Complexity of PEComas : Diagnostic approach, molecular background, clinical management.
Ontology highlight
ABSTRACT:
SUBMITTER: Utpatel K
PROVIDER: S-EPMC7286949 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Complexity of PEComas : Diagnostic approach, molecular background, clinical management.
Utpatel K K Calvisi D F DF Köhler G G Kühnel T T Niesel A A Verloh N N Vogelhuber M M Neu R R Hosten N N Schildhaus H-U HU Dietmaier W W Evert M M
Der Pathologe 20200601 Suppl 1
Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. B ...[more]
Similar Datasets
Project description:Avoiding detection through camouflage is often key to survival. However, an animal's appearance is not the only factor affecting conspicuousness: background complexity also alters detectability. This has been experimentally demonstrated for both artificially patterned backgrounds in the laboratory and natural backgrounds in the wild, but only for targets that already match the background well. Do habitats of high visual complexity provide concealment to even relatively poorly camouflaged animals? Using artificial prey which differed in their degrees of background matching to tree bark, we were able to determine their survival, under bird predation, with respect to the natural complexity of the background. The latter was quantified using low-level vision metrics of feature congestion (or 'visual clutter') adapted for bird vision. Higher background orientation clutter (edges with varying orientation) reduced the detectability of all but the poorest background-matching camouflaged treatments; higher background luminance clutter (varying achromatic lightness) reduced average mortality for all treatments. Our results suggest that poorer camouflage can be mitigated by more complex backgrounds, with implications for both camouflage evolution and habitat preferences.
| S-EPMC8611345 | biostudies-literature
Project description:IntroductionGeneral pediatricians have a major role in the care of children with medical complexity (CMC) in hospital and community settings. CMC are often affected by chronic multisystem diseases and functional limitations and may use a wheelchair or other aids for mobility. Dedicated training opportunities to perform comprehensive clinical assessments for this specialized population are lacking.MethodsWe developed a module focused on special considerations for CMC history taking and physical examination that was piloted in a pediatric residency program. The 60-minute session included a video of a clinical assessment of a child in a wheelchair. The module offered suggestions for incorporating patients or standardized patients as optional activities. Target learners answered formative pre- and posttest questions to check understanding and completed a 1-minute paper to convey lessons learned. Qualitative content analysis identified themes in written responses.ResultsFifteen pediatrics residents in a single program participated in the module. Most had not received any formal training in complex care. Themes in learner knowledge of steps in a clinical encounter included defining family goals and providing anticipatory guidance. Themes from responses about anticipated changes in clinical practice included systematic and comprehensive approach to history taking, thorough examination, and importance of safe transfers.DiscussionDeveloped as part of a national initiative in complex care curriculum development, this module can be adapted for interprofessional learners who provide care for CMC, with the goal of enabling future members of health care teams to provide high-quality clinical assessments for CMC.
| S-EPMC6342381 | biostudies-literature
Project description:Generation of intratumoral phenotypic and genetic heterogeneity has been attributed to clonal evolution and cancer stem cells that together give rise to a tumor with complex ecosystems. Each ecosystem contains various tumor cell subpopulations and stromal entities, which, depending upon their composition, can influence survival, therapy responses, and global growth of the tumor. Despite recent advances in breast cancer management, the disease has not been completely eradicated as tumors recur despite initial response to treatment. In this review, using data from clinically relevant breast cancer models, we show that the fates of tumor stem cells/progenitor cells in the individual tumor ecosystems comprising a tumor are predetermined to follow a limited (unipotent) and/or unlimited (multipotent) path of differentiation which create conditions for active generation and maintenance of heterogeneity. The resultant dynamic systems respond differently to treatments, thus disrupting the delicate stability maintained in the heterogeneous tumor. This raises the question whether it is better then to preserve stability by preventing takeover by otherwise dormant ecosystems in the tumor following therapy. The ultimate strategy for personalized therapy would require serial assessments of the patient's tumor for biomarker validation during the entire course of treatment that is combined with their three-dimensional mapping to the tumor architecture and landscape.
| S-EPMC5693662 | biostudies-literature
Project description:Vasospastic angina (VSA) refers to chest pain experienced as a consequence of myocardial ischaemia caused by epicardial coronary spasm, a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen. Coronary artery spasm is a heterogeneous phenomenon that can occur in patients with non-obstructive coronary arteries and obstructive coronary artery disease, with transient spasm causing chest pain and persistent spasm potentially leading to acute myocardial infarction (MI). VSA was originally described as Prinzmetal angina or variant angina, classically presenting at rest, unlike most cases of angina (though in some patients, vasospasm may be triggered by exertion, emotional, mental or physical stress), and associated with transient electrocardiographic changes (transient ST-segment elevation, depression and/or T-wave changes). Ischaemia with non-obstructive coronary arteries (INOCA) is not a benign condition, as patients are at elevated risk of cardiovascular events including acute coronary syndrome, hospitalization due to heart failure, stroke and repeat cardiovascular procedures. INOCA patients also experience impaired quality of life and associated increased healthcare costs. VSA, an endotype of INOCA, is associated with major adverse events, including sudden cardiac death, acute MI and syncope, necessitating the study of the most effective treatment options currently available. The present literature review aims to summarize current data relating to the diagnosis and management of VSA and provide details on the sequence that treatment should follow.
| S-EPMC10860484 | biostudies-literature
Project description:The phenotypic consequences of a given mutation can vary across individuals. This so-called background effect is widely observed, from mutant fitness of loss-of-function variants in model organisms to variable disease penetrance and expressivity in humans; however, the underlying genetic basis often remains unclear. Taking insights gained from recent large-scale surveys of genetic interaction and suppression analyses in yeast, we propose that the genetic network context for a given mutation may shape its propensity of exhibiting background-dependent phenotypes. We argue that further efforts in systematically mapping the genetic interaction networks beyond yeast will provide not only key insights into the functional properties of genes, but also a better understanding of the background effects and the (un)predictability of traits in a broader context.
| S-EPMC6085889 | biostudies-literature
Project description:Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.
| S-EPMC8021949 | biostudies-literature
Project description:Pazopanib, a multitarget tyrosine kinase (TK) inhibitor, has been approved for treatment of soft tissue sarcoma. Elucidation of the molecular background of pazopanib resistance should lead to improved clinical outcomes in sarcomas; accordingly, we investigated this in synovial sarcoma using a proteomic approach. Pazopanib sensitivity was examined in four synovial sarcoma cell lines: SYO-1, HS-SYII, 1273/99, and YaFuSS. The 1273/99 cell line showed significantly higher IC50 values than the others for pazopanib. Expression levels of 90 TKs in the cell lines were examined by western blotting. Among these, the levels of PDGFRB, DDR1, AXL, MET, and PYK2 were higher, and those of FGFR1 and VEGFR3 were lower in the 1273/99 cell line than the other cell lines. Gene silencing analysis of the TKs upregulated in 1273/99 cells showed differing effects on cell growth: PDGFRB, MET, and PYK2 knockdown induced cell growth inhibition, whereas DDR1 and AXL knockdown did not influence cell growth. Using the PamChip peptide microarray, we found that 18 peptide substrates were highly phosphorylated in the 1273/99 cell line compared with other cell lines. Using the PhosphoNet database, we found that kinases FGFR3, RET, VEGFR1, EPHA2, EPHA4, TRKA, and SRC phosphorylated these 18 peptide substrates. Moreover, the results for overexpressed and aberrantly activated TKs in pazopanib-resistant cells showed no overlap. Taken together, our study indicates that identification of comprehensive TK profiles represents an essential approach to determining the molecular background of pazopanib resistance in synovial sarcoma.
| S-EPMC5752544 | biostudies-literature
Project description:OBJECTIVE. The purposes of this study were to describe the prevalence of background parenchymal uptake categories observed at screening molecular breast imaging (MBI) and to examine the association of background parenchymal uptake with mammographic density and other clinical factors. MATERIALS AND METHODS. Adjunct MBI screening was performed for women with dense breasts on previous mammograms. Two radiologists reviewed images from the MBI examinations and subjectively categorized background parenchymal uptake into four groups: photopenic, minimal-mild, moderate, or marked. Women with breast implants or a personal history of breast cancer were excluded. The association between background parenchymal uptake categories and patient characteristics was examined with Kruskal-Wallis and chi-square tests as appropriate. RESULTS. In 1149 eligible participants, background parenchymal uptake was photopenic in 252 (22%), minimal-mild in 728 (63%), and moderate or marked in 169 (15%). The distribution of categories differed across BI-RADS density categories (p < 0.0001). In 164 participants with extremely dense breasts, background parenchymal uptake was photopenic in 72 (44%), minimal-mild in 55 (34%), and moderate or marked in 37 (22%). The moderate-marked group was younger on average, more likely to be premenopausal or perimenopausal, and more likely to be using postmenopausal hormone therapy than the photopenic or minimal-mild groups (p < 0.0001). CONCLUSION. Among women with similar-appearing mammographic density, background parenchymal uptake ranged from photopenic to marked. Background parenchymal uptake was associated with menopausal status and postmenopausal hormone therapy but not with premenopausal hormonal contraceptives, phase of menstrual cycle, or Gail model 5-year risk of breast cancer. Additional work is necessary to fully characterize the underlying cause of background parenchymal uptake and determine its utility in predicting subsequent risk of breast cancer.
| S-EPMC4423612 | biostudies-literature
Project description:Idiopathic inflammatory myopathies (IIM) are a group of chronic, autoimmune conditions affecting primarily the proximal muscles. The most common types are dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myopathy (NAM), and sporadic inclusion body myositis (sIBM). Patients typically present with sub-acute to chronic onset of proximal weakness manifested by difficulty with rising from a chair, climbing stairs, lifting objects, and combing hair. They are uniquely identified by their clinical presentation consisting of muscular and extramuscular manifestations. Laboratory investigations, including increased serum creatine kinase (CK) and myositis specific antibodies (MSA) may help in differentiating clinical phenotype and to confirm the diagnosis. However, muscle biopsy remains the gold standard for diagnosis. These disorders are potentially treatable with proper diagnosis and initiation of therapy. Goals of treatment are to eliminate inflammation, restore muscle performance, reduce morbidity, and improve quality of life. This review aims to provide a basic diagnostic approach to patients with suspected IIM, summarize current therapeutic strategies, and provide an insight into future prospective therapies.
| S-EPMC4873503 | biostudies-literature
Project description:Abnormal septal motion (commonly referred to as septal bounce) is a common echocardiographic finding that occurs with several conditions, including the following: mitral stenosis, left bundle branch block, pericardial syndromes and severe pulmonary hypertension. We explore the subtle changes that occur on M-mode imaging of the septum, other associated echocardiographic features, the impact of inspiratory effort on septal motion and relevant clinical findings. Finally, we discuss the impact of abnormal septal motion on cardiac form and function, proposing there is a clinically significant impact on biventricular filling and ejection.
| S-EPMC8409894 | biostudies-literature