Post-Polycytemic and Primary Myelofibrosis Display Different Morphologic and Karyotypic Features
Leonardo Boiocchi, Umberto Gianelli, Alessandra Iurlo, Tommaso Radice, Attilio Orazi. Weill Cornell Medical College, New York, NY; Universita' di Milano, IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy
Background: Polycythemia Vera (PV) and Primary Myelofibrosis (PMF) share propensity to progress towards a fibrotic terminal stage with overlapping clinical characteristics (e.g., splenomegaly). Bone marrow features potentially useful for distinguishing between them have not been much investigated and only clinical history is currently used for purpose of disease classification.
Design: We studied 25 cases of post-polycythemic myelofibrosis (post-PVMF) and 15 cases of PMF in advanced fibrotic stage (MF-2 or -3) from two large medical centers. H&E, reticulin and trichrome stains were used to evaluate morphology and fibrosis, the latter assessed by the European Grading System. CD42b and CD34 were used to identify megakaryocytes and blasts, respectively. Cytogenetic results were available in 15 post-PVMF and in all PMF cases. JAK2V617F mutation status and follow up information were available in all cases.
Results: All post-PVMF cases carried JAK2V617F mutation vs. 8 (53%) of PMF cases. In both groups cellularity was increased but more so in post-PVMF (mean: 95%) than in PMF (mean: 66%); p<0.05. In post-PVMF the majority of megakaryocytes retained PV-like features including normally folded or hyperlobulated nuclei devoid of severe maturation defects; rare tight clusters were only seen in few cases. In contrast, in PMF cases the megakaryocytes showed more pronounced anomalies including increased nuclear: cytoplasmic ratio, abnormally clumping of chromatin and more tight clustering. No differences in blasts number (<10% in all cases) or in myeloid:erythroid ratio (M:E) were observed between the two groups (M:E, 4.2 in post-PVMF vs. 4.4 in PMF). Post-PVMF cases showed a complex karyotype in 7 cases (46%) and a normal karyotype in the remaining cases. PMF cases showed karyotypic alterations in all 8 cases with isolated del(20q) being the commonest; only 2 cases had a complex karyotype. Two patients, 1 post-PVMF and 1 PMF died from disease; no survival differences were noted.
Conclusions: Our results show that in the myelofibrotic stage, PV still retains a distinct megakaryocytic morphology that represents a useful clue for its separation from PMF. In addition, post-PVMF cases often display a complex karyotype, whereas this is much rarer in PMF. This suggests that myelofibrosis in PV represents a form of disease progression characterized by profound genetic damage whereas in PMF it is an intrinsic part of the phenotypic manifestation of the disease and not necessarily associated with adverse cytogenetics.
Monday, March 19, 2012 1:00 PM
Platform Session: Section C, Monday Afternoon