Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis

Background and Objectives. Diagnosis of essential thrombocythemia (ET) rema ins a challenging problem and has been predominantly established by exclusi on of other thrombocythemic disorders. in this context the updated diagnost ic criteria of the Polycythemia Vera Study Group (PVSG) are generally accep ted, although histopathologic features of the bone marrow were only margina lly considered. Design and Methods. A retrospective evaluation was performed of 168 patient s presenting with ET in accordance with the criteria of the PVSG. Analysis was focused on the discriminating impact of bone marrow morphology. Results. Histopathology revealed that our cohort of patients could be divid ed into three distinct groups (true ET, questionable ET and false ET). Thes e groups were characterized by certain diagnostic constellations of clinica l data on admission. True ET was found in 53 patients presenting with no or a borderline splenomegaly and no relevant anemia or leuko-erythroblastic b lood picture. The other patients showed clinical signs and symptoms which w ere more compatible with initial-prefibrotic (52 patients) or early (68 pat ients) idiopathic-primary myelofibrosis (IMF) with severe thrombocythemia. In true ET no significant hypercellularity of the bone marrow including mye loid precursors or an increase in reticulin fibers was detectable. Most pro minent were changes of megakaryopoiesis which revealed large to giant-sized cells lacking a definite maturation defect. Their appearance in true ET co ntrasted with the clusters of abnormally differentiated, often bizarre elem ents of this lineage in patients with initial and early IMF (questionable o r false ET). Calculation of survival disclosed a relevant disparity with a non-significant loss in life expectancy of 10.9% in true ET compared to 29. 6% in questionable and 51.3% in false ET. Follow-up studies and repeated bo ne marrow biopsies revealed no transition into myelofibrosis in true ET, wh ereas this did occur in 22 of 27 patients with questionable and false FT. I n the latter cohort bone marrow changes were accompanied by increasing anem ia, splenomegaly, tear-drop poikilocytosis and reduction of the platelet co unt consistent with IMF. Interpretation and Conclusions. A detailed evaluation of bone marrow featur es, in particular megakaryopoiesis is recommended to establish positive cri teria for the diagnosis of ET and thus to accomplish a significant improvem ent of the PVSG postulates. In this context ongoing clinical trials on ET m ust regard pretreatment bone marrow biopsies as a major clue to diagnosis. (C) 2000 Ferrata Stori Foundation.