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1.
Sounak Gupta Rafael E. Jimenez Loren Herrera-Hernandez Christine M. Lohse R. Houston Thompson Stephen A. Boorjian Bradley C. Leibovich John C. Cheville 《Mayo Clinic proceedings. Mayo Clinic》2021,96(6):1470-1489
ObjectiveTo study the clinical features and identify unique renal neoplasia subtypes and their prognostic implications in individuals with tuberous sclerosis complex (TSC).Patients and MethodsThe Mayo Clinic nephrectomy registry included 37 patients with TSC diagnosed between 1970 and 2018. Four additional patients were identified from the pathology consultation and autopsy files. All available renal tumors were further characterized using immunohistochemistry and fluorescence in situ hybridization. Clinicopathologic features and follow-up were obtained from the medical record. The American Association for Cancer Research Project GENIE registry was accessed using cBioPortal for molecular profiling of angiomyolipoma (AML).ResultsA total of 276 renal tumors from 41 patients were analyzed. Renal tumors were classified into 9 distinct morphological subtypes, with AML predominating (238 [86%]). Interestingly, all these tumors acted in a benign fashion except one renal cell carcinoma with clear cells and fibromyomatous stroma and one epithelioid AML that metastasized. Molecular profiling studies revealed that epithelioid AMLs were enriched for alterations of TP53, RB1, and ATRX. Eight patients died of direct complications of TSC, including 3 of end-stage renal disease. To date, none have died of a renal epithelial neoplasm.ConclusionThe identification of unique renal neoplasia subtypes may provide important clues to establish a diagnosis of TSC, and in the somatic setting, this finding has important implications for accurate prognostication. These tumors tend to be indolent, and only 2 of 276 tumors in our study exhibited metastatic behavior. Our results support multidisciplinary management with a focus on preservation of renal function. 相似文献
2.
The specificity with which past experiences can be remembered varies across the lifespan, possibly due to differences in how precisely information is encoded. Memory formation can be investigated through repetition effects, the common finding that neural activity is altered when stimuli are repeated. However, whether differences in this indirect measure of memory formation relate to lifespan differences in memory specificity has not yet been established. In the present study, we examined repetition effects in event-related potentials and their relation to recognition. During incidental encoding, children (aged 7–9 years), young adults (18–30 years), and older adults (65–76 years) viewed repeated object images from different categories. During subsequent recognition, we distinguished memory for the specific items versus the general categories. We identified repetition suppression in all age groups, and repetition enhancement for adults. Furthermore, individual item recognition performance comprising lure discrimination was positively associated with the magnitude of the neural repetition effects, which did not differ between groups, indicating common neural mechanisms of memory formation. Our findings demonstrate that neural repetition effects reflect the formation of highly specific memory representations and highlight their significance as a neural indicator of individual differences in episodic memory encoding across the lifespan. 相似文献
3.
4.
Aleodor A Andea 《Histopathology》2022,80(1):150-165
The work-up of melanocytic tumors has undergone significant changes in the last years following the exponential growth of molecular assays. For the practicing pathologist it is often difficult to sort through the myriad of different tests available currently for clinical use. The molecular tests used in melanocytic pathology can be broadly divided into 4 categories: (i) Tests useful in the differential diagnosis of nevus versus melanoma (primarily used as an aid in the diagnosis of histologically ambiguous melanocytic tumors), (ii) Tests that predict prognosis in melanoma, (iii) Tests useful in the classification of melanocytic tumors and (iv) Tests that predict response to systemic therapy in melanoma. This review will present an updated overview of major ancillary tests used in clinical practice. 相似文献
5.
Recent work provides evidence that the infant brain is able to make top-down predictions, but this has been explored only in limited contexts and domains. We build upon this evidence of predictive processing in infants using a new paradigm to examine auditory repetition suppression (RS). RS is a well-documented neural phenomenon in which repeated presentations of the same stimulus result in reduced neural activation compared to non-repeating stimuli. Many theories explain RS using bottom-up mechanisms, but recent work has posited that top-down expectation and predictive coding may bias, or even explain, RS. Here, we investigate whether RS in the infant brain is similarly sensitive to top-down mechanisms. We use fNIRS to measure infants’ neural response in two experimental conditions, one in which variability in stimulus presentation is expected (occurs 75% of the time) and a control condition where variability and repetition are equally likely (50% of the time). We show that 6-month-old infants exhibit attenuated frontal lobe response to blocks of variable auditory stimuli during contexts when variability is expected as compared to the control condition. These findings suggest that young infants’ neural responses are modulated by predictions gained from experience and not simply by bottom-up mechanisms. 相似文献
6.
Chrystalle Katte Carreon Annachiara Benini Christopher Baird David Hoganson Michele Borisuk Sitaram Emani Sophie Hofferberth Robert F. Padera Stephen P. Sanders 《The Journal of thoracic and cardiovascular surgery》2019,157(1):342-350.e3
Objectives
Although valved venous homografts (VVHs) are used for establishing right ventricle-to-pulmonary artery continuity in some complex heart defects, the tissue changes that occur in situ have not been described. We review the gross and microscopic changes observed in explanted VVH conduits and their effects on functionality.Methods
In total, 20 explanted VVH conduits were evaluated for valve integrity, presence of thrombus, and stenosis. Hematoxylin and eosin– and trichrome-stained sections were reviewed for neointima formation, wall remodeling, inflammation, and calcification. Regurgitation and narrowing were assessed on pre-explant echocardiogram, and angiographic video clips were correlated with tissue findings. The source of the proliferating cells within the conduits was investigated by fluorescent in situ hybridization.Results
Thirteen male and 7 female infants underwent VVH implantation either as part of a composite Sano shunt (65%) or to establish right ventricle-to-pulmonary artery continuity in biventricular hearts (35%). The median duration of conduits in situ was 140 days (range: 98-340 days). Conduits were predominantly explanted for staged conversion to bidirectional Glenn (60%) and conduit upsizing (20%). The valves remained intact and functional in 75% of cases. Occlusive thrombosis was absent in all. Wall thickening due to neointima formation and wall remodeling was uniformly present and appeared to be driven by smooth muscle actin–expressing cells, which by fluorescent in situ hybridization are predominantly of recipient origin. Minimal calcification and mild adventitial chronic inflammation were present.Conclusions
Vein wall thickening is a uniform finding and can cause stenosis. The valves remain functional in most, and vein walls undergo remodeling with only minimal inflammation and calcification. 相似文献7.
《Clinical lung cancer》2019,20(4):e421-e429
BackgroundDetection of ALK and ROS1 gene rearrangements in non–small-cell lung cancer is required for directing patient care. Although fluorescence in situ hybridization (FISH) and immunohistochemistry have been established as gold standard methods, next-generation sequencing (NGS) platforms are called to be at least equally successful. Comparison of these methods for translation into daily use is currently under investigation.Patients and MethodsForty non–small-cell lung cancer paraffin-embedded samples with previous ALK (n = 33) and ROS1 (n = 7) FISH results were examined with the Oncomine Focus Assay and tested for ALK and ROS1 immunoreactivity. Clinical implications of concurrent molecular alterations and concordance between methods were evaluated.ResultsNGS was successful in 32 (80%) cases: 25 ALK and 7 ROS1. Few concomitant alterations were detected: 1 ALK rearranged case had an ALK p.L1196M-resistant mutation, 4 had CDK4, MYC, and/or ALK amplifications, and 1 ROS1 rearranged case showed a FGFR4 amplification. Comparison between techniques revealed 5 (16%) discordant cases that had lower progression-free survival than concordant cases: 7.6 (95% confidence interval, 2.2-13) versus 19.4 (95% confidence interval, 10.1-28.6). Remarkably, 4 of these cases had isolated 3' signal FISH pattern (P = .026).ConclusionOur data support that the identification of 3' isolated signal FISH pattern in ALK and ROS1 cases might suggest a false-positive result. NGS seems a reliable technique to assess ALK and ROS1 rearrangements, offering the advantage over immunohistochemistry of detecting other molecular alterations with potential therapeutic implications. 相似文献
8.
Xinran Wang Ying Jia Huiyan Deng Yao Liu Yueping Liu 《Pathology, research and practice》2019,215(2):308-314
Recent studies have shown that intratumoral heterogeneity is prevalent in esophageal squamous cell cancer (ESCC) based on DNA sequencing and chromosome analysis in multiple regions from the same tumor. This study aimed to investigate the expression of ZNF750, EP300, MTOR and KMT2D and their intratumoral heterogeneity (ITH) in patients with ESCC. A total of 106 cases, who underwent esophagectomy from 2008 to 2010, with two foci from each case, were tested by immunohistochemistry(IHC) as well as 12 cases were tested by RNAscope in this study.We found that 58/106 (54.72%), 66/106 (62.26%), 75/106 (70.75%%) of ESCC showed high expression of ZNF750, EP300, MTOR, respectively by IHC, and 8/12 (66.67%), 10/12 (83.33%), 4/12 (33.33%) and 6/12 (50%) showed high expression of ZNF750, EP300, MTOR and KMT2D, respectively by RNAscope. Multivariate analysis showed that MTOR expression was an independent infavorable prognostic factor of overall survival (OS) (HR?=?1.921; P?=?0.000). This study also found that 44/106(4151%), 37/106 (34.91%), 39/106(36.79%) of ESCC showed heterogeneous expression of ZNF750, EP300 and MTOR respectively by IHC, 8/12(66.67%), 8/12(66.67%), 4/12(33.33%), 4/12(33.33%) of ZNF750, EP300, MTOR and KMT2D respectively by RNAscope, IHC and RNAscope could successfully detect a high prevalence of ITH. In conclusion, findings of this study showed that ZNF750, EP300, MTOR and KMT2D heterogeneously expressed in ESCC. High expression of ZNF750 related to a better outcome, while EP300 and MTOR related to a poor prognosis. 相似文献
9.
《Medical Journal Armed Forces India》2020,76(1):103-108
BackgroundLight chain restriction needs to be established on the paraffin embedded tissue in certain types of plasma cell dyscrasias when serum levels of monoclonal immunoglobulins and light chain assays in the urine and serum may be normal. Rapid-in-situ-hybridisation (RISH) is thought to be a superior to immunohistochemistry (IHC) for kappa and lambda staining due to brighter and crisp staining without any background.MethodsFifty cases were included in this pilot study. Serum light chain restriction status of the case was taken as gold standard. The results of standard IHC for kappa and lambda immunoglobulins on the bone marrow biopsy of these cases was compared with RISH performed by the two commercially available kits. The results of the two methods were compared for sensitivity, need to repeat the test and background staining.ResultsThe study found that in IHC first run sensitivity was 58% which improved to 88% after the second run. For RISH the sensitivity was 100%.ConclusionRapid-in-situ-hybridisation (RISH) is a superior technique to IHC for detecting kappa and lambda light chain in plasma cells. The test is as labour intensive and time consuming as the routine IHC but has no background staining with more bright and crisp staining quality. 相似文献