Impact of Molecular Testing for JAK2^V617F in the Diagnosis of Polycythemia in An Integrated Community Based Hematology/Oncology Group Practice

In 2005, a specific mutation in the gene for JAK2 (JAK2^V617F) was documented in virtually all patients with Polycythemia vera (PV). In 2009, the WHO issued new diagnostic criteria for PV, listing erythrocytosis and a positive test for JAK2^V617F as major diagnostic criteria; and listing either a low serum erythropoietin level or characteristic bone marrow histopathological abnormalities as minor criteria for the diagnosis of PV. The importance of testing for JAK2 V617F in making the diagnosis of PV was documented by Seaman et al Cancer Epidemiol Biomarkers Prev 2009;18(2). February 2009. In Seaman's study of PV patients in Northeast Pa., molecular testing confirmed that only 33 of 62 patients thought to have PV were correctly diagnosed. This study was initiated at the request of the ATSDR with goals of determining if similar discrepancies existed in another, larger population; as well as determining whether community hematologists were integrating molecular testing into their diagnostic paradigms.

The Geisinger Medical Center is an integrated health provider, with facilities throughout much of north central and east Pennsylvania. A single EMR has been utilized at outpatient locations since 2004. After obtaining approval from the Institutional Review Board, the records of all patients being followed between 2004 and 2009 for PV by a Geisinger hematologist/oncologist were identified.

A total of 279 records were located. These records were reviewed for the physician's narrative diagnosis, the use of molecular testing, serum erythropoietin levels, bone marrow histology, as well as other tests historically used to assess polycythemia (red cell volume, spleen size by imaging, etc.). Of these records 252 contained adequate physician documentation to be evaluable.

While all progress notes listed PV as the final diagnosis, the progress notes documented sufficient data to make a diagnosis of PV in only 139 patients. 89 were diagnosed with secondary polycythemia, while twenty one were ultimately found to have spurious polycythemia. Once the patient was diagnosed with PV, it was rarely changed when further testing indicated either secondary or spurious polycythemia.

JAK2^V617F mutation testing was performed in 132 of these patients, with 94 of these tests obtained in 2008 or later. 80 of the 132 patients tested for this mutation were JAK2^V617F positive. Seventy eight of the JAK2^V617F positive. patients underwent additional testing. Serum erythropoietin levels were measured in 39, while bone marrow samples were obtained in 20 patients. Only 41 JAK2^V617F positive patients met the 2009 WHO “minor” criteria by having either a serum erythropoietin level near or below the lower limit of normal, and/or a bone marrow characteristic of PV. In 14 patients, JAK2^V617F testing led to a change in diagnosis, excluding PV in eleven, while three patients initially diagnosed with secondary polycythemia were found to have PV.

Of patients who did not undergo molecular testing, only six had low serum erythropoietin levels and abnormal bone marrow findings. Determinations of the red cell mass with, or without plasma volume was rarely performed after 2004.

From these data we conclude that JAK2^V617F testing has made a major impact in facilitating the successful delineation of the cause of polycythemia in patients evaluated in a large, community – based Hematology/Oncology practice. In contrast the complete WHO diagnostic criteria do not appear to be widely utilized by these physicians, nor does it appear that these additional tests add to the diagnostic evaluation in most patients. The necessity of utilizing the minor criteria while assessing JAK2^V617F positive patients requires further evaluation.

Furthermore this study demonstrates that physicians do not change their initial diagnosis to reflect the impact of the additional testing. This has implications for those utilizing ICD – 9 codes to study myeloproliferative neoplasms.

No relevant conflicts of interest to declare.