Approach

The diagnostic workup of hairy cell leukaemia (HCL) includes a full history and physical examination, laboratory tests (including examination of peripheral blood to identify leukaemic [hairy] cells), bone marrow evaluation (including morphological, immunophenotypic, and molecular analysis), and in some cases imaging.[7][33][34]

Clinical presentation

Patients may present with fatigue, lethargy, infection, and/or weight loss.[7][35] The spleen may be palpable. 

Other patients are asymptomatic at presentation, and are diagnosed following an incidental finding of splenomegaly or pancytopenia discovered during evaluation for an unrelated cause.[7][35]

Patients may report recurrent infections, bleeding (gingival bleeding, epistaxis), or easy bruising.[33][35]​ Petechiae may be present.

Physical examination findings

Splenomegaly is a common physical finding.[7][36][37]

Hepatomegaly is present in 40% to 50% of patients, while lymphadenopathy is present in 10% of patients.[7][36][37][38]

Pallor (due to anaemia) and petechiae (due to thrombocytopenia) are common findings during physical examination.​[36][37]​ Less commonly, skin lesions can be due to vasculitis related to infiltration of the vessel wall by hairy cells.[39]

Neurological findings, though rare, may be present (e.g., Guillain-Barre syndrome, signs of meningitis, and nerve compression).[40]

HCL may manifest as a variety of immune dysfunctions (e.g., polyarteritis nodosa, pyoderma gangrenosum, scleroderma, polymyositis, and erythematous maculopapules), but this is uncommon.[41]

Initial laboratory workup

Initial tests to order include a full blood count (FBC) with differential, and peripheral blood smear.[33][37][42]

The FBC may show pancytopenia (decreased cell count in all three cell lines), which is characteristic of classic HCL.[6][35]

The majority of patients with classic HCL present with leukopenia.[7][43]​​ However, in approximately 10% of patients, leukocytosis (WBC count >10×10⁹/L to 20×10⁹/L [>10,000 to 20,000/microlitre]) is present.[7][43]​​​ Neutropenia and monocytopenia are generally present.[7][35]​ Monocytopenia is a consistent finding (present in approximately 90% of patients) and is characteristic of classic HCL.[7][36][44]​​ Some automated haematology analysers may classify hairy cells as monocytes, which can mask monocytopenia unless peripheral blood is examined.[45]

Hairy cells are identified on the peripheral blood smear in almost all patients (95%).[7] The hairy cells usually account for ≤20% of the total WBC count.[45] In patients who present with leukocytosis, hairy cells are the predominant circulating WBC.

Confirmatory diagnostic tests

To confirm the diagnosis of HCL, a bone marrow trephine biopsy and aspiration should be carried out for morphology assessment and immunophenotyping (using immunohistochemistry or flow cytometry).[7][34]

Bone marrow aspiration is often difficult to carry out in patients with classic HCL and usually results in a dry tap (due to bone marrow fibrosis).

Morphology assessment

Assessment of the bone marrow specimen will show hairy cell infiltration and reticulin fibrosis. Hypocellular bone marrow is present in approximately 10% of patients; avoiding a misdiagnosis of aplastic anaemia is important in these patients.[33]

Immunophenotyping

Immunohistochemistry (using bone marrow biopsy specimen) or flow cytometry (using bone marrow aspirate or peripheral blood) can help differentiate classic HCL from other lymphoproliferative disorders (including HCL variant [HCL-V]; also known as splenic B-cell lymphoma/leukaemia with prominent nucleoli [SBLPN]), and is important for establishing the diagnosis.[7][34]

Immunophenotyping should test for CD19, CD20, CD5, CD10, CD11c, CD22, CD25, CD103, CD123, cyclin D1, CD200, and annexin A1 (ANXA1).[34]

Immunohistochemistry may test for tartrate-resistant acid phosphatase (TRAP), which is expressed on HCL cells.[23][46][Figure caption and citation for the preceding image starts]: Cytospin prepared from bone marrow aspirate illustrates the typical cell cytology, with oval- to bean-shaped nuclei and moderate amounts of cytoplasm with irregular cytoplasmic borders (Wright Giemsa 100x oil)From the collection of Lynn Moscinski, MD [Citation ends].com.bmj.content.model.Caption@230d97e7[Figure caption and citation for the preceding image starts]: Sections of core biopsy demonstrate lymphocytes with obvious cytoplasm within the marrow interstitium, associated with dilatation of marrow sinuses and red blood cell collections (H&E 50x oil)From the collection of Lynn Moscinski, MD [Citation ends].com.bmj.content.model.Caption@3167a942

Pre-treatment evaluation

The following tests can guide treatment and should be ordered before initiating pharmacotherapy:[37]

  • Comprehensive metabolic panel (including urea, serum creatinine, electrolytes, serum albumin, and liver function tests [LFTs])

  • Serum lactate dehydrogenase (LDH)

  • Viral serology for hepatitis B and C

Other tests to order

A number of tests may be of value in specific circumstances.

Molecular analysis

May be considered to detect the BRAF V600E mutation (if there is diagnostic uncertainty following immunophenotyping) and IGHV4-34 rearrangements.[7][34]

The BRAF V600E mutation is present in almost all patients with classic HCL, but absent in HCL-V/SBLPN.[27]​ Patients with IGHV4-34 mutant HCL do not respond well to standard HCL treatments and have a poor prognosis. The BRAF V600E mutation is usually absent in these patients.[47]

Imaging studies

Imaging is not required except in milder forms of disease, in which computed tomography (CT) scans of the chest, abdomen, and pelvis may be used to detect mild organomegaly and adenopathy.[37][34][48] CT can detect internal adenopathy in approximately 15% of patients.[48]

Osteolytic lesions have been described rarely in HCL and have been reported as a finding on x-rays, typically when patients present with bone pain.[49]

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