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Novel findings of splenic extramedullary hematopoiesis during primary myelofibrosis, post-essential thrombocythemia, and post-polycythemia vera myelofibrosis

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Abstract

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).

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Acknowledgements

The authors thank the technical team of the Pathology Department, Haut-Lévêque Hospital, University Hospital of Bordeaux, for sectioning tissue samples and immunohistochemical labeling. The authors thank Janet Jacobson for editorial assistance and helpful discussions.

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Authors and Affiliations

  1. UMR 1034, Inserm, Biology of Cardiovascular Diseases, University of Bordeaux, 33600, Pessac, France

    Alexandre Guy & Jean-François Viallard

  2. Laboratory of Hematology, University Hospital Center of Bordeaux, Haut-Lévêque Hospital, 33600, Pessac, France

    Alexandre Guy, Audrey Bidet & Lisa Boureau

  3. Pathology Department, University Hospital Center of Bordeaux, Haut-Lévêque Hospital, 33600, Pessac, France

    Catherine Ling & Marie Parrens

  4. Tumor Biology Department, University Hospital Center of Bordeaux, Haut-Lévêque Hospital, 33600, Pessac, France

    Charline Caumont

  5. Internal Medicine Department, University Hospital Center of Bordeaux, Haut-Lévêque Hospital, 33600, Pessac, France

    Jean-François Viallard

  6. INSERM U1053, University of Bordeaux, 33076, Bordeaux, France

    Marie Parrens

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  1. Alexandre Guy
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  2. Audrey Bidet
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Contributions

A. Guy, M. Parrens, and J.-F. Viallard designed the research. A. Guy, A. Bidet, C. Ling, C. Caumont, L. Boureau, and M. Parrens carried out the research. A. Guy, A. Bidet, C. Ling, C. Caumont, L. Boureau, M. Parrens, and J.-F. Viallard analyzed data and wrote the manuscript. All authors have read and approved the manuscript.

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Correspondence to Alexandre Guy.

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This study was approved by the Ethics Committee of the University Hospital of Bordeaux (GP-CE2020-37).

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Jean-François Viallard and Marie Parrens are joint last authors.

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Guy, A., Bidet, A., Ling, C. et al. Novel findings of splenic extramedullary hematopoiesis during primary myelofibrosis, post-essential thrombocythemia, and post-polycythemia vera myelofibrosis . Virchows Arch 479, 755–764 (2021). https://doi.org/10.1007/s00428-021-03110-9

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