Autophagy in cardiac myxoma: An important puzzle piece in understanding its inflammatory environment.

BACKGROUND: Cardiac myxomas are rare, predominantly sporadic tumors that can cause heart failure and systematic inflammatory symptoms, and increase the risk of emboli. Their pathophysiology remains poorly understood, but intra-tumoral inflammation and senescence seem to be implicated in it. One of the principal cellular mechanisms implicated in tumor progression is autophagy, largely unknown in myxomas. Thus, our study aimed to investigate the presence of autophagic markers in myxomas and to correlate it with their immune microenvironment. METHODS: Twenty-five cardiac myxomas were studied for the autophagic markers LC3B and p62/sequestosome 1 and were compared with markers of the immune microenvironment. RESULTS: Most myxomas showed expression of both autophagic markers. We found a positive correlation between LC3B and PD-L1, as well as CD163, and a negative correlation between LC3B and CD8, CD20, CD138, and CD117 infiltration. CONCLUSION: Our data not only confirm the presence of autophagic markers within cardiac myxomas but also suggest a possible association with their immune microenvironment.

Senescence, immune microenvironment, and vascularization in cardiac myxomas.

AIMS: Cardiac myxomas are rare tumors of incompletely elucidated pathogenesis. The aim of this study is to explore the possible presence of a senescence phenotype in cardiac myxomas, associated with an inflammatory and vasculogenic tumor microenvironment. METHODS AND RESULTS: This is a retrospective study of 29 cardiac myxomas with immunohistochemical detection of various inflammatory, vascular, and senescence markers. We show that all myxomas contain tumor cells in senescence overexpressing p16, and a fraction of senescent endothelial cells. Macrophages are the principal inflammatory cell population, followed by cytotoxic T cells, with fewer plasma cells, mastocytes, and B lymphocytes. These populations are found in different intratumoral localizations. Larger tumor volume is associated with a lower percentage of myxoid matrix, higher cellularity, higher macrophage, and lower number of mast cells as well as higher PD-L1 expression by inflammatory cells. Higher vascular density is associated with higher percentage of B cells, a lower number of macrophages and higher number of mastocytes, and lower PD-L1 expression by inflammatory cells. Tumors with higher vascular density and higher cellularity show higher amounts of p16 senescent endothelial cells. CONCLUSIONS: Myxoma tumor cells are in senescence and reside inside a tumor microenvironment with a distinct inflammatory profile rich in macrophages and cytotoxic T cells, and a rich vasculature, probably attributed to a senescence-associated secretory phenotype.

Occult primary cardiac lymphomas causing unexpected/sudden death or acute heart failure.

Three cases of unexpected/sudden death (N = 2) or acute heart failure (N = 1) were investigated in our centre. The first patient died unexpectedly after surgery for cardiac tamponade and constrictive pericarditis; at autopsy, gross features mimicked a pericardial mesothelioma. The second patient died suddenly after recovering from a respiratory insufficiency episode; autopsy revealed an epicardial mass encircling the right coronary artery. The third patient presenting symptoms mimicked a fulminant myocarditis and she underwent endomyocardial biopsy. In all cases, histology disclosed a diffuse large B cell non-Hodgkin lymphoma, localized to the pericardium together with the right ventricle and the conduction system, to the epicardium and the right coronary artery or to the myocardium, respectively. Histology was crucial for the diagnosis, the atypical presentation favouring other diagnostic hypotheses. Although primary cardiac lymphoma is uncommon and usually shows a sub-acute onset, it may also cause unexpected/sudden death or acute heart failure.

Primary cardiac natural killer/T-cell lymphoma, a very rare form of lymphoma.

Extranodal natural killer/T-cell lymphoma is a rare non-Hodgkin lymphoma that is divided into nasal, non-nasal, and aggressive/leukemia subtypes, according to anatomic origin and clinical manifestations, with each subtype carrying a different prognosis. We present a case of primary cardiac natural killer/T-cell lymphoma with extension to other organs in a 38-year-old man, to highlight the role of imaging in categorizing nasal versus non-nasal types. This distinction has relevant implications for patient care because the non-nasal type has a much lower survival rate.

Successful Transcatheter Diagnosis and Medical Treatment of Right Atrial Involvement in IgG4-related Disease.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder characterized by lymphoplasmacytic infiltration of numerous IgG4-positive plasma cells, leading to fibrous thickening in the affected tissue. Typical cardiovascular manifestations of IgG4-RD are periaortitis, coronary arteritis, and pericarditis. Rare cases of myocardial involvement in IgG4-RD have been reported, but surgical resection or open biopsy was required for the diagnosis in those cases. Here, we report a case in which percutaneous transcatheter biopsy under the guidance of intracardiac echocardiography was useful for diagnosis of IgG4-RD manifested as an intracavitary right atrial mass, extending into the superior vena cava. Successful transcatheter diagnosis of myocardial involvement of IgG4-RD led to immediate favorable response to steroid therapy. Including the present case, previous IgG4-RD cases with myocardial involvement are reviewed to delineate its clinical characteristics.

Innate immunity in cardiac myxomas and its pathological and clinical correlations.

Cardiac myxomas are the most common benign cardiac tumor. We investigated the immunohistochemical properties of 11 surgically excised cardiac myxomas, in order to analyze the correlation between macrophages and mast cell populations and clinical parameters. CD68+/CD163-/iNOS- (M0) cells represent the most abundant macrophage phenotype; however, CD68+/CD163+ cells (M2) were also frequent. CD68+/iNOS+ (M1) elements were rare. Mast cells, defined as a population of c-kit (CD117)+ and/or tryptase+ cells were also detected. Statistical analysis showed significant correlations between c-kit (CD117)+ and tryptase, CD68 and erythrocyte sedimentation rate (ESR), ESR and red blood cell count (RBC), and prothrombin time and platelet count. The inverse correlation between RBCs in peripheral blood and ESR suggested that anemia associated with chronic inflammatory disease is a noncasual event in patients suffering from cardiac myxoma. Mechanical hemolysis may be only a minor component of anemia, according to the lack of correlation between echographic surface and RBCs. Moreover, tumor size did not correlate with ESR, showing that inflammatory state may depend from both tumor cells population and inflammatory infiltrate. In the future, modulation of macrophage polarization in cardiac myxomas might represent important therapeutic target.

Lymphocyte-rich capillary-cavernous hemangioma of the mitral valve: a case report and review of the literature.

Valvular hemangioma incidence is extremely low. In this report, we describe a 62-year-old man who presented with mild edema of the lower limbs. An echocardiogram revealed an incidental 1.3-cm diameter mass on the anterior mitral valve leaflet for which he underwent surgical resection and mitral valve replacement. Histopathological examination showed a lymphocyte-rich capillary-cavernous hemangioma. The exuberant lymphoid stroma is unusual for hemangioma and represents an undescribed pattern of cardiac hemangioma. Including the present report, only 13 cases of mitral valve hemangioma have been reported to date. Most patients are adult. Mitral hemangioma originates in the atrial aspect of the valve and involves more commonly the anterior leaflet. The average maximum diameter of the lesion is 1.7 (S.D.=0.75) cm. Pure cavernous hemangioma is the predominant type of mitral hemangioma. Most of them are described as pedunculated or polypoid. Surgical excision appears to be curative. Recurrences have not been reported. Lymphocyte-rich cardiac hemangioma represents a peculiar type of hemangioma which should be included in the differential diagnosis of other vascular lesions.

EBV lymphoproliferative-associated disease and primary cardiac T-cell lymphoma in a STK4 deficient patient: A case report.

RATIONALE: Primary cardiac lymphoma (PLC) is an extremely uncommon malignancy. PCL is more common in secondary immunodeficient patients. In this report, we describe a unique case of PLC who had been diagnosed as a STK4 deficient patient. This case is the first Primary immunodeficiency (PID) patient developing PCL in the world. PATIENT CONCERNS: An eleven-year-old girl, a known case of PID, was referred to the pediatric cardiology department because of chest pain and dyspnea. Her CXR revealed cardiomegaly without mediastinal involvement and the echocardiography showed a mild pericardial effusion and cystic-shape echogenic masses. DIAGNOSES: After a period of missed follow up, she presented with respiratory distress following with syncope at the clinic because of a pressure effect of a large mass on the right ventricular outflow tract (RVOT) .An emergency operation was done for debulking of the tumors and resolving of RVOT obstruction. Biopsy and immunohistochemical staining was revealing "T-cell lymphoma", non-Hodgkin's type. INTERVENTIONS: Chemotherapy was done with cyclophosphamide, methotrexate, adriamycine, vincristine, hydrocortisone and allopurinol. OUTCOMES: The tumors shrank after chemotherapy initiation and she stayed stable for almost one month. Finally, she developed sever thrombocytopenia during her chemotherapy and died because of lung hemorrhage two months after her operation. LESSONS: Although PCL is very rare, it must be considered in the differential diagnosis of intracardiac mass or refractory pericardial effusions, especially in PIDs which are widely known for developing EBV-associated diseases such as lymphoma.

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.

Primary Cardiac Lymphoma in an Immunocompetent 71-Year-Old Man.

Isolated cardiac lymphomas are very rare, especially in immunocompetent patients. As a consequence, little is known about the best therapeutic management and about patients' outcomes in these cases. Diffuse large B-cell lymphoma is the most frequent subtype; anthracycline-based chemotherapy has been the most successful treatment. We describe the case of a primary cardiac lymphoma in an immunocompetent 71-year-old man. As of December 2015, the patient had been in clinical remission for 2 years. The most relevant literature on primary cardiac lymphoma is reported and discussed.

Esophageal ulcer of unknown origin complicated by left atrial myxoma.

Myxoma induces the onset of paraneoplastic syndromes by excreting various humoral mediators and is therefore known to present with diverse symptoms. A 40-year-old woman was admitted to our hospital for the treatment of an esophageal ulcer, the cause of which could not be identified on various examinations. Notably, a left atrial tumor was incidentally found on chest enhanced computed tomography. The esophageal ulcer, which was intractable to conventional therapy, improved with the administration of 5-aminosalicylate, a drug known to inhibit IL-1ß. This inhibitory action effectively suppressed the development of myxoma-induced paraneoplastic syndrome.

AIDS-Associated Cardiac Lymphoma-A Review: Apropos a Case Report.

Despite treatment with potent and effective combination antiretroviral medications, the incidence of non-Hodgkin lymphoma (NHL) in the population living with HIV/AIDS remains significantly higher than that in noninfected individuals. The majority of the HIV-infected patients with NHL present with advanced stage extranodal disease of the B-cell phenotype. Lymphomas are the second most common tumors involving the heart in HIV-infected patients. Although the heart may serve as the primary focus of the lymphoma, in most HIV-related cases, cardiac lymphomatous involvement is part of a metastatic process that originated elsewhere.

T-cell prolymphocytic leukemia with extensive cardiovascular infiltrate leading to multiple myocardial infarctions and cardiac death.

Lymphocytic neoplasm involving the heart is not common and usually presents with pericardial effusion or focal myocardial infiltration. Myocardial infarctions due to leukemic infiltration of the coronary arteries are rarely reported. We present the case of a 52-year-old Guatemalan man with a one-year history of untreated T-cell prolymphocytic leukemia. He was admitted to our hospital for chemotherapy and evaluation of a pulmonary cavitary lesion by wedge resection. During sedation, the patient experienced acute respiratory failure and hypovolemic shock, from which he could not be resuscitated. Autopsy revealed that leukemic cells extensively infiltrated the aorta, myocardium, and coronary arteries. The lumina of the 3 major coronary artery branches showed 70% to 95% stenosis, with multifocal remote myocardial infarctions. Tumor cells were also detected in the lungs and other organs. The acute cardiorespiratory insufficiency secondary to leukemia-particularly the extensive infiltration of the coronary arteries and myocardium, and the multiple myocardial infarctions-eventually resulted in cardiac death.

Benefits and limitations of multimodality imaging in the diagnosis of a primary cardiac lymphoma.

Primary cardiac tumors are far rarer than tumors metastatic to the heart. Angiosarcoma is the primary cardiac neoplasm most frequently detected; lymphomas constitute only 1% of primary cardiac tumors. We present the case of a 55-year-old woman with a recently diagnosed intracardiac mass who was referred to our institution for consideration of urgent orthotopic heart transplantation. Initial images suggested an angiosarcoma; however, a biopsy specimen of the mass was diagnostic for diffuse large B-cell lymphoma. The patient underwent chemotherapy rather than surgery, and she was asymptomatic 34 months later. We use our patient's case to discuss the benefits and limitations of multiple imaging methods in the evaluation of cardiac masses. Certain features revealed by computed tomography, cardiac magnetic resonance, and positron emission tomography can suggest a diagnosis of angiosarcoma rather than lymphoma. Cardiac magnetic resonance and positron emission tomography enable reliable distinction between benign and malignant tumors; however, the characteristics of different malignant tumors can overlap. Despite the great usefulness of multiple imaging methods for timely diagnosis, defining the extent of spread and the hemodynamic impact, and monitoring responses to treatment, we think that biopsy analysis is still warranted in order to obtain a correct histologic diagnosis in cases of suspected malignant cardiac tumors.

Massive pericardial effusion caused by "inflammatory myofibroblastic tumour" in a 3-month-old child.

Tumours originating from cardiac tissues are rarely encountered during childhood, and fortunately most of these tumours are benign in nature. Inflammatory myofibroblastic tumour, which has unique clinical, pathological, and molecular characteristics, is a relatively new entity compared with previously mentioned tumoural processes originating from the heart. Most of the cardiac intima-media thickness patients are in the age group of 4 months to 17 years. This rarely seen tumoural process has not been subject of any specific research and the prognosis is not well known. Here we present the case of a 3-month-old child who was admitted to our outpatient clinic with massive pericardial effusion and who has shown excellent progress after surgical resection of over 1 year.

Primary cardiac diffuse large B-cell lymphoma, non-germinal centre B-cell type in an immunocompetent woman.

Primary cardiac lymphomas are extremely rare and always occur in immunodeficient persons. Here, we report a very rare case of a primary cardiac diffuse large B-cell lymphoma in an immunocompetent 41-year old woman. Echocardiography and computed tomography revealed a mass measuring 74 mm 49 mm in the right atrium. No tumour formations were recognized in other organs. Laboratory data did not reveal immunosuppression, and the human immunodeficiency virus was negative. Histological and immunohistochemical studies showed that the cardiac tumour was diffuse large B-cell lymphoma, non-germinal centre B-cell type. Epstein-Barr Virus-encoded small RNA was negative by in situ hybridization. The patient died 6 months after the operation.