Castleman disease and TAFRO syndrome.

Although Castleman disease was first described in 1956, this disease includes various conditions, including unicentric Castleman disease with hyaline vascular histology, human herpesvirus-8 (HHV-8) related multicentric Castleman disease, idiopathic multicentric Castleman disease, and mimics of Castleman disease associated with other conditions. To date, Castleman disease remains incompletely understood due to its rareness and difficulties in clinical and pathological diagnosis. TAFRO syndrome was reported in Japan in 2010. Because lymph node histology is similar in patients with TAFRO syndrome and Castleman disease, TAFRO syndrome is described as a related disorder of Castleman disease. Clinically, however, these conditions differ markedly. Although elevated interleukin-6 (IL-6) expression is characteristic of Castleman disease, increased expression of IL-6 may occur in patients with other diseases, making elevated IL-6 unsuitable for differential diagnosis. Further understanding of these disorders requires the identification of novel disease-specific biomarkers. This review article therefore outlines the characteristics of Castleman disease and TAFRO syndrome.

Patient's age and D-dimer levels predict the prognosis in patients with TAFRO syndrome.

OBJECTIVES: To identify prognostic factors for TAFRO syndrome, a rare inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. METHODS: Data of patients with TAFRO syndrome were extracted from a Japanese patient registry. Patients were divided into groups according to the clinical and laboratory parameters at initial presentation. Cut-off values for the laboratory parameters were determined using receiver operating characteristic curve analysis and by clinical relevance. Patient survival was analyzed by the Kaplan-Meier method. Univariable analysis was performed using log-rank tests. Multivariable analyses were performed with the logistic regression model and the Cox proportional hazards model. RESULTS: We extracted the data of 83 patients with TAFRO syndrome from the registry. Univariable analysis identified several potential prognostic factors. Of these factors, age ≥60 years and D-dimer ≥18 µg/dL remained significant predictors of poor overall survival in the multivariable Cox proportional hazards model. Based on these results, we developed a simple prognostic scoring system for TAFRO syndrome (TS-PSS). CONCLUSION: Patients in our cohort were stratified into low, intermediate, and high-risk groups by the TS-PSS. This system should be verified with independent patient cohorts in future studies.

A 10-year observational single-center study of retroperitoneal unicentric Castleman disease.

ABSTRACT: Diagnosis of unicentric Castleman disease (UCD) is not easy before the resection and obtainment of pathological result. We retrospectively summarized 10-year experience of clinical evaluation and management for retroperitoneal UCD in Peking Union Medical College Hospital (PUMCH) between December 1, 2009 and December 31, 2019. Seventy two UCD patients with pathological diagnosis after resection were screened out. Among them 25 patients had retroperitoneal UCD. The average age of the 25 patients was 43.80 ±â€Š12.79, and 52.00% were male. No patients had systemic symptoms, and 1 patient got preoperative treatment. The average size of masses was 5.59 ±â€Š2.86 cm. The UCD sites included kidney, adrenal area, perinephric area, pancreas, peripancreatic area, area of descending part of duodenum, periaortic area or beside iliac artery, and others. The masses presented different degree of enhancement on CT scans and hypoecho or isoecho on ultrasound. Increased metabolism could be found on 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT). Some patients had positive results on somatostatin receptor imaging, but none had positive results on 131I-metaiiodo-benzylguanidine (131I-MIBG). Some patients presented the elevated level of interleukin-6 (IL-6), 24hour-urinary catecholamine and tumor markers. All the patients received complete resection of masses and 96.00% had hyaline-vascular type pathology except 1 patient (plasma cell-type). Ninety two percent patients received a long-term follow-up with an average follow-up time of 35.48 ±â€Š33.90 months. No patients died or experienced relapse during follow-up. Differential diagnosis of retroperitoneal UCD may be difficult according to imaging and laboratorial examinations. Differential diagnosis with pheochromocytomas/paragangliomas should be taken into special consideration. Different imaging examinations, such as CT/MRI, 18F-PET/CT, somatostatin receptor imaging and 131I-MIBG, can be combined for differential analysis. Complete resection is the best treatment and could provide a final pathological diagnosis.

Sequential change in serum VEGF levels in a case of tocilizumab-resistant TAFRO syndrome treated effectively with rituximab.

Recently, a unique clinicopathologic variant of multicentric Castleman disease, TAFRO (i.e. thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis and organomegaly) syndrome, has been identified in Japan. Previous reports have shown that affected patients usually respond to anti-interleukin 6 (IL-6) receptor antibody, but not all patients achieve remission. Here, we present a 62-year-old man meeting the criteria of TAFRO syndrome. Serum, plasma and ascites levels of cytokines, including IL-6 and vascular endothelial growth factor, were markedly elevated. Tocilizumab, an anti-IL-6 receptor antibody, and corticosteroids were initially used to treat the increase in acute inflammatory proteins and the anasarca, resulting in decreased cytokine levels. However, the patient showed a rapidly progressive course of anasarca and ascites, and an increase in acute inflammatory proteins and cytokine levels shortly thereafter. Rituximab, an anti-CD20 antibody, successfully induced remission of disease symptoms and decreased cytokine levels. The patient was successfully treated with rituximab despite being refractory to tocilizumab and corticosteroids. During our patient's clinical course, monitoring cytokine profiles, especially vascular endothelial growth factor, was useful in tracking the disease activity of TAFRO syndrome.

Analysis of Clinical Characteristics, Pathological Changes and Changes of Interleukin-6 (IL-6) and C-Reactive Protein (CRP) in Children with Castleman's Disease.

BACKGROUND The aim of this study was to analyze the pathological changes, clinical characteristics and changes in immunity, interleukin-6 (IL-6) and C-reactive protein (CRP) in children with Castleman's disease (CD). MATERIAL AND METHODS A total of 15 CD child patients were enrolled as observation group, while 20 normal children receiving healthy examination were enrolled as healthy control group. The pathological changes, clinical characteristics and changes in immunity and serum IL-6 and CRP expressions were retrospectively analyzed in observation group. RESULTS The clinical manifestation of unicentric CD (UCD) was mainly enlargement of cervical lymph nodes without liver-spleen enlargement and fever, and the major pathological type was the hyaline-vascular type. Multicentric CD (MCD) child patients all had anemia, fever and other systemic symptoms, and the major pathological type was the plasma-cell type. There were expressions of the immune indexes, including cluster of differentiation 3 (CD3), CD4, CD8, CD20, and CD79, in a certain degree, while CD138 and VS38C expressions displayed the polyclonal proliferation of plasma cells, rather than neoplastic proliferation. The Epstein-Barr virus and human herpes virus-8 detection results were negative, and CD21 in follicular dendritic cells in abnormal germinal center was positive. The expression levels of serum IL-6 and CRP in observation group were higher than those in control group (P.

Unexplained cause of thrombocytopenia, fever, anasarca and hypothyroidism: TAFRO syndrome with thrombotic microangiopathy renal histology.

TAFRO (thrombocytopenia, anasarca, fever, reticulin myelofibrosis or renal dysfunction and organomegaly) syndrome is a systemic inflammatory disease characterised by thrombocytopenia, anasarca, fever or inflammatory syndrome, reticulin myelofibrosis or renal dysfunction and organomegaly. It was first described as a subtype of idiopathic multicentric Castleman disease. Here, we report the case of a 42-year-old woman presenting with thrombocytopenia, anasarca, inflammatory syndrome, renal insufficiency, reticulin myelofibrosis at bone marrow biopsy and cervical and axillary lymph nodes. Kidney biopsy showed double contours of the glomerular basement membrane, mesangiolysis and endothelial swelling compatible with thrombotic microangiopathy (TMA) as well as with TAFRO syndrome. She was successfully treated by corticosteroids, tocilizumab and rituximab. This new case description of TAFRO syndrome underlines three features of this disease rarely described in the literature and never simultaneously in the same patient: the association to severe hypothyroidism, the presence of TMA-like lesions on kidney biopsy and the treatment by the association of steroids, tocilizumab and rituximab.

Hemosiderin deposition in lymph nodes of patients with plasma cell-type Castleman disease.

Plasma cell-type Castleman disease (PCD) is a rare idiopathic atypical lymphoproliferative disorder. It is difficult to differentiate between PCD and IgG4-related disease (IgG4-RD) based on histology alone. As PCD often presents with abundant hemosiderin deposition, lymph node lesions obtained from 22 PCD patients and 12 IgG4-RD patients were analyzed using Prussian blue staining to clarify whether hemosiderin deposition is effective in distinguishing between these two diseases. The analysis disclosed that hemosiderin was more densely deposited in PCD than in IgG4-RD. The median number of Prussian blue-positive cells ± standard deviation (SD) in PCD and IgG4-RD cases was 13 ± 36 cells/3HPFs and 4 ± 8 cells/3HPFs (P = 0.034), respectively. In addition, we analyzed the relationship between hemosiderin deposition and levels of serum interleukin (IL)-6, serum C-reactive protein (CRP), and anemia-related biomarkers. We found that hemosiderin deposition was significantly correlated with the level of serum CRP (P = 0.045); however, no significant correlation was observed between hemosiderin deposition and serum IL-6 levels (P = 0.204). A non-significant positive correlation was observed between hemosiderin deposition and serum hemoglobin levels (P=0.09). Furthermore, no significant correlation was observed between hemosiderin deposition and serum iron levels (P = 0.799). In conclusion, hemosiderin deposition characteristically observed in PCD may be related to the inflammatory aggressiveness of the disease and could be used for its differential diagnosis.

AA amyloidosis associated with Castleman disease: A case report and review of the literature.

RATIONALE: AA amyloidosis (AA) is caused by a wide variety of inflammatory states, but is infrequently associated with Castleman disease (CD). CD describes a heterogeneous group of hematologic disorders that share characteristic lymph node histopathology. CD can present with a solitary enlarged lymph node (unicentric CD, UCD) or with multicentric lymphadenopathy (MCD), constitutional symptoms, cytopenias, and multiple organ dysfunction due to an interleukin-6 driven cytokine storm. PATIENT CONCERNS: We are reporting a case of a 26-year-old woman with no significant past medical history who presented with a 3-month history of fatigue and an unintentional 20-pound weight loss. DIAGNOSIS: A CT-scan of the abdomen and pelvis revealed hepatosplenomegaly and a mesenteric mass. Congo Red staining from a liver biopsy showed apple-green birefringence and serum markers were suggestive of an inflammatory process. Post-excision examination of the resected mass revealed a reactive lymph node with follicular hyperplasia with kappa and lambda stains showing polyclonal plasmacytosis consistent with CD. INTERVENTIONS: The patient underwent surgery to remove the affected lymph node. OUTCOMES: IL-6, anemia, leukocytosis, and thrombocytosis resolved or normalized 2 weeks after resection; creatinine normalized 9 months postsurgery. Twenty two months post-surgery her IFN-γ normalized, her fatigue resolved, her proteinuria was reduced by >90% and she had returned to her baseline weight. LESSONS: Our case and literature review suggest that patients presenting with UCD or MCD along with organ failure should prompt consideration of concurrent AA amyloidosis.

Clinicopathologic characteristics of 342 patients with multicentric Castleman disease in Japan.

Objectives: To assess the clinicopathologic features of Multicentric Castleman disease (MCD) patients in Japan.Methods: We assessed baseline data for 342 Japanese MCD patients with a biopsy-proven diagnosis, enrolled in a prospective, observational study for tocilizumab treatment.Results: Of 342 patients, 86.0% had plasma-cell type. None had a family history of MCD. Median disease duration of MCD was 3.7 years. Mean body weight and body mass index tended to be lower than those in the general Japanese population. The most common clinical presentations besides lymphadenopathy included fatigue (61.7%), pulmonary involvement (42.7%), and splenomegaly (41.8%). Secondary amyloidosis was reported in 34 patients (9.9%). Laboratory abnormalities included decreased hemoglobin and albumin, and increased acute-phase proteins, serum immunoglobulins, and interleukin-6 (IL-6). IL-6 levels among the MCD patients tested in this study were correlated with levels of albumin, hemoglobin, triglyceride, total cholesterol, C-reactive protein, fibrinogen and immunoglobulin G (Spearman's correlation coefficient, |r| = 0.28-0.59).Conclusion: The clinical features and laboratory abnormalities are similar to those previously reported in other countries, besides higher rates of pulmonary involvement, secondary amyloidosis, and ECG abnormalities. Our results imply that IL-6 is involved in MCD pathogenesis. These findings would be informative for diagnosis and appropriate treatment for MCD.

Is TAFRO syndrome a subtype of idiopathic multicentric Castleman disease?

Castleman disease (CD) is a rare lymphoproliferative disorder that can be unicentric or multicentric. Multicentric CD (MCD) is further subdivided into human herpesvirus type-8-associated, POEMS syndrome-associated, and idiopathic (iMCD). TAFRO syndrome is a newly identified disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The TAFRO syndrome is sometimes regarded as a subtype of iMCD (TAFRO-iMCD), whereas iMCD without TAFRO syndrome is considered "not otherwise specified" (iMCD-NOS). However, a proportion of patients with TAFRO syndrome have been diagnosed without lymph node biopsies (TAFRO syndrome without proven iMCD; TAFRO-w/op-iMCD). To clarify the clinical features of iMCD-NOS, TAFRO-iMCD, and TAFRO-w/op-iMCD, we retrospectively analyzed 220 patients extracted from the database of the Multicenter Collaborative Retrospective Study for Establishing the Concept of TAFRO Syndrome. The patients included 87 with iMCD-NOS, 63 with TAFRO-iMCD, and 19 with TAFRO-w/op-iMCD. Patients in all three groups exhibited anemia, hypoalbuminemia, and elevated serum C-reactive protein and interleukin-6 levels. No significant differences in clinical, laboratory, and prognostic features were noted between the TAFRO-iMCD, and TAFRO-w/op-iMCD groups. However, the iMCD-NOS group exhibited polyclonal hyper-γ-globulinemia. The five-year survival rates of patients in the iMCD-NOS and TAFRO-involved groups were 100% and 66.5%, respectively (dropping markedly during the first few months in the latter). The iMCD-NOS and the TAFRO-iMCD samples typically showed plasma cell and mixed-type histologies, respectively. Thus, iMCD can be classified into two distinct subtypes, iMCD-NOS and TAFRO-iMCD. As such, TAFRO-iMCD and TAFRO-w/op-iMCD may be considered the same entity, requiring prompt diagnosis and intensive care.

Rheumatoid arthritis-like active synovitis with T-cell activation in a case of idiopathic multicentric Castleman disease: A case report.

RATIONALE: Idiopathic multicentric Castleman disease (iMCD) is a systemic disease with multiple regions of lymphadenopathy and systemic symptoms and associated with rheumatoid arthritis (RA) and collagen diseases. However, few reported have described the coexistence of iMCD and RA and the mechanisms by which iMCD induces arthritis remain elusive. We experienced a rare case of iMCD, wherein the patient exhibited symptoms of polyarthritis with high-grade fever. PATIENT CONCERNS: A 34-year-old woman was admitted to our hospital for further evaluation of a high fever with polyarthritis. The levels of both rheumatoid factor and anticitrullinated protein antibody were negative. F-fluorodeoxyglucose/positron emission tomography-computed tomography showed lymphadenopathy with increased fluoro-2-deoxy-D-glucose uptake. Magnetic resonance imaging and musculoskeletal ultrasonography revealed active synovitis in the hands which was consistent with RA. DIAGNOSES: We diagnosed iMCD based on human herpesvirus 8 negativity, HIV negativity, systemic lymphadenopathy, and pathologic findings of the lymph nodes. The patient did not satisfy the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA. Cytokine assay showed elevated serum levels of interleukin-17 and CXCL10, comparable to those in patients with RA. INTERVENTIONS: We administered 15 mg/d of predonisolone. OUTCOMES: After this treatment, the patient's symptoms showed improvement. As of this writing, we tapered the prednisolone to 7.5 mg/d, and the patient's remission has been maintained for >4 months. LESSONS: The present case suggests that RA-like active synovitis may coexist in iMCD, resulting from aberrant T-cell activation and histologic examination using lymph node biopsy may help enable early diagnosis of iMCD.

Pathological findings of progressive renal involvement in a patient with TAFRO syndrome.

TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) is thought of as an atypical type of idiopathic multicentric Castleman's disease. Interleukin-6, vascular endothelial growth factor (VEGF), and other cytokines are considered etiological factors. A 45-year-old woman was admitted to hospital with unknown fever and abdominal pain. She had thrombocytopenia, anasarca, proteinuria/hematuria, and slight hepatosplenomegaly. Based on her clinical course and laboratory data, she was diagnosed as having TAFRO syndrome. Kidney biopsy showed a membranoproliferative glomerulonephritis (MPGN)-like lesion containing lobulations of glomeruli, endothelial cell swelling, double contours of the glomerular basement membrane, and mesangiolysis. She was treated with methylprednisolone pulse (500 mg/day) and oral prednisolone (60 mg/day) therapy. The pleural effusion and ascites disappeared, and renal function normalized. Cyclosporine was added to prevent relapse. She went home, with no relapse 8 months after hospitalization. MPGN-like lesions were found frequently in patients with TAFRO syndrome in recent reports. However, there are few reports of pathologically confirmed cases of progressive renal involvement in TAFRO syndrome. The relationship between VEGF expression in renal tissue and the pathogenesis of renal injury in TAFRO syndrome was investigated in the present case.

POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. DIAGNOSIS: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal PCD, and at least one of the minor criteria. RISK STRATIFICATION: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR. RISK-ADAPTED THERAPY: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.

TAFRO Syndrome with an Anterior Mediastinal Mass and Lethal Autoantibody-Mediated Thrombocytopenia: An Autopsy Case Report.

TAFRO syndrome, a rare systemic inflammatory disease, can lead to multiorgan failure without appropriate treatment. Although thrombocytopenia is frequently seen in patients with TAFRO syndrome, little is known about its pathogenesis. Moreover, while recent studies have reported the presence of an anterior mediastinal mass in some patients, the pathological status of this remains unclear. Here, we report a case of fatal bleeding in a patient with TAFRO syndrome accompanied by an anterior mediastinal mass. A 55-year-old female was transferred to our hospital with a 2-week history of fever, epistaxis, and dyspnea. Laboratory tests revealed severe thrombocytopenia, computed tomography (CT) showed pleural effusions, and bone marrow biopsy revealed reticulin myelofibrosis. We suspected TAFRO syndrome, but the CT scan showed an anterior mediastinal mass that required a biopsy to exclude malignancy. She soon developed severe hemorrhagic diathesis and died of intracranial hemorrhage despite intensive treatment. She had multiple autoantibodies against platelets, which caused platelet destruction. An autopsy of the mediastinal mass revealed fibrous thymus tissues with infiltration by plasma cells. Our case suggests that thrombocytopenia could be attributed to antibody-mediated destruction and could be lethal. Hence, immediate treatment is imperative in cases of severe thrombocytopenia, even when accompanied by an anterior mediastinal mass.

Predictors of response to anti-IL6 monoclonal antibody therapy (siltuximab) in idiopathic multicentric Castleman disease: secondary analyses of phase II clinical trial data.

Siltuximab is the only US Food and Drug Administration-approved treatment for idiopathic multicentric Castleman disease (iMCD), a rare haematological disorder associated with substantial morbidity and mortality. Although siltuximab induces a response in a significant proportion of iMCD patients via interleukin 6 (IL6) neutralization, it is not universally effective. To develop a predictive model of response, we performed an in-depth analysis of 38 baseline laboratory parameters in iMCD patients from the phase II siltuximab trial who met criteria for treatment response or treatment failure. Univariate analyses identified eight baseline laboratory parameters that were significantly different between responders and treatment failures: albumin, immunoglobulin G (IgG), immunoglobulin A, C reactive protein (CRP), fibrinogen, haemoglobin, sodium and triglycerides. Stepwise logistic regression analysis of these candidate parameters identified a top performing model that included fibrinogen, IgG, haemoglobin and CRP. Based on cross-validation of the final multivariate logistic regression model, the model accurately discriminated responders from those who failed treatment (area under the receiver operator characteristic curve 0·86, 95% confidence interval: 0·73-0·95). All four laboratory parameters associated with response to siltuximab have biological relationships with IL6 and acute inflammation. Our model suggests that iMCD patients with laboratory evidence of an inflammatory syndrome are the best candidates for siltuximab therapy.

IgG4-related respiratory disease.

IgG4-related diseases (IgG4-RDs), such as autoimmune pancreatitis and IgG4-related Mikulicz disease, are often accompanied by intrathoracic lesions, which are called IgG4-related respiratory disease (IgG4-RRD). IgG4-RRD has few subjective symptoms, and is usually detected during workup of patients with extra-thoracic lesions of IgG4-RD. IgG4-RRD is characterized by various conditions, including masses, nodules, thickening, and infiltration at numerous sites in the thorax through lymphatic routes. Although elevated serum IgG4 concentrations and pathologic evidence of lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells are characteristic findings of IgG4-RD, other intrathoracic diseases, such as multicentric Castleman disease and malignancy, may present with similar findings. Developing diagnostic criteria for IgG4-RRD, including clinicoradiological and pathological characteristics, is necessary for its appropriate diagnosis.

Comparison of IgG4-Related Lymphadenopathy and Multicentric Castleman's Disease: a Retrospective Study.

BACKGROUND: It can be difficult to distinguish between IgG4-related lymphadenopathy and multicentric Castleman's disease (MCD) because these conditions cannot be differentially diagnosed using immunohistochemical staining alone. In this study, we analyzed the clinical features of IgG4-related lymphadenopathy and MCD patients. METHODS: We retrospectively analyzed 27 patients with MCD, including 20 with plasma cell-type (PC-type) and 7 with hyaline vascular (HV) features (mixed-type). An additional 15 patients with IgG4-related lymphadenopathy were enrolled. Clinical data and immune pathological characteristics, including serum interleukin-6 (IL-6) levels, lymph node lesion biopsies, IgG4+/IgG+ expression, and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images, were collected. RESULTS: The serum levels of C-reactive protein (CRP), IgA, and IL-6 were significantly elevated in the PC/mixedtype group compared with the IgG4-related lymphadenopathy group (p < 0.05). By contrast, the mean age, eosinophilia, globulin, and serum levels of IgG and IgG4 were significantly higher in the IgG4-RD lymphadenopathy group (all p < 0.05). Thirty percent of patients with IgG4-RD lymphadenopathy had elevated IL-6 levels, and 50% with MCD had elevated serum IgG4 levels. Immunohistochemical studies demonstrated the presence of numerous IgG4+ plasma cells, which accounted for > 40% of IgG4/IgG+ cells in 7 of 27 cases in the PC/mixed-type group. We first found that the mean maximum standard uptake value (SUVmax) was strongly associated with albumin and IL-6 in the IgG4-RD lymphadenopathy group, but not in the MCD group. The number of involved organs, but not the standard uptake value (SUV), helped to distinguish between the two diseases. Most PC/mixed-type group patients responded poorly to glucocorticoids when administered alone or in combination with immunosuppressant drugs. CONCLUSIONS: MCD cannot be differentiated from IgG4-related lymphadenopathy using histology alone. Systematic comparative analysis; clinical and laboratory analyses, especially 18F-FDG-PET/CT; and responses to drug treatment are therefore important parameters for distinguishing between these two diseases.

[Clinical significance of chronologic immature platelet fraction analysis in TAFRO syndrome].

TAFRO syndrome is characterized by thrombocytopenia with unknown etiology. The assessment of immature platelet fraction (IPF) is useful for differential diagnoses that include thrombocytopenia. However, the significance of IPF in cases of TAFRO syndrome remains to be reported. We present a case of TAFRO syndrome wherein the patient demonstrated a marked increase in IPF without thrombocytopenia, which offers vital information concerning TAFRO diagnosis and the serial measurements of IPF during treatment. A 65-year-old man presenting with fever was admitted to our hospital. He exhibited mild splenomegaly and lymphadenopathy, as well as rapidly worsening renal failure and fluid retention. These indications prompted the initiation of corticosteroid therapy. A normal platelet count and aberrantly high IPF implied abnormal thrombopoiesis, and subsequent bone-marrow findings suggested TAFRO syndrome. The platelet counts started to decrease following the corticosteroid therapy, but the treatment refractoriness prompted the urgent administration of rituximab. Thereafter, the platelet count nadir remained for approximately one month, whereas the decreasing IPF trend preceded platelet recovery. In the present case, a high pre-treatment IPF was demonstrated before the emergence of thrombocytopenia, and a decreasing trend of IPF was observed before platelet recovery during treatment. Therefore, serial IPF measurements could be useful for the early diagnosis and prognostication of TAFRO syndrome.