A Differential Diagnosis of Hairy Cell Leukemia

Transcript:Leslie Andritsos, MD: For most patients a bone marrow biopsy is required to make the diagnosis of hairy cell leukemia because the leukemic cells do not typically circulate in the peripheral blood. And so while peripheral blood immunophenotyping could be performed in patients with an abnormal white blood cell count or an elevated white blood cell count, typically a bone marrow biopsy is needed to see if there are hairy cells in the bone marrow that express the typical or expected immunophenotype. The differential diagnosis of course includes variant hairy cell leukemia, which is typically CD25-negative and CD123-negative, as well as splenic marginal zone lymphoma, which may have hairy like projection and splenic diffuse red pulp lymphoma.

For classical hairy cell leukemia, the major molecular test is typical BRAF V600E mutation testing, which can be done by immunohistochemical stains on the bone marrow biopsy or by PCR [polymerase chain reaction]. And if either of those is positive, it’s certainly a classical hairy cell leukemia. For variant hairy cell leukemia, additional testing that can be helpful would include MAP2K1 mutation testing, as well as abnormalities of p53, which are present in about 40% of patients and can portend worse prognosis.

The risk stratification of hairy cell leukemia is not as full developed as it is in many other hematological malignancies. I think part of the reason for that is because hairy cell leukemia tends to have such a good prognosis in patients who are treated with upfront purine nucleoside analog therapy, where the majority of patients, about 80% of patients, will achieve a complete remission and stay in a complete remission for a prolonged period of time.

However, for the minority of patients who don’t achieve a remission, the risk stratification profiling is not very well developed. We do know that back in the 1980s, a group led by Janssen and others performed a clinical trial for risk stratification, where they found that patients who presented with severe anemia with a hemoglobin less than 8 and massive splenomegaly measuring more than 10 cm below the left costal margin tended to have a worse prognosis and were less likely to achieve remission. However, none of that research has been repeated in the modern era. And so that’s an area of research that is badly needed at this time.

For patients with variant hairy cell leukemia who have p53 mutations or deletions, we know that their response to chemotherapy is likely to be inferior, and probably other treatment approaches are going to be required.

Transcript Edited for Clarity