Clinicopathological features of immunoglobulin G4-related constrictive pericarditis.

AIM: Constrictive pericarditis (CP) is characterised by scarring fibrosis and a loss of pericardial elasticity, which causes heart failure. IgG4 (immunoglobulin G4)-related disease (IgG4-RD) is a systemic fibro-inflammatory disease characterised by the infiltration of IgG4-immunopositive plasmacytes and high serum IgG4 levels that frequently shape tumorous lesions. Although pericardial involvement of IgG4-RD is rare, with indications of CP, pericardial effusion and irregular masses, the clinical and pathological features remain unclear. In this study, we examined the relationship between CP and IgG4-RD. METHODS: Among 35 thick-walled CP cases (histologically pericardial thickening ≥2 mm), eight cases were aetiology identified. Using the diagnostic criteria for IgG4-RD, 11 cases were classified as IgG4-CP, whereas the remainder were considered true idiopathic CP (16 cases) and the clinical pathological features were evaluated. RESULTS: Compared with the other groups, the IgG4-CP group was more common in men and associated with low-grade fever and massive pericardial effusion with frequent recurrence. Deaths resulting from heart failure occurred in a few cases of the IgG4-CP group, but not in other groups. An increase in C-reactive protein and a high positivity rate of anti-nuclear antibodies frequently occurred in the IgG4-CP group. Histologically, the IgG4-CP group included lymphoid follicle, eosinophil infiltration and few calcifications. CONCLUSIONS: Pericardial IgG4-RD occurs not only as nodular lesions, but also as thick-walled CP, and accounts for approximately 40% of thick-walled CP cases of unknown cause. The predominant clinical characteristic was refractory and recurrent pericardial effusion. Recognising IgG4-RD as a cause of CP is important to initiate appropriate therapy.

Recurrent cardiac tamponade following coronavirus disease 2019 mRNA vaccination: A case report.

A 64-year-old woman with a history of subarachnoid hemorrhage, breast cancer, cervical spine tumor, and syringomyelia developed recurrent pericardial effusion and cardiac tamponade after receiving the third dose of coronavirus disease 2019 mRNA vaccine, mRNA-1273 (Spikevax, Moderna). The cardiac tamponade of unknown etiology was intractable with nonsteroidal anti-inflammatory drugs, colchicine, and prednisolone. She underwent thoracoscopic pericardiectomy, and microthrombi were detected in the pericardial tissue. Although the exact causal relationship between vaccination and recurrent cardiac tamponade was unclear, the vaccine possibly caused or triggered the microthrombi formation, resulting in recurrent cardiac tamponade. Because of the potential for cardiovascular side effects such as thrombosis and myocarditis following vaccination, it was deemed necessary to accumulate and analyze such cases.

Cytomorphology, Immunophenotype, and cytogenetic profile of leukemic serous effusions.

BACKGROUND: Serous effusions (SE) in leukemic patients can be due to infections, therapy, volume overload, lymphatic obstruction or malignancy having implications on treatment and mortality. The objective of the present study is to highlight the spectrum of cytomorphology, immunophenotype, and cytogenetics in leukemic serous effusions (LSE). MATERIALS: Present study is retrospective and descriptive. We reviewed all the SE, which were reported as suspicious or positive of leukemic infiltration from 2016 to 2019 for cytomorphological features. CSF and effusions involved by lymphomas were excluded. Cyto-diagnosis was compared with primary proven diagnosis (by ancillary techniques) and disconcordant cases were analyzed. RESULTS: Out of total 9723 effusions, only 0.4% (n = 40) showed leukemic involvement and included nine cases of AML, three of B-ALL, 13 T-ALL, 2 MPAL, 6 CML, 5CLL, one each of chronic myelomonocytic leukemia and AML with myelodysplasia. The most common site of involvement was the pleural cavity (n = 30), followed by the peritoneal cavity (n = 7) and the pericardial cavity (n = 3). T -ALL (41.9%) was the most common leukemia involving pleural fluid followed by AML (23.3%). CML (42.8%) was the most common leukemia involving the ascitic fluid followed by B-ALL (28.6%). Accurate diagnosis was given on cytomorphology in 72.5% (29/40) cases and 15.0% (6/40) were reported as non-Hodgkin lymphoma. CONCLUSION: Cytology is an effective tool available to make a diagnosis of LSE. Nuclear indentations in large atypical cells and cells with eosinophilic granular cytoplasm with sparse or abundant eosinophils in the background are an important clue in favor of leukemia over lymphoma.

MOC31 Immunostaining in the Diagnosis of Metastatic Adenocarcinoma in Serous Fluid: Special Emphasis on Atypical Cytological Cases.

BACKGROUND: The diagnosis of atypical cases in the effusion cytology sample often poses a challenge to the cytologists. AIMS AND OBJECTIVES: We evaluated the diagnostic role of MOC31 in the metastatic adenocarcinoma in effusion fluid. MATERIALS AND METHODS: The cytological examination and MOC31 immunostaining in the cell block sections were carried out in 64 cases of serous effusion. A total of 23 cases showed atypical cytology, out of which suspicious for malignancy (SFM) and atypia of undetermined significance (AUS) were 19 and 4 cases, respectively. In these cases, we also performed calretinin immunostaining. The cytological features, results of MOC31 immunostaining, and follow-up data were correlated to find out the sensitivity and specificity of MOC31 immunostaining in the diagnosis of metastatic adenocarcinoma. RESULT: The sensitivity and specificity of MOC31 were 100%. MOC31 detected all the cases of metastatic adenocarcinoma. MOC31 showed strong positivity in 19 cases of SFM. All these cases had a malignant outcome in histopathology or follow-up data. In AUS cases, MOC31 immunostaining was negative with a benign outcome. In all the atypical but malignant cases calretinin stain showed diffuse cytoplasmic and nuclear positivity. In contrast, MOC31 showed strong membranous positivity and occasionally cytoplasmic positivity. CONCLUSION: MOC31 is an excellent marker of metastatic adenocarcinoma in the serous effusion. The membranous positivity of MOC31 and negative calretinin immuno-staining are helpful in atypical cytological cases to avoid the diagnostic dilemma. The MOC31 positivity is significantly useful in discrete atypical cells which are more challenging to recognize.

Responses to Treatment According to the Cytokine Profiles of Pericardial Effusion in Two Children with Idiopathic Pericarditis.

Acute pericarditis is inflammation of the pericardium with or without pericardial effusion. In the pediatric population, most patients with acute pericarditis are diagnosed with idiopathic pericarditis. Herein, we present two children with idiopathic pericarditis who underwent immunological assessment of pericardial effusion for the first time. Both patients showed equally high levels of interleukin-6 in the pericardial effusion. However, they had different treatment responses, in accordance with the pericardial effusion and serum interleukin-10 concentrations. Our present cases suggest that interleukin-10 may be associated with the response to anti-inflammatory therapy in idiopathic acute pericarditis.

Pericardial effusion under nivolumab: case-reports and review of the literature.

BACKGROUND: Nivolumab, a programmed death-1 (PD-1) inhibitor, is an immune checkpoint inhibitor particularly used in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. Immune-related adverse events are frequent under immunotherapies. Cardiotoxic side effects, initially thought to be rare, are more often encountered paralleling the expanding use of immune checkpoint blockade. Among them, pericardial effusion and tamponade deserve attention as they may present with unusual symptomatology. CASE PRESENTATION: We report three cases of pericardial effusion under nivolumab for lung adenocarcinoma. Two cases of early and late-onset pericardial effusion were symptomatic with tamponade and one case occurred without any symptoms. Pericardiocentesis with pericardial biopsy was performed in symptomatic pericardial effusion followed by the administration of a corticotherapy. Pericardial biopsies showed infiltration of T-lymphocytes, mostly CD4+. Nivolumab was stopped in two cases and resumed for one patient. Pericardial effusion evolved positively in all cases with or without treatment. CONCLUSIONS: We review the literature on pericardial effusion under nivolumab to further discuss the hallmarks of pericardial effusion under nivolumab and the management of nivolumab therapy in this situation. In conclusion, pericardial effusion as an immune-related adverse event under nivolumab appears less rare than initially thought and may require particular attention.

Infliximab Induced Cardiac Tamponade

Aim To report the first case of cardiac tamponade related to Infliximab induction therapy in an Ulcerative Colitis patient. Methods Review of published case reports. Results This complication was likely due to a type 3 hypersensitivity immune-complex reaction resulting in a reactive pericardial effusion Discussion Though rare, this case demonstrates how autoimmune reaction to anti-TNF𝛼 therapy can initially mimic infection, as our patient presented with tachycardia, hypotension, raised inflammatory and infective markers and fever.

Pericardial effusion due to pembrolizumab-induced immunotoxicity: A case report and literature review.

The advent of immune checkpoint inhibitors has revolutionized cancer treatment. These novel agents have provided promising treatment options in patients with different types of cancers. One of these agents is pembrolizumab, which works by blocking the binding of T-lymphocytes to programmed cell death ligand 1 receptors on tumor cells, thus enabling immune activation of T-lymphocytes against tumor cells. Pembrolizumab is commonly used in metastatic nonsmall cell lung cancer and melanoma. However, despite the remarkable efficacy this agent has achieved, multiple immune-related adverse events have been reported including hepatitis, colitis, thyroid dysfunction, and pneumonitis. Only 2 other cases of pericardial effusion as a side effect of pembrolizumab have been cited in the literature; however, its incidence may be on the rise. Despite the rarity of this side effect, its complications are potentially life threatening and no clear platform currently exists to help guide healthcare professionals in the management of these adverse events. Herein we present the case of a 66-year-old female who developed pericardial effusion as a side effect of pembrolizumab and review the data currently available to assist in the management of this life-threatening condition.

Mechanism of fowl adenovirus serotype 4-induced heart damage and formation of pericardial effusion.

Fowl adenovirus serotype 4 (FAdV-4) is the causative agent of hydropericardium syndrome (HPS), which is characterized by the accumulation of a clear, straw-colored fluid in the pericardial sac, and high mortality rates. In order to explore the mechanism of FAdV-4-induced cardiac damage, dynamic pathology, apoptosis, and inflammatory reactions were analyzed in vivo. Moreover, we detected viral proliferation, and ultrastructure, inflammation and apoptosis of cardiomyocytes (CM) after FAdV-4 infection in vitro. The results showed that FAdV-4 impaired cardiac integrity and function by causing apoptosis and inflammation in vivo. Flow cytometry showed that CM infected with FAdV-4 did not show apoptosis in vitro. In addition, the mRNA expression of four inflammatory cytokines (interleukin (il)1B, il6, il8, and tumor necrosis factor), and activity of three myocardial enzymes were significantly different between FAdV-4 and control groups. However, in vitro, these indexes showed no significant difference between the groups. These observations collectively indicated that the heart was not the target organ of FAdV-4, and the virus may not directly lead to the occurrence of CM apoptosis and inflammation. To explore the source of pericardial effusion, we measured total protein, albumin, aspartate aminotransferase, creatine kinase isoenzyme, lactate dehydrogenase, potassium, sodium, and chloride ions in serum and pericardial effusion. Pericardial effusion was derived from vascular exudation rather than CM degeneration. Further studies are needed to investigate the exudation mechanism of vascular endothelial cells in FAdV-4 infection then weakened or eliminated pericardial effusion to minimize heart injury and/or restore damaged CM.

Bronchiolitis obliterans organising pneumonia as an initial manifestation in a patient with systemic lupus erythematosus: a rare presentation.

Bronchiolitis obliterans organising pneumonia as an initial manifestation of systemic lupus erythematosus (SLE) is a rare and uncommon presentation. We describe a case of SLE presenting with shortness of breath, found to have pneumothorax, bilateral nodular infiltrates along with pleural effusions and pericardial effusion. Work-up suggested a diagnosis of active SLE with anaemia, thrombocytopenia, positive antinuclear antibodies (ANAs) and positive anti-double-stranded DNA. On retrospective review of patient records, from 8 years prior to presentation, lung biopsy histology consistent with bronchiolitis obliterans organising pneumonia with positive ANA serology was found, without any further autoimmune work-up. In our opinion, bronchiolitis obliterans organising pneumonia was the index presentation of SLE. Treatment with steroids and subsequent management with immunosuppressive therapy could have prevented subsequent hospitalisations. Prompt work-up for autoimmune diseases should be considered in patients with positive ANA and histological evidence of bronchiolitis obliterans organising pneumonia.

Forty-nine cases of acute lymphoblastic leukaemia/lymphoma in pleural and pericardial effusions: A cytological-histological correlation.

INTRODUCTION: Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive entity of precursor lymphoid neoplasm and may cause malignant serous effusion (SE). The current study aimed to analyse the characteristics of SE cytology of ALL/LBL including cytomorphology, immunophenotyping, clonality and evaluate the effectiveness of SE cytology as a diagnostic method for ALL/LBL. METHODS: SE specimens with final diagnosis of ALL/LBL from 2006 to 2016 were reviewed for clinical data, cytomorphological features and ancillary studies. Cytodiagnoses were compared with histodiagnoses, and the discordant cases were analysed. RESULTS: A total of 49 specimens including 47 pleural fluids and 2 pericardial fluids from 49 patients were evaluated. Cytomorphology revealed lymphoblasts varied from small size with scant cytoplasm, condensed nuclear chromatin and indistinct nucleoli to large size with dispersed nuclear chromatin and multiple variably prominent nucleoli. Nuclear clefts and hand mirror-shaped blasts were demonstrated. The positive rates of CD99 and terminal deoxynucleotidyl transferase were 90.9% and 81.6%, respectively. Both monoclonal immunoglobulin (Ig)H and T-cell receptor-γ gene rearrangements were demonstrated in 1 of 3 cases. Monoclonal T-cell receptor-γ gene rearrangement was found in 10 of 11 cases. Monoclonal IgH and/or Ig? gene rearrangements were revealed in 2 of 3 cases. Cytodiagnoses included 4 ALL/LBL, 3 B-ALL/LBL and 42 T-ALL/LBL. Histodiagnoses were available in 24 cases including 2 ALL/LBL, 2 B-ALL/LBL and 20 T-ALL/LBL. The concordance rates of cytological-histological diagnoses were 66.7%, 0% and 95.2% in the three categories, respectively. There were 3 cases with discrepancies of cell lineages. CONCLUSIONS: SE cytological evaluation is a reliable and effective method for the diagnosis of ALL/LBL.

IgG4-related disease manifesting as pericarditis with elevated adenosine deaminase and IL-10 levels in pericardial fluid.

A 78-year-old female with massive pericardial effusion fulfilled diagnostic criteria for immunoglobulin G4 (IgG4)-related disease. Although her adenosine deaminase (ADA) level in the pericardial effusion was high, all the tests for tuberculosis infection were negative. Immunostaining of the pericardium biopsy specimen revealed remarkably increased IgG4-positive cells. This is the first report describing IgG4-related pericarditis with elevated ADA level. We also demonstrate the elevated interleukin-10 (IL-10) level in pericardial fluid and IL-10-producing T-cells in the pericardium.

Immunoglobulin G4-related constrictive pericarditis identified by cytological examination of pericardial effusion: a case report.

BACKGROUND: Immunoglobulin G4-related disease is increasingly recognized as a systemic autoimmune disorder characterized by immunoglobulin G4-positive lymphocyte infiltration. Organ biopsy and histopathology are the most important diagnostic methods; however, the significance of a cytological examination in immunoglobulin G4-related disease cases is still unclear. CASE PRESENTATION: A 73-year-old Asian man who was a former tobacco smoker presented with progressive exertional dyspnea, systemic edema, and pericardial effusion. A cytological examination of his pericardial effusion detected three or four plasma cells per high-power field by Giemsa staining. Moreover, immunoglobulin G4-positive plasma cells were detected by immunostaining. Cardiac catheterization after pericardiocentesis revealed that both ventricular pressure traces showed an early diastolic dip and plateau. Positron-emission tomography with 18F-fluorodeoxyglucose imaging revealed inflammatory foci in his pericardium. A surgical pericardiectomy was performed and the resultant specimen showed significant immunoglobulin G4-positive plasma cell infiltration and marked fibrous thickening of his pericardium; therefore, a diagnosis of constrictive pericarditis due to immunoglobulin G4-related disease was made. Oral administration of 0.6-mg/kg/day prednisolone resolved his heart failure and he was discharged on foot 1 week later. CONCLUSION: Our experience with this case indicates that cytological examination of pericardial effusion was useful in the diagnosis of immunoglobulin G4-related disease.

Curative Effects of Dendritic Cells Combined with Cytokine-Induced Killer Cells in Patients with Malignant Pericardial Effusion.

BACKGROUND To determine the effects of dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with malignant pericardial effusion. MATERIAL AND METHODS All patients underwent pericardial puncture and indwelling catheter insertion. After pericardial drainage, the 16 patients in the treatment group received an infusion of 20 mL DCs and CIK cells (>1.0×10¹° cells) and 500,000 U interleukin (IL)-2 for 3 successive days. The 15 control-group patients received 30 mg/m² cisplatin and 500,000 U IL-2 for 3 successive days. The treatment effects were assessed using imaging data. RESULTS The total efficiency and complete remission rates were higher in the treatment group than in the control group at 4 weeks (total efficiency: 87.50% vs. 73.33%; complete remission: 62.50% vs. 46.67%) and 3 months after the treatment (total efficiency: 81.25% vs. 66.67%; complete remission: 50.00% vs. 40.00%; P<0.05 for all). In both groups, the Karnofsky scores for quality of life improved after treatment. However, the curative effects were better in the treatment group than in the control group (P<0.05). The following adverse reactions occurred: fever, 6 treatment-group patients and 3 control-group patients; chest pain, 2 treatment-group patients and 7 control-group patients; gastrointestinal reactions, 1 treatment-group patient and 6 control-group patients; and bone marrow suppression, 1 treatment-group patient and 5 control-group patients. The between-group differences in adverse reactions were significant (P<0.05). CONCLUSIONS The combination of DCs and CIK cells effectively treated malignant pericardial effusion, produced few side effects, and improved the patients' quality of life.

Serosal involvement in IgG4-related disease: report of two cases and review of the literature.

IgG4-related disease (IgG4-RD) is a recently described entity characterized by lymphoplasmacytic infiltrates, usually mimicking tumors, affecting almost every organ or system. Nevertheless, serosal involvement has been rarely reported. In this article, we report two cases of IgG4-RD with serosal involvement and review the literature. Because of the varied clinical pictures found in our review, we suggest a new terminology for the description of IgG4-RD with serosal involvement.

Anticardiac Antibodies in Patients with Chronic Pericardial Effusion.

OBJECTIVES: Chronic pericardial effusion may be challenging in terms of diagnosis and treatment. Specific laboratory parameters predicting the frequency and severity of recurrences after initial drainage of pericardial effusion are lacking. MATERIALS AND METHODS: Pericardial fluid (PF) and serum (SE) samples from 30 patients with chronic pericardial effusion (PE) who underwent pericardiocentesis and pericardioscopically guided pericardial biopsy were compared with SE and PF samples from 26 control patients. The levels of antimyolemmal (AMLA) and antifibrillary antibodies (AFA) in PE and SE from patients with pericardial effusion as well as PF and SE from controls were determined and compared. RESULTS: AMLAs and AFAs in PF and SE were significantly higher in patients with chronic pericardial effusion than in the control group (AMLAs: p = 0,01 for PF and p = 0,004 for serum; AFAs: p < 0,001 for PF and p = 0,003 for serum). Patients with recurrence of PE within 3 months after pericardiocentesis had significantly higher levels of AMLAs in SE (p = 0,029) than patients without recurrence of PE. CONCLUSIONS: The identification of elevated anticardiac antibodies in PE and SE indicates increased immunological reactivity in chronic pericardial effusion. High titer serum levels of AMLAs also correlate with recurrence of pericardial effusion.

Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study.

BACKGROUND: Tuberculous pericarditis (TBP) is associated with high morbidity and mortality, and is an important treatable cause of heart failure in developing countries. Tuberculous aetiology of pericarditis is difficult to diagnose promptly. The utility of the new quantitative PCR test (Xpert MTB/RIF) for the diagnosis of TBP is unknown. This study sought to evaluate the diagnostic accuracy of the Xpert MTB/RIF test compared to pericardial adenosine deaminase (ADA) and unstimulated interferon-gamma (uIFNγ) in suspected TBP. METHODS: From October 2009 through September 2012, 151 consecutive patients with suspected TBP were enrolled at a single centre in Cape Town, South Africa. Mycobacterium tuberculosis culture and/or pericardial histology served as the reference standard for definite TBP. Receiver-operating-characteristic curve analysis was used for selection of ADA and uIFNγ cut-points. RESULTS: Of the participants, 49% (74/151) were classified as definite TBP, 33% (50/151) as probable TBP and 18% (27/151) as non TBP. A total of 105 (74%) participants were human immunodeficiency virus (HIV) positive. Xpert-MTB/RIF had a sensitivity and specificity (95% confidence interval (CI)) of 63.8% (52.4% to 75.1%) and 100% (85.6% to 100%), respectively. Concentration of pericardial fluid by centrifugation and using standard sample processing did not improve Xpert MTB/RIF accuracy. ADA (≥35 IU/L) and uIFNγ (≥44 pg/ml) both had a sensitivity of 95.7% (88.1% to 98.5%) and a negative likelihood ratio of 0.05 (0.02 to 0.10). However, the specificity and positive likelihood ratio of uIFNγ was higher than ADA (96.3% (81.7% to 99.3%) and 25.8 (3.6 to 183.4) versus 84% (65.4% to 93.6%) and 6.0 (3.7 to 9.8); P = 0.03) at an estimated background prevalence of TB of 30%. The sensitivity and negative predictive value of both uIFNγ and ADA were higher than Xpert-MT/RIF (P < 0.001). CONCLUSIONS: uIFNγ offers superior accuracy for the diagnosis of microbiologically confirmed TBP compared to the ADA assay and the Xpert MTB/RIF test.

Cytokines in pericardial effusion of patients with inflammatory pericardial disease.

BACKGROUND: The role of inflammatory and angiogenic cytokines in patients with inflammatory pericardial effusion still remains uncertain. METHODS: We assessed pericardial and serum levels of VEGF, bFGF, IL-1ß and TNF-α by ELISA in patients with inflammatory pericardial effusion (PE) of autoreactive (n = 22) and viral (n = 11) origin, and for control in pericardial fluid (PF) and serum (n = 26) of patients with coronary artery disease (CAD) undergoing coronary artery bypass graft surgery. RESULTS: VEGF levels were significantly higher in patients with autoreactive and viral PE than in patients with CAD in both PE (P = 0.006 for autoreactive and P < 0.001 for viral PE) and serum (P < 0.001 for autoreactive and P < 0.001 for viral PE). Pericardial bFGF levels were higher compared to serum levels in patients with inflammatory PE and patients with CAD (P ≤ 0.001 for CAD; P ≤ 0.001 for autoreactive PE; P = 0, 005 for viral PE). Pericardial VEGF levels correlated positively with markers of pericardial inflammation, whereas pericardial bFGF levels showed a negative correlation. IL-1ß and TNF-α were detectable only in few PE and serum samples. CONCLUSIONS: VEGF and bFGF levels in pericardial effusion are elevated in patients with inflammatory PE. It is thus possible that VEGF and bFGF participate in the pathogenesis of inflammatory pericardial disease.