Hairy cell leukemia (HCL) is a rare, slow-growing cancer of mature B lymphocytes. It is named after the fine, hair-like projections on the cancer cells, which can be seen under the microscope on a peripheral blood smear. The smear often gives the first clue, alongside low blood counts and an enlarged spleen. The diagnosis is then confirmed with flow cytometry, a bone marrow biopsy and testing for the BRAF V600E mutation. Treatment with purine analog chemotherapy produces long remissions in most patients.
In my practice, hairy cell leukemia is one of those diagnoses where a careful look at the blood film changes everything. Automated counters often label these cells simply as lymphocytes or monocytes, so the diagnosis depends on someone looking.
What Is Hairy Cell Leukemia?
HCL is a chronic lymphoproliferative disorder, meaning a clonal overgrowth of lymphocytes. It accounts for only a small fraction of all leukemias. It mainly affects middle-aged adults, most often in their fifties, and is several times more common in men than in women.
The malignant B cells gather in the bone marrow, spleen and liver rather than circulating in large numbers. In the marrow, they trigger fibrosis that crowds out normal blood production. That explains the disease’s defining features: low counts of all blood cell types, and a spleen that can grow very large.
Virtually all cases of classic HCL carry the BRAF V600E mutation. It switches on the MAPK signaling pathway, driving cell survival and producing the cells’ distinctive shape and behavior. The cause of the mutation is unknown. Some occupational exposures, including farming and certain chemicals, have been linked to HCL, but the evidence is not conclusive.
Symptoms and Clinical Presentation
Because HCL progresses slowly, many people are diagnosed after a routine blood test shows unexplained low counts. When symptoms occur, they usually stem from low blood counts or an enlarged spleen:
- Fatigue and breathlessness from anemia
- Recurrent or unusual infections from low neutrophils and monocytes
- Easy bruising or bleeding from low platelets
- Fullness or discomfort in the left upper abdomen, or feeling full early after meals, from splenomegaly
- Less often, weight loss, fever or night sweats
Enlarged lymph nodes are uncommon in classic HCL, which helps distinguish it from other B-cell cancers such as chronic lymphocytic leukemia.
The Blood Smear: What We Look For
The blood count typically shows pancytopenia, a reduction in red cells, white cells and platelets. A very characteristic clue is monocytopenia, a marked shortage of monocytes. When I see pancytopenia with almost no monocytes and a large spleen, HCL moves to the top of my list.
On a well-prepared Wright- or Giemsa-stained smear, hairy cells have recognizable features:
- Medium to large size, larger than a normal small lymphocyte
- An oval, bean-shaped or indented nucleus with finely spread chromatin, and usually no prominent nucleolus
- A generous rim of pale blue-grey cytoplasm
- Fine, irregular, hair-like projections extending around the whole cell edge
These cells are often scarce in the blood, and the projections can be damaged when the smear is spread, so a careful manual review matters. Hairy cells can resemble other abnormal lymphocytes, so the smear raises the suspicion while other tests make the diagnosis.
| Feature | Classic hairy cell leukemia | Splenic marginal zone lymphoma | HCL-like variant disorders |
|---|---|---|---|
| Cell projections | Fine, all around the cell | Short, often at one or both poles | Hair-like, often with a prominent nucleolus |
| Monocytes | Markedly low | Usually preserved | Usually preserved |
| White cell count | Usually low | Variable | Often raised |
| CD25 and CD103 | Positive | Usually negative | CD103 often positive, CD25 negative |
| BRAF V600E | Present | Absent | Absent |
Confirming the Diagnosis
Flow cytometry identifies the immunophenotype of the abnormal cells. Classic HCL cells are mature B cells (CD19 and bright CD20 positive) that also express CD11c, CD25, CD103 and CD123. This combination is highly characteristic.
A bone marrow examination is usually performed. Attempts to draw liquid marrow often produce a “dry tap”, because reticulin fibrosis traps the cells. The biopsy core shows cells with a “fried egg” appearance, each nucleus surrounded by a clear halo of cytoplasm. Immunohistochemistry for annexin A1, TRAP (tartrate-resistant acid phosphatase), cyclin D1 and CD20 supports the diagnosis and shows how much of the marrow is involved.
BRAF V600E testing confirms classic HCL and can guide targeted therapy later. An ultrasound or CT scan may be used to measure the spleen.
Treatment and Outlook
Not everyone needs treatment right away. People with stable, modestly reduced counts and no symptoms may be watched. Treatment is started when blood counts fall significantly, infections recur, or the spleen causes symptoms.
- Purine analogs: cladribine or pentostatin are the standard first-line therapy. Most patients achieve remission, often lasting many years. Adding rituximab, an anti-CD20 antibody, is increasingly used to deepen responses.
- Relapsed disease: a further course of a purine analog, often with rituximab, or a BRAF inhibitor such as vemurafenib, sometimes combined with rituximab.
- Supportive care: infection prevention and prompt treatment of fever, especially during the period of low counts after cladribine.
Splenectomy is now rarely needed. For most patients, HCL has become a chronic, manageable condition with a life expectancy close to normal. Our leukemia guide compares HCL with other leukemias.
Key Takeaways
- Hairy cell leukemia is a rare, indolent B-cell cancer, driven in classic cases by BRAF V600E.
- Pancytopenia, monocytopenia and splenomegaly are the classic triad of clues.
- The blood smear shows cells with fine circumferential projections, but these cells can be few and easily overlooked.
- Flow cytometry (CD11c, CD25, CD103), bone marrow biopsy and BRAF testing confirm the diagnosis.
- See a doctor for unexplained low counts, recurrent infections, easy bruising or left-sided abdominal fullness.
Frequently Asked Questions
Can a blood smear alone diagnose hairy cell leukemia?
A smear can strongly suggest it, but it is not enough on its own. Other lymphomas can produce cells with projections, so flow cytometry and usually a bone marrow biopsy are needed to confirm it.
Why is the bone marrow aspirate often a “dry tap”?
Hairy cells stimulate reticulin fibers in the marrow, which trap the cells so liquid marrow cannot be drawn up. The solid core biopsy therefore becomes the key sample.
Is hairy cell leukemia curable?
Most patients achieve long remissions after a single course of cladribine or pentostatin, and many live a normal lifespan. Relapse can occur years later, but it usually responds to further treatment.
Is hairy cell leukemia inherited?
No. The BRAF V600E mutation is acquired in the leukemic cells during life, not passed down in families, so relatives do not need screening.
