Skip to main content

Advertisement

SpringerLink
Log in

Advanced extramedullary hematopoiesis with a marked increase in reticulin fibers and hemorrhage on various organs: the first autopsy case report

  • Case Report
  • Published:
Medical Molecular Morphology Aims and scope Submit manuscript

Abstract

Myelofibrosis is characterized by stem cell-derived clonal proliferation potentially resulting in bone marrow fibrosis. As the disease progresses, extramedullary hematopoiesis is frequently detected in the spleen and the liver but rarely in other organs. We report a case of a 68-year-old woman with myelofibrosis with a JAK2 mutation, showing extramedullary hematopoiesis (EMH) in various organs with a marked increase in reticulin fibers, and myeloproliferative neoplasm (MPN)-related necrotizing crescent glomerulonephritis. She was admitted to our hospital owing to respiratory discomfort. Computed tomography revealed a mass in the anterior mediastinum. Ten days later, the patient died owing to respiratory distress. At autopsy, EMH were detected in the anterior mediastinum, heart, lung, spleen, and the kidney with a marked increase in reticulin fibers. We considered that respiratory distress was partially caused by EMH. In the kidney, necrotizing crescent glomerulonephritis was observed. Immunohistochemically, the glomerular basement and mesangial area were IgA- and C3d-positive. Ultrastructural examination revealed the presence of dense deposits in the subendothelial space and the mesangial and paramesangial areas. Thus, we suspected that MPN-related necrotizing crescentic glomerulonephritis harbored a pathogenesis similar to that of IgA-dominant post-infectious glomerulonephritis or IgA nephropathy. This case report could widen the spectrum of MPN- or EMH-related lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ANCA:

Antineutrophil cytoplasmic antibodies

EMH:

Extramedullary hematopoiesis

GBM:

glomerular basement membrane

HE:

Hematoxylin–eosin

Ig:

Immunoglobulin

MF:

Myelofibrosis

MPN:

Myeloproliferative neoplasm

MPO:

Myeloperoxidase

PAM:

Periodic acid–methenamine silver

PAS:

Periodic acid–Schiff

TMA:

Thrombotic microangiopathy

References

  1. Tefferi A (2018) Primary myelofibrosis: 2019 update on diagnosis, risk-stratification and management. Am J Hematol 93:1551–1560

    Article  Google Scholar 

  2. Wang X, Prakash S, Lu M, Tripodi J, Ye F, Najfeld V, Li Y, Schwartz M, Weinberg R, Roda P, Orazi A, Hoffman R (2012) Spleens of myelofibrosis patients contain malignant hematopoietic stem cells. J Clin Invest 122:3888–3899

    Article  CAS  Google Scholar 

  3. Keikhaei B, Shirazi AS, Pour MM (2012) Adrenal extramedullary hematopoiesis associated with β-thalassemia major. Hematol Rep 4:e7

    Article  Google Scholar 

  4. Uminski K, Kumar R, Seftel M (2018) Bilateral adrenal hemorrhage as a manifestation of extramedullary hematopoiesis in a patient with primary myelofibrosis. Ann Hematol 97:2011–2012

    Article  Google Scholar 

  5. Harbin LJ, Burnett S, Ghilchik M, Lee DM, Rajan P (2002) Extramedullary haematopoiesis in a hyalinized mammary fibroadenoma. Histopathology 41:475–477

    Article  CAS  Google Scholar 

  6. Sirgi KE, Swanson PE, Gersell DJ (1994) Extramedullary hematopoiesis in the endometrium. Report of four cases and review of the literature. Am J Clin Pathol 101:643–646

    Article  CAS  Google Scholar 

  7. Valeri RM, Ibrahim N, Sheaff MT (2002) Extramedullary hematopoiesis in the endometrium. Int J Gynecol Pathol 21:178–181

    Article  Google Scholar 

  8. Humphrey PA, Vollmer RT (1991) Extramedullary hematopoiesis in the prostate. Am J Surg Pathol 15:486–490

    Article  CAS  Google Scholar 

  9. Gallo G, Bigliardi S, Cesinaro AM (2019) A case of extramedullary hematopoiesis presenting as hemorrhagic panniculitis and evolving in acute myeloid leukemia. J Cutan Pathol 46:775–777

    Article  Google Scholar 

  10. Gibbins J, Pankhurst T, Murray J, McCafferty I, Baiden-Amissahk K, Shafeek S, Lipkin GW (2005) Extramedullary haematopoiesis in the kidney: a case report and review of literature. Clin Lab Haematol 27:391–394

    Article  CAS  Google Scholar 

  11. Holt SG, Field P, Carmichael P, Mehta A, Jarmulowicz M, Clarke D, Hilson A, Burns A (1995) Extramedullary haematopoiesis in the renal parenchyma as a cause of acute renal failure in myelofibrosis. Nephrol Dial Transplant 10:1438–1440

    CAS  PubMed  Google Scholar 

  12. Alexander MP, Nasr SH, Kurtin PJ, Casey ET, Hernandez LP, Fidler ME, Sethi S, Cornell LD (2015) Renal extramedullary hematopoiesis: interstitial and glomerular pathology. Mod Pathol 28:1574–1583

    Article  CAS  Google Scholar 

  13. Maruyama K, Nakagawa N, Suzuki A, Kabara M, Matsuki M, Shindo M, Iwasaki S, Ogawa Y, Hasebe N (2019) Novel detection of CALR-mutated cells in myeloproliferative neoplasm-related glomerulopathy with interstitial extramedullary hematopoiesis: a case report. Am J Kidney Dis 74:844–848

    Article  CAS  Google Scholar 

  14. Pamuk ON, Pamuk GE, Altiparmak MR, Sonsuz A, Solakoğlu S, Kiliçaslan I (2002) Nephrotic syndrome associated with agnogenic myeloid metaplasia. Leuk Lymphoma 43:661–663

    Article  Google Scholar 

  15. Perazella MA, Buller GK (1994) Nephrotic syndrome associated with agnogenic myeloid metaplasia. Am J Nephrol 14:223–225

    Article  CAS  Google Scholar 

  16. Said SM, Leung N, Sethi S, Cornell LD, Fidler ME, Grande JP, Herrmann S, Tefferi A, D’Agati VD, Nasr SH (2011) Myeloproliferative neoplasms cause glomerulopathy. Kidney Int 80:753–759

    Article  Google Scholar 

  17. Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A (2005) European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 90:1128–1132

    PubMed  Google Scholar 

  18. Yang X, Chen D, Long H, Zhu B (2020) The mechanisms of pathological extramedullary hematopoiesis in diseases. Cell Mol Life Sci 77:2723–2728

    Article  CAS  Google Scholar 

  19. Ardakani NM, Kumarasinghe MP, Spagnolo DV, Stewart CJ (2014) Extramedullary hematopoiesis associated with organizing peritoneal hemorrhage: a report of 5 cases in patients presenting with primary gynecologic disorders. Int J Gynecol Pathol 33:317–322

    Article  Google Scholar 

  20. Kanauchi M, Dohi K, Shiiki H, Fujii Y, Ishikawa H (1994) Henoch-Schönlein purpura nephritis associated with polycythemia vera. Intern Med 33:36–40

    Article  CAS  Google Scholar 

  21. Nasr SH, D’Agati VD (2011) IgA-dominant postinfectious glomerulonephritis: a new twist on an old disease. Nephron Clin Pract 119:c18-25 (Discussion c26)

    Article  CAS  Google Scholar 

  22. Couser WG, Johnson RJ (2015) What is myeloperoxidase doing in ANCA-associated glomerulonephritis? Kidney Int 88:938–940

    Article  CAS  Google Scholar 

  23. Hanamura K, Tojo A, Kinugasa S, Asaba K, Onozato ML, Uozaki H, Fukayama M, Fujita T (2011) Detection of myeloperoxidase in membranous nephropathy-like deposits in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. Hum Pathol 42:649–658

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Ms. Aoyama and Ms. Adachi for assistance in the preparation of the images for immunohistochemistry and electron microscopy.

Author information

Authors and Affiliations

  1. Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan

    Hirofumi Watanabe, Fumiyoshi Fujishima & Hironobu Sasano

  2. Department of Hematology, Tohoku University Hospital, Sendai, Miyagi, Japan

    Noriko Fukuhara

  3. Department of Pathology, Osaki Citizen Hospital, Miyagi, Ōsaki, Japan

    Shinji Taniuchi

  4. Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan

    Kensuke Joh

Authors
  1. Hirofumi Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fumiyoshi Fujishima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noriko Fukuhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shinji Taniuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kensuke Joh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hironobu Sasano
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HW, FF, and NF participated in writing of the manuscript and in preparing the figures. ST, KJ, and HS reviewed the manuscript.

Corresponding author

Correspondence to Hirofumi Watanabe.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

795_2021_300_MOESM1_ESM.tiff

Supplementary file1 Additional File 1 contains Supplementary Figure 1, showing microscopic findings of the spleen. (a) Hematoxylin–eosin (HE) staining showing the foci of hemorrhage and (b) silver impregnation revealing increases in reticulin fiber (a and b: scale bar = 5 mm). (c and d) High-power view of the selected area (red square) in a and b, respectively (c and d: scale bar = 100 μm). (c) HE staining showing extramedullary hematopoiesis including dysplastic megakaryocytes (blue arrow) and (d) silver impregnation revealing mild increases in reticulin fiber. (e and f) High-power view of the selected area (blue square) in a and b, respectively (e and f: scale bar = 100 μm). (e) HE staining showing hemorrhage including erythroblastic islands (blue arrow) and (f) silver impregnation revealing a marked increase in reticulin fiber (TIFF 33972 kb)

795_2021_300_MOESM2_ESM.tiff

Supplementary file2 Additional File 2 contains Supplementary Figure 2, showing microscopic findings of the spleen, heart, and kidney. Masson–Goldner stain revealing increases in collagen fiber (a) around the hematoma (red arrow) in the spleen, (b) in the cardiac adventitia, and (b) in the sinus fat of the kidney where extramedullary hematopoiesis was observed (scale bar = 100 μm) (TIFF 33972 kb)

795_2021_300_MOESM3_ESM.tiff

Supplementary file3 Additional File 3 contains Supplementary Figure 3 showing microscopic findings of the mass on the anterior mediastinum. (a) Silver impregnation showing increases in reticulin fiber around the hematoma (red arrow) in the mass (scale bar = 1 mm). (b) High-power view of the selected area (red square) in a (scale bar = 500 μm). Silver impregnation revealing a marked increase in reticulin fiber on the periphery of the mass (TIFF 33972 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Watanabe, H., Fujishima, F., Fukuhara, N. et al. Advanced extramedullary hematopoiesis with a marked increase in reticulin fibers and hemorrhage on various organs: the first autopsy case report. Med Mol Morphol 55, 68–75 (2022). https://doi.org/10.1007/s00795-021-00300-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00795-021-00300-x

Keywords

Search

Navigation