Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
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Esophageal epidermoid metaplasia is a rare condition that involves the proximal-to-middle third of the esophagus. It is sharply demarcated and defined histologically by epithelial hyperplasia, a prominent granular cell layer, and superficial hyperorthokeratosis. In addition, preliminary studies have suggested an association between esophageal epidermoid metaplasia and esophageal squamous neoplasia (squamous dysplasia and esophageal squamous cell carcinoma). ⋯ No genetic alterations were detected in uninvolved esophageal squamous mucosa. On the basis of these findings, we conclude esophageal epidermoid metaplasia is a precursor to in situ and invasive esophageal squamous neoplasia. Further, the detection of TP53 mutations in esophageal epidermoid metaplasia specimens may serve as an early detection biomarker for high-grade squamous dysplasia/esophageal squamous cell carcinoma.
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Head and neck squamous cell carcinoma is typically characterized by a high incidence of local recurrences. It has been extensively shown that mucosa from head and neck squamous cell carcinoma patients carries both genetic and gene expression alterations, which are mostly attributable to major etiologic agents of head and neck squamous cell carcinoma. We previously identified a signature of microRNAs (miRNAs) whose high expression in tumors is predictive of recurrence. ⋯ The predictive power of the miRNA signature increased when using the expression levels derived from both the peritumoral and the tumoral tissues. The expression signal of the miRNAs composing the predictive signature correlated with the transcriptional levels of genes mostly associated with proliferation. Our results show that expression of miRNAs in tumor-surrounding mucosa may strongly contribute to the identification of head and neck squamous cell carcinoma patients at high risk of local recurrence.
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Dysregulated NF-κB signaling is critical for lymphomagenesis, however, the expression and clinical relevance of NF-κB subunit p50 in diffuse large B-cell lymphoma have not been evaluated. In this study, we analyzed the prognostic significance and gene expression signatures of p50 nuclear expression as a surrogate for p50 activation in 465 patients with de novo diffuse large B-cell lymphoma. We found that p50+ nuclear expression, observed in 34.6% of diffuse large B-cell lymphoma, predominantly composed of activated B-cell-like subtype, was an independent adverse prognostic factor in patients with activated B-cell-like diffuse large B-cell lymphoma. ⋯ Gene expression profiling revealed multiple signaling pathways potentially upstream the p50 activation through either canonical or noncanonical NF-κB pathways, and suggested that immune suppression, including that by the immune checkpoint TIM-3 and that through leukocyte immunoglobulin-like receptors, but not antiapoptosis and proliferation, may underlie the observed poorer survival rates associated with p50+ nuclear expression in diffuse large B-cell lymphoma. In conclusion, these data show that p50 is important as a unique mechanism of R-CHOP-resistance in activated B-cell-like diffuse large B-cell lymphoma and in patients without TP53 mutations. The results also provide insights into the regulation and function of p50 in diffuse large B-cell lymphoma and its cross talk with the p53 pathway with important therapeutic implications.
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Thyroid tumors formerly classified as non-invasive encapsulated follicular variant of papillary thyroid carcinoma were recently renamed 'non-invasive follicular thyroid neoplasm with papillary-like nuclear features'. The current study investigated the frequency of lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such tumors based on the complete absence of papillae or presence of ≤1% papillae. ⋯ Our findings suggest that non-invasive follicular thyroid neoplasm with papillary-like nuclear features should not be regarded as a benign thyroid neoplasm as it can present with lymph node micrometastasis and should not be diagnosed in the presence of even a single papillary structure. Our findings underscore the original American Thyroid Association recommendation that defined non-invasive encapsulated follicular variants as low risk thyroid cancers. Clinical surveillance similar to low risk differentiated thyroid cancers and capture of this diagnostic category by Cancer Registries should be considered.
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Post-transplantation lymphoproliferative disorder is an aggressive complication of transplantation, most frequently of diffuse large B-cell lymphoma morphology and associated with Epstein-Barr virus (EBV) infection/reactivation. In this study the microenvironment of EBV+ (n=23) and EBV- (n=9) post-transplant non-germinal center B-cell diffuse large B-cell lymphoma was characterized. Of EBV+ cases somatic hypermutation analysis, gene expression profiling, and extensive phenotyping were performed. ⋯ In these tumors T-cell signaling was enhanced associated with increased T-cell infiltration compared with IgM+ cases. Overall, our results allow further molecular classification of EBV+ post-transplant diffuse large B-cell lymphoma and provide a rationale for the use of subtype-specific-targeted therapies (eg, bortezomib in IgM+ tumors). Our findings also provide a biological basis for the clinical differences between post-transplant lymphoproliferative disorder following solid organ and stem cell transplantation, which are regarded as different disorders.