Objective, planimetry-based assessment of megakaryocyte histological pictures in Philadelphia-chromosome-negative chronic myeloproliferative disorders: a perspective for a valuable adjunct diagnostic tool

Abstract

Philadelphia-chromosome-negative chronic myeloproliferative disorders (Ph- CMPDs)--essential thrombocythemia (ET), chronic idiopathic myelofibrosis (CIMF), and polycythemia vera (PV)--may show clinical and morphological similarities, particularly at the early stages. The differential diagnosis of Ph- CMPDs is important due to their different treatment and prognosis. Cytological features of megakaryocytes are considered valuable in this differentiation. To establish an objective measure of megakaryocyte dysplasia in Ph- CMPDs, we performed computer-assisted morphometry of more than 4,000 cells from 20 cases of ET, 10 of CIMF, 10 of PV, and 10 controls. Megakaryocyte sets from three Ph- CMPDs differed significantly in respect to many planimetric parameters, but not a single shape or size parameter could have been used as a discriminative tool between the entities. However, the discriminant function analysis with the simultaneous assessment of 12 planimetric variables allowed for a proper classification of 20 of 20 ET, 10 of 10 PV, and 9 of 10 CIMF cases based solely on the morphometric features of megakaryocytes. Additionally, we identified certain new patterns of megakaryocytes specific for ET, PV, and CIMF, which, although not dominating in one Ph- CMPD, are unlikely to occur in two others. Objective measurements of megakaryocyte sizes and shapes may assist the diagnosis of Ph- CMPDs.