Hairy Cell Leukaemia and Leukaemoid Reaction
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Direct answer
Hairy cell leukaemia is a chronic B-cell lymphoproliferative disorder with characteristic cytoplasmic villous projections, diagnosed by flow cytometry showing CD11c, CD25 and CD103 positivity and treated with a single course of cladribine. A leukaemoid reaction is a reactive leucocytosis that mimics leukaemia, typically with a raised leucocyte alkaline phosphatase score, and it resolves once the cause is treated. The two are separated by whether the white count is clonal or an appropriate response to infection, inflammation or marrow stimulation.
What you must remember
- Morphology: lymphoid cells with fine hairy cytoplasmic projections; the bone marrow aspirate is often a dry tap because of reticulin fibrosis.
- TRAP stain: tartrate-resistant acid phosphatase positivity was the classic test, though flow cytometry now carries more weight.
- Immunophenotype: CD11c, CD25, CD103 and annexin A1 positive, with CD5 and CD10 negative.
- BRAF V600E: present in most cases, supporting the diagnosis and enabling BRAF inhibition in refractory disease.
- Treatment: a single course of cladribine is first-line, with pentostatin as an alternative; many patients remain in remission for years, and relapse is treated again.
- Leukaemoid reaction: neutrophilia with left shift and toxic granulation, a raised LAP score, and a clear precipitant such as severe infection, inflammation or metastatic malignancy.
- Pertussis: a classic cause of lymphocytic leukaemoid reaction in children.
A worked case: pancytopenia with splenomegaly
A 55-year-old man has fatigue, infections, splenomegaly and pancytopenia, and the bone marrow aspirate is a dry tap. The table contrasts him with a reactive white count.
| Feature | Hairy cell leukaemia | Leukaemoid reaction |
|---|---|---|
| Nature | Clonal B-cell disorder | Reactive neutrophilia |
| Key marker | CD11c, CD25, CD103 and BRAF V600E | Raised leucocyte alkaline phosphatase score |
| Typical setting | Pancytopenia with splenomegaly | Severe infection, inflammation or malignancy |
| Management | Single course of cladribine | Treat the precipitant |
Flow cytometry is positive for CD11c, CD25 and CD103 on B cells, and BRAF V600E is detected, which confirms hairy cell leukaemia, so cladribine is planned with infection prophylaxis and attention to the nadir period.
A 60-year-old with pneumonia and a white count of 55,000 per microlitre, with neutrophilia, left shift and toxic granules, no splenomegaly and a negative clonal flow result, has a leukaemoid reaction.
The same white count in chronic myeloid leukaemia would carry a low LAP score and BCR-ABL1 positivity, so the score alone is not diagnostic. The marrow trephine and the flow panel together give the most reliable answer, while a single stain rarely settles the question.
Where the examiner sets the trap
Look-alike diagnoses are the main trap here.
- Trap: confusing hairy cell leukaemia with splenic marginal zone lymphoma with villous lymphocytes. Correct: hairy cells express CD25 and CD103 and carry BRAF V600E, whereas the other entity generally does not, so immunophenotype and molecular testing decide.
- Trap: treating the LAP score as diagnostic on its own. Correct: it is low in chronic myeloid leukaemia and high in reactive states, so the answer adds flow cytometry and BCR-ABL1.
- Trap: calling a dry tap a failed aspirate. Correct: it should prompt thought of hairy cell leukaemia, and the reticulin fibrosis behind it is the viva answer.
Frequently asked questions
What immunophenotype confirms hairy cell leukaemia?
Flow cytometry typically shows CD11c, CD25 and CD103 positivity on B cells, with CD5 and CD10 negativity, and annexin A1 supports the diagnosis. BRAF V600E is present in most cases and is a useful confirmatory marker.
Which drug is the standard first-line treatment for hairy cell leukaemia?
A single course of cladribine is the standard first-line treatment, with pentostatin as an alternative. Many patients remain in remission for years, although relapse can occur and may be treated again or, in selected cases, with BRAF inhibition.
How does a leukaemoid reaction differ from chronic myeloid leukaemia?
A leukaemoid reaction is a reactive neutrophilia with a high leucocyte alkaline phosphatase score, whereas chronic myeloid leukaemia has a low score and BCR-ABL1 positivity. Clinical context and cytogenetics decide when the picture is ambiguous.
What is a frequent cause of a leukaemoid reaction in an adult?
Severe bacterial infection and tuberculosis are frequent causes of a leukaemoid reaction in adults, along with inflammatory disease and metastatic malignancy. In children, pertussis is a classic cause of a lymphocytic leukaemoid reaction.