but may be positive in other B cell lymphoproliferative disorders. CD68 coexpression is unusual in other B cell lymphoproliferative disorders.

Variant

• Hairy cell leukaemia variant (HCL-V) is a rare disorder. Patients typically present with a high WBC (50.10⁹/l). HCL-V has features intermediate between HCL and B-prolymphocytic leukaemia (B-PLL). HCL-V cells are weakly TRAP-positive (as are some B-PLL) HCL-V is usually CD5- and variably CD25+, whereas B-PLL may be CD5+ and is usually CD25-¹.

• Blastoid transformation is very rare and is associated with loss of TRAP positivity².

Differential diagnosis

• Other low grade non-Hodgkin's lymphomas: immunophenotypes

• HCL-V: splenic marginal zone lymphoma, B-prolymphocytic leukaemia

Prognosis

Prolonged remission may follow splenectomy. HCL-V has a poor response to treatment and a shorter survival.

References

World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas. Current Diagnostic Pathology 2000;6:55-63.

¹EJ Schlette. B-cell prolymphocytic leukaemia. Pathology Case Reviews 2000;5 (5):274-280.

²Nazeer, T., Burkart, P., Dunn, H., Jennings, T.A. and Wolf, B. Blastic transformation of hairy cell leukemia. Arch Pathol Lab Med 1997;121:707-13.

³Mori, N., Y. I. Murakami, et al. (2004). "TIA-1 expression in hairy cell leukemia." Mod Pathol 17(7): 840-6.

This page last revised 1.9.2004.

©SMUHT/PW Bishop