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.
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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.
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.
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.
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.
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.
Szalat R, Munshi NC. Diagnosis of castleman disease. Hematol Oncol Clin N Am. 2018;32:53–64.
Dispenzieri A, Kourelis T, Buandi F. POEMS syndrome diagnosis and investigative work-up. Hematol Oncol Clin N Am. 2018;32:119–39.
Igawa T, Sato Y. TAFRO syndrome. Hematol Oncol Clin N Am. 2018;32:107–18.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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
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DOI: https://doi.org/10.1007/s13730-018-0363-9