Thiele J, Kvasnicka H M, Zankovich R, Diehl V
Institute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, D-50924 Cologne, Germany.
Haematologica. 2000 Nov;85(11):1126-34.
Diagnosis of essential thrombocythemia (ET) remains a challenging problem and has been predominantly established by exclusion of other thrombocythemic disorders. In this context the updated diagnostic criteria of the Polycythemia Vera Study Group (PVSG) are generally accepted, although histopathologic features of the bone marrow were only marginally considered.
A retrospective evaluation was performed of 168 patients presenting with ET in accordance with the criteria of the PVSG. Analysis was focused on the discriminating impact of bone marrow morphology.
Histopathology revealed that our cohort of patients could be divided into three distinct groups (true ET, questionable ET and false ET). These groups were characterized by certain diagnostic constellations of clinical data on admission. True ET was found in 53 patients presenting with no or a borderline splenomegaly and no relevant anemia or leuko-erythroblastic blood picture. The other patients showed clinical signs and symptoms which were more compatible with initial-prefibrotic (52 patients) or early (68 patients) idiopathic-primary myelofibrosis (IMF) with severe thrombocythemia. In true ET no significant hypercellularity of the bone marrow including myeloid precursors or an increase in reticulin fibers was detectable. Most prominent were changes of megakaryopoiesis which revealed large to giant-sized cells lacking a definite maturation defect. Their appearance in true ET contrasted with the clusters of abnormally differentiated, often bizarre elements of this lineage in patients with initial and early IMF (questionable or 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 bone marrow biopsies revealed no transition into myelofibrosis in true ET, whereas this did occur in 22 of 27 patients with questionable and false ET. In the latter cohort bone marrow changes were accompanied by increasing anemia, splenomegaly, tear-drop poikilocytosis and reduction of the platelet count consistent with IMF.
A detailed evaluation of bone marrow features, in particular megakaryopoiesis is recommended to establish positive criteria for the diagnosis of ET and thus to accomplish a significant improvement of the PVSG postulates. In this context ongoing clinical trials on ET must regard pretreatment bone marrow biopsies as a major clue to diagnosis.
原发性血小板增多症（ET）的诊断仍然是一个具有挑战性的问题，主要通过排除其他血小板增多性疾病来确立诊断。在此背景下，真性红细胞增多症研究组（PVSG）的更新诊断标准已被普遍接受，尽管骨髓的组织病理学特征仅被略微考虑。
根据PVSG标准对168例ET患者进行回顾性评估。分析重点在于骨髓形态学的鉴别影响。
组织病理学显示，我们的患者队列可分为三个不同的组（真性ET、可疑ET和假性ET）。这些组的特征是入院时临床数据的某些诊断组合。53例真性ET患者表现为无脾肿大或轻度脾肿大，无相关贫血或白细胞-红细胞造血象。其他患者表现出的临床体征和症状更符合早期纤维化前（52例患者）或早期（68例患者）伴有严重血小板增多症的特发性原发性骨髓纤维化（IMF）。在真性ET中，未检测到包括髓系前体细胞在内的骨髓明显细胞增多或网状纤维增加。最显著的是巨核细胞生成的变化，表现为大至巨大的细胞，无明确的成熟缺陷。它们在真性ET中的表现与早期和早期IMF患者（可疑或假性ET）中该谱系异常分化、通常怪异的细胞簇形成对比。生存计算显示出显著差异，真性ET患者的预期寿命无显著损失，为10.9%，而可疑ET患者为29.6%，假性ET患者为51.3%。随访研究和重复骨髓活检显示，真性ET患者未转变为骨髓纤维化，而27例可疑和假性ET患者中有22例发生了转变。在后者队列中，骨髓变化伴有贫血加重、脾肿大、泪滴状异形红细胞增多和血小板计数降低，符合IMF表现。
建议对骨髓特征进行详细评估，尤其是巨核细胞生成，以建立ET诊断的阳性标准，从而显著改进PVSG的假设。在此背景下，正在进行的ET临床试验必须将治疗前骨髓活检视为诊断的主要线索。
