Hairy Cell Leukemia and Hairy Cell Variant: BSH Updates in Diagnosis and Management

Hairy cell leukemia (HCL) is a rare, chronic B-cell leukemia that was first described as a distinct entity in 1958.^1,2 The indolent malignancy accounts for 2% of lymphoid leukemias, with approximately 1240 new cases diagnosed in the US per year.^1,2 The malignancy is more prevalent in men, and median age at diagnosis is 58 years.¹ HCL variant (HCL-V) is a separate entity from classical HCL, with unique immunophenotypic, cytologic, and hematologic characteristics. Given recent updates in both diagnostics and the treatment landscape, updated clinical practice guidelines are key to ensuring optimal care for patients with either form of HCL.¹

The British Society for Haematology (BSH) recently published a guideline update for the diagnosis and treatment of HCL and HCL-V in the British Journal of Haematology.¹ Lead author Nilima Parry-Jones, MD, of the Aneurin Bevan University Health Board in Abergavenny, UK, and colleagues updated previous guidelines released in 2012.

Diagnosis, Staging, and Indications for Treatment

The initial clinical presentation of HCL is variable (Table 1), with some patients appearing asymptomatic but exhibiting an incidental pancytopenia, while others may present with fatigue, infection, or palpable splenomegaly. The hallmark laboratory feature is cytopenias, often affecting 2 or more lineages. Leukopenia is a common characteristic of classical HCL, with monocytopenia almost always present. By comparison, monocytopenia is not a characteristic of HCL-V, whereas leukocytosis is frequently seen in this form of the leukemia.¹

Table 1. Selected Clinical and Laboratory Features of Classical HCL at Diagnosis¹

Feature	Prevalence
Hairy cells in blood film	95%
Hemoglobin <100 g/L	70%
Platelet count <100 x 109/L	80%
WBC count <5 x 109/L	65%
Neutrophils <1 x 109/L	70%
Monocytes <1 x 109/L	>90%
Abdominal lymphadenopathy on CT	10%
Palpable hepatomegaly	40-50%
Palpable splenomegaly	60-70%

Several diagnostic tests and investigations are useful to help establish a diagnosis of HCL (Table 2).

Table 2. Selected Diagnostic Modalities for Diagnosis of Classical HCL and HCL-V^1,2

Diagnostic Test	Description
Peripheral blood film1	Findings characteristic of classical HCL: • Medium-sized lymphoid cells with an oval or indented (kidney-shaped) nucleus with homogeneous, ground-glass chromatin, slightly less clumped than that of a normal lymphocyte • Usually absent (or inconspicuous) nucleolus • Cytoplasmic abundance, pale blue, and with circumferential “hairy” projections • Discrete cytoplasmic vacuoles or rod-shaped inclusions (ribosome lamellar complexes) may be observed
Bone marrow aspirate and trephine biopsy1	• Bone marrow aspiration is often unsuccessful, reflecting fibrosis caused by the hairy cell infiltrate • Trephine biopsy routinely shows patchy infiltration, making it important to obtain a good-sized specimen
Flow cytometry and IHC1	• The classic immunophenotypic profile of HCL consists of bright co-expression of CD20, CD22, and CD11c and expression of CD103, CD23, CD123, TBX21 (TBET), annexin A1, FMC7, CD200, and cyclin D1 • Annexin A1 is the most specific marker and can be useful to distinguish classical HCL from HCL-V
Molecular genetics1,2	• The BRAF V600E mutation is present in >85% of patients with classic HCL2 • Early detection of BRAF V600E allows for more precise monitoring of disease-eradicating therapies1 • NGS has the potential to be the preferred testing methodology in the longer term1