Bone Marrow Histology and Red Cell Mass Allow Accurate Identification of Early Stage Polycythemia Vera
Attilio Orazi, Leonardo Boiocchi, William Chow, Katherine Vandris, Ivy Tam, Anita Narayan, Maria T De Sancho, Wayne Tam, Yue Wu, Yen-Chun Liu, Stanley J Goldsmith, Richard T Silver. Weill Cornell Medical College, New York, NY
Background: The WHO diagnosis for polycythemia vera (PV) includes 2 major criteria, increased red cell volume (RCV) and JAK2 mutation, and 3 minor criteria, bone marrow biopsy (BMB) showing features of PV, low serum erythropoietin (EPO), and endogenous erythroid colony formation. Increased RCV is defined as Hb >18.5 g/dL in men or >16.5 g/dL in women, or Hct >99th percentile of institutional normal range, or Hb >17g/dL in men or >15 g/dL in women if sustained increase of ≥2 g/dL exists, or red cell mass (RCM)>25% above mean normal predicted value. However, RCM determination is often not done and the diagnosis is based on Hb and/or Hct.
Design: We prospectively evaluated 30 patients with a clinical phenotype of PV including presence of JAK2 mutation. Increased RCV was determined by simultaneous Cr-51 RCM and I-125 plasma volume determinations (adjusted for BMI >25 kg/m2). Corresponding Hb and Hct values were compared. JAK2V617F was determined by ARMS PCR and quantitated by pyrosequencing. BMB stained for H&E, reticulin and trichrome were interpreted by 3 observers. All patients had been followed for a median of 4 years for diagnostic confirmation.
Results: 28 of 30 cases were diagnosed as PV based on increased RCM. In all 28 cases BMB showed hypercellularity due to increased erythropoiesis and granulopoiesis and increased pleomorphic megakaryocytes. Their median phlebotomy requirement in the first year was 4. The remaining 2 cases would have met the WHO criterion for PV because of increased Hct value (and JAK2) but had a normal RCM and were diagnosed as essential thrombocythemia (ET) confirmed by BMB showing normal cellularity associated with increased number of hyperlobulated megakaryocytes lacking pleomorphism. They had no increase in RCV or need for phlebotomies in the succeeding 4 years. Eighteen PV patients, met major criterion #1 by elevated RCM but not for increased Hb. The median Hb value was 15.2 g/dL in the 4 women; 17.2 g/dL in the 14 men. Only 21 patients had a low EPO level (<5 mU/mL), as did 1 ET.
Conclusions: Early stage PV may be missed if RCM determination is not done. In our series, using Hb or Hct as a single criterion, 18 (64.3%) and 9 patients (32.1%) respectively would not have been diagnosed as PV. BMB remains crucial for confirming the diagnosis. In fact, all PV cases showed the expected histologic findings which are distinct from those seen in ET. Despite sporadic reports to the contrary, we believe that BMB analysis in PV and ET is reproducible and easily integrable with clinical data. A correct diagnosis of PV even in its early phase has important clinical implications.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 225, Wednesday Morning