Fibrotic Transformation of Polycythemia Vera & Essential Thrombocythemia Is Biologically Indistinguishable from Primary Myelofibrosis.
Nikhil A Sangle, Carolin Teman, Sherrie Perkins, Andrew Wilson, David Bahler, Josef Prchal, Mohamed E Salama. University of Utah & ARUP Laboratories, Salt Lake City
Background: Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are Philadelphia chromosome negative myeloproliferative disorders that share and exhibit the JAK2 mutation. Fibrotic transformations of PV & ET obscure the underlying disorder, making morphological distinction from PMF difficult. It is not clear if cases of post-PV/ET progressed to myelofibrosis (MF) are biologically or prognostically similar to PMF, or if they represent a distinct entity. We visited the post-PV/ET MF cases, in light of the new 2008 WHO criteria, to look for potential morphologic, biologic and prognostic differences between PMF and post PV/ET MF.
Design: Study included 17 post PV/ET MF and 19 PMF cases from 1981 till 2010. All cases were classified according to WHO 2008 criteria and initial diagnosis was confirmed on all the cases. The inclusion criteria was defined by cases that had sufficient diagnostic material in the form of bone marrow aspirate and core biopsy, JAK2, cMPL, clonality study, CD34+count and phenotype including CD133, CD38 and CD184, and LDH. We also compared morphemic features, grade of myelofibrosis and degree of osteosclerosis as well outcome in ET/PV following fibrotic transformation to those of PMF.
Results: The morphologic features of PMF, namely hypercellular or normocelluar marrow, clustering of atypical megakaryocytes, intrasinusoidal hematopoiesis and osteosclerosis, were seen with variable frequencies in all post-PV/ET MF cases. 37.5% of post-PV & post-ET MF cases maintained their original relative cellular composition [panmyelosis-PV and megakaryocytic hyperplasia-ET] and predominant original megakaryocytic morphology / histotopography in 18.7%. Amongst all parameters evaluated, only a high JAK2 allele burden seen in post-PV/ET MF attained statistical significance (p=0.011), when compared to the PMF group. A statistically significant difference was not observed amongst the other biologic parameters including CD34 number or maturation pattern using CD133, CD38 or expression of CD184 molecule, cMPL, LDH), grade of myelofibrosis, degree of osteosclerosis or clinical outcome (including overall or event free survival) amongst these 2 groups.
Conclusions: Except for a higher JAK2 level (P=0.011) observed in the post-PV/ET MF group, there are no morphologic, phenotypic or prognostic differences between the post-PV/ET MF and the PMF cases. Our study indicates that these 2 groups are biologically indistinguishable and may suggest that these be considered as such for diagnostic and management purposes.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 168, Monday Morning