Skip to main content

Advertisement

SpringerLink
Log in

An autopsy case of TAFRO syndrome with membranoproliferative glomerulonephritis-like lesions

  • Case Report
  • Published:
CEN Case Reports Aims and scope Submit manuscript

Abstract

TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) is an atypical manifestation of multicentric Castleman’s disease. Although overproduction of interleukin-6, vascular endothelial growth factor, and other cytokines may partially explain the pathophysiology of this rare syndrome, the precise mechanisms underlying the renal dysfunction associated with the condition remain unclear. Here, we describe a case of a 69-year-old male with TAFRO syndrome. He was treated with immunosuppressive agents and his renal function improved. Tapering of immunosuppressive agents resulted in a deterioration of renal function and an elevation of C-reactive protein. After 20 months of treatment, the patient died from tuberculous peritonitis and gastrointestinal bleeding. An autopsy revealed miliary tuberculosis, mediastinal lymphadenopathy, and gastric ulcers. Renal histopathology showed a membranoproliferative glomerulonephritis-like appearance. Almost all glomeruli showed lobular formations with mesangial proliferation and duplication of glomerular capillary walls on light microscopy. Immunofluorescence showed deposition of C1q and IgM along the glomerular capillary walls. Electron microscopy showed mesangial expansion and widening of the subendothelial space with a large number of electron-dense deposits. The glomerular lesions might be characteristic of TAFRO syndrome, and were regarded as the main cause of the patient’s renal dysfunction.

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

Similar content being viewed by others

References

  1. Kawabata H, Takai K, Kojima M, Nakamura N, Aoki S, Nakamura S, Kinoshita T, Masaki Y. Castleman-Kojima disease (TAFRO Syndrome), a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly: a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012). J Clin Exp Hematop. 2013;53:57–61.

    Article  PubMed  Google Scholar 

  2. Takai K, Nikkuni K, Motomi A, Nagai K, Igarashi N, Saeki T. Thrombocytopenia with reticulin fibrosis accompanied by fever, anasarca and hepatosplenomegaly: a clinical report of five cases. J Clin Exp Hematop. 2013;53:63–8.

    Article  PubMed  Google Scholar 

  3. Kawabata H, Kadowaki N, Nishikori M, Kitawaki T, Kondo T, Ishikawa T, Yoshifuji H, Yamakawa N, Imura Y, Minori T, Mtsumura Y, Miyachi Y, Matsubara T, Yanagita M, Haga H, Takaori-Kondo A. Clinical features and treatment of multicentric Castleman’s disease: a retrospective study of 21 Japanese patients at a single institute. J Clin Exp Hematop. 2013;53:69–77.

    Article  PubMed  Google Scholar 

  4. Takai K, Nikkuni K, Shibuya H, Hashidate H. Thrombocytopenia with mild bone marrow fibrosis accompanied by fever, pleural effusion, ascites and hepatosplenomegaly. Rinsho Ketsueki. 2010;51:320–5.

    PubMed  Google Scholar 

  5. Masaki Y, Kawabata H, Takai K, Kojima M, Tsukamoto N, Ishigaki Y, Kurose N, Ide M, Murakami J, Nara K, Yamamoto H, Ozawa Y, Takahashi H, Miura K, Miyauchi T, Yoshida S, Momoi A, Awano N, Ikushima S, Ohta Y, Furuta N, Fujimoto S, Kawanami H, Sakai T, Kawanami T, Fujita Y, Fukushima T, Nakamura S, Kinoshita T, Aoki S. Proposed diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, 2015 version. Int J Hematol. 2016;103:686–92.

    Article  CAS  PubMed  Google Scholar 

  6. Szalat R, Munshi NC. Diagnosis of castleman disease. Hematol Oncol Clin N Am. 2018;32:53–64.

    Article  Google Scholar 

  7. Dispenzieri A, Kourelis T, Buandi F. POEMS syndrome diagnosis and investigative work-up. Hematol Oncol Clin N Am. 2018;32:119–39.

    Article  Google Scholar 

  8. Igawa T, Sato Y. TAFRO syndrome. Hematol Oncol Clin N Am. 2018;32:107–18.

    Article  Google Scholar 

  9. Iwaki N, Sato Y, Takata K, Kondo E, Ohno K, Takeuchi M, Orita Y, Nakao S, Yoshino T. Atypical hyaline vascular-type Castleman’s disease with thrombocytopenia, anasarca, fever, and systemic lymphadenopathy. J Clin Exp Hematop. 2013;53:87–93.

    Article  PubMed  Google Scholar 

  10. Inoue M, Ankou M, Hua J, Iwaki Y, Hagihara M. Complete resolution of TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly) after immunosuppressive therapies using corticosteroids and cyclosporine A: a case report. J Clin Exp Hematop. 2013;53:95–9.

    Article  PubMed  Google Scholar 

  11. Iwaki N, Fajgenbaum DC, Nabel CS, Gion Y, Kondo E, Kawano M, Masunari T, Yoshida I, Moro H, Nikkuni K, Takai K, Matsue K, Kurosawa M, Hagihara M, Saito A, Okamoto M, Yokota K, Hiraiwa S, Nakamura N, Nakao S, Yoshino T, Sato Y. Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease. Am J Hematol. 2016;91:220–6.

    Article  CAS  PubMed  Google Scholar 

  12. Furuichi K, Wada T, Shimizzu M, Segawa C, Ohta S, Takasawa K, Kobayashi K, Yokoyama H. Antimyeloperoxidase-antibody-positive rapidly progressive glomerulonephritis associated with Castleman’s disease. Nephrol Dial Transplant. 1998;13:1556–8.

    Article  CAS  PubMed  Google Scholar 

  13. Kawabata H, Kotani S, Matsumura Y, Kondo T, Katsurada T, Haga H, Kadowaki N, Takaori-Kondo A. Successful treatment of a patient with multicentric Castleman’s disease who presented with thrombocytopenia, ascites, renal failure and myelofibrosis using tocilizumab, an anti-interleukin-6 receptor antibody. Intern Med. 2013;52:1503–7.

    Article  PubMed  Google Scholar 

  14. Fujiwara S, Mochinaga H, Nakata H, Ohshima K, Matsumoto M, Uchida M, Mikami Y, Hata H, Okuno Y, Mitsuya H, Nosaka K. Successful treatment of TAFRO syndrome, a variant type of multicentric Castleman disease with thrombotic microangiopathy, with anti-IL-6 receptor antibody and steroids. Int J Hematol. 2016;103:718–23.

    Article  CAS  PubMed  Google Scholar 

  15. Konishi Y, Takahashi S, Nishi K, Sakamaki T, Mitani S, Kaneko H, Mizutani C, Ukyo N, Hirata H, Tsudo M. Successful treatment of TAFRO syndrome, a variant of multicentric Castleman’s disease, with cyclosporine A: possible pathogenetic contribution of interleukin-2. Tohoku J Exp Med. 2015;236:289–95.

    Article  PubMed  Google Scholar 

  16. Yamaga Y, Tokuyama K, Kato T, Yamada R, Murayama M, Ikeda T, Yamakita M, Kunieda T. Successful treatment with cyclosporin A in tocilizumab-resistant TAFRO syndrome. Intern Med. 2016;55:185–90.

    Article  CAS  PubMed  Google Scholar 

  17. Ozawa T, Kosugi S, Kito M, Onishi M, Kida T, Nakata S, Take H, Katagiri S. Efficacy of rituximab for a variant type of multicentric Castleman’s disease termed the TAFRO syndrome. Rinsho Ketsueki. 2013;55:350–5.

    Google Scholar 

  18. Masaki Y, Nakajima A, Iwao H, Kurose N, Sato T, Nakamura T, Miki M, Sakai T, Kawanami T, Sawaki T, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Umehara H. Japanese variant of multicentric Castleman’s disease associated with serositis and thrombocytopenia—a report of two cases: Is TAFRO syndrome (Castleman-Kojima disease) a distinct clinicopathological entity? J Clin Exp Hematop. 2013;53:79–85.

    Article  PubMed  Google Scholar 

  19. Tadokoro A, Kanaji N, Hara T, Matsumoto K, Ishii T, Takagi T, Watanabe N, Kita N, Kawauchi M, Ueno M, Kadowaki N, Bandoh S. An uncharted constellation: TAFRO syndrome. Am J Med. 2016;129:938–41.

    Article  PubMed  Google Scholar 

  20. José FF, Kerbauy LN, Perini GF, Blumenschein DI, Pasqualin DC, Malheiros DMAC, Neto GCC, Santos FPS, Piovesan R, Hamerschlak N. A life-threatening case of TAFRO syndrome with dramatic response to tocilizumab, rituximab, and pulse steroids. Medicine. 2017;96(13):e6271.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mizuno H, Sekine A, Oguro M, Oshima Y, Kawada M, Sumida K, Yamanouchi M, Hayami N, Suwabe T, Hiramatsu R, Hasegawa E, Hoshino J, Sawa N, Fujii T, Takaichi K, Ohashi K, Ubara Y. Renal histology in a patient with TAFRO syndrome: a case report. Hum Pathol. 2018. https://doi.org/10.1016/j.humpath.2018.03.021.

    Article  PubMed  Google Scholar 

  22. Tanaka M, Tsujimoto H, Yamamoto K, Shimoda S, Oka K, Takeoka H. Clinicopathological features of progressive renal involvement in TAFRO syndrome. Medicine. 2017;96(40):e8216.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ozeki T, Tsuji M, Yamamoto J, Shigematu C, Maruyama S. Thrombotic microangiopathy on kidney biopsy in a patient with TAFRO syndrome. Cen Case Rep. 2018. https://doi.org/10.1007/s13730-018-0338-x.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Furuto Y, Hashimoto H, Horiuti H, Shibuya Y. Membranoproliferative glomerulonephritis-like findings for TAFRO syndrome, associated with an anterior mediastinal tumor: a case report. Medicine. 2018;97(24):e11057.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Xu D, Lv J, Dong Y, Wang S, Su T, Zhou F, Zou W, Zhao M, Zhang H. Renal involvement in a large cohort of Chinese patients with Castleman disease. Nephrol Dial Transplant. 2012;27(supple3):iii119–25.

    Article  PubMed  Google Scholar 

  26. Nakamoto Y, Imai H, Yasuda T, Wakui H, Miura AB. A spectrum of clinicopathological features of nephropathy associated with POEMS syndrome. Nephrol Dial Transplant. 1999;14:2370–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nephrology, Kitasato University School of Medicine, Sagamihara, Japan

    Keiko Hashimoto, Takashi Sano, Yukari Honma, Maoko Ida, Hiroshi Tominaga, Aya Sawada, Tetsuya Abe, Haruka Takahashi, Yoshitaka Shimada, Takanori Masaki, Mariko Kamata, Shokichi Naito, Togo Aoyama & Yasuo Takeuchi

  2. Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan

    Masashi Akiya, Madoka Inukai & Norihiro Nakata

Authors
  1. Keiko Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Sano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yukari Honma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maoko Ida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroshi Tominaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aya Sawada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tetsuya Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haruka Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoshitaka Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takanori Masaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mariko Kamata
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Shokichi Naito
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Togo Aoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yasuo Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Masashi Akiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Madoka Inukai
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Norihiro Nakata
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takashi Sano.

Ethics declarations

Conflict of interest

The authors have declared no conflicts of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hashimoto, K., Sano, T., Honma, Y. et al. An autopsy case of TAFRO syndrome with membranoproliferative glomerulonephritis-like lesions. CEN Case Rep 8, 48–54 (2019). https://doi.org/10.1007/s13730-018-0363-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13730-018-0363-9

Keywords

Search

Navigation