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Leukemia Nov 2023Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders....
Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n = 120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and aberrant differentiation. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure.
Topics: Humans; Histones; Trans-Activators; Interferons; Cell Line, Tumor; Mutation; Signal Transduction; Chromatin; Lymphoma, B-Cell
PubMed: 37648814
DOI: 10.1038/s41375-023-02013-9 -
Ear, Nose, & Throat Journal Dec 2023Ganglioneuroma is a rare benign tumor originating in the sympathetic ganglia, composed of differentiated ganglion cells, nerve sheath cells, and nerve fibers, which tend... (Review)
Review
Ganglioneuroma is a rare benign tumor originating in the sympathetic ganglia, composed of differentiated ganglion cells, nerve sheath cells, and nerve fibers, which tend to occur in the posterior mediastinum, adrenal gland, retroperitoneal, and other locations, occurring in the head and neck is relatively rare, and parapharyngeal space involvement is extremely rare. In our report, we present 2 adult male patients whose preoperative imaging and fine needle cytology did not confirm the diagnosis of a parapharyngeal space mass and who completely resected the tumor through a combined cervical and oral approach. Finally, pathology confirmed ganglioneuroma; we also reviewed the English articles on parapharyngeal ganglioneuroma over the past 40 years, and summarized the diagnostic and treatment characteristics of parapharyngeal ganglioneuroma in combination with our cases to improve understanding of the disease.
Topics: Adult; Humans; Male; Parapharyngeal Space; Ganglioneuroma; Neck; Needles
PubMed: 36450599
DOI: 10.1177/01455613221142658 -
Topics in Magnetic Resonance Imaging :... Aug 2023This report presents imaging from a mediastinal mass in a patient with colon cancer. At baseline and surveillance chest computed tomography examinations, it was...
This report presents imaging from a mediastinal mass in a patient with colon cancer. At baseline and surveillance chest computed tomography examinations, it was characterized as a pericardial cyst. However, during chemotherapy, complications arose and this mass was further characterized with a chest MRI. It was then decided to be removed, and histopathology confirmed the diagnosis of a hemangioma.
Topics: Humans; Mediastinal Cyst; Mediastinal Neoplasms; Hemangioma; Tomography, X-Ray Computed; Radiography
PubMed: 37540631
DOI: 10.1097/RMR.0000000000000305 -
Cureus Jul 2023Myasthenia gravis (MG) complicated by myocarditis is a rare autoimmune manifestation. We present a patient who initially presented with a suspected ST-segment elevation...
Myasthenia gravis (MG) complicated by myocarditis is a rare autoimmune manifestation. We present a patient who initially presented with a suspected ST-segment elevation myocardial infarction (STEMI) with angiographically normal coronary arteries. A chest CT scan revealed a large homogenous soft-tissue density anterior mediastinal mass suspicious of thymoma. Neurological deterioration in the hospital suggested a diagnosis of MG with subsequent electromyography and nerve conduction studies (EMG/NCS) and repetitive nerve stimulation (RNS) confirmation. A cardiac magnetic resonance imaging study (CMR) demonstrated diffuse myocardial edema and severe left ventricular (LV) dysfunction and sub-epicardial late gadolinium enhancement (LGE) involving all basal and mid-LV segments in addition to apical inferior and lateral segments. A diagnosis of thymoma-associated MG with myocarditis was made and the patient was successfully treated with immunosuppression. This case highlights the association of myocarditis with MG as a potential complication that should be considered in patients with cardiac symptoms, ECG changes, or biomarker elevation.
PubMed: 37637534
DOI: 10.7759/cureus.42473 -
Mediastinum (Hong Kong, China) 2023
PubMed: 37701641
DOI: 10.21037/med-23-27 -
Mediastinum (Hong Kong, China) 2023Lymphomas are among the most common malignant tumors occurring in the anterior/prevascular mediastinum. Their diagnoses can be challenging in small biopsies, the current... (Review)
Review
Lymphomas are among the most common malignant tumors occurring in the anterior/prevascular mediastinum. Their diagnoses can be challenging in small biopsies, the current most common method of sampling of an anterior mediastinal mass. Because the initial clinical and/or imaging impression may not be that of lymphoma, these specimens may first be evaluated by cytopathologists, surgical pathologists, and thoracic pathologists rather than hematopathologists. Therefore, it is crucial for this group of pathologists to have a practical diagnostic approach to these neoplasms, know their common diagnostic pitfalls, and their main differential diagnoses. This is important because the diagnosis of lymphoma carries significant therapeutic implications (chemotherapy and/or radiotherapy and not surgical resection). Similarly, securing and properly triaging a sample at the time of tissue collection will translate into direct patient benefit since a subset of lymphomas (T-lymphoblastic lymphoma) may present exclusively as an anterior mediastinal mass and the tissue obtained from this site may be the only one available to evaluate prognostic markers and potential targetable molecular alterations. Once a proper initial diagnostic work-up has been performed, a case can be transferred to a hematopathologist for assistance with a refined diagnosis. In this review, we focus on the practical diagnostic approach to the most common prevascular/anterior mediastinal lymphomas with an emphasis on the findings in small biopsies and provide best practice tips for case triage.
PubMed: 38090035
DOI: 10.21037/med-22-54 -
Respiratory Medicine Sep 2023Paragangliomas are rarely found in the mediastinum, where they account for a small proportion of mediastinal masses. This study aimed to better characterize the...
BACKGROUND
Paragangliomas are rarely found in the mediastinum, where they account for a small proportion of mediastinal masses. This study aimed to better characterize the presenting features and relevant aspects in optimizing the diagnosis and treatment of mediastinal paragangliomas.
METHODS
A computer-assisted search of electronic health records was performed to identify adult patients (≥18 years) who underwent evaluation for a primary mediastinal paraganglioma at Mayo Clinic between January 2000 and April 2022. Medical charts, laboratory tests and radiology images were reviewed to collect data.
RESULTS
The study included 51 patients, each with a single mediastinal paraganglioma. The median age was 47 years (IQR: 39-67), 67% females. Symptoms of catecholamine excess were manifest in 39% of patients, and 14% presented with mass effect, while the remaining 47% had no paraganglioma-related symptoms. Genetic testing was performed in 35 patients; 66% harbored a pathogenic variant in the succinate dehydrogenase enzyme complex. Most paragangliomas (71%) were in the middle mediastinum and showed uptake of intravenous contrast on chest imaging. Biopsies were performed in 30 (59%) patients; 27% were inconclusive and 10% resulted in major complications. Surgical resection occurred in 75%, primarily for relief of symptoms (50%) followed by proximity to critical structures (45%). Perioperative complications were common (66%), but there were no cases of local tumor recurrence during the follow-up period (median 8 years; IQR: 4-13).
CONCLUSION
Mediastinal paragangliomas are most located in the middle mediastinum and can often be diagnosed noninvasively using a combination of clinical, biochemical, and radiological features.
Topics: Adult; Female; Humans; Middle Aged; Male; Retrospective Studies; Paraganglioma, Extra-Adrenal; Paraganglioma; Mediastinal Neoplasms; Mediastinum
PubMed: 37257785
DOI: 10.1016/j.rmed.2023.107296