Clinical diagnosis
Case 263
【Discussion】
TAFRO is an initial of indicating Thrombocytopenia, Anasarca, Fever, Reticular fibrosis, Organomegaly (1-3). TAFRO was first considered to be subtype of multicentric Castleman disease because of similar histologic findings of lymph-node as Castleman disease (lymphoproliferative disease) with respects of mantle layer proliferation which compose of plasma cells, producing antibody, and of vessel formation with hyaline hyperplasia (4, 5).
Mantle layer proliferation, vessel formation, fever and CRP high values can be explicable by hyper secretion of IL6. Anasarca, edematous whole body might be explicable with secretion of VEGF (vascular endothelial growth factor) known as vascular permeability factor. VEGF is secreted by macrophages and platelet via IL6. However, thrombocytopenia and reticular fibrosis of bone marrow is inexplicable by IL6 that produces platelets and osteoclast formation.
Meanwhile, it is reported that a case with TAFRO syndrome which was resistant to steroid and various immunosuppressives, but with cyclosporine that inhibit T cell function yielded complete resolution of TAFRO symptoms (4, 6, 7). Cyclosporine is an immunosuppressive agent that blocks helper T cell function. Helper T cell secretes IL2 when it gets information of antigen from macrophages or dendritic cells. IL2 functions to activate macrophages and B cells producing antibody, and to preserve function of repressor T cells releasing IL10 that repress immune system. The exact mechanism of causing TAFRO syndrome is yet to be clarified, however, it is related to be releasing IL2 from helper T cells.
In our case, IL2R was 1740 U/mL, not so high for malignant lymphoma whose IL2R is usually around 20000 U/mL or more, but might be compatible with immune disorder. Platelets rapidly decreased indicating consumption of platelet or formation of thrombus. Further, hypoalbuminemia was found, probably due to protein loosing gastroenteropathy. TAFRO and Castleman disease are ones of lymphoproliferative disorders. It is suspected that albumin leakage from lymphatic channels of digestive tract might occur.
As radiologic findings of TAFRO syndrome, pleural effusion and ascites, hepatomegaly, splenomegaly might encounter on CT(8). But these findings are not specific. Para-aortic lymph node are not so marked. Para-aortic edema can be hardly realized. However, swollen adrenal or ischemic damaged adrenal is often demonstrated on CT (8). Then, unknown pleural effusion & ascites and swollen adrenal gland might be findings suspicious for TAFRO syndrome. Small para-aortic lymph nodes and para-aortic edema are additional findings.
In our case, CT showed marked swollen adrenal gland, ascites, pleural effusion and small para-aortic lymph nodes.
【Summary】
We presented a forty eight-year-old female for diarrhea and epigastric pain. During admission in our hospital, marked thrombocytopenia, pleural effusion, ascites and systemic edema were found. General condition were rapidly worsened. Laboratory test revealed IL2R 1740 U/mL that was relatively increased and consistent with TAFRO syndrome. It is borne in mind that TAFRO syndrome composes of thrombocytopenia, anasarca, fever, reticular fibrosis and organomegaly. Although its etiology is yet to be clarified, the participation of IL 2 to TAFRO is definite. Histologic pattern of TAFRO is similar with Castleman disease with respects of Mantle zone proliferation, hyaline vessel formation. Castleman disease is a lymphoproliferative disease caused by IL 6 participation. Radiologic images between TAFRO syndrome and Castleman disease are different but histologic pattern is indistinguishable. Clinical symptoms and prognosis are also distinct between them.
【References】
1.Takai K, et al. Thrombocytopenia with mild bone marrow fibrosis accompanied by fever, pleural effusion, ascites and hepatosplenomegaly. Rinsho Ketsueki 2010; 51:320–325
2.Kawabata H, et al. 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
3.Sakashita K, et al. TAFRO syndrome: current perspectives. J Blood Med. 2018; 9: 15–23.
4.Konishi Y, et al. 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 Aug;236(4):289-95.
5.Frizzera G, et al. A systemic lymphoproliferative disorder with morphologic features of Castleman's disease: clinical findings and clinicopathologic correlations in 15 patients. J Clin Oncol 1985; 3: 1202–1216
6.Sunderkotter C, et al. Macrophages and angiogenesis. J Leukoc Biol. 1994;55:410–422.
7.Verheul HM, et al. Platelet: Transporter of vascular endothelial growth factor. Clin Cancer Res. 1997;3:2187–2190.
8. Kurokawa R, et al. Computed tomography findings of early-stage TAFRO syndrome and associated adrenal abnormalities. Eur Radiol. 2020 Oct;30(10):5588-5598
2022.4.8