- Case Report
- Open Access
A case of TAFRO syndrome with a large mediastinal mass treated with debulking surgery
© The Author(s). 2016
Received: 24 March 2016
Accepted: 12 June 2016
Published: 17 June 2016
Multicentric Castleman’s disease is a polyclonal lymphoproliferative disorder. Recently, a new variant of the disease was reported and named TAFRO syndrome, an acronym for thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly. A 55-year-old woman presented to our hospital with dyspnea on exertion and high fever. Laboratory tests revealed anemia, thrombocytopenia, and proteinuria. Computed tomography (CT) revealed a large anterior mediastinal mass, mild splenomegaly, bilateral pleural effusion, pericardial effusion, and mild systemic lymphadenopathy. A CT-guided biopsy was unable to establish a definitive diagnosis, so we resected the mediastinal mass for diagnostic and therapeutic purposes. Pathological findings were consistent with the hyaline vascular type of Castleman’s disease (CD), and she was diagnosed with TAFRO syndrome. There has been no description of a patient with TAFRO syndrome with a large mass, and this is the first case of TAFRO syndrome treated with debulking surgery.
Castleman’s disease (CD) is a rare, non-neoplastic lymphoproliferative disorder first reported in 1956 . Multicentric Castleman’s disease (MCD) is a CD subtype with multiple lesions and systemic symptoms that includes a heterogeneous group of disorders with various etiologies. A new disease entity—TAFRO syndrome—has been proposed as a rare variant of MCD , which poses serious diagnostic and therapeutic challenges because its precise pathophysiology remains unknown.
CD cases are pathologically classified into three types: hyaline vascular, plasma cell, and mixed . Unicentric CD is often asymptomatic and associated with the hyaline vascular histological type. However, MCD often demonstrates episodic systemic inflammatory symptoms and multiple organ impairment due to excessive proinflammatory cytokines, such as interleukin-6 . The diagnosis of MCD is established when histopathological lymph node features of CD and clinical features are observed. Therefore, MCD describes a heterogeneous group of disorders with various etiologies .
The HHV-8 and HIV infections are a well-established cause of hypercytokinemia in MCD patients with plasma cell histology . However, a group of HIV-negative and HHV-8 negative MCD cases has been reported  and defined as idiopathic MCD . Idiopathic MCD pathogenesis is poorly understood, but polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome), paraneoplastic syndromes, and secretion of other cytokines by malignant plasma cells have been reported to co-occur with idiopathic MCD .
The histopathological and systemic features in idiopathic MCD are thought to be secondary to hypercytokinemia caused by these diseases, and the new disease concept of TAFRO syndrome was recently proposed in Japan as a unique clinicopathological variant of idiopathic MCD. TAFRO syndrome was described in a group of idiopathic MCD patients with thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly . This syndrome also demonstrates milder lymphadenopathy, mixed or hyaline vascular histopathology, normal or mildly elevated levels of interleukin-6, presence of autoantibodies, severe anasarca, and normal immunoglobulin levels. The clinical and pathological features in our case were compatible with TAFRO syndrome, but there has been no description of a patient with TAFRO syndrome with a large mass. This is then the first case of TAFRO syndrome with a large anterior mediastinal mass.
Treatment strategies differ for unicentric CD and MCD. Although surgery is the gold-standard treatment for unicentric CD presenting at any organ, the combination of surgery and medical therapy is often used in MCD patients . Three medical treatment strategies have been used in MCD patients with TAFRO syndrome: anti-inflammatory and immunosuppressive therapies such as corticosteroids and cyclosporine A, cytotoxic elimination of cells responsible for hypercytokinemia with cyclophosphamide and doxorubicin, and blockade of interleukin-6 signaling with monoclonal antibodies such as tocilizumab . Surgery in MCD patients is performed to obtain tissue for a full histopathological diagnosis because sufficient specimens of lymph nodes or solid organs are required for a histopathological analysis of CD. The other role of surgery in MCD patients is for debulking, i.e., to excise the majority of the tissues affected by the disease. No long-term survival difference in MCD patients treated with debulking surgery, immunosuppressive therapy, or a combination of both has been demonstrated, suggesting that debulking surgery could be potentially beneficial for the treatment of MCD . Here, mediastinal tumor resection was effective to improve the patient’s symptoms for 6 months. Although TAFRO syndrome may require systemic therapy in the long term, debulking surgery for patients with TAFRO syndrome with a main tumor is thought to be very useful in terms of both diagnosis and treatment.
In conclusion, we describe the first case of a patient with TAFRO syndrome with a large anterior mediastinal mass. The surgical approach was very beneficial in terms of diagnosis and treatment because it enabled us to confirm the TAFRO syndrome and transiently control disease progression with a resection of the large mediastinal mass.
Consent was obtained from the patient for the publication of this case report.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
- Castleman B, Towne VW. Case records of the Massachusetts General Hospital: weekly clinicopathological exercises. N Engl J Med. 1954;251:396–400.View ArticlePubMedGoogle Scholar
- 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.View ArticlePubMedGoogle Scholar
- Frizzera G, Peterson BA, Bayrd ED, Goldman A. A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease: clinical findings and clinicopathologic correlations in 15 patients. J Clin Oncol. 1985;3:1202–16.PubMedGoogle Scholar
- Kawabata H, Kadowaki N, Nishikori M, Kitawaki T, Kondo T, Ishikawa T, Yoshifuji H, Yamakawa N, Imura Y, Mimori T, Matsumura Y. 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.View ArticlePubMedGoogle Scholar
- Fajgenbaum DC, van Rhee F, Nabel CS. HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy. Blood. 2014;123:2924–33.View ArticlePubMedGoogle Scholar
- Dupin N, Diss TL, Kellam P, Tulliez M, Du MQ, Sicard D, Weiss RA, Isaacson PG, Boshoff C. HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked HHV-8 positive plasmablastic lymphoma. Blood. 2000;95:1406–12.PubMedGoogle Scholar
- Suda T, Katano H, Delsol G, Kakiuchi C, Nakamura T, Shiota M, Sata T, Higashihara M, Mori S. HHV-8 infection status of AIDS-unrelated and AIDS-associated multicentric Castleman’s disease. Pathol Int. 2001;51:671–9.View ArticlePubMedGoogle Scholar
- Talat N, Belgaumkar AP, Schulte KM. Surgery in Castleman’s disease: a systematic review of 404 published cases. Ann Surg. 2012;255:677–84.View ArticlePubMedGoogle Scholar