Neuroblastoma is the second most common solid tumor in children. Most tumors arise in the adrenal glands or paravertebral region. Rarely, patients present with metastatic disease but no primary site can be found despite extensive imaging. We report here a patient with a large periorbital bone metastasis and bone marrow involvement but with no known primary site.
A man in his late 70s with chronic myelomonocytic leukaemia presented for evaluation of acute leukaemic transformation and initiation of cytoreductive therapy after being found to have asymptomatic hyperleucocytosis. Within 24 hours, the patient developed vasopressor-refractory shock, severe lactic acidosis and multiorgan failure. Serial echocardiographic assessments revealed interval enlargement of the right ventricle with development of the McConnell’s sign, and abdominal CT showed diffuse bowel wall thickening, likely due to ischaemia. CT angiography excluded pulmonary embolism or occlusion of intra-abdominal arteries. Despite aggressive care, the patient died from cardiovascular collapse within 8 hours of the onset of hypotension. An autopsy revealed extensive infiltration of early myeloid cells in pulmonary, myocardial, hepatic and intestinal microvasculature. This case illustrates different mechanisms by which leucostasis causes acute cardiovascular collapse and stresses the emergent nature of this diagnosis.
The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.
Introduction: Optical imaging has the potential to revolutionize cardiothoracic surgery by allowing for the real-time visualization of structures often inadvertently damaged due to inadequate visibility. The cardiac conduction system (CCS) consists of specialized cells embedded within the heart that are essential for cardiac function yet indistinguishable from heart muscle tissue. Intraoperative CCS injury is a major complication in cardiac surgery, representing a significant source of morbidity and mortality. To date, there exists no intraoperative method to visualize the CCS. Hypothesis: We hypothesized that unique, CCS-specific cell surface markers could be used for the in vivo labelling of the CCS. Objectives: Use single-cell RNA sequencing (scRNAseq) to discover cell surface markers that may serve as the basis for generating optical imaging agents for real-time CCS visualization. Methods/Results: Gene expression analysis of a comprehensive scRNAseq dataset of the entire murine CCS revealed significant enrichment of a host of CCS-specific cell surface genes. A subset of genes were subsequently validated in the CCS of mice and/or human tissue. In total, 7 novel cell surface markers were confirmed to have unique expression patterns throughout or within distinct components of the CCS. Next, optical imaging agents were created consisting of a near-infrared (NIR) dye conjugated to antibodies directed against two distinct CCS-specific cell surface markers. Each optical imaging agent demonstrated high sensitivity and specificity in labeling the entire CCS in vivo following a single intravenous injection in mice. Specificity was confirmed within intact, whole hearts using both closed-field NIR imaging and whole mount immunolabeling with volume imaging (iDISCO+). Dosage, timecourse and biodistribution analyses were performed as well as safety validation by surface ECG. Conclusions: In summary, we coupled scRNAseq with optical imaging to create novel tools for the real-time visualization of a complex tissue substructure. We provide a proof-of-principle for broadening the scope of optical imaging but also address a significant unmet clinical need, laying the foundation for translational opportunities in cardiac intervention and imaging.
We report a child with thrombotic thrombocytopenic purpura (TTP) secondary to systemic lupus erythematosus. The diagnosis was confirmed by low ADAMTS13 activity (<5%) along with the presence of a low titer inhibitor. Her clinical course was complicated by systemic lupus erythematosus, immunosuppressant therapy, and septic shock. She responded to plasma exchange and ADAMTS13 activity levels recovered. This case illustrates the heterogeneity of TTP and the difficulty of making a diagnosis of TTP. ADAMTS13 activity assay can be useful in the differential diagnosis of diseases with clinical features of thrombotic microangiopathy in pediatric patients. However, treatment needs to be decided carefully case-by-case.
Abstract Blockage of blood flow in arteries or veins by blood clots can lead to serious medical conditions. Mechanical thrombectomy (MT), minimally invasive endovascular procedures that utilize aspiration, stent retriever, or cutting mechanisms for clot removal have emerged as an effective treatment modality for ischemic stroke, myocardial infarction, pulmonary embolism, and peripheral vascular disease. However, state-of-the-art MT technologies still fail to remove clots in approximately 10% to 30% of patients, especially when treating large-size clots with high fibrin content. In addition, the working mechanism of most current MT techniques results in rupturing or cutting of clots which could lead to clot fragmentation and distal emboli. Here, we report a new MT technology based on an unprecedented mechanism, in which a milli-spinner mechanically debulks the clot by densifying its fibrin fiber network and discharging red blood cells (RBCs) to significantly reduce the clot volume and facilitate complete clot removal. This mechanism is achieved by the spin-induced compression and shearing of the clot. With the computational fluid dynamics guided structural design of the milli-spinner, we demonstrate its effective clot-debulking performance with clot volumetric reduction of up to 90% on various sizes of clots and on diverse clot compositions ranging from RBC-rich soft clots to fibrin-rich tough clots. Milli-spinner MT in both in-vitro pulmonary and cerebral artery flow models and in-vivo swine models demonstrate high-fidelity revascularization. The milli-spinner MT is the first reported mechanism that directly modifies the clot microstructure to facilitate clot removal, which also results in markedly improved MT efficacy compared to the existing MT mechanisms that are based on clot rupturing and cutting. This technology introduces a unique mechanical way of debulking and removing clots for future MT device development, especially for treatment of ischemic stroke, pulmonary emboli, and peripheral thrombosis.
