Kidney biopsy findings in two patients with TAFRO syndrome: case presentations and review of the literature

Abstract Background TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis (or renal dysfunction), and organomegaly. TAFRO syndrome has only recently been described, and many clinicians are unaware of this disease, leading to delays in diagnosis and treatment. We present two patients with TAFRO syndrome in whom renal biopsies were performed. Case presentation Both patients had subacute onset and exhibited renal insufficiency, edema, anemia, thrombocytopenia, polyserositis and lymphadenopathy over the disease course. However, there were many differences in their clinical manifestations. Case 1 was a 30-year-old woman admitted due to intermittent vaginal bleeding for 3 weeks. Laboratory tests on admission showed severe renal insufficiency (creatinine: 624 μmol/L), severe anemia (Hb: 41 g/L), and moderate thrombocytopenia (61 × 109/L). Case 2 was a 42-year-old man. Acute epigastric pain was his initial complaint, and computed tomography (CT) revealed retroperitoneal exudation around the pancreas. He was diagnosed with acute pancreatitis, and after treatment with a proton pump inhibitor (PPI) and somatostatin, his abdominal pain still recurred. During treatment, renal failure gradually increased, with oliguria, fever, anemia, thrombocytopenia, edema and massive ascites. Lymph node histologies were consistent with the hyaline-vascular (HV) type and mixed type, respectively, and renal histopathologies were consistent with thrombotic microangiopathy (TMA)-like renal lesions and membranoproliferative glomerulonephritis (MPGN), respectively. Their general conditions improved after glucocorticoid therapy, but their renal functions did not recover completely. On the basis of glucocorticoids, second-line treatments with tocilizumab and rituximab, respectively, were applied. Conclusions The diagnosis of TAFRO syndrome is based mainly on clinical manifestations and lymph node biopsies. A reliable early diagnosis and appropriate rapid treatment are essential to improve patient outcomes. Clinicians should deepen their understanding of this disease and similar conditions. Once the disease is suspected, lymph node biopsies should be performed as soon as possible. In addition, renal biopsies should be actively performed in patients with renal involvement.

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Clinical spectrum of POEMS-associated multicentric Castleman disease with renal involvement: a diagnostic challenge

Journal of Nephropathology ◽

10.15171/jnp.2019.21 ◽

2019 ◽

Vol 8 (2) ◽

pp. 21-21

Author(s):

Caroline Kullmann Ribeiro ◽

Fernanda Bresciani ◽

Samile Echeverria Silveira ◽

Pedro Guilherme Schaefer ◽

Elvino Guardão Barros ◽

...

Keyword(s):

Renal Function ◽

Lymph Node ◽

Plasma Cells ◽

Clinical Laboratory ◽

Renal Involvement ◽

Case Series ◽

Human Herpesvirus ◽

Castleman Disease ◽

Diagnostic Challenge ◽

Multicentric Castleman Disease

Background: Castleman disease (CD) is a rare and heterogeneous lymphoproliferative disorder with a wide variety of clinical presentations and outcomes. Human herpesvirus-8 (HHV-8) related CD corresponds to the most common subtype of the multicentric Castleman disease (MCD). However, if HHV-8 is negative, POEMS (peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) associated with MCD or idiopathic MCD are the cause in a subgroup of patients. Considering the rarity of POEMS and MCD association, we herein describe a patient with a typical presentation based on clinical, laboratory and tissue biopsy data. Case Presentation: We report a diabetic patient who presented with asthenia, edema, skin lesions manifested by scarring in chiropodactyls, multiple lymph node enlargement in the neck, armpits and inguinal areas, splenomegaly, severe anemia, thrombocytopenia, and mixed polyneuropathy. Hematuria and proteinuria were detected. The patient developed progressive renal failure requiring dialysis. Renal biopsy showed mesangial expansion with mesangial hypercellularity, and lymphoplasmacytoid cells focally distributed in tubules and interstitium, which were compatible with acute tubulointerstitial nephritis. In immunofluorescence, no deposits of IgG, IgA, IgM, C1q, C3 or fibrinogen were found, and kappa and lambda were also negative. Lymph node biopsy revealed lymphoid tissue with follicular hyperplasia, sinusoidal and medullary infiltration of plasma cells. Immunohistochemistry confirmed positivity for B lymphocytes, T lymphocytes, and plasma cells in sub-capsular and para-follicular areas. The patient was diagnosed as POEMS-associated MCD variant, and chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was started. The patient did not recover renal function and remained dialysis-dependent. Conclusions: To date, the renal involvement in MCD and POEMS syndrome seems to be uncommon as reported in few case series. Its pathophysiology is not well understood. In the spectrum of MCD, decreased renal function may have impact in patient survival. Early diagnosis and treatment are needed to control the systemic manifestations, and most importantly to avoid chronic organ damage.

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Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease

American Journal of Hematology ◽

10.1002/ajh.24242 ◽

2016 ◽

Vol 91 (2) ◽

pp. 220-226 ◽

Cited By ~ 111

Author(s):

Noriko Iwaki ◽

David C. Fajgenbaum ◽

Christopher S. Nabel ◽

Yuka Gion ◽

Eisei Kondo ◽

...

Keyword(s):

Castleman Disease ◽

Tafro Syndrome ◽

Multicentric Castleman Disease ◽

Distinct Subtype

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Castleman Disease In Children: Diagnosis and Treatment

Journal of Clinical Medicine- Hue Central Hospital ◽

10.38103/jcmhch.2020.64.11 ◽

2020 ◽

Author(s):

Hung Dinh Viet

Keyword(s):

Lymph Node ◽

Postoperative Period ◽

Case Reports ◽

Abdominal Mass ◽

Clinical Manifestations ◽

Castleman Disease ◽

Results Of Treatment ◽

Benign Lymph Node ◽

Lymph Node Hyperplasia

Background: We describe the experiences in diagnosis and results of treatment in pediatric Castleman disease. Method: Serial case reports. Result: From 2016 to 2019, we had 7 cases of pediatric Castleman disease: 3 boys and 4 girl. The median age at diagnosis was 147 months (121-173 months). Clinical manifestations were found in five cases. They were all unicentric Castleman disease (6 abdominal mass, one left infraclavicular mass). All patients were operated with postoperative period uneventful. The median time of postoperative follow up was 22.7 months (11-53 months) with no signs of relapse. Conclusions: Pediatric Castleman disease is a rare benign lymph node hyperplasia, it can be localised or disseminated. Operation is the treatment of choice for localised Castleman disease.

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Five biopsies, one diagnosis: challenges in idiopathic multicentric Castleman disease

BMJ Case Reports ◽

10.1136/bcr-2020-236654 ◽

2020 ◽

Vol 13 (11) ◽

pp. e236654

Author(s):

Julie Semenchuk ◽

Asad Merchant ◽

Ali Sakhdari ◽

Vishal Kukreti

Keyword(s):

Lymph Node ◽

Kidney Injury ◽

Lymph Node Biopsy ◽

Castleman Disease ◽

Pleuritic Chest Pain ◽

Multicentric Castleman Disease ◽

Node Biopsy ◽

Significant Clinical Improvement ◽

Night Sweats ◽

Inflammatory Changes

A previously healthy 29-year-old man initially presented to the hospital with pleuritic chest pain and shortness of breath. Over the next 2 months he developed ongoing fevers and night sweats with recurrent exudative pleural effusions and ascites. He had an extensive infectious and autoimmune workup that was unremarkable. He had an initial lymph node biopsy that showed reactive changes only. He had an acute kidney injury and his renal biopsy revealed thrombotic microangiopathy. His liver biopsy showed non-specific inflammatory changes. His bone marrow biopsy showed megakaryocyte hyperplasia and fibrosis, which raised suspicion for the thrombocytopenia, ascites, reticulin fibrosis, renal dysfunction and organomegaly syndrome subtype of multicentric Castleman disease. This prompted a repeat lymph node biopsy, showing changes consistent with mixed type Castleman disease that fit with his clinical picture. He was initiated on steroids and siltuximab with significant clinical improvement.

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The potential role of follicular helper T cells in idiopathic multicentric Castleman disease with and without TAFRO syndrome

Pathology - Research and Practice ◽

10.1016/j.prp.2019.152563 ◽

2019 ◽

Vol 215 (10) ◽

pp. 152563

Author(s):

Nozomu Kurose ◽

Xin Guo ◽

Akihiro Shioya ◽

Ken-ichi Mizutani ◽

Motona Kumagai ◽

...

Keyword(s):

T Cells ◽

Potential Role ◽

Castleman Disease ◽

Helper T Cells ◽

Follicular Helper T Cells ◽

Tafro Syndrome ◽

Multicentric Castleman Disease ◽

Follicular Helper

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Acute Kidney Injury Caused by TAFRO Syndrome in a Chinese Patient: Efficacy of Long-Term Corticosteroids Combined with Bortezomib and Cyclophosphamide

Kidney & Blood Pressure Research ◽

10.1159/000505458 ◽

2020 ◽

Vol 45 (4) ◽

pp. 623-630 ◽

Cited By ~ 1

Author(s):

Peng Xia ◽

Lu Zhang ◽

Menglian Zou ◽

Tengyue Zhang ◽

Ran Li ◽

...

Keyword(s):

Renal Failure ◽

Renal Function ◽

Poor Prognosis ◽

Renal Involvement ◽

Castleman Disease ◽

High Dose ◽

Axillary Lymph ◽

Tafro Syndrome ◽

Vascular Type

Introduction: Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized and rare clinical subtype of Castleman disease. Renal involvement in TAFRO syndrome usually presents with mild proteinuria, microscopic hematuria, and acute renal injury requiring temporary renal replacement. There is no standard therapy available and treatment failures are common, leading to a poor prognosis. We report a case of acute renal failure caused by TAFRO syndrome, successfully managed by long-term corticosteroids combined with bortezomib and cyclophosphamide. Case Presentation: The patient was a 52-year-old female who presented with fever, anasarca, oliguria, and abdominal distension at first. She progressed rapidly to anuric renal failure requiring hemodialysis. She also demonstrated thrombocytopenia, anemia, coagulopathy, and a hyperinflammatory status. Her CT scan showed severe polyserositis, splenomegaly, and lymphadenopathy. Her serum vascular epithelial growth factor level was significantly elevated. Axillary lymph node biopsy showed hyaline-vascular type Castleman disease, supporting the diagnosis of TAFRO syndrome. Her renal function recovered after high-dose steroids and supportive treatment. A weekly dosing regimen of bortezomib, cyclophosphamide, and dexamethasone combined with medium dose prednisone in between were deployed. Her blood cell count and renal function remained stable after 6 months. The inflammation was suppressed and the polyserositis resolved completely. Conclusion: TAFRO syndrome is rare and has a poor prognosis due to the lack of standard treatment. Our patient might be the first TAFRO case successfully treated by bortezomib, cyclophosphamide, and corticosteroids.

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