Updates in the Management of Hairy Cell Leukemia - Episode 4

Differential Diagnosis and Molecular Tests in Identifying HCL

June 30, 2020
Steven Coutre, MD, Stanford University Medical Center

,
Farhad Ravandi-Kashani, MD, MD Anderson Cancer Center

,
Jae Park, MD, Memorial Sloan Kettering Cancer Center

,
Alan Saven, MD, Scripps Health

,
Andrea Sitlinger, MD, Duke University Cancer Institute

Jae Park, MD: With differential diagnosis of hairy cell leukemia, the bone marrow biopsies, and cell marker and flow findings, and perhaps some of the lymphadenopathy issues may point in one direction or another. When we see patients like this, similar to leukemia or lymphoma, what other blood cancers should we be considering or rule out, for suspected hairy cell leukemia, because it's a rare disease? Dr Ravandi, please comment on some of the differentials for hairy cell leukemia.

Farhad Ravandi-Kashani, MD: The morphology of hairy cell is characteristic. They have these standard projections from the cells, but there are some other conditions that can be fairly similar in terms of morphology. For example, a splenic marginal zone lymphoma, which also has these projections from the cells. Then there is the very uncommon hairy cell variant, which is perhaps 5% to 10% of all the cases of potential hairy cell leukemia diagnosis. In terms of morphology, it’s typically characteristic for the pathologist, and the flow cytometry markers that were described by a previous presenter are also typical in hairy cell leukemia. As mentioned, the B-cell markers as well as CD11, CD103, and CD25 are positive, and there are a number of markers that we explained are negative. In variant hairy cell leukemia, CD25 and sometimes also CD103 are negative. Variant patients tend to present with a higher white blood cell count, so at presentation hairy cell leukemia patients tend to be pancytopenic, although, you can have classical hairy cell leukemia with a higher white count as well. But the ones who have a high white count tend to be variant hairy cell, and patients with variant hairy cell also tend to be older. The median age for classical hairy cell is about mid-50s, but in variant hairy cell they tend to be older, middle-to-late 60s typically, and even older. This is important in terms of management because variant hairy cell doesn't respond as well to nucleoside analogue, so if you do come up with a diagnosis of variant, you need to think about your treatment strategy to be a bit different.

Another thing with variant hairy cell is they are not BRAF mutated. That's a good marker to distinguish variant from classical hairy cell leukemia. The use of flow markers is not limited to diagnosis. We can monitor hairy cell leukemia clearance in a number of ways. For example, we have been using a soluble IL-2 [interleukin-2] receptor, which is soluble CD25. Also, you can use soluble CD22. But you can also use flow markers for looking for minimal residual disease. Now, the debate about the relevance of minimal residual disease clearance in hairy cell is extensive. The flow markers are important to use both for diagnosis and for follow-up, and BRAF mutation is important in terms of distinguishing classical hairy cell from variant hairy cell.

Jae Park, MD: What assays are you using to detect BRAF mutations? Because I think sometimes we have a targeted gene panel dedicated for BRAF, and then some are more NGS [next-generation sequencing] panels, or targeted gene sequencing. I’m curious whether we routinely do it for all patients with hairy cell leukemia, and then come to what assays you are using.

Steven Coutre, MD: Increasingly, we tend to use our institutional NGS panels on most of our hematologic malignancies, for better or worse. Sometimes a patient with hairy cell leukemia has that done for that reason. In the past, we've simply used immunohistochemistry, for example.

Farhad Ravandi-Kashani, MD: We use a PCR for specific patients and then complement that with immunohistochemistry.

Alan Saven, MD: We use Sanger sequencing, but I'm not going to go through all the differences between that and next-generation sequencing. My understanding is it's a little simpler and it’s more targeted.

Transcript Edited for Clarity