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BACKGROUND: Tumor-Stroma Ratio (TSR) has been recognized as a valuable prognostic indicator in various solid tumors. This study aimed to examine the clinicopathological relevance of TSR in Merkel cell carcinoma (MCC) using artificial intelligence (AI)-based parameterization of the stromal landscape and validate TSR scores generated by our AI model versus human-assessed. METHODS: 112 MCC cases with Whole Slide Images (WSIs) were collected from four different institutions. WSIs were first partitioned into 128x128-pixel "mini-patches" then classified by a novel framework, termed Pre-TumOr And STroma (Pre-TOAST) and TOAST, whose output equaled the probability of the mini-patch representing tumor cells rather than stroma. Hierarchical random samplings of 50 mini-patches per region were performed throughout 50 regions per slide. TSR and Tumor-Stromal Landscape (TSL) parameters were estimated by the maximum-likelihood algorithm. RESULTS: Receiver Operating Characteristic (ROC) curves showed the areas under the curve (AUCs) of Pre-TOAST in discriminating classed of interest (COI) including tumor cells, collagenous stroma, and lymphocytes from non-classes of interest (non-COI) including hemorrhage, space, and necrosis were 1.00. AUCs of TOAST in differentiating tumor cells from related stroma were 0.93. MCC stroma was categorized into TSR-high (TSR≥50%) and TSR-low (TSR<50%) using both AI- and human pathology-based methods. AI-based TSR-high subgroup exhibited notably shorter Metastasis-Free Survival (MFS) with a statistical significance of p=0.029. Interestingly, pathologist-determined TSR subgroups lacked statistical significance in Recurrence-Free Survival (RFS), MFS, and Overall Survival (OS) (p>0.05). Density-based spatial clustering of applications with noise (DBSCAN) analysis identified two distinct Tumor-Stroma Landscape (TSL) clusters: TSL1 and TSL2. TSL2 showed significantly shorter RFS (p=0.045) and markedly reduced MFS (p<0.001) compared to TSL1. CONCLUSION: TSL classification appears to offer better prognostic discrimination than traditional TSR evaluation in MCC. TSL can be reliably calculated using an AI-based classification framework and predict various prognostic features of MCC.
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INTRODUCTION: PReferentially expressed Antigen in MElanoma (PRAME) has shown utility in differentiating benign from malignant melanocytic neoplasms. In this study, we investigated the clinical significance of PRAME expression in dysplastic nevi (DN) and nevus-associated melanoma in situ (MIS). METHODS: We included 172 DN and 38 nevus-associated MIS from our institutional archive. PRAME positive expression was defined as nuclear staining in at least 75% of melanocytes. In addition, relevant studies from PubMed and Web of Science were incorporated into a meta-analysis using the random-effects model to assess PRAME expression in MIS and DN. RESULTS: Our institutional data revealed that 71.1% of nevus-associated MIS cases exhibited positive PRAME expression in the MIS components, whereas all DN components were negative for PRAME. 5.7% of cases diagnosed as DN in our cohort demonstrated diffuse positivity for PRAME. Notably, MIS associated with DN displaying epidermal and dermal components displayed a higher likelihood of PRAME positivity compared to those arising on a background of DN with solely epidermal (junctional) components (84% vs. 46%, p = 0.024). The meta-analysis indicated that the pooled PRAME positivity in MIS and DN was 54.5% and 1.9%, respectively. CONCLUSION: PRAME is a valuable immunohistochemical marker for differentiating MIS from DN, particularly in the context of nevus-associated MIS.
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CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.
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Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a common subtype of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients. The current systematic review and meta-analysis was performed to evaluate the clinicopathological, and genetic characteristics of patients with ACD-RCC. A systematic search on three electronic databases including the Pubmed, Scopus, and Web of Science databases were performed until December 31, 2022. A meta-analysis was performed following the PRISMA 2020 Guidelines. Of 888 identified articles, full-text screening in 69 articles, there were 26 articles analyzed, with a total of 2314 tumors in 2199 patients, including 418 ACD-RCC tumors in 363 patients, 1340 clear cell RCC (ccRCC) tumors, 308 papillary RCC (pRCC) tumors. Most ACD-RCC patients were male (80.2%). All the ACD-RCC patients underwent prior dialysis with 148.2 months of mean dialysis duration. There were 8.7%, 3.4%, and 5.8% tumors at the T3-4 stage, N1 stage, and M1 stage, respectively. The mean overall survival of ACD-RCC patients was 39.6 months (95% CI, 26.6-52.5). Compared to ccRCC and pRCC, ACD-RCC patients had a longer duration of dialysis (MD: 103.5 and 31.77 months, respectively; 95% CI: [75.48; 131.53] and [0.95; 62.58], respectively), and a higher rate of multifocal tumors (MD: 3.46 and 2.45 tumors, respectively; 95% CI [1.71; 6.98] and [1.26; 4.79], respectively). Regarding genetic characteristics, chromosomes 3 and 16 were the 2 most frequent chromosomal aberrations. The missense mutation in KMT2C (25%) and TSC2 (18.75%) were the 2 most common gene mutations in ACD-RCC. In conclusion, the ACD-RCC subtype exhibited several distinct clinicopathological and genetic characteristics compared to others RCC subtypes. Further researchs are needed to assess the survival outcome and the genetic characteristics of this subtype.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Neoplasias Renais/patologia , Masculino , Falência Renal Crônica , Doenças Renais Císticas/genética , Doenças Renais Císticas/complicações , Feminino , PrognósticoRESUMO
Differentiating BRAF V600E- and RAS-altered encapsulated follicular-patterned thyroid tumors based on morphology remains challenging. This study aimed to validate an 8-score scale nuclear scoring system and investigate the importance of nuclear pseudoinclusions (NPIs) in aiding this differentiation. A cohort of 44 encapsulated follicular-patterned tumors with varying degrees of nuclear atypia and confirmed BRAF V600E or RAS alterations was studied. Nuclear parameters (area, diameter, and optical density) were analyzed using a deep learning model. Twelve pathologists from eight Asian countries visually assessed 22 cases after excluding the cases with any papillae. Eight nuclear features were applied, yielding a semi-quantitative score from 0 to 24. A threshold score of 14 was used to distinguish between RAS- and BRAF V600E-altered tumors. BRAF V600E-altered tumors typically demonstrated higher nuclear scores and notable morphometric alterations. Specifically, the nuclear area and diameter were significantly larger, and nuclear optical density was much lower compared to RAS-altered tumors. Observer accuracy varied, with two pathologists correctly identifying genotype of all cases. Observers were categorized into proficiency groups, with the highest group maintaining consistent accuracy across both evaluation methods. The lower group showed a significant improvement in accuracy upon utilizing the 8-score scale nuclear scoring system, with notably increased sensitivity and negative predictive value in BRAF V600E tumor detection. BRAF V600E-altered tumors had higher median total nuclear scores. Detailed reevaluation revealed NPIs in all BRAF V600E-altered cases, but in only 2 of 14 RAS-altered cases. These results could significantly assist pathologists, particularly those not specializing in thyroid pathology, in making a more accurate diagnosis.
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Proteínas Proto-Oncogênicas B-raf , Neoplasias da Glândula Tireoide , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Feminino , Pessoa de Meia-Idade , Masculino , Mutação , Adulto , Reprodutibilidade dos Testes , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/diagnóstico , Idoso , Núcleo Celular/patologia , Variações Dependentes do Observador , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Aprendizado Profundo , Diagnóstico Diferencial , Proteínas ras/genética , Valor Preditivo dos TestesRESUMO
Background: Several centers have reported their experience with single-port robot-assisted partial nephrectomy (SP-RAPN); however, it is uncertain if utilization of this platform represents an improvement in outcomes compared to multiport robot-assisted partial nephrectomy (MP-RAPN). To evaluate this, we performed a meta-analysis to compare the perioperative, oncological, and functional outcomes between SP-RAPN and MP-RAPN. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 1, 2023. A meta-analysis has been reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and assessing the methodological quality of systematic reviews (AMSTAR) guidelines. The odds ratio (OR) and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 374 retrieved abstracts, 29 underwent full-text review, and 8 studies were included in the final analysis, comprising a total cohort of 1007 cases of RAPN (453 SP-RAPN cases and 554 MP-RAPN cases). Compared to MP-RAPN, the SP-RAPN group had a significantly longer ischemia time (MD = 4.6 minutes, 95% CI 2.8 to 6.3, p < 0.001), less estimated blood loss (MD = -12.4 mL, 95% CI -24.6 to -0.3, p = 0.045), higher blood transfusion rate (OR = 2.97, 95% CI 1.33 to 6.65, p = 0.008), and higher postoperative estimated glomerular filtration rate (eGFR) at 6 months (MD = 4.9 mL/min, 95% CI 0.2 to 9.7, p = 0.04). There was no significant difference in other outcomes between the two approaches, including the intraoperative complication, overall postoperative complication, minor postoperative complication (Clavien-Dindo I - II), major postoperative complication (Clavien-Dindo III-V), conversion to radical nephrectomy, pain score on day #1, pain score on discharge, morphine milligram equivalent usage, hospital stay, positive surgical margins, and postoperative eGFR. Conclusions: SP-RAPN represents an emerging technique using a novel platform. Initial studies have demonstrated that SP-RAPN is a safe and feasible approach to performing partial nephrectomy, although with inferior outcomes for ischemia time and blood transfusion rates. Further studies will be necessary to define the best usage of SP-RAPN within the surgeon's armamentarium.
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Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Neoplasias Renais/cirurgia , Resultado do Tratamento , Nefrectomia/métodos , Transfusão de Sangue , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias/etiologia , Isquemia , Dor , Estudos RetrospectivosRESUMO
Importance: Personalized surveillance, prophylaxis, and cancer treatment options for individuals with hereditary cancer predisposition are informed by results of germline genetic testing. Improvements to genomic technology, such as the availability of RNA sequencing, may increase identification of individuals eligible for personalized interventions by improving the accuracy and yield of germline testing. Objective: To assess the cumulative association of paired DNA and RNA testing with detection of disease-causing germline genetic variants and resolution of variants of uncertain significance (VUS). Design, Setting, and Participants: Paired DNA and RNA sequencing was performed on individuals undergoing germline testing for hereditary cancer indication at a single diagnostic laboratory from March 2019 through April 2020. Demographic characteristics, clinical data, and test results were curated as samples were received, and changes to variant classification were assessed over time. Data analysis was performed from May 2020 to June 2023. Main Outcomes and Measures: Main outcomes were increase in diagnostic yield, decrease in VUS rate, the overall results by variant type, the association of RNA evidence with variant classification, and the corresponding predicted effect on cancer risk management. Results: A total of 43â¯524 individuals were included (median [range] age at testing, 54 [2-101] years; 37â¯373 female individuals [85.7%], 6224 male individuals [14.3%], and 2 individuals of unknown sex [<0.1%]), with 43â¯599 tests. A total of 2197 (5.0%) were Ashkenazi Jewish, 1539 (3.5%) were Asian, 3077 (7.1%) were Black, 2437 (5.6%) were Hispanic, 27â¯793 (63.7%) were White, and 2049 (4.7%) were other race, and for 4507 individuals (10.3%), race and ethnicity were unknown. Variant classification was impacted in 549 individuals (1.3%). Medically significant upgrades were made in 97 individuals, including 70 individuals who had a variant reclassified from VUS to pathogenic/likely pathogenic (P/LP) and 27 individuals who had a novel deep intronic P/LP variant that would not have been detected using DNA sequencing alone. A total of 93 of 545 P/LP splicing variants (17.1%) were dependent on RNA evidence for classification, and 312 of 439 existing splicing VUS (71.1%) were resolved by RNA evidence. Notably, the increase in positive rate (3.1%) and decrease in VUS rate (-3.9%) was higher in Asian, Black, and Hispanic individuals combined compared to White individuals (1.6%; P = .02; and -2.5%; P < .001). Conclusions and Relevance: Findings of this diagnostic study demonstrate that the ability to perform RNA sequencing concurrently with DNA sequencing represents an important advancement in germline genetic testing by improving detection of novel variants and classification of existing variants. This expands the identification of individuals with hereditary cancer predisposition and increases opportunities for personalization of therapeutics and surveillance.
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Testes Genéticos , Neoplasias , Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Testes Genéticos/métodos , Neoplasias/genética , Predisposição Genética para Doença , Análise de Sequência de RNA , RNARESUMO
The Asian Thyroid Working Group was founded in 2017 at the 12th Asia Oceania Thyroid Association (AOTA) Congress in Busan, Korea. This group activity aims to characterize Asian thyroid nodule practice and establish strict diagnostic criteria for thyroid carcinomas, a reporting system for thyroid fine needle aspiration cytology without the aid of gene panel tests, and new clinical guidelines appropriate to conservative Asian thyroid nodule practice based on scientific evidence obtained from Asian patient cohorts. Asian thyroid nodule practice is usually designed for patient-centered clinical practice, which is based on the Hippocratic Oath, "First do not harm patients," and an oriental filial piety "Do not harm one's own body because it is a precious gift from parents," which is remote from defensive medical practice in the West where physicians, including pathologists, suffer from severe malpractice climate. Furthermore, Asian practice emphasizes the importance of resource management in navigating the overdiagnosis of low-risk thyroid carcinomas. This article summarizes the Asian Thyroid Working Group activities in the past 7 years, from 2017 to 2023, highlighting the diversity of thyroid nodule practice between Asia and the West and the background reasons why Asian clinicians and pathologists modified Western systems significantly.
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INTRODUCTION: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described entity. The clinicopathological features and prognosis of the molecular subgroups of these rare tumors is poorly understood. In this study, we presented a small case series of three new cases and integrated the data with published cases in the literature to characterize the similarities and differences of molecular subgroups of PLNTY. METHODS: We searched our institutional archive for PLNTY cases and searched PubMed and Web of Science for relevant data. Demographic, clinical, radiologic, histopathological, molecular, and follow-up data of our four cases with published cases were integrated for final analyses. RESULTS: We identified three institutional cases of PLNTY. The median age of our patients was 17 years (range: 13-42). All patients had a prior history of chronic seizures and all had tumors affecting the temporal lobes. Histopathologically, all cases showed oligodendroglial-like morphology with intratumoral calcifications and at least partially infiltrative growth patterns. Tumor cells were immunoreactive with CD34 and GFAP. Genetically, all cases harbored BRAF V600E mutations. Integrated analyses, including a total of 67 cases, demonstrated that PLNTYs with FGFR2 mutation were significantly younger (median age 11.0 years) than those with BRAF V600E or FGFR3 fusions (median age 41.0 and 16.0 years, respectively). All BRAF V600E-positive PLNTYs were free of tumor recurrence, while four of PLNTYs in other molecular subgroups developed tumor recurrence by imaging. CONCLUSION: Our study suggests that PLNTYs have distinct clinicopathological features and are driven by genetic alterations in the MAPK pathway. The molecular subgroups of PLNTYs share similar findings, but also demonstrate distinct patient demographics.
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Neoplasias Encefálicas , Neoplasias Neuroepiteliomatosas , Humanos , Adolescente , Adulto Jovem , Adulto , Criança , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia , Proteínas Proto-Oncogênicas B-raf/genética , Relevância Clínica , Neoplasias Neuroepiteliomatosas/genética , MutaçãoRESUMO
BACKGROUND: PRAME (PReferentially expressed Antigen in MElanoma) is a biomarker studied in various human cancers. Little is known about the biological implications of PRAME in glioma. We aimed to perform a comprehensive analysis to explore PRAME gene expression and its biological and clinicopathological significance in gliomas. METHODS AND MATERIALS: We accessed the human cancer atlas (TCGA) database to collect glioma patients (n = 668) with primary tumors and gene expression data. Single nucleotide variants, copy number variation, DNA methylation data, and other clinicopathological factors were also extracted for the analysis. RESULTS: Overall, 170, 484, and 14 tumors showed no expression, low expression (FPKM≤1), and overexpression (FPKM>1) of the PRAME gene, respectively. The principal component analysis and pathway analyses showed that PRAME-positive gliomas (n = 498), which consisted of tumors with PRAME low expression and overexpression, expressed different oncogenic profiles, possessing higher activity of Hedgehog, P3IK-AKT-mTOR, and Wnt/ß-catenin pathways (p<0.001). DNA methylation analysis also illustrated that PRAME-positive tumors were distributed more densely within a grade 4-related cluster (p<0.001). PRAME positivity was an independent prognostic factor for poor outcomes in a multivariate cox analysis adjusted for clinical characteristics and genetic events. Kaplan-Meier analysis stratified by revised classification showed that PRAME positivity was solely associated with IDH-wildtype glioblastoma, grade 4. Finally, PRAME-overexpressing cases (n = 14) had the worst clinical outcome compared to the PRAME-negative and PRAME-low cohorts (adjusted p<0.001) in pairwise comparisons. CONCLUSION: PRAME expression statuses may dictate different biological and clinicopathological profiles in IDH-wildtype glioblastoma.
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Glioblastoma , Glioma , Humanos , Adulto , Prognóstico , Variações do Número de Cópias de DNA , Glioma/genética , Glioma/metabolismo , Estimativa de Kaplan-Meier , Antígenos de Neoplasias/genéticaRESUMO
INTRODUCTION: Sparsely granulated somatotroph adenoma/tumor (SGST) is thought to be more clinically aggressive than densely granulated somatotroph adenoma/tumor (DGST). However, the literature is not entirely consistent as to the disparate demographic and behavioral features of these subtypes. In this study, we conducted a meta-analysis to further clarify the demographic, clinicopathological, prognostic, and molecular characteristics of SGST versus DGST. METHODS: We accessed two electronic databases to search for potential data. Pooled estimates of odds ratio (OR), mean difference (MD), and corresponding 95% confidence interval (CI) were calculated using the random-effect model. RESULTS: SGST was associated with younger patient age and lower male-to-female ratio (p < 0.001) compared to DGST. Clinically, SGST had larger tumor size and high rate of cavernous sinus and suprasellar extension (p < 0.001) than DGST. During postoperative follow-up, SGST was associated with a lower endocrinological remission rate (OR 0.60; 95% CI 0.40 to 0.90; p = 0.01) and a poorer response rate to SRL (OR 0.16; 95% CI 0.08-0.35; p < 0.001) in comparison to DGST. The prevalence of GSP mutations was significantly lower in SGST (OR 0.36; 95% CI 0.17 to 0.79; p = 0.01). CONCLUSION: SGST and DGST were demographically, clinicopathologically, and molecularly different from each other with the former associated with adverse treatment outcomes and poor response to medical therapy. There are still gaps in translational studies that could help us better understand the behavior of these tumors and identify potential targets in the treatment of sparsely granulated tumors.
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Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Neoplasias Hipofisárias , Masculino , Humanos , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Adenoma/cirurgia , Prognóstico , Resultado do TratamentoRESUMO
INTRODUCTION: Data on silent corticotroph tumor (SCT) are still heterogeneous and controversial. In this study, we aimed to compare the demographic, clinicopathological manifestations, postoperative complications, and patient outcomes of SCTs with other non-functioning pituitary neuroendocrine tumor (NFT) and functioning corticotroph tumor (FCT) or so-called Cushing disease adenoma. METHODS: We searched PubMed and Web of Science for data of interest. Odds ratio (OR), mean difference (MD), hazard ratio (HR), and their 95% confidence intervals (CI) were pooled using the random-effect model. RESULTS: Twenty-nine studies with 985 SCTs were included in meta-analyses. In comparison to other NFTs, SCTs were more commonly associated with female gender, younger age, cavernous sinus invasion, apoplexy, and radiotherapy administration. Postoperatively, SCT patients were more likely to experience hypocortisolism, new-onset visual disturbances, and a higher risk for tumor progression than other NFTs. We did not find any significant differences between SCT type I and type II. Compared to FCTs, SCTs were more likely male, older age, and had larger tumor sizes. The prevalence of a USP8 mutation was significantly higher in FCT than in SCT. CONCLUSION: SCT was demographically, clinicopathologically, and prognostically distinct from other NFTs and FCTs. These tumors should be considered high-risk; appropriate treatment decisions and more stringent follow-up should be tailored to improve patient outcomes.
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Adenoma Hipofisário Secretor de ACT , Adenoma , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Humanos , Masculino , Feminino , Corticotrofos , Adenoma/cirurgia , Neoplasias Hipofisárias/patologia , Hipersecreção Hipofisária de ACTH/complicações , Prognóstico , Adenoma Hipofisário Secretor de ACT/complicaçõesRESUMO
NAA10 is a novel biomarker of cancer progression. The oncogenic and biological mechanisms of NAA10 in human malignancies are controversial and remain to be elucidated. Herein, we investigated the biological and clinicopathological implications of NAA10 gene expression in adult gliomas. We collected data from The Human Cancer Genome Atlas (TCGA) database, including patients from TCGA-GBM and TCGA-LGG projects. In total, there were 666 patients from the 2 projects (513 and 153 from TCGA-LGG and TCGA-GBM, respectively). Different analyses (pathway, DNA methylation, and survival analyses) require further specific case eliminations. Based on NAA10 expression, we divided 666 tumors into 2 subgroups: NAA10-high and NAA10-low glioma. There were higher activities of cell proliferation, metabolic reprogramming, DNA repair, angiogenesis, epithelial-mesenchymal transition, TNF-α, IL6/JAK/STAT6, mTORC1 signaling, and MYC targets in NAA10-high glioma, while P53, TGF-ß, Wnt, and Hedgehog pathways were highly expressed by NAA10-low gliomas. t-distributed stochastic neighbors embedding dimension reduction of DNA methylation also showed a high distribution of NAA10-high gliomas in distinct clusters. Survival analyses showed that high NAA10 expression was an independent prognostic factor. NAA10 expression dictated epigenetic, genetic, and clinicopathological differences in adult glioma. Further studies are required to investigate the detailed NAA10 oncogenic mechanisms and to validate NAA10 immunohistochemistry.
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Neoplasias Encefálicas , Glioma , Humanos , Adulto , Neoplasias Encefálicas/patologia , Proteínas Hedgehog/genética , Glioma/patologia , Metilação de DNA , Epigênese Genética , Prognóstico , Acetiltransferase N-Terminal A/genética , Acetiltransferase N-Terminal A/metabolismo , Acetiltransferase N-Terminal E/genética , Acetiltransferase N-Terminal E/metabolismoRESUMO
Introduction: We investigated the clinicopathological features and prognoses of the new molecularly defined entities in latest edition of the World Health Organization (WHO) classification of sinonasal carcinoma (SNC). Methods: Integrated data were combined into an individual patient data (IPD) meta-analysis. Results: We included 61 studies with 278 SNCs including 25 IDH2-mutant, 41 NUT carcinoma, 187 SWI/SNF loss, and 25 triple negative SNCs (without IDH2 mutation, NUTM1 rearrangement, and SWI/SNF inactivation) for analyses. Compared to other molecular groups, NUT carcinoma was associated with a younger age at presentation and an inferior disease-specific survival. Among SNCs with SWI/SNF inactivation, SMARCB1-deficient tumors presented later in life and were associated with a higher rate of radiotherapy administration. SMARCA4-deficiency was mostly found in teratocarcinosarcoma while SMARCB1-deficient tumors were associated with undifferentiated carcinoma and non-keratinizing squamous cell carcinoma. Conclusion: Our study facilitates our current understanding of this developing molecular-defined spectrum of tumors and their prognoses.
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OBJECTIVE: There is a lack of data about the clinicopathological and molecular characteristics of de novo versus secondary dedifferentiated chordoma (DC). This integrated study aimed to investigate the similarities and differences in clinicopathological manifestations, prognoses, and molecular profiles of these 2 subtypes. METHODS: We accessed the Surveillance, Epidemiology, and End Results (SEER) Program for DC cases from 1975 to 2020. Three electronic databases were also searched for additional DCs. Individual patient data of DC patients from SEER and published literature were combined in integrated analyses. RESULTS: After excluding duplicated patients, we identified 14 and 116 DC patients from SEER and published literature, respectively. There were 74 de novo, 39 secondary, and 18 cases with unknown origin. Our results showed that de novo and secondary DCs were not statistically different in terms of age, gender, primary location, tumor size, distant metastasis at diagnosis, extent of resection, and chemotherapy receipt. There was limited available molecular data for de novo and secondary DCs, though examples TP53 mutations were found in both. In addition, the rates of tumor relapse, metastasis during follow-up, and patient mortality were also comparable between the 2 groups. In the multivariate Cox regression model, we demonstrated that gross total removal and radiotherapy use were associated with prolonged survival of DCs. CONCLUSIONS: De novo and secondary DCs were statistically comparable in terms of patient demographics, clinical manifestations, and prognoses. Gross total excision and radiotherapy were optimal treatments associated with better outcomes of DC patients.
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Cordoma , Humanos , Cordoma/patologia , Prognóstico , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Bases de Dados Factuais , Programa de SEERRESUMO
Mucoepidermoid carcinoma (MEC) and sclerosing MEC with eosinophilia (SMECE) are rare primary thyroid carcinomas. In this study, we aimed to present our multicenter series of MEC and SMECE and integrated our data with published literature to further investigate the clinicopathological characteristics and prognoses of these tumors. We found 2 MECs and 4 SMECEs in our multicenter archives. We performed fluorescence in situ hybridization (FISH) to determine the MAML2 gene rearrangement. We screened for mutations in BRAF, TERT promoter, and RAS mutations using Sanger sequencing and digital polymerase chain reaction. Histopathologically, MECs and SMECEs were composed of two main cell types including epidermoid and mucin-secreting cells, arranged in cords, nests, and tubules. SMECEs were characterized by a densely sclerotic stroma with abundant eosinophils. We did not detect any MAML2 fusion in any of our cases. Two MEC cases harbored concomitant BRAF p.V600E and TERT C228T mutations. RAS mutations were absent in all cases. Concurrent foci of another thyroid malignancy were more commonly seen in MECs (p < 0.001), whereas SMECEs were associated with chronic lymphocytic thyroiditis (p < 0.001). MECs and SMECEs had equivalent recurrence-free survival (RFS) but MECs conferred significantly dismal disease-specific survival (DSS) as compared to SMECEs (p = 0.007). In conclusion, MECs and SMECEs not only shared some similarities but also demonstrated differences in clinicopathological characteristics, prognoses, and molecular profiles. SMECEs had a superior DSS in comparison to MECs, suggesting that they are low-grade cancers. This could help clinicians better evaluate patient outcomes and decide appropriate treatment plans.
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Carcinoma Mucoepidermoide , Eosinofilia , Humanos , Glândula Tireoide/patologia , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas B-raf/genética , Fatores de Transcrição/genética , Eosinofilia/genética , Eosinofilia/patologiaRESUMO
Objective: To compare the perioperative, oncological, and functional outcomes between single-port robot-assisted radical prostatectomy (SP-RARP) and multiport robot-assisted radical prostatectomy (MP-RARP) via a meta-analysis. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 15, 2022. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. The risk ratio and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 368 retrieved abstracts, 41 underwent full-text review, and seven studies were included in the final analysis, comprising a total cohort of 1,934 cases of RARP (355 SP-RARP cases and 1,579 MP-RARP cases). Compared to MP-RARP, the SP-RARP group had less postoperative pain score (MD = -0.7, 95% CI -1 to -0.4, P<0.001), morphine milligram equivalents usage (MD = -3.8, 95% CI -7.5 to -0.1, P=0.04), hospital stay (MD = -1, 95% CI -1.8 to -0.1, P=0.019), and urinary catheterization time (MD = -1.1, 95% CI -1.9 to -0.3, P=0.008). However, the SP-RARP group had a longer console time than the MP-RARP group (MD = 5.3, 95% CI 2.6 to 7.9, P<0.001). Conclusions: Our study demonstrated that early results were mostly equivalent with the single-port approach. This technology may help to reduce the hospital stay and postoperative pain for patients undergoing radical prostatectomy compared to MP-RARP, without compromising the functional and early oncological outcomes.
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Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey-Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism.
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INTRODUCTION: Fusion oncogenes (e.g., NTRK, RET, ALK, BRAF) are rare genetic events in papillary thyroid carcinoma (PTC). It is still unclear regarding the similarities and differences in clinicopathological manifestations and prognostic outcomes of these genetic alterations. This individual patient data (IPD) meta-analysis analyzed the clinicopathological significance and prognoses of different types of oncogenic fusions in PTC patients. METHODS: Categorical variables were compared by using Chi-square and Fisher's exact tests while Wilcoxon rank-sum and analysis of variance (ANOVA) tests were utilized for continuous covariates. Progression-free survival (PFS) and overall survival (OS) were computed using Kaplan-Meier analysis and log-rank test. RESULTS: We included 27 studies for meta-analyses. NTRK-, RET-, BRAF-, and ALK-rearranged PTCs had a unique demographic/clinicopathological profile but similar PFS and OS. NTRK1-positive PTCs demonstrated more aggressive clinical behaviors and shorter PFS in comparison to NTRK3-positive PTCs whereas RET rearrangement variants shared comparable clinicopathological backgrounds. CONCLUSION: This study provides new insights and facilitates our current understanding of clinicopathological features and survival outcomes of different fusion oncogenes in PTCs. It may help clinicians better counsel the patients and tailor appropriate treatment decisions.
Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/patologia , Mutação , Oncogenes/genética , Receptores Proteína Tirosina Quinases/genética , Rearranjo GênicoRESUMO
OBJECTIVE: COVID-19 has not only impacted healthcare systems directly via hospitalizations and resource utilization, but also indirectly via adaptations in healthcare practice, such as the evolution of the academic environment and the rise of telemedicine and virtual education. This void in clinical responsibilities has been filled with academic productivity in various fields. In this study the authors investigate the influence of COVID-19 on the academic focus within pediatric neurosurgery. METHODS: All data were obtained from the Journal of Neurosurgery: Pediatrics (JNS Peds). The number of submissions for each month from January 2017 to December 2021 was collected. Data including number of publications, publication level of evidence (LOE), and COVID-19-related articles were collected and verified. Each publication was categorized by manuscript and LOE according to adaptations from the Canadian Task Force on Periodic Health Examination. Publication groups were categorized as pre-COVID-19 (January 2017-February 2020), peri-COVID-19 (March 2020-July 2020), and post-COVID-19 (August 2020-December 2021). Statistical analysis was performed to compare pre-COVID-19, peri-COVID-19, and post-COVID-19 academic volume and quality. RESULTS: During the study time period, a total of 3116 submissions and 997 publications were identified for JNS Peds. Only 2 articles specifically related to COVID-19 and its impact on pediatric neurosurgery were identified, both published in 2021. When analyzing submission volume, a statistically significant increase was seen during the shutdown relative to pre-COVID-19 and post-shutdown time periods, and a significant decrease was seen post-shutdown relative to pre-COVID-19. LOE changed significantly as well. When comparing pre-COVID-19 versus post-COVID-19 articles, a statistically significant increase was identified only in level 4 publications. When analyzing pre-COVID-19 versus post-COVID-19 (2020) and post-COVID-19 (2021), a statistically significant decrease in level 3 and increases in levels 4 and 5 were identified during post-COVID-19 (2020), with a rebound increase in level 3 and a decrease in level 5 during post-COVID-19 (2021). CONCLUSIONS: There was a significant increase in manuscript submission during the initial pandemic period. However, there was no change during subsequent spikes in COVID-19-related hospitalizations. Coincident with the initial surge in academic productivity, despite steady publication volume, was an inverse decline in quality as assessed by LOE.