Human pathology
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Case Reports
Molecular classification of adult diffuse gliomas: conflicting IDH1/IDH2, ATRX, and 1p/19q results.
Until recently, the diagnosis of brain tumors was primarily based on microscopic examination of hematoxylin and eosin-stained tissue sections. The updated World Health Organization (WHO) Classification of Tumours of the Central Nervous System incorporates genetic alterations into the classification system, with the goal of creating more homogenous disease categories with greater prognostic value. Hence, under the new classification system, the diagnosis of diffuse gliomas incorporates the evaluation of mutations in the IDH1 and IDH2 genes and simultaneous deletion of chromosomes 1p and 19q. ⋯ Here we present 6 cases of diffuse glioma that presented a diagnostic challenge due to conflicting molecular testing results. These cases exemplify some of the potential complications that arise when introducing the new 2016 central nervous system WHO classification system diagnostic criteria into routine clinical practice. We aim to alert the general practice pathology community to these potential conflicts to help mitigate the risk of potential misdiagnosis.
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Comparative Study
Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma.
Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non-small cell lung carcinoma (NSCLC) patients for treatment with anti-PD-1 or anti-PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). ⋯ The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases.
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Renal cell carcinomas (RCCs) with Xp11 translocation (Xp11 RCC) constitute a distinctive molecular subtype characterized by chromosomal translocations involving the Xp11.2 locus, resulting in gene fusions between the TFE3 transcription factor with a second gene (usually ASPSCR1, PRCC, NONO, or SFPQ). RCCs with Xp11 translocations comprise up to 1% to 4% of adult cases, frequently displaying papillary architecture with epithelioid clear cells. To better understand the biology of this molecularly distinct tumor subtype, we analyze the microRNA (miRNA) expression profiles of Xp11 RCC compared with normal renal parenchyma using microarray and quantitative reverse-transcription polymerase chain reaction. ⋯ Finally, Xp11 RCC is most strongly associated with miRNA expression profiles modulating DNA damage responses, cell cycle progression and apoptosis, and the Hedgehog signaling pathway. In summary, we describe here for the first time the miRNA expression profiles of a molecularly distinct type of renal cancer associated with Xp11.2 translocations involving the TFE3 gene. Our results might help understanding the molecular underpinning of Xp11 RCC, assisting in developing targeted treatments for this disease.
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One of the major breakthroughs in oncology in the past decade has been the research and development of immune checkpoint inhibitors. Since the discovery of the PD-1/PD-L1 axis as a key mediator in peripheral self-tolerance and the subsequent discovery of its role promoting immune escape in cancers, the PD-1/PD-L1 pathway has produced considerable excitement from both a scientific and therapeutic standpoint. The past decade has seen an explosion in the number of clinical trials utilizing anti-PD-1/PD-L1 therapy. ⋯ However, many open questions remain in a rapidly changing therapeutic and scientific landscape. In this review, we describe the basic functioning of the PD-1/PD-L1 axis in normal biology, how it is coopted by cancers to promote immune escape, and then review the literature regarding the prognostic value of tumoral PD-L1 expression on its own before discussing recent therapeutic advances, and the emerging role for pathologists in predicting response to anti-PD-1/PD-L1 therapies. Special attention is given to melanoma and non-small cell lung cancer, malignancies that have seen the broadest applications of anti-PD-L1/PD-1 therapies.
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Lymphoplasmacytic infiltrates in esophageal adenocarcinoma (EAC) tissue following chemoradiotherapy (CRT) reflect alterations in the tumor immunoenvironment. The presence and role of plasma cells in this process are poorly understood. Our aim was to characterize the IgG4+ plasma cell population in EAC following CRT. ⋯ Multivariate analysis revealed that both posttherapy pathologic stage and high IgG4+ plasma cells in ulcers were independent predictors of overall survival (P = .05 and P = .01), whereas only posttherapy pathologic stage was associated with recurrence-free survival (P < .01). This is the first study describing a dense IgG4+ plasma cell infiltrate in EAC following CRT. The presence of increased IgG4+ plasma cells may be a novel reliable factor to predict prognosis of EAC patients following CRT.