scholarly journals Clinical and Molecular Features of Disseminated Pediatric Low Grade Glioma - A Systematic Review of Literature

2021 ◽  
Author(s):  
Joseline Haizel-Cobbina ◽  
Rut Thakkar ◽  
Kelsey Richard ◽  
Adrian Levine ◽  
Julie Bennett ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Surveillance ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Risk Of Bias ◽  
Low Grade ◽  
Molecular Alterations ◽  
Molecular Features ◽  
1P Deletion ◽  
Csf Diversion

Abstract INTRODUCTIONGliomas account for approximately 46% of all pediatric CNS tumors. There is growing awareness of pediatric low-grade gliomas (PLGG) that disseminate to distant parenchymal or leptomeningeal locations either at the time of initial diagnosis or upon disease surveillance. Disseminated PLGGs (dPLGGs) are associated with a poorer prognosis than non-disseminated PLGGs. To date there is no comprehensive report characterizing the genome profile of dPLGGs and their associated management. This systematic review aims to identify the pattern of genetic alterations and treatment outcomes described for dPLGG.METHODSA systematic review of the literature was performed to identify relevant articles. A quality and risk of bias assessment of articles was done using the GRADE framework and ROBINS-I tool, respectively.RESULTSFifty-two studies published from 1994 to 2020 were included in this review with 368 cases reported. There was sporadic reporting of genetic alterations. The most common genetic alteration observed among study subjects was 1p deletion (76%) and BRAF-KIAA1549 fusion (55%). BRAF p.V600E mutation was found in 7% of subjects. A higher proportion of cases demonstrated primary dissemination compared to secondary dissemination (65% vs 25%). First-line chemotherapy consisted primarily of an alkylation-based regimen and vinca alkaloids. Surgical intervention ranged from biopsy alone to surgical resection and CSF diversion, and depended largely upon tumor location and timing of dissemination. Overall, 73% of cases were alive at last follow-up (median, 40.2 months). All studies reviewed either ranked low or moderate for both quality and risk of bias assessments. CONCLUSIONWhile 1p deletion and BRAF-KIAA1549 fusion are the most commonly described molecular alterations in dPLGG, these tumors appear to express heterogeneous molecular and biological characteristics distinct from non-disseminated PLGGs. Additional studies on the molecular and biological features of these tumors are needed to better understand the pathogenesis of dPLGG and to inform the development of additional targeted regimens.

scholarly journals Clinical impact of combined epigenetic and molecular analysis of pediatric low-grade gliomas

2020 ◽  
Vol 22 (10) ◽  
pp. 1474-1483 ◽  
Author(s):  
Kohei Fukuoka ◽  
Yasin Mamatjan ◽  
Ruth Tatevossian ◽  
Michal Zapotocky ◽  
Scott Ryall ◽  
...  
Keyword(s):  
Molecular Analysis ◽  
Progression Free Survival ◽  
Lymphocytic Infiltration ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Pleomorphic Xanthoastrocytoma ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Additional Information ◽  
Molecular Alterations

Abstract Background Both genetic and methylation analysis have been shown to provide insight into the diagnosis and prognosis of many brain tumors. However, the implication of methylation profiling and its interaction with genetic alterations in pediatric low-grade gliomas (PLGGs) are unclear. Methods We performed a comprehensive analysis of PLGG with long-term clinical follow-up. In total 152 PLGGs were analyzed from a range of pathological subtypes, including 40 gangliogliomas. Complete molecular analysis was compared with genome-wide methylation data and outcome in all patients. For further analysis of specific PLGG groups, including BRAF p.V600E mutant gliomas, we compiled an additional cohort of clinically and genetically defined tumors from 3 large centers. Results Unsupervised hierarchical clustering revealed 5 novel subgroups of PLGG. These were dominated by nonneoplastic factors such as tumor location and lymphocytic infiltration. Midline PLGG clustered together while deep hemispheric lesions differed from lesions in the periphery. Mutations were distributed throughout these location-driven clusters of PLGG. A novel methylation cluster suggesting high lymphocyte infiltration was confirmed pathologically and exhibited worse progression-free survival compared with PLGG harboring similar molecular alterations (P = 0.008; multivariate analysis: P = 0.035). Although the current methylation classifier revealed low confidence in 44% of cases and failed to add information in most PLGG, it was helpful in reclassifying rare cases. The addition of histopathological and molecular information to specific methylation subgroups such as pleomorphic xanthoastrocytoma–like tumors could stratify these tumors into low and high risk (P = 0.0014). Conclusion The PLGG methylome is affected by multiple nonneoplastic factors. Combined molecular and pathological analysis is key to provide additional information when methylation classification is used for PLGG in the clinical setting.

scholarly journals Transcriptional Characterization of Stage I Epithelial Ovarian Cancer: A Multicentric Study

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1554
Author(s):  
Enrica Calura ◽  
Matteo Ciciani ◽  
Andrea Sambugaro ◽  
Lara Paracchini ◽  
Giuseppe Benvenuto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Stage I ◽  
Molecular Heterogeneity ◽  
Low Grade ◽  
Multicentric Study ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Signaling Axis ◽  
Tumor Biopsies

Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs. It is characterized by a complex histopathological and molecular heterogeneity, and it is composed of five main histological subtypes (mucinous, endometrioid, clear cell and high, and low grade serous), which have peculiar genetic, molecular, and clinical characteristics. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. In this study, using in silico approaches and gene expression data, on a multicentric cohort composed of 208 snap-frozen tumor biopsies, we explored the subtype-specific molecular alterations that regulate tumor aggressiveness in stage I EOC. We found that single genes rather than pathways are responsible for histotype specificities and that a cAMP-PKA-CREB1 signaling axis seems to play a central role in histotype differentiation. Moreover, our results indicate that immune response seems to be, at least in part, involved in histotype differences, as a higher immune-reactive behavior of serous and mucinous samples was observed with respect to other histotypes.

scholarly journals Pancreatic Solid Pseudopapillary Neoplasm: Key Pathologic and Genetic Features

2020 ◽  
Vol 144 (7) ◽  
pp. 829-837 ◽  
Author(s):  
Stefano La Rosa ◽  
Massimo Bongiovanni
Keyword(s):  
Good Prognosis ◽  
Low Grade ◽  
Solid Pseudopapillary Neoplasm ◽  
Prognostic Features ◽  
Molecular Alterations ◽  
Immunohistochemical Markers ◽  
Molecular Features ◽  
Pubmed Database ◽  
Genetic Features ◽  
Solid Pseudopapillary Neoplasms

Context.— Solid pseudopapillary neoplasm of the pancreas is a low-grade malignant tumor generally associated with a good prognosis. Solid pseudopapillary neoplasms show peculiar morphologic features, but sometimes the differential diagnosis with other pancreatic neoplasms (ie, pancreatic neuroendocrine tumors) can be a challenging task, especially in cytologic or biopsy specimens. In these cases immunohistochemistry is a useful tool, but the diagnostic utility of several proposed immunohistochemical markers is questionable. In recent years, despite several attempts to characterize the pathogenetic, molecular, and prognostic features of solid pseudopapillary neoplasms, they still remain unclear. Objective.— To give the reader a comprehensive update on this entity. Data Sources.— The PubMed database (US National Library of Medicine) was searched using the following string: pseudopapillary tumor [AND/OR] neoplasm [AND/OR] pancreas. All articles written in English were included. In addition, because a heterogeneous terminology has been used in the past to define solid pseudopapillary neoplasms, the reference lists of each paper selected in the PubMed database were also reviewed. Conclusions.— This review gives a comprehensive update on the pathologic, clinical, and molecular features of solid pseudopapillary neoplasms, particularly addressing issues and challenges related to diagnosis. In addition, we have tried to correlate the molecular alterations with the morphologic and clinical features.

scholarly journals Performance of custom made videolaryngoscope for endotracheal intubation: A systematic review

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261863
Author(s):  
Pawan Kumar Hamal ◽  
Rupesh Kumar Yadav ◽  
Pragya Malla
Keyword(s):  
Systematic Review ◽  
Endotracheal Intubation ◽  
Low Income ◽  
Risk Of Bias ◽  
Low Income Countries ◽  
Low Grade ◽  
Laryngoscopic View ◽  
Level Of Evidence ◽  
Airway Injury ◽  
Custom Made

Introduction Videolaryngoscope is regarded as the standard of care for airway management in well-resourced setups however the technology is largely inaccessible and costly in middle and low-income countries. An improvised and cost-effective form of customized videolaryngoscope was proposed and studied for patient care in underprivileged areas however there were no distinct conclusions on its performances. Method The study follows PRISMA guidelines for systematic review and the protocol in International Prospective Register for Systematic Reviews. The primary aim was to assess the first attempt success of customized videolaryngoscope for endotracheal intubation. The secondary objective was to evaluate the number of attempts, laryngoscopic view in terms of Cormack Lehane score and Percentage of glottic opening, use of external laryngeal maneuver and stylet and, the airway injuries after the endotracheal intubation. Result Five studies were analyzed for risk of bias using the National Institute of Health Quality Assessment Tool for cross-sectional studies. Most of the studies had a poor to a fair level of evidence with only one study with a good level of evidence. Certainty of evidence was “very low” for all eligible studies when graded using the Grading of Recommendation, Assessment, Development and Evaluation approach for systematic review. Conclusions The certainty of the evidence regarding performance of custom-made videolaryngoscope compared to conventional laryngoscope was very low and the study was performed in small numbers with fair to the poor risk of bias. It was difficult to establish and do further analysis regarding whether the customized form of videolaryngoscope will improve the first attempt success rate for tracheal intubation, reduce the number of attempts, improve the laryngoscopic view, require fewer external aids and reduce the incidences of airway injury with the given low-grade evidence. Some properly conducted randomised clinical trials will be required to further analyze the outcome and make the strong recommendations.

Colorectal cancer: Impact of primary tumor location on genetic alterations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3578-3578 ◽  
Author(s):  
Mohamed E. Salem ◽  
Heinz-Josef Lenz ◽  
Joanne Xiu ◽  
Jimmy J. Hwang ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Tumor Location ◽  
Genetic Alterations ◽  
Hepatic Flexure ◽  
Missense Mutations ◽  
Chi Square ◽  
Molecular Alterations ◽  
Clear Cut ◽  
Comparison Results ◽  
Her 2 ◽  
The Right

3578 Background: Recent data show that patients with left sided colon tumors (LT) have better survival and respond differently to biologics compared to patients with right-sided tumors (RT), likely due to molecular differences. We sought to examine these differences. Methods: Primary colorectal tumors (n = 1730) with origins clearly defined as RT (cecum to hepatic flexure; n = 273), LT (splenic flexure to sigmoid colon; n = 585), or rectal (RC; n = 872) were examined by NextGen sequencing, protein expression and gene amplification. Tumor mutational load (TML) was calculated in 1001 of these tumors using only somatic nonsynonymous missense mutations. Chi-square was used for comparison. Results: When compared to LT, RT carried a significantly higher rate of BRAF (25% vs 7%; p < 0.0001), PTEN (5.4% vs 1.3%; p = 0.008), and ATM (4% vs 1%; p = 0.04) mutations. RT were likely to have more MSI-high tumors (22% vs 5%; p < 0.0001) and PD-1 overexpression (58% vs 44%; p = 0.01). There were no differences in the rate of KRAS (50% vs 42%; p = 0.07) or NRAS mutations (2.2% vs 3.4%; p = 0.4). When compared to RC, RT had a higher rate of BRAF (25% vs 3%; p = 7E-07), PIK3CA (22% vs 11%; p = 0.001), CTNNB1 (3% vs 0.3%; p = 0.02); ATM (3% vs 1%; p = 0.04), PTEN (5% vs 1%; p = 0.004), and BRCA1 mutations (4% vs 0%; p = 0.02), and a lower rate of TP53 (56% vs 71%; p = 0.001) and APC (53% vs 66%; p = 0.003) mutations. When compared to RC, LT showed higher rates of BRAF (6.7% vs 3.2%; p = 0.04) and CTNNB1 (2.1% vs 0.3%; p = 0.04) mutations, and a higher rate of MSI-high tumors (4.6% vs 0.7%; p = 0.04), whereas RC had a higher rate of KRAS mutation (50% vs 42%; p = 0.04). There were no differences between RT, LT, and RC for the frequency of PD-L1 (2%, 2%, and 1%) or Her-2 (1%, 2%, and 3%) overexpression, although Her-2 amplification was significantly different (1%, 3%, and 5%, RT vs RC; p = 0.03). Mean TML was 12, 11, and 8 mutations/megabase for RT, LT, and RC, respectively (RT vs RC; p = 0.01). There was a correlation between TML and PD-L1 (p = 0.04) and PD-1 (p = 0.01). Conclusions: Tumors arising in the right colon carry genetic alterations that are different from LT as well as RC. However, it appears that CRCs carry a continuum of molecular alterations from the right to the left side, rather than displaying sharp, clear-cut differences.

Treatment of Adult Lower-Grade Glioma in the Era of Genomic Medicine

2016 ◽  
pp. 75-81 ◽  
Author(s):  
Susan M. Chang ◽  
Daniel P. Cahill ◽  
Kenneth D. Aldape ◽  
Minesh P. Mehta
Keyword(s):  
Molecular Genetic ◽  
Genomic Medicine ◽  
Genetic Alterations ◽  
World Health ◽  
Low Grade ◽  
Lower Grade ◽  
Cell Of Origin ◽  
Low Grade Gliomas ◽  
Molecular Features ◽  
Anaplastic Gliomas

By convention, gliomas are histopathologically classified into four grades by the World Health Organization (WHO) legacy criteria, in which increasing grade is associated with worse prognosis and grades also are subtyped by presumed cell of origin. This classification has prognostic value but is limited by wide variability of outcome within each grade, so the classification is rapidly undergoing dramatic re-evaluation in the context of a superior understanding of the biologic heterogeneity and molecular make-up of these tumors, such that we now recognize that some low-grade gliomas behave almost like malignant glioblastoma, whereas other anaplastic gliomas have outcomes comparable to favorable low-grade gliomas. This clinical spectrum is partly accounted for by the dispersion of several molecular genetic alterations inherent to clinical tumor behavior. These molecular biomarkers have become important not only as prognostic factors but also, more critically, as predictive markers to drive therapeutic decision making. Some of these, in the near future, will likely also serve as potential therapeutic targets. In this article, we summarize the key molecular features of clinical significance for WHO grades II and III gliomas and underscore how the therapeutic landscape is changing.

Mucinous Adenomyomatous Pulmonary Hamartoma: Clinicopathologic, Immunohistochemical, and Molecular Features of 6 Cases

2020 ◽  
pp. 106689692094501
Author(s):  
Giulio Rossi ◽  
Alberto Cavazza ◽  
Camilla Comin ◽  
Genny Jocollé ◽  
Agita Jukna ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Frozen Section ◽  
Gene Mutations ◽  
Low Grade ◽  
Basal Cells ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Small Series ◽  
Asymptomatic Patients ◽  
Pulmonary Hamartoma

Pulmonary hamartoma (PH) may show various combinations of mesenchymal tissues with entrapment of respiratory epithelium. An uncommon variant of PH prevalently consisting of smooth muscle with mucinous proliferation has been reported in literature under several definitions as sporadic reports. We collected a series of 6 leiomyomatous PH associated with mucinous growth from consultation files (3 cases) and multicentric revision of archival files among 128 consecutive surgically resected PH. The lesions have a prevalence for male gender (5:1) and lower lobes (5:1), with a mean age at diagnosis of 61 years. All cases were incidentally disclosed in asymptomatic patients and had an indolent behavior. At histology, 2 cases consisted uniquely of smooth muscle and 4 also showed mature adipose tissue. The mucinous proliferation consisted of a monotonous growth of columnar cells lacking p63-positive basal cells and expressing pan-CKs, MUC5A, and CK7, but negative with TTF-1, napsin, MUC1, MUC2, MUC6, CK20, and CDX2. Smooth muscle was negative with hormonal receptors. Molecular analysis using a multiplex gene panel did not reveal gene mutations, while ALK, BRAF, and ROS1 were negative. In conclusion, we describe a small series of uncommon PH with prevalent leiomyomatous mesenchymal component associated with a mucinous growth (mucinous adenomyomatous hamartoma). Despite the lack of basal cells coating mucinous proliferation and irregular architecture, the favorable outcome and lack of molecular alterations most likely lay for a benign/low-grade tumor. Pathologists should be aware of this unusual occurrence to prevent a diagnosis of overt malignancy, particularly in frozen section, small biopsy, and cytology.

scholarly journals The genetic basis of intradural spinal tumors and its impact on clinical treatment

2015 ◽  
Vol 39 (2) ◽  
pp. E3 ◽  
Author(s):  
Michael Karsy ◽  
Jian Guan ◽  
Walavan Sivakumar ◽  
Jayson A. Neil ◽  
Meic H. Schmidt ◽  
...  
Keyword(s):  
Treatment Options ◽  
Cancer Recurrence ◽  
Genetic Alterations ◽  
Spinal Tumors ◽  
Therapeutic Effects ◽  
Low Grade ◽  
Primary Therapy ◽  
Targeted Interventions ◽  
Molecular Alterations ◽  
The Impact

Genetic alterations in the cells of intradural spinal tumors can have a significant impact on the treatment options, counseling, and prognosis for patients. Although surgery is the primary therapy for most intradural tumors, radiochemothera-peutic modalities and targeted interventions play an ever-evolving role in treating aggressive cancers and in addressing cancer recurrence in long-term survivors. Recent studies have helped delineate specific genetic and molecular differences between intradural spinal tumors and their intracranial counterparts and have also identified significant variation in therapeutic effects on these tumors. This review discusses the genetic and molecular alterations in the most common intradural spinal tumors in both adult and pediatrie patients, including nerve sheath tumors (that is, neurofibroma and schwannoma), meningioma, ependymoma, astrocytoma (that is, low-grade glioma, anaplastic astrocytoma, and glioblastoma), hemangioblastoma, and medulloblastoma. It also examines the genetics of metastatic tumors to the spinal cord, arising either from the CNS or from systemic sources. Importantly, the impact of this knowledge on therapeutic options and its application to clinical practice are discussed.

scholarly journals Radiohistogenomics of pediatric low-grade neuroepithelial tumors

2021 ◽  
Author(s):  
Asim K. Bag ◽  
Jason Chiang ◽  
Zoltan Patay
Keyword(s):  
Holistic Approach ◽  
Genetic Alterations ◽  
Genetic Alteration ◽  
World Health ◽  
Low Grade ◽  
Neuroepithelial Tumors ◽  
Molecular Features ◽  
Standard Clinical Practice ◽  
Imaging Characteristics ◽  
Health Organization

Abstract Purpose In addition to histology, genetic alteration is now required to classify many central nervous system (CNS) tumors according to the most recent World Health Organization CNS tumor classification scheme. Although that is still not the case for classifying pediatric low-grade neuroepithelial tumors (PLGNTs), genetic and molecular features are increasingly being used for making treatment decisions. This approach has become a standard clinical practice in many specialized pediatric cancer centers and will likely be more widely practiced in the near future. This paradigm shift in the management of PLGNTs necessitates better understanding of how genetic alterations influence histology and imaging characteristics of individual PLGNT phenotypes. Methods The complex association of genetic alterations with histology, clinical, and imaging of each phenotype of the extremely heterogeneous PLGNT family has been addressed in a holistic approach in this up-to-date review article. A new imaging stratification scheme has been proposed based on tumor morphology, location, histology, and genetics. Imaging characteristics of each PLGNT entity are also depicted in light of histology and genetics. Conclusion This article reviews the association of specific genetic alteration with location, histology, imaging, and prognosis of a specific tumor of the PLGNT family and how that information can be used for better imaging of these tumors.

scholarly journals PATH-35. RETROSPECTIVE ANALYSIS OF 145 PATIENTS WITH GLIOBLASTOMA; CORRELATING MOLECULAR ALTERATION INCIDENCE WITH DEMOGRAPHICS, TUMOR LOCATION, AND PROGNOSIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi150-vi151
Author(s):  
Mina Lobbous ◽  
ZacK Tucker ◽  
Elizabeth Coffee ◽  
Louis Nabors
Keyword(s):  
Progression Free Survival ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Primary Brain Tumor ◽  
Demographic Variables ◽  
The Cancer Genome Atlas ◽  
Missense Mutations ◽  
Molecular Alteration ◽  
Molecular Alterations ◽  
Cdkn2a Deletion

Abstract Glioblastoma is the most common and most aggressive primary brain tumor in adults. Glioblastoma was the first neoplasm to be systemically studied by The Cancer Genome Atlas and is one of the most molecularly well-characterized tumors in humans. Molecular profiling of glioblastoma is increasingly available and had led to the identifications of multiple prognostic factors as well as potential actionable targets for novel therapies. We identified 145 patients diagnosed with glioblastoma whose tumor tissue was analyzed using next generation sequencing (NGS). The NGS was performed using validated, commercially available panels. We studied somatic genetic alterations with a particular focus on TERT (which was altered in 55.9% of patients in the dataset), CDKN2A (44%), TP53 (39%), EGFR (38.6%), PTEN (31%), IDH1 (20%), and CDK4 (9%). These molecular alterations were analyzed in relation to the patients’ tumor locations, demographics, and outcomes. We used multiple binary logistic regressions to assess whether demographics and tumor location were predictive of the above alterations We also assessed the relationship between molecular alterations and outcomes when controlling for treatment and demographic variables. Among demographic variables, age predicted alterations in IDH1, EGFR, TERT, TP53, and PTEN. Frontal lobe tumors were more likely to be IDH1-mutated, irrespective of patient age. Sex and race did not predict the incidence of the molecular alterations of interest. Analysis of outcomes revealed that, when controlling for treatment and demographic variables, TERT promoter mutations, TP53 nonsense mutations, and EGFR A289V were predictive of a decreased progression-free survival, while CDKN2A deletion, PTEN missense mutations, and EGFR A289V were predictive of decreased overall survival. Our experience highlights the importance of incorporating routine NGS in the management of patients with glioblastoma. More studies are required to evaluate the predictive and/or prognostic values of different molecular alterations.

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