Value of bone marrow biopsy in the diagnosis of essential thrombocythemia

Abstract

BACKGROUND AND OBJECTIVES: Essential thrombocythemia (ET) is a Philadelphia chromosome-negative chronic myeloproliferative disorder (CMPD) whose diagnosis, according to the Polycythemia Vera Study Group (PVSG) criteria, does not include histopathological data. The new WHO classification of CMPD has supplied new diagnostic guidelines which highlight the value of histopathology and facilitate a more precise differentiation of ET from reactive conditions and other CMPDs. DESIGN AND METHODS: Bone marrow biopsies from 142 adult patients diagnosed with ET according to PVSG criteria were evaluated using the new WHO classification. Megakaryocyte morphology and arrangement, amount of fibrosis and a clustering index were studied along with determination of microvessel density (MVD), amount of CD34+ cells and percentage of MIB-1+ cells and megakaryocytes. The last value, indicated as megakaryocyte proliferation index (MPI), was determined and expressed as a percentage of the counted cells. RESULTS: According to WHO criteria the 142 biopsies were classified as follows: ET (21%); Idiopathic myelofibrosis (IMF) grade 0 (30%); IMF-1 (34%); IMF-2 (10%) ET/IMF-0 (5%). A significant difference (p<0.001) was observed between clustering index values in ET and IMF cases. A peculiar proliferative feature of megakaryocytes, defined coupling, was detected in all ET cases. MVD was more pronounced and the number of CD34+ cells higher in cases of IMF than in cases of ET (p <0.005; p = 0.001, respectively) and MVD significantly correlated with the extent of fibrosis (r=0.861). ET cases showed the lowest values of proliferation; IMF-0 and IMF-1 showed higher values while a decrease of MPI was observed in IMF-2 in accordance with the increase of fibrosis. INTERPRETATION AND CONCLUSIONS: In the diagnosis of thrombocythemic disorders, a multidisciplinary approach must include the evaluation of bone marrow biopsies. Some histopathological criteria, along with the use of markers related to activity and proliferation such as CD34 and MIB-1, underline the biological differences between ET and prefibrotic states of IMF.