Project description:A right atrial (RA) mass was incidentally found by transthoracic echocardiography in a 79-year-old man with atrial fibrillation rhythms but without a history of anticoagulation. Transesophageal echocardiography revealed a pedunculated immobile mass in the RA appendage. In addition, some calcification was detected in computed tomography. The mass was excised, and pathological examinations revealed organized thrombosis. Accordingly, in the presence of predisposing factors, thrombi, which may mimic some imaging features of tumors, should be considered in the differential diagnosis of RA masses.
Project description:This report describes a patient with severe mitral stenosis who underwent mitral valve replacement. After completion of cardiopulmonary bypass, an unexpected finding of a right atrial mass was noticed on transesophageal echocardiography. The actual finding, possible differential diagnosis, and the management strategy are discussed.
Project description:We present a case of an intensely hypermetabolic intracavitary cardiac mass, standardized uptake values max 44.4, that was pathologically proved to be organizing and organized thrombus, negative for tumor. Our patient had previous right atrial mass resection 2 years prior that was pathologically described as either thrombus or infarcted atrial myxoma. She had since been on lifelong controlled anticoagulation; and on routine follow-up imaging, she had recurrent slow growth of a new right atrial mass. During a later hospital admission for chest pain, the mass was evaluated on both transthoracic and transesophageal echo cardiogram, which could not differentiate thrombus vs neoplasm. Cardiac magnetic resonance imaging was equivocal for mass enhancement. The patient underwent fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) evaluation, which revealed intensely hypermetabolic activity within the mass concerning for malignancy, potentially an aggressive tumor. Subsequently, the mass was surgically excised for pathological diagnosis.
Project description:Refractory and/or recurrent Ewing's sarcoma (EWS) remains a clinical challenge because the disease's resistance to therapy makes it difficult to achieve durable results with standard treatments that include chemotherapy, radiation, and surgery. Recently, insulin-like-growth-factor-1-receptor (IGF1R) antibodies have been shown to have a modest single-agent activity in EWS. Patient selection using biomarkers and understanding response and resistance mechanisms in relation to IGF1R and mammalian target of rapamycin pathways are areas of active research. Since EWS has a unique tumor-specific EWS-FLI1 t(11;22) translocation and oncogenic fusion protein, inhibition of EWS-FLI1 transcription, translation, and/or protein function may be key to eradicating EWS at the stem-cell level. Recently, a small molecule that blocks the protein-protein interaction of EWS-FLI1 with RNA helicase A has been shown in preclinical models to inhibit EWS growth. The successful application of this first-in-class protein-protein inhibitor in the clinic could become a model system for translocation-associated cancers such as EWS.
Project description:The presence of left atrial thrombus is a contraindication to cardioversion or catheter ablation in patients with atrial fibrillation, due to the increased risk of systemic thromboembolism. Management of this situation includes changes in the anticoagulation regimen and repeat imaging tests. Accurate diagnosis of left atrial appendage thrombus is therefore essential but can sometimes be challenging. Multiple imaging modalities may sometimes be required in the setting of anatomical variations of the left atrial appendage and surrounding structures. We present the case of a patient awaiting ablation for atypical atrial flutter, who underwent a transthoracic echocardiogram that showed an echodense, mobile structure within the vicinity of the left atrial appendage, suggesting a possible thrombus. A cardiac CT demonstrated the image to correlate with an epicardial fat pad within the transverse sinus.
Project description:Prion-like domains have emerged as important drivers of neurodegenerative disease. Now, Boulay et al. establish that the translocated prion-like domain of the oncogenic EWS-FLI1 fusion protein enables phase-separation events, which inappropriately recruit chromatin-remodeling factors to elicit the aberrant transcriptional programs underlying Ewing's sarcoma.
Project description:The hallmark of Ewing's sarcoma (EWS) is a translocation--t(11;22)(q24;q12)--that most frequently results in the EWS/FLI1 aberrant chimeric gene. Because EWS afflicts young patients, it stands out among the diverse sarcoma subtypes. The frontline, standard-of-care cytotoxic chemotherapy regimens produce minimal benefit in patients with metastases at presentation or those with relapsed disease. While the outcomes of chemorefractory EWS patients are generally poor, recent developments have led to the promising use of targeted therapy. Specifically, inhibition of insulin-like growth factor 1 receptor (IGF1R) signaling and the mammalian target of rapamycin (mTOR) pathways has emerged as a targeted therapy in EWS, with select patients experiencing dramatic therapeutic responses. However, targeted therapies in general, and these responders in particular, are faced with the ultimate conundrum of eventual resistance. To optimize response, combining IGF1R and mTOR inhibitor-based regimens with chemotherapy in the upfront setting in newly diagnosed high-risk EWS may clarify the true benefit of IGF1R inhibitors in these patients. Another option is to explore novel targeted multikinase inhibitors and poly(ADP-ribose) polymerase (PARP) inhibitors, which have experienced a surge in supporting preclinical data. Drugs inhibiting the downstream targets of EWS/FLI1 are also in preclinical development. However, ultimately, the underlying biomarker correlates of resistance and response must be delineated along with ways to overcome them. Novel agents, together with integration of advances in multimodal approaches (including surgery and radiation), as well as offering targeted therapies early in the disease course represent new strategies for confronting the challenges of EWS.
Project description:A 20-year-old female presented to the Pulmonary Medicine Department with complaints of fever, left sided chest pain and progressive dyspnoea of four months duration. Radiological examination revealed a mass lesion with massive pleural effusion and rib erosion. Histopathology showed neoplastic cells with scanty cytoplasm, hyperchromatic nuclei and rosette formation suggestive of Ewing sarcoma. The rarity of this tumor and its unusual presentation prompted this report.
Project description:Despite longstanding reliance upon monolayer culture for studying cancer cells, and numerous advantages from both a practical and experimental standpoint, a growing body of evidence suggests that more complex three-dimensional (3D) models are necessary to properly mimic many of the critical hallmarks associated with the oncogenesis, maintenance and spread of Ewing's sarcoma (ES), the second most common pediatric bone tumor. And as clinicians increasingly turn to biologically-targeted therapies that exert their effects not only on the tumor cells themselves, but also on the surrounding extracellular matrix, it is especially important that preclinical models evolve in parallel to reliably measure antineoplastic effects and possible mechanisms of de novo and acquired drug resistance. Herein, we highlight a number of innovative methods used to fabricate biomimetic ES tumors, encompassing both the surrounding cellular milieu and the extracellular matrix (ECM), and suggest potential applications to advance our understanding of ES biology, preclinical drug testing, and personalized medicine.