Hairy cell leukemia: symptoms and diagnosis
Hairy cell leukemia (HCL) is a rare, slow-growing B-cell leukemia. It takes its name from the fine, hair-like projections on the surface of the leukemia cells. This topic covers the signs of HCL, which situations are urgent, the tests used for diagnosis and what the results mean. The good news: HCL responds very well to treatment.
01Short answer
02Simple explanation
In HCL, one type of B lymphocyte changes and slowly multiplies. Under the microscope, fine hair-like projections can be seen around the edge of these cells — hence the name. They gather mainly in the bone marrow and the spleen.
Because they take up space in the marrow and cause fibrous tissue to build up there, the production of healthy cells falls. As a result there are fewer red cells (anemia — tiredness, breathlessness), neutrophils and monocytes (infections) and platelets (bruising, bleeding). A fall in several cell types at once is called pancytopenia.
The spleen can become very large. This is felt as heaviness under the left ribs, feeling full after small meals, and sometimes discomfort or pain. Some people have weight loss or night sweats. Enlarged lymph nodes are uncommon in HCL.
HCL is rare: about 1,200–1,300 new cases are diagnosed each year in the United States. It is more common in men and in middle-aged and older adults. Because symptoms come on slowly, people may put them down to tiredness or stress for a long time.
The diagnosis is made step by step: a blood count and smear, flow cytometry on blood, then a bone marrow biopsy and a genetic test. Almost every case of classic HCL carries a mutation called BRAF V600E, which helps confirm the diagnosis. Modern treatment for HCL is very effective, and many people achieve long-lasting remission.
03Scientific explanation
Typical blood count findings are pancytopenia and especially monocytopenia — a very characteristic sign of classic HCL; the white cell count is usually low. Hairy cells may be seen on the smear, but they are few and not always easy to find. Examination and ultrasound or CT show splenomegaly, sometimes an enlarged liver and lymph nodes inside the abdomen.
Flow cytometry (often on peripheral blood) is the key diagnostic test. Hairy cells carry B-cell markers (CD19, bright CD20, CD22) and the combination typical of HCL: CD11c (bright), CD25, CD103 and CD123, as well as bright CD200; CD5 and usually CD10 are negative. This profile helps distinguish HCL from splenic marginal zone lymphoma and other look-alike conditions.
Bone marrow: because the marrow is filled with fibrous tissue (reticulin), no fluid can often be drawn during aspiration — this is called a “dry tap”. That is why a trephine biopsy is especially important: it shows an interstitial infiltrate of hairy cells with a typical “fried egg” appearance and, on immunohistochemistry, positive CD20, annexin A1 and BRAF V600E (VE1 antibody). The biopsy also shows how much of the marrow is involved and serves as the baseline for judging the response to treatment.
The BRAF V600E mutation is found in almost 100% of classic HCL and almost never in other B-cell leukemias and lymphomas, including the HCL variant; it is tested by PCR, NGS or immunohistochemistry. Cases without a BRAF mutation, negative for CD25 and annexin A1 and with a high white cell count, used to be called “HCL variant”; WHO 2022 groups them separately as “splenic B-cell lymphoma/leukemia with prominent nucleoli” — a condition with a different course and treatment. Under the 2017 consensus guidelines, treatment usually starts with: hemoglobin <11 g/dL, platelets <100×10⁹/L, an absolute neutrophil count <1×10⁹/L, or a symptomatic enlarged spleen. Before treatment, active infections are looked for and brought under control.
04What happens in the body?
Symptoms that need urgent help
Contact your doctor straight away or call emergency services if: you have a temperature of 38 °C or higher, shivering, a cough or breathlessness (with low neutrophils and monocytes, infections can worsen quickly); bleeding will not stop, or petechiae and bruises are spreading quickly; you suddenly get severe pain in the left side of the abdomen or the left shoulder, especially with dizziness and weakness — injury to an enlarged spleen is rare but an emergency; you have severe breathlessness or faint.
In what order are the tests done?
Usually: history and examination (spleen, liver) → complete blood count (pancytopenia, monocytopenia) → blood smear (hairy cells) → flow cytometry on blood (CD11c, CD25, CD103, CD123) → bone marrow aspirate and trephine biopsy with immunohistochemistry (annexin A1, BRAF V600E) → molecular BRAF V600E test → ultrasound or CT to assess spleen size and abdominal lymph nodes → infection screening.
What do the results roughly mean?
A typical flow profile together with annexin A1 and BRAF V600E confirms classic HCL. If there is no BRAF mutation and the marker profile is different, doctors consider similar but distinct conditions. How low the blood counts are and the state of the spleen decide when treatment should start.
Why does BRAF V600E matter?
This mutation is the “signature” of classic HCL and makes the diagnosis precise. It also matters for targeted treatment: in relapse or when standard treatment does not work, BRAF inhibitors can be one of the options. After treatment, BRAF or other markers can also be used to assess residual disease.
Questions you can ask your doctor
Is my diagnosis classic HCL or a similar condition? What did the BRAF V600E test show? How much of my bone marrow is involved? Do my blood counts mean I need treatment now, or is monitoring possible? How large is my spleen and what should I watch for? How should I protect myself from infection, and which vaccinations are suitable? Whom do I call at night if I have a fever?
Rare, but well understood
Being diagnosed with a rare disease can feel lonely. But HCL has been well studied for decades, and its treatment is among the most successful in leukemia care. It can help to consult a centre experienced in HCL, get a second opinion and use reliable information from patient organisations.
05HCL: from symptom to precise diagnosis
An HCL diagnosis usually takes shape in four steps.
06Key tests in HCL and typical findings
| Test | What does it check? | What is often seen in HCL? |
|---|---|---|
| Complete blood count | Red cells, white cells, platelets | Pancytopenia, especially low monocytes |
| Blood smear | How the cells look | Hairy cells with fine projections (may be few) |
| Flow cytometry | B-cell and HCL markers | CD19, bright CD20, CD22, CD11c, CD25, CD103, CD123 |
| Bone marrow aspirate | Cell sample | Often a “dry tap” — because of fibrous tissue |
| Trephine biopsy | Marrow structure, immunohistochemistry | Hairy cell infiltrate; annexin A1 and BRAF V600E positive; increased reticulin |
| BRAF V600E test | Gene mutation | Almost always positive in classic HCL |
| Ultrasound / CT | Spleen, liver, lymph nodes | Splenomegaly; sometimes abdominal lymph nodes |
* This table is general information; the set of tests may differ between centres. Discuss your own results with your hematologist.
07Key terms
- Hairy cell
- An abnormal B lymphocyte with fine, hair-like projections on its surface.
- Pancytopenia
- A fall in red cells, white cells and platelets at the same time.
- Monocytopenia
- Low monocytes in the blood; typical of HCL.
- Splenomegaly
- An enlarged spleen.
- Dry tap
- When no fluid can be drawn from the marrow during aspiration; often due to fibrosis.
- Reticulin
- Fine fibrous tissue that makes aspiration difficult when it increases.
- Annexin A1
- A biopsy marker that distinguishes classic HCL from look-alike conditions.
- BRAF V600E
- A gene mutation present in almost all cases of classic HCL.
- CD103, CD25, CD11c
- Surface markers typical of HCL on flow cytometry.
- HCL variant
- A former name; a BRAF-negative look-alike condition grouped separately in WHO 2022.
08Key points
- HCL is a rare, slow-growing B-cell leukemia.
- Signs: tiredness, infections, bruising, a heavy feeling under the left ribs.
- Fever, bleeding that will not stop or sudden severe left-sided abdominal pain are emergencies.
- Pancytopenia and monocytopenia are typical on the blood count.
- Flow cytometry shows a CD11c, CD25, CD103, CD123 profile.
- The marrow aspirate is often “dry”, so a biopsy is important.
- BRAF V600E is the genetic signature of classic HCL.
- HCL responds very well to treatment; discuss your results with your hematologist.
09Frequently asked questions
Do I need treatment immediately after diagnosis?
Not always. If your blood counts are acceptable and you have no symptoms, monitoring without treatment is possible. Treatment usually starts with anemia, a significant fall in platelets or neutrophils, or symptoms from the spleen.
Is a “dry tap” a bad sign?
No, it is a typical finding in HCL, linked to the build-up of fibrous tissue in the marrow. That is why doctors take an adequate sample with a trephine biopsy. After treatment, the fibrosis often lessens.
Why am I advised to take special care to avoid infections?
In HCL, neutrophils and monocytes can be low, which weakens defence against some infections. If you get a fever, seek help without delay. Plan vaccinations with your doctor; live vaccines may need to be avoided.
What if the BRAF V600E test is negative?
Then doctors re-examine the diagnosis: it may be another condition that resembles HCL, or a rare BRAF-negative classic HCL (for example in certain IGHV4-34 cases). An accurate diagnosis matters for choosing the right treatment.
Is HCL inherited?
No, HCL is not considered an inherited disease, and relatives do not need screening. The BRAF V600E mutation is acquired by the leukemia cells during life.
Is a normal life possible after treatment?
Yes. HCL responds very well to modern treatment, and many people live in long-term remission. If it comes back, effective options are available again. Regular follow-up continues.
10Questions for your doctor
Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.
Was a BRAF test done for the hairy cell leukemia diagnosis?
What is the size of my spleen?
What are the treatment options?
How will response to treatment be assessed?
12Sources
- National Cancer Institute (NCI). Hairy Cell Leukemia Treatment (PDQ®) — Patient Version
- National Cancer Institute (NCI). Hairy Cell Leukemia Treatment (PDQ®) — Health Professional Version
- Blood Cancer United (formerly The Leukemia & Lymphoma Society). Hairy cell leukemia (HCL) diagnosis
- Cancer Research UK. Symptoms of hairy cell leukaemia
- Cancer Research UK. Getting diagnosed with hairy cell leukaemia
- Hairy Cell Leukemia Foundation. Hairy Cell Leukemia Foundation — information for patients
- Blood (American Society of Hematology), 2017. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia
- British Journal of Haematology, 2020. The revised guidelines for the diagnosis and management of hairy cell leukaemia and the hairy cell leukaemia variant
- Annals of Oncology (ESMO), 2015. Hairy cell leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
- American Journal of Hematology, 2024. Hairy cell leukemia 2024: Update on diagnosis, risk-stratification, and treatment
- Leukemia (Nature) — WHO 5th edition. WHO Classification of Haematolymphoid Tumours: Lymphoid Neoplasms
- Blood (American Society of Hematology), 2022. The International Consensus Classification of Mature Lymphoid Neoplasms