Michiels Jan Jacques
Goodheart Institute, MPD Center Europe, Rotterdam, The Netherlands.
Hematol J. 2004;5(2):93-102. doi: 10.1038/sj.thj.6200368.
Clinical, hematological and morphological peripheral blood and bone marrow characteristics, in particular, megakaryopoiesis and bone marrow cellularity, reveal diagnostic clues and pathognomonic features, which enable a clear-cut distinction between essential thrombocythemia (ET), polycythemia vera (PV) and prefibrotic and fibrotic agnogenic myeloid metaplasia (AMM). The characteristic increase of enlarged mature megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or slightly increased cellular bone marrow represent the hallmark of ET. The characteristic increase and clustering of enlarged mature and pleiomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses are the specific diagnostic features of untreated PV. ET may precede PV for many years to more than one decade. Prefibrotic and fibrotic AMM appears to be a distinct dual proliferation of abnormal megakaryopoiesis and myelopoiesis. The histopathology of the bone marrow in prefibrotic and fibrotic AMM is dominated by atypical enlarged and immature megakaryocytes with cloud-like immature nuclei, which are not seen in ET and PV at diagnosis and during follow-up. Myelofibrosis is not a feature of ET at diagnosis and during long-term follow-up. Myelofibrosis, which is secondary to the megakaryocytic/granulocytic myeloproliferation, and extramedullary myeloid metaplasia constitute a prominent feature and usually progress more or less rapidly during the natural history of PV and AMM. Life expectancy is normal in ET, normal in the first and decreased in the second decade of follow-up in PV, but significantly shortened in thrombocythemia associated with prefibrotic AMM as well as in the various fibrotic stages of AMM. These clinical and pathological characteristics of the Ph-negative MPDs, by including bone marrow histopathology, enable a clear-cut distinction between ET, PV and prefibrotic and fibrotic AMM. The use of established and new biological markers of MPDs, like spontaneous EEC, PRV-1 gene expression etc, should be validated in large prospective multicenter studies of newly diagnosed and previously treated MPD patients using the proposed European clinical and pathological (ECP) criteria as the only gold standard available for the proper diagnosis and differential diagnosis of ET, PV and AMM.
临床、血液学以及外周血和骨髓的形态学特征，尤其是巨核细胞生成和骨髓细胞成分，揭示了诊断线索和特征性表现，这使得真性红细胞增多症（ET）、真性红细胞增多症（PV）以及纤维化前期和纤维化期的原发性骨髓化生（AMM）能够被明确区分。特征性表现为成熟的巨核细胞增大，胞质成熟，核呈多叶状，且它们倾向于在正常或细胞成分轻度增加的骨髓中聚集，这是ET的标志。特征性表现为增大的成熟和异形巨核细胞增多且聚集，核呈多叶状，在中度至显著细胞增多的骨髓中红细胞生成增殖，伴有扩张窦的增生，这是未经治疗的PV的特异性诊断特征。ET可能在PV之前存在数年至十多年。纤维化前期和纤维化期的AMM似乎是异常巨核细胞生成和粒细胞生成的独特双重增殖。纤维化前期和纤维化期的AMM骨髓组织病理学以非典型增大和未成熟的巨核细胞为主，其核呈云雾状未成熟，在ET和PV的诊断及随访期间均未见到。骨髓纤维化在ET的诊断及长期随访中并非特征性表现。继发于巨核细胞/粒细胞骨髓增殖的骨髓纤维化以及髓外骨髓化生是PV和AMM自然病程中的突出特征，通常或多或少会迅速进展。ET患者的预期寿命正常，PV患者随访的第一个十年预期寿命正常，第二个十年预期寿命降低，但与纤维化前期AMM相关的血小板增多症患者以及AMM各纤维化阶段患者的预期寿命显著缩短。通过纳入骨髓组织病理学，这些Ph阴性骨髓增殖性疾病（MPD）的临床和病理特征能够明确区分ET、PV以及纤维化前期和纤维化期的AMM。对于MPD的既定和新生物标志物，如自发EEC、PRV-1基因表达等，应在新诊断和既往治疗过的MPD患者的大型前瞻性多中心研究中进行验证，使用拟议的欧洲临床和病理（ECP）标准作为ET、PV和AMM正确诊断和鉴别诊断的唯一可用金标准。
