Case 1: Diagnosis of P. Vera

Experts in MPN discuss diagnostic considerations for polycythemia vera.

Ruben Mesa, MD: Prithviraj, bringing this all together, how do we then make a formal diagnosis?

Prithviraj Bose, MD: That, too, has evolved. The new WHO [World Health Organization] 2016 criteria have intentionally lowered the hemoglobin and hematocrit cutoffs so as to not miss patients termed masked PV [polycythemia vera]. The hemoglobin and hematocrit thresholds are now lower than they were in the 2008 classification. Because of that, the bone marrow biopsy has become more important because you obviously don’t want the red herrings, or false positives, either. Currently, by the 2016 criteria, the bone marrow biopsy is actually a major criterion, as is the hemoglobin hematocrit level. The JAK2 V617F or exon 12 mutations, which you can see in about 4% of cases, makes up the third major criterion. Finally, a low EPO [erythropoietin] level is your minor criteria. All 3 major criteria will do it. For those very rare JAK2-negative cases, if you have the hemoglobin, the hematocrit, the bone marrow, and the low EPO, that will do it as well.

Jamile M. Shammo, MD: There’s 1 caveat I love to point out, being the ex-pathologist. At the bottom of the WHO 2016 criteria, there’s something in the fine print that lot of people miss. If you have someone who may have a hemoglobin of 19 or 20 g/dL, a hematocrit of 68% or 70%, and a JAK2-positive mutation, you frankly don’t need a bone marrow biopsy. For any hemoglobin above 18%, hematocrit above the 2008 cutoffs, and a JAK2-positive mutation, you don’t need to do a bone marrow biopsy. Obviously, when you have lower cutoffs and you need to meet the first 3 major criteria, you need a bone marrow biopsy, but not otherwise if you have the higher levels.

Prithviraj Bose, MD: Absolutely.

Ruben Mesa, MD: Jamile, on the other end of the spectrum, the higher the count, and the JAK2—in practice, few in the community are doing the bone marrow if they feel comfortable with the diagnosis. We’ll get around to risk in a moment. I do find it to be helpful sometimes as a baseline assessment for the disease, not necessarily to confirm the diagnosis, although according to the WHO, it certainly is recommended. It’s a nice confirmation and nice baseline. But I do find the flip side: individuals who don’t quite reach that degree of erythrocytosis, particularly younger women, individuals who have mild iron deficiency, etc. People have floated this concept of “mass polycythemia vera.” What are your thoughts on this, Stephen? Do you think that’s a real entity? Or should we say that it’s just polycythemia vera and they’re a little iron deficient, so the actual degree of erythrocytosis is a very fluid number?

Stephen Oh, MD, PhD: It’s somewhere in between. Whether you call it masked PV or not, this is definitely a real entity. As you described patients who are iron deficient, I like to say that their hemoglobin is not as high as it would be naturally if they weren’t iron deficient. We know that to be the case if they have GI [gastrointestinal] bleeding. You correct that, and their hemoglobin can increase. If they are given supplemental iron, their hemoglobin can increase. Then it gets to the question of, is making this distinction between so-called masked PV and ET [essential thrombocythemia] important? Do we need to make that distinction? There is some reason for that to be an important distinction. That can relate to prognosis, treatment, etc. We would probably all agree that PV and ET are much more similar than they are different, but there are distinctions, so making that distinction in terms of diagnosis is relevant.

This transcript has been edited for clarity.

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