Myeloproliferative Neoplasms: Diagnosing Polycythemia Vera

An expert in hematologic malignancies, Jamile Shammo, MD, FASCP, FACP, provides an overview of the 2016 WHO diagnostic criteria for polycythemia vera and considers the role of genetic testing.

Jamile Shammo, MD, FASCP, FACP: The diagnostic criteria for polycythemia vera [PV] were published in 2016, and the WHO [World Health Organization] suggests that we can make the diagnosis of PV if 3 major criteria have been met. The first is a hemoglobin level of greater than 16 g/dL for women,
16.5 g/dL for men; a hematocrit greater than 49% for men or 48% for women; or, of course, an increased blood cell mass beyond 25% of the upper limit of normal, and that is assuming we are able to identify a lab that can do a red cell mass test. That constitutes the first major criterion. The second major criterion is a bone marrow biopsy demonstrating hypercellularity for age with panmyelosis affecting all 3 lineages. The third major criterion is the presence of a JAK2 [Janus kinase 2] mutation, either an exon 12 or exon 14; 95% of patients who have PV will have the JAK V617F mutation, which is present on exon 14. If your patient meets all 3 criteria, then you’re able to make the diagnosis.

Some patients may not have a clonal hematopoiesis with the presence of the JAK2 mutation, in which case you need to meet the first 2 major criteria, which are the hemoglobin, hematocrit, or positive bone marrow biopsy with panmyelosis, and the single minor criterion of a subnormal serum erythropoietin level. A single caveat is that if your patient has a high hemoglobin, such as 18 g/dL or 18.5 g/dL in men and women, respectively, plus a JAK2 mutation and a low serum erythropoietin level, you could avoid doing a bone marrow biopsy. In this case, you are able to make a diagnosis of PV.

Clearly, being able to identify clonal hematopoiesis and a JAK2 mutation is exceedingly important in this patient population. Remember that it isn’t just erythrocytosis that manifests in patients with PV. If you have a patient who may be iron deficient, then you may not be able to identify that patient with PV because the hemoglobin may not meet those criteria. Pay attention to patients who may have leukocytosis or thrombocytosis, and always remember to look at the iron stain in the bone marrow biopsy as you may be able to identify mass polycythemia. Any cytosis should trigger testing for the JAK2 mutation to identify those patients.

JAK2 mutational analysis is typically performed on the peripheral blood. That is not to say that you couldn’t do this on the bone marrow. If I’m performing a bone marrow biopsy on a patient, it’s because I’m ruling out an MPN [myeloproliferative neoplasm]. I would generally perform next-generation sequencing [NGS] panel. I would be looking at a much broader evaluation for a driver mutation, not just the JAK2 mutation. It wouldn’t just be the JAK2, obviously. You’d be looking at a much broader genetic panel in this situation. Clearly, the value of finding additional mutations in polycythemia vera is debatable. There are some data suggesting that perhaps finding additional mutational abnormalities on top of JAK2 mutations may portent a worse prognosis, but in general, you’re looking for that mutation to make a diagnosis in PV. Relative to prognosis, we need a bit more data to make a case for looking for additional mutations and NGS panels in PV.


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