This week we discussed a 65 year old gentleman who was about to undergo curative surgery for gastric carcinoma. His admission blood tests showed pancytopenia and monocytopenia.
The differential diagnosis of pancytopenia includes:
- Haematological malignancy e.g. myelodysplasia or infiltration from leukaemia/lymphoma/myeloma
- Systemic autoimmune disease e.g. lupus
- Aplastic anaemia
- Inherited genetic changes e.g. dyskeratosis congenita, Shwachman–Diamond syndrome
- Infiltration from metastatic non-haematopoietic malignancy
- Severe sepsis/infection including tropical infections
- Metabolic syndromes e.g. Gaucher’s disease, osteopetrosis
- B12/folate/trace metal deficiency
- Viral including HIV
- Medications e.g. anti-epileptics, chemotherapy
History and examination will hopefully help you exclude many of these conditions (see references below). As always it is worth repeating the test if the result was unexpected.
Close examination of the blood film revealed a notable absence of monocytes and an infiltration from mature lymphocytes with voluminous pale cytoplasm and hairy projections along with a mature oval nucleus and loose chromatin pattern.
After review of the patient’s previous CT scans splenomegaly is noted, which together with the blood count and blood film would be very suspicious for hairy cell leukaemia. Other low grade lymphomas can cause similar patterns (e.g. hairy cell leukaemia variant and splenic marginal zone lymphoma) however immunophenotyping of the peripheral blood showed a kappa-restricted B cell population expressing CD11c, CD103, CD123, CD25 and negative for CD5, CD10 and CD23. This would be consistent with HCL.
Hairy cell leukaemia
This is an uncommon B cell malignancy that affects mainly adults in the later half of life (average age 50). Men are more affected than women (ratio 4.5:1). Many patients are asymptomatic but some may complain of abdominal pain due to splenomegaly, night sweats, weight loss, bleeding/bruising, fatigue and atypical infections. Lymphocyte count may be normal. This is an indolent lymphoma/leukaemia which progresses very slowly.
HCL is diagnosed by clinical assessment and morphological appearances. Hairy cell leukaemia has a typical immunophenotype by flow cytometry or by immunohistochemistry on a trephine biopsy. The aspirate may be difficult due to marrow fibrosis (dry tap). Trephine histology is rather unique with cells having a ‘fried egg’ appearance. HCL cells express B cell antigens (e.g. CD19, CD20, CD22, CD79a) along with CD11c, CD103, CD123, CD25, Annexin A1, DBA44, cyclin D1, TRAP. Genetic analysis shows the BRAF V600E mutation in almost all cases.
The prognosis of hairy cell leukaemia is excellent with a 95% five year survival. If complete remission is achieved then disease free survival can be over 20 years. However HCL is generally incurable with late relapses occurring.
In asymptomatic patients watch and wait may be a reasonable way to start especially if blood counts are not too bad.
The standard treatment is cladribine or pentostain. Both produce a complete remission of over 80%. Cladribine is often preferred as it can be given as a subcutaneous injection daily for five days as a one off treatment. Pentostatin must be given IV every two weeks. There are a variety of ways to deliver cladribine therapy and this depends on local policy. Pentostatin and cladribine have not been tested against each other. Patients are at risk of viral and PCP infections so aciclovir and co-trimoxazole prophylaxis is usually used. Both these purine analogues require lifelong irradiated blood to prevent against transfusion-associated graft versus host disease.
Interferon alpha can also be used but the response is not satisfactory so it is not generally required. It could be used in a pregnant patient or to gain control of counts in the face of severe neutropenia prior to definitive therapy. Splenectomy may also be used as first line therapy and can lead to durable remissions especially if the majority of the disease is in the spleen. Rituximab is often left for residual or refractory disease. BRAF inhibitors can also be used but generally not first line.
He underwent an urgent bone marrow biopsy which confirmed hairy cell leukaemia. As the patient had a potentially curable gastric malignancy it was felt surgery for this should take priority and this was performed a week later. GCSF was given preoperatively to prevent infection. The patient recovered well following the operation.
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