Guy Alexandre, Bidet Audrey, Ling Catherine, Caumont Charline, Boureau Lisa, Viallard Jean-François, Parrens Marie
UMR 1034, Inserm, Biology of Cardiovascular Diseases, University of Bordeaux, 33600, Pessac, France.
Laboratory of Hematology, University Hospital Center of Bordeaux, Haut-Lévêque Hospital, 33600, Pessac, France.
Virchows Arch. 2021 Oct;479(4):755-764. doi: 10.1007/s00428-021-03110-9. Epub 2021 May 1.
BCR-ABL-fusion-negative myeloproliferative neoplasms (MPNs) with myelofibrosis (MF) include primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF. Clonal extramedullary hematopoiesis (EMH) can occur during MPN pathogenesis. Although histopathological bone-marrow (BM) features during clonal EMH have been investigated, those of the spleen have been poorly described. We analyzed splenectomy samples from 28 patients with MF and BM samples from 20 of them. Slides were stained with hematoxylin and eosin, reticulin, and trichrome, with immunohistochemical labeling of glycophorin A, myeloperoxidase, CD61, CD34, and CD117. We also subjected splenectomy and BM samples from six patients and spleen samples from seven patients to next-generation sequencing (NGS). Megakaryocyte-rich spleen nodules (MRSNs), seen in seven of the 28 patients, were significantly associated with megakaryocyte proliferation in the spleen (p = 0.04). We devised a grading system for spleen fibrosis (SF) and found that SF was increased in 20 of 28 patients. Notably, patients with SF were more likely to have MRSNs, suggesting that megakaryocytes might participate in SF, as previously described in BM. Comparisons of spleen and BM NGS findings of six patients' specimens revealed identical mutational status in the two organs for half of the patients. We observed additional mutations in the spleen of two patients. However, the meaning of this finding remains unknown since there was a long interval between BM and spleen samplings (68 and 82 months, respectively).
伴有骨髓纤维化（MF）的BCR-ABL融合阴性骨髓增殖性肿瘤（MPN）包括原发性MF、真性红细胞增多症后MF和原发性血小板增多症后MF。克隆性髓外造血（EMH）可在MPN发病过程中发生。虽然已经对克隆性EMH期间的组织病理学骨髓（BM）特征进行了研究，但脾脏的特征描述较少。我们分析了28例MF患者的脾切除样本以及其中20例患者的BM样本。玻片用苏木精和伊红、网状纤维和三色染色，并对血型糖蛋白A、髓过氧化物酶、CD61、CD34和CD117进行免疫组化标记。我们还对6例患者的脾切除和BM样本以及7例患者的脾脏样本进行了二代测序（NGS）。在28例患者中有7例出现富含巨核细胞的脾结节（MRSN），其与脾脏中的巨核细胞增殖显著相关（p = 0.04）。我们设计了一种脾脏纤维化（SF）分级系统，发现28例患者中有20例SF增加。值得注意的是，SF患者更有可能出现MRSN，这表明巨核细胞可能参与了SF，正如之前在BM中所描述的那样。对6例患者标本的脾脏和BM NGS结果进行比较，发现一半患者的两个器官突变状态相同。我们在两名患者的脾脏中观察到了额外的突变。然而，由于BM和脾脏采样之间间隔时间较长（分别为68个月和82个月），这一发现的意义尚不清楚。
