Prognostic Factors for Long-Term Survival after Surgical Resection of Primary Cardiac Sarcoma.

BACKGROUND: Primary cardiac sarcoma (CS) is an extremely rare disease. This study aims to identify possible prognostic factors for long-term survival. METHODS: A total of 17 consecutive patients who were treated for primary CS between 2003 und 2018 at two cardiac centers were investigated. Clinical data and histological characteristics of the tumors were analyzed. Long-term follow-up of all patients were performed. RESULTS: The median age was 54 years (range: 23-74). The tumors originated from the left side of the heart in nine patients. Histologically, there were four angiosarcomas, three intimal sarcomas, and three synovial sarcomas. One- and 7-year survivals were 81.9 and 18.2%, respectively. Low expression levels of Ki-67 tended to be associated with increased survival (log-rank p = 0.06). Adjuvant chemotherapy but not radiotherapy regardless of existing metastases was associated with significantly increased survival (log-rank p = 0.001). CONCLUSION: Angiosarcoma was the most common type of CS. The survival of CS patients is poor but prognostic factors, such as Ki-67, may help estimate the course of the disease. Survival could be improved significantly with chemotherapy.

[Cardiac intimal sarcoma: A case report of a rare tumor with peculiar histopathological findings]. / Le sarcome intimal cardiaque : tumeur rare illustrée par un cas de présentation histopathologique inhabituelle.

Primary cardiac sarcomas are rare tumors with poor prognosis. Intimal sarcoma, a mesenchymal malignant tumor described mainly in the great vessels, may rarely involve the heart. Herein we describe the case of a 70-years-old female who was found to have a left atrial mass during an investigation of a new onset dyspnea. The patient underwent surgery and the resected mass was found to be an intimal sarcoma. The objectives of this report were to describe a case of this rare disease entity and to discuss its pathological and molecular findings based on relevant literature.

An optimized procedure for on-tissue localized protein digestion and quantification using hydrogel discs and isobaric mass tags: analysis of cardiac myxoma.

An optimized workflow for multiplexed and spatially localized on-tissue quantitative protein analysis is here presented. The method is based on the use of an enzyme delivery platform, a polymeric hydrogel disc, allowing for a localized digestion directly onto the tissue surface coupled with an isobaric mass tag strategy for peptide labeling and relative quantification. The digestion occurs within such hydrogels, followed by peptide solvent extraction and identification by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-MS/MS). Since this is a histology-directed on-tissue analysis, multiple hydrogels were placed onto morphologically and spatially different regions of interest (ROIs) within the tissue surface, e.g., cardiac myxoma tumor vascularized region and the adjacent hypocellular area. After a microwave digestion step (2 min), enzymatically cleaved peptides were labeled using TMT reagents with isobaric mass tags, enabling analysis of multiple samples per experiment. Thus, N = 8 hydrogel-digested samples from cardiac myxoma serial tissue sections (N = 4 from the vascularized ROIs and N = 4 from the adjacent hypocellular areas) were processed and then combined before a single LC-MS/MS analysis. Regulated proteins from both cardiac myxoma regions were assayed in a single experiment. Graphical abstract The workflow for histology-guided on-tissue localized protein digestion followed by isobaric mass tagging and LC-MS/MS analysis for proteins quantification is here summarized.

Cardiac myxoma with glandular differentiation: an immunohistochemical and ultrastructural study.

A case of cardiac myxoma with glandular differentiation is reported. The patient did not have elements of the Carney triad or syndrome. The tumor was mainly composed of characteristic stellate cells in a focally collagenized, myxoid stroma, along with aggregates of glandular-forming epithelial cells, with mucin-containing intra- and intercellular lumina. Ultrastructurally, these gland spaces displayed short, straight microvilli and junctional complexes. The epithelial cells were positive for cytokeratin 7 and negative for cytokeratin 20. Calretinin was positive in the stellate cells and negative in the epithelial component. The potential origin from pluripotent mesenchymal cells or from seeded stem cells is hypothesized for glandular differentiation in myxomas. Further studies are required to unravel the relationship between stellate cells and the diverse heterologous components reported in these tumors.

Detection of herplex simplex virus-1 and -2 in cardiac myxomas.

The etiology of sporadic cardiac myxomas remains elusive. The tendency for these lesions to recur following resection, their immunopathological characteristics, along with their histological and molecular profile, may implicate the presence of an infective agent in this type of tumor. In this study, we investigated the presence of herpes simplex virus (HSV) DNA in a cohort of cardiac myxomas in a tertiary referral centre. Twenty-nine formalin-fixed paraffin-embedded (FFPE) sporadic cardiac myxomas were obtained, 17 of which were shown to be informative. These were compared to 19 macroscopically and microscopically normal heart tissue specimens. The detection of HSV-1 and -2 genomic sequences was achieved with the use of a combined nested PCR-Restriction Fragment Length Polymorphism methodology. The presence of HSV-1 and/or -2 DNA was demonstrated in 6 of 17 (35%) informative sporadic cardiac myxomas, whereas no HSV DNA was detected in normal heart tissues (P < 0.01). The existence of HSV-1/2 DNA in sporadic cardiac myxomas, along with its absence from normal heart tissues, reinforces the possibility that HSV infection might be involved in the development of these lesions. Our findings raise the point of anti-HSV medication postsurgically with a potential benefit in reducing the rate of recurrences.

Heart failure resulting from giant left atrial synovial sarcoma metastasis.

Synovial sarcoma metastasis affecting the heart and infiltrating the mitral valve is a very rare pathology. We report the case of a 44-year-old male treated with chemotherapy for atypical synovial sarcoma of the oral mucosa who presented to our clinic after cardiac decompensation with a presumptive diagnosis of myxoma of the left atrium. A large necrotic tumour positive for CK 22, EMA, CD 99 and BCL-2 but negative for translocation in COBRA-FISH analysis by break-apart probe could be excised and revealed a very rare subtype of synovial sarcoma metastasis arising from the endocard of the left atrium. The tumour was resected and the mitral valve reconstructed through ring annuloplasty.

Primary cardiac synovial sarcoma: a clinicopathological, immunohistochemical, and molecular genetics study of five clinical cases.

BACKGROUND: Primary cardiac synovial sarcoma was an exceedingly rare tumor that less reported. The study investigated the clinicopathologic, immunohistochemical, and molecular features of primary cardiac synovial sarcoma. METHODS: A total of five cardiac synovial sarcoma cases were assessed and reviewed using H&E, immunohistochemical and fluorescence in situ hybridization staining methods. Clinicopathological data were retrospectively analyzed and followed up. RESULTS: The cases occurred in four males and one female ranging in age from 23 to 48 years (mean, 32 years). The tumors were grossly large and solid (7.4-13.7 cm; mean 8.6 cm). Microscopically, clinical cases were biphasic (n = 2) and monophasic (n = 3) types and were diffusely immunoreactive for EMA, vimentin, and BCL-2. All cases demonstrated SS18 rearrangement by fluorescence in situ hybridization staining. Clinically, three patients died within 1 year after surgery, while one patient had bone metastasis and still carried the disease. One last patient underwent a heart transplant and survived without evidence of the disease. CONCLUSION: Cardiac synovial sarcoma was an aggressive tumor whose differentiation may be a continuous and complex morphologic spectrum. SS18 rearrangement demonstration by fluorescence in situ hybridization was decisive in our study for differential diagnosis of cardiac synovial sarcoma and other tumors. Cardiac synovial sarcoma usually endured poor survival rates. Patients in advanced stages may undergo heart transplantation as a means of improving their survival rates.

A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata.

Using novel antibodies of high avidity to--and specificity for--the constitutive desmosomal plaque protein, plakophilin-2 (Pkp2), in a systematic study of the molecular composition of junctions connecting the cells of soft tissue tumors, we have discovered with immunocytochemical, biochemical and electron microscopical methods, a novel type of adherens junctions in all 32 cardiac myxomata examined. These junctions contain cadherin-11 as their major transmembrane glycoprotein, which we could repeatedly show in colocalization with N-cadherin, anchored in a cytoplasmic plaque formed by α- and ß-catenin, together with the further armadillo-type proteins plakoglobin, p120, p0071 and ARVCF. Surprisingly, all adherens junctions of these tumors contained, in addition, another major armadillo protein Pkp2, hitherto known as an obligatory and characteristic constituent of desmosomes in epithelium-derived tumors. We have not detected Pkp2 in a series of noncardiac myxomata studied in parallel. Therefore, we conclude that this acquisition of Pkp2, which we have recently also observed in some mesenchymally derived cells growing in culture, can also occur in tumorigenic transformations in situ. We propose to examine the marker value of Pkp2 in clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic reagents.

Fibrin-associate diffuse large B-Cell lymphoma arising in a left atrial myxoma: A case report and literature review✰,✰✰.

We report a 60-year-old male with fibrin-associated diffuse large B-cell lymphoma (fa-DLBCL) in left atrial myxoma. Echocardiography showed a mass (63 mm × 33 mm) in the left atrium. Histological inspection indicated fa-DLBCL on the surface of atrial myxoma incidentally, together with extensive fibrinous like exudation on myxoma surface. Malignant cells were localized in solid sheets and nests at the peripheral area of the fibrinous exudation which were positive for B-lineage markers (CD20+, CD79a+, PAX-5+) and in situ hybridization of EBV-encoded RNA (EBER). PCR amplification showed clonal rearrangement of immunoglobulin heavy chain (IgH) genes. The patient was still alive with no recurrence in the 35-month follow-up after surgery. We also did a detailed clinicopathological analysis and literature review, which indicated that fa-DLBCL was a heterogeneous entity.

Primary cardiac epithelioid angiosarcoma with frond-like features: a rare and ominous radiological mimicker of benign cardiac tumors.

Most primary cardiac tumors are benign neoplasms, which generally can be differentiated from malignant neoplasms via certain radiological features. We present briefly a case of a 26-year-old man undergoing resection of a right atrial mass that based on preceding radiologic findings represent a myxoma. After pathologic examination, the lesion was determined to be an epithelioid angiosarcoma with unique frond-like architecture and multiple pedicular attachments to the atrial wall.

Primary cardiac malignant peripheral nerve sheath tumor: a case report.

Malignant peripheral nerve sheath tumors are rare sarcomas of children and adolescents, and they are aggressive tumors with a high rate of local recurrence. Here we report a case of a primary cardiac malignant peripheral nerve sheath tumor without neurofibromatosis type I. A 53-year old woman presented having had cough, expectoration, and dyspnea for 20 days and was found to have a heart-involving tumor diagnosed as a malignant peripheral nerve sheath tumor, a rare cardiac sarcoma of 9 × 4.5 × 3 cm in size. The patient underwent a successful resection of the tumor but died 14 months postoperative. We report this case for its rarity and peculiar mode of morphologic and immunohistochemical presentation.

Malignant small round cell tumor of the heart: a diagnostic dilemma.

We report a rare malignant small round cell tumor of the heart in a 26-year-old woman. She had been symptomatic 15 days after vaginal delivery. Immunohistochemistry revealed divergent differentiation; hence, the tumor was designated as desmoplastic small round cell tumor. This is the first report of such a tumor in the heart.

Cardiac Metastases from Malignant Melanoma: The "Charcoal Heart".

The column in this issue is supplied by Herbert L. Fred, M.D., M.A.C.P., and Hendrik A. van Dijk, both from McGovern Medical School-UT Health, Houston, Texas. Dr. Fred is emeritus professor of medicine and a well-known medical educator and diagnostician. A graduate of Johns Hopkins University School of Medicine, he has authored just under 500 publications including six books. Mr. van Dijk, former director of the University of Texas Health Science Center Medical School's Graphic Communications Group, has devoted 50 years to biomedical communications and is a national expert in that field.

Primary intracardiac leiomyoma arising from cardiomyocyte progenitors at the right ventriculoseptal interface: case report with literature review.

Primary cardiac neoplasms are rare and are usually benign myxomas and rhabdomyomas. Cardiac leiomyomas are usually seen as a part of the spectrum of intravenous leiomyomatosis or benign metastasizing leiomyoma. De novo occurrence of primary intracardiac leiomyomas (PICL) is a rarity. Herein we describe a 14-year-old boy presenting with intermittent dyspnea for 2 years, with a large right ventricular mass suggestive of myxoma on transthoracic echocardiography, without any extracardiac lesions. Histology and immunohistochemistry of the tumor excised under cardiopulmonary bypass confirmed a PICL arising at the cardiomyocyte-smooth muscle septal interface. A review of existing literature highlights an increased incidence in young patients and an overwhelming right ventricular anatomical predilection. Abnormalities in the multipotent cardiac progenitor cells of the second heart field may provide a potential microenvironment for the histogenesis of PICL.

Cardiac angiosarcoma: histopathologic, immunohistochemical, and cytogenetic analysis of 10 cases.

Angiosarcoma (AS) is the most common cardiac sarcoma with differentiation, and is poorly characterized from a molecular genetic standpoint. Prognosis remains poor, owing to several factors including aggressive tumor biology, poor response to adjuvant therapy, and lack of targeted therapy. The clinical, pathologic and molecular cytogenetic features were studied in ten cardiac AS surgically resected at Mayo Clinic (1994-2015) using a whole-genome, single-nucleotide polymorphism-based platform (OncoScan). Mean patient age was 47.8 years, male/female ratio was 1:1.5, and overall median survival was 5.2 months. The most common location was the right atrium (n=7), with one case each occurring in the epicardium, pericardium, and right ventricle. No patients had received thoracic irradiation. The most common morphology was spindle cell (n=8), with one case each of epithelioid and biphasic. ERG was the most sensitive vascular marker, with diffuse immunoreactivity in all cases. Several recurrent (present in at least 3 cases) aberrations were identified, including trisomies in chromosomes 4, 8, 11, 17, 20, as well as 1q+, and homozygous deletion of CDKN2. Patients who received adjuvant therapy had longer overall survival than those who did not (median 13.4 vs 3.2 months; P=.0283). There were no significant associations between tumor location, histology, immunohistochemical findings, cytogenetic profile, and clinical outcome; however, there was a trend towards improved overall survival in patients with tumors harboring 1q+(median 31.8 vs 3.7 months, P=.06). This study confirms recurrent cytogenetic aberrations in cardiac AS, some of which may have prognostic or predictive implications.

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.

Atrial angioleiomyoma with myopericytoma-like features: a case report.

A 66-year-old female patient was referred to our hospital for resection of a right atrial mass. Four months earlier, she had suffered an acute cerebrovascular accident due to occlusion of the sylvian segment of the right middle cerebral artery from atheromatous tight stenosis in the right internal carotid artery. Later, investigations with transthoracic and transesophageal echocardiography revealed a 3.4-cm right atrial mass that was resected surgically. Microscopic evaluation revealed a well-circumscribed nodular tumor, located within the interatrial septum, and corresponding to an angioleiomyoma (ALM). This tumor differs histologically from atrial myxoma. ALM is a ubiquitous benign tumor but has never been reported to occur in the atrium. ALM can mimic cardiac myxoma and should be considered in the differential diagnosis of atrial tumors.

Cardiac calcified amorphous tumor in a hemodialysis patient.

We present a case of cardiac calcified amorphous tumor, a rare intracardiac non-neoplastic tumor, in a hemodialysis patient. A 72-year-old woman with no history of thromboembolic, malignant, or inflammatory disease presented with dyspnea. Echocardiography revealed a highly echoic, slightly mobile mass with an acoustic shadow originating from the mitral subvalvular apparatus, extending to the left ventricular outflow tract. She underwent surgical resection of the mass through the aortic valve, which was easily excised from the papillary muscle and chordae tendineae. Histopathologic examination revealed nodular calcium deposits on a background of amorphous degenerated fibrin material, consistent with calcified amorphous tumor.

Ruptured pericardial perivascular epithelioid cell tumor (PEComa) leading to sudden death: an autopsy case report and review of the literature.

A 30-year-old man with past medical history of atrial fibrillation/flutter passed away after presenting with sudden-onset cardiac dysfunction. The postmortem examination revealed cardiac tamponade secondary to rupture of a 7.2-cm pericardial perivascular epithelioid cell tumor (PEComa). The tumor grossly appeared to arise from the transverse pericardial sinus and focally penetrated the epicardium of the right atrium. Microscopically, it was composed of predominately spindle cells with low nuclear grade, no pleomorphism, or readily apparent mitoses. Immunohistochemistry revealed cytoplasmic reactivity for HMB-45, desmin, and smooth muscle actin. Electron microscopic findings were characterized by melanosome-like structures intermixed with intermediate filaments and abundant stacked endoplasmic reticulum. The present case is unique among previously reported pericardial/myocardial PEComas as a first example resulting in unexpected cardiac tamponade and sudden cardiac death.