Hairy cell leukaemia (HCL) is a rare chronic lymphoproliferative disorder, accounting for about 2% of all leukaemias [1]. It consists of mature clonal B lymphocytes with distinctive microfilamentous membrane projections. The disease was first comprehensively described in 1958 by Bouroncle et al. as ‘leukemic reticuloendotheliosis’, characterised by fatigue, weakness, splenomegaly, pancytopenia, frequent infections and often a ‘dry tap’ on bone marrow aspiration due to marrow fibrosis [2]. These non-specific features make early diagnosis challenging. HCL occurs predominantly in men (male-to-female ratio approximately 4:1) and is most common in Caucasians [1].

The hallmark morphological feature – the cytoplasmic projections – arises from actin cytoskeleton rearrangements driven by the BRAF V600E mutation and activation of the MAPK/ERK signalling pathway, which regulates cell growth, survival and adhesion [1,3]. These changes alter cell shape and promote interactions with the microenvironment, giving the cells their distinctive ‘hairy’ appearance.

The BRAF V600E mutation is present in virtually all cases of classic HCL and is considered a disease-defining event [1].

Although recognising hairy cells on a peripheral blood smear can guide diagnosis, their presence is not exclusive to HCL and not all abnormal cells display projections. Usually, only a small proportion of hairy cells is observed in blood smears. As highlighted by Troussard et al., morphology alone is insufficient; accurate classification requires integration of immunophenotypic markers (CD11c, CD103, CD123, CD25) and molecular confirmation, particularly detection of the BRAF V600E mutation [4,5].

HCL and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), form a heterogeneous group of mature B-cell neoplasms that share morphological similarities (hairy-appearing cells on smear) but differ in genetic profile, clinical course and treatment approach [4,5].

Case results

An 87-year-old man with no significant recent medical history and no symptoms presented for a routine check-up at the cardiology unit. A complete blood count was performed, revealing an increased white blood cell (WBC) count of 16.43 × 10³/µL and a low platelet (PLT) count of 44 × 10³/µL. The haemoglobin concentration was within the reference range, but the red blood cell (RBC) count was slightly decreased [6].

The haematology analyser flagged several abnormalities, including ‘WBC Abn Scattergram’, ‘Blasts/Abn Lympho?’, ‘IG present’, as well as ‘Lymphocytosis’ and ‘Monocytosis’.

Digital imaging analysis of the peripheral blood smear (see Fig. 2) revealed 65.5% lymphocytes, some of which displayed fine cytoplasmic projections (hairy cells); 8.3% monocytes; 25% segmented neutrophils; and 1.2% band cells.

Based on these haematology findings, the sample was referred to the flow cytometry laboratory and further investigated; flow cytometry confirmed the diagnosis of hairy cell leukaemia (HCL).

Fig. 2: Hairy cells in the patient’s smear review

Hairy cells typically measure 10–25 µm, with a round, oval or bean-shaped nucleus, sparse chromatin and abundant pale cytoplasm with shaggy projections; fine granules may occasionally be present [1].

References

[1] Maćkowiak K et al. (2023): Hairy cell leukemia – etiopathogenesis, diagnosis and modern therapeutic approach. Biochem Med (Zagreb) 2024;34(2): 020502.

[2] Bouroncle BA et al. (1958): Leukemic reticuloendotheliosis. Blood 13(7): 609–630.

[3] Tiacci E et al. (2006): Evolving concepts in the pathogenesis of hairy-cell leukaemia. Nat Rev Cancer 6, 437–448.

[4] Maitre E et al. (2022): Immunophenotypic Analysis of Hairy Cell Leukemia and HCL-like Disorders. Cancers (Basel). 14(4): 1050.

[5] Troussard X et al. (2024): Hairy Cell Leukemia 2024: Update on Diagnosis, Risk-Stratification, and Treatment. Am J Hematol. 99(4): 679–696.

[6] L van Pelt J et al. (2022): Reference intervals for Sysmex XN hematological parameters as assessed in the Dutch Lifelines cohort. Clin Chem Lab Med; 60(6): 907.