Fungal rhinosinusitis (FRS) comprises a spectrum of disease processes that vary in clinical presentation, histologic appearances, and biological significance. FRS can be acute or chronic and is most ...commonly classified as non-invasive or invasive based on whether fungi have invaded into tissue. This manuscript will review the pathologic classification of FRS.
In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (lncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of lncRNA genes were located ...in regions with focal SCNAs. By integrating bioinformatics analyses of lncRNA SCNAs and expression with functional screening assays, we identified an oncogene, focally amplified lncRNA on chromosome 1 (FAL1), whose copy number and expression are correlated with outcomes in ovarian cancer. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A. The oncogenic activity of FAL1 is partially attributable to its repression of p21. FAL1-specific siRNAs significantly inhibit tumor growth in vivo.
Display omitted
•Copy number of lncRNA genes is altered in human cancer with high frequency•FAL1 amplification and high expression correlate with poor outcome in cancer•FAL1 stabilizes BMI1 by RNA-protein interaction and represses p21 transcription•Repressing FAL1 expression by siRNA inhibits tumor growth in vivo
Large-scale screening by Hu et al. reveals frequent SCNAs of lncRNAs in many cancers. One of these lncRNAs, FAL1, associates with poor outcomes in ovarian cancer patients and stabilizes BMI1 to promote tumor growth.
Men of predominantly African Ancestry (AA) have higher prostate cancer (CaP) incidence and worse survival than men of predominantly European Ancestry (EA). While socioeconomic factors drive this ...disparity, genomic factors may also contribute to differences in the incidence and mortality rates. To compare the prevalence of prostate tumor genomic alterations and transcriptomic profiles by patient genetic ancestry, we evaluated genomic profiles from The Cancer Genome Atlas (TCGA) CaP cohort (n = 498). Patient global and local genetic ancestry were estimated by computational algorithms using genotyping data; 414 (83.1%) were EA, 61 (12.2%) were AA, 11 (2.2%) were East Asian Ancestry (EAA), 10 (2.0%) were Native American (NA), and 2 (0.4%) were other ancestry. Genetic ancestry was highly concordant with self-identified race/ethnicity. Subsequent analyses were limited to 61 AA and 414 EA cases. Significant differences were observed by ancestry in the frequency of SPOP mutations (20.3% AA vs. 10.0% EA; p = 5.6×10-03), TMPRSS2-ERG fusions (29.3% AA vs. 39.6% EA; p = 4.4×10-02), and PTEN deletions/losses (11.5% AA vs. 30.2% EA; p = 3.5×10-03). Differentially expressed genes (DEGs) between AAs and EAs showed significant enrichment for prostate eQTL target genes (p = 8.09×10-48). Enrichment of highly expressed DEGs for immune-related pathways was observed in AAs, and for PTEN/PI3K signaling in EAs. Nearly one-third of DEGs (31.3%) were long non-coding RNAs (DE-lncRNAs). The proportion of DE-lncRNAs with higher expression in AAs greatly exceeded that with lower expression in AAs (p = 1.2×10-125). Both ChIP-seq and RNA-seq data suggested a stronger regulatory role for AR signaling pathways in DE-lncRNAs vs. non-DE-lncRNAs. CaP-related oncogenic lncRNAs, such as PVT1, PCAT1 and PCAT10/CTBP1-AS, were found to be more highly expressed in AAs. We report substantial heterogeneity in the prostate tumor genome and transcriptome between EA and AA. These differences may be biological contributors to racial disparities in CaP incidence and outcomes.
Currently, there is no uniform classification scheme available for reporting of salivary gland fine‐needle aspiration (FNA) specimens. Recently, an International group of pathologists has recommended ...a tiered classification scheme for reporting of salivary gland FNA results known as the “Milan System for Reporting Salivary Gland Cytopathology (MSRSGC).” We performed a comprehensive review of the published literature on FNA of salivary gland lesions by employing the diagnostic categories of the MSRSGC to evaluate their reliability in the management of salivary gland lesions. A comprehensive review of the literature was carried out through PubMed from 1987 to 2015 to identify studies which categorized the cytologic diagnoses and included surgical follow‐up. Only cases with histopathologic follow‐up were included in the analysis. Twenty‐nine studies comprising 4514 cases of salivary gland FNAs with surgical follow‐up were included in this study. The cytologic diagnoses were categorized into the following categories proposed by MSRSGC. The number of cases in each diagnostic category and the risk of malignancy (ROM) were as follows: Non‐Diagnostic—100 cases (ROM‐ 25.0% ± 16.7%), Non‐Neoplastic—587 cases (ROM: 10.2% ± 5.5%), Benign Neoplasm −2673 cases (ROM: 3.4% ± 1.3%), Salivary Gland Neoplasm of Undetermined Malignant Potential (SUMP)—64 cases(ROM: 37.5% ± 24.7%), Suspicious for Malignant neoplasm—70 cases(ROM: 58.6% ± 19.5%), and Malignant—1012 cases(ROM: 91.9% ± 3.5%). A tiered classification scheme as proposed by MSRSGC may prove helpful in effectively guiding clinical management of patients with salivary gland lesions.
Disparities in cancer care have been a long-standing challenge. We estimated the genetic ancestry of The Cancer Genome Atlas patients, and performed a pan-cancer analysis on the influence of genetic ...ancestry on genomic alterations. Compared with European Americans, African Americans (AA) with breast, head and neck, and endometrial cancers exhibit a higher level of chromosomal instability, while a lower level of chromosomal instability was observed in AAs with kidney cancers. The frequencies of TP53 mutations and amplification of CCNE1 were increased in AAs in the cancer types showing higher levels of chromosomal instability. We observed lower frequencies of genomic alterations affecting genes in the PI3K pathway in AA patients across cancers. Our result provides insight into genomic contribution to cancer disparities.
Display omitted
•The genetic ancestry of TCGA patients was estimated at global and local levels•The Cancer Genetic Ancestry Atlas, a publicly accessible resource, was developed•The frequencies of TP53 mutations and CCNE1 amplification were higher among AAs•The frequencies of the alterations in the PI3K pathway were lower among AAs
By analyzing TCGA cohorts, Yuan et al. show that breast, head and neck, and endometrial cancers of African Americans (AA) have higher levels of chromosomal instability than those of European Americans whereas the frequency of genetic alternations in the PI3K pathway in AA patients is lower across cancers.
We investigated the role of chemokines in regulating T cell accumulation in solid tumors. CCL5 and CXCL9 overexpression was associated with CD8+ T cell infiltration in solid tumors. T cell ...infiltration required tumor cell-derived CCL5 and was amplified by IFN-γ-inducible, myeloid cell-secreted CXCL9. CCL5 and CXCL9 coexpression revealed immunoreactive tumors with prolonged survival and response to checkpoint blockade. Loss of CCL5 expression in human tumors was associated with epigenetic silencing through DNA methylation. Reduction of CCL5 expression caused tumor-infiltrating lymphocyte (TIL) desertification, whereas forced CCL5 expression prevented Cxcl9 expression and TILs loss, and attenuated tumor growth in mice through IFN-γ. The cooperation between tumor-derived CCL5 and IFN-γ-inducible CXCR3 ligands secreted by myeloid cells is key for orchestrating T cell infiltration in immunoreactive and immunoresponsive tumors.
Display omitted
•CD8+ T cell infiltration in tumors is associated with CCL5 and CXCL9 coexpression•CCL5 is expressed in tumor cells and CXCL9 is induced in APCs in response to IFN-γ•CCL5hiCXCL9hi tumors are immunoreactive and respond to checkpoint blockade•Cancer cells negatively regulate CCL5 expression by epigenetic silencing mechanisms
Dangaj et al. show that tumor cell-expressed CCL5 and macrophage- and DC-expressed CXCL9 are important for the infiltration of T cells into tumors, a process that also requires recognition of tumor antigens by T cells. CCL5 is often epigenetically silenced in tumor cells but can be reactivated by Decitabine.
A number of entities may result in necrosis in the sinonasal tract and lead to significant morbidity and mortality. These include infections, necrotizing vasculitis, neoplastic processes, and drug ...dependency. This review will concentrate on the differential diagnosis of sinonasal necrotizing lesions.
To review the differential diagnoses of necrotizing destructive lesions of the sinonasal tract.
The current literature was reviewed to provide updated information regarding the differential diagnosis of sinonasal necrotizing lesions, including infectious disease processes; antineutrophilic cytoplasmic antibody-associated vasculitides; neoplastic processes, particularly natural killer/T-cell lymphomas; and drug abuse.
The differential diagnosis of necrotizing sinonasal lesions is broad, with often overlapping diagnostic features that lead to diagnostic challenges. Ancillary tests such as special stains and immunohistochemical studies can offer significant assistance.
Recent research suggests that endothelial activation plays a role in coronavirus disease 2019 (COVID-19) pathogenesis by promoting a pro-inflammatory state. However, the mechanism by which the ...endothelium is activated in COVID-19 remains unclear.
To investigate the mechanism by which COVID-19 activates the pulmonary endothelium and drives pro-inflammatory phenotypes.
The "inflammatory load or burden" (cytokine storm) of the systemic circulation activates endothelial NADPH oxidase 2 (NOX2) which leads to the production of reactive oxygen species (ROS) by the pulmonary endothelium. Endothelial ROS subsequently activates pro-inflammatory pathways.
The inflammatory burden of COVID-19 on the endothelial network, was recreated in vitro, by exposing human pulmonary microvascular endothelial cells (HPMVEC) to media supplemented with serum from COVID-19 affected individuals (sera were acquired from patients with COVID-19 infection that eventually died. Sera was isolated from blood collected at admission to the Intensive Care Unit of the Hospital of the University of Pennsylvania). Endothelial activation, inflammation and cell death were assessed in HPMVEC treated with serum either from patients with COVID-19 or from healthy individuals. Activation was monitored by measuring NOX2 activation (Rac1 translocation) and ROS production; inflammation (or appearance of a pro-inflammatory phenotype) was monitored by measuring the induction of moieties such as intercellular adhesion molecule (ICAM-1), P-selectin and the NLRP3 inflammasome; cell death was measured via SYTOX™ Green assays.
Endothelial activation (i.e., NOX2 activation and subsequent ROS production) and cell death were significantly higher in the COVID-19 model than in healthy samples. When HPMVEC were pre-treated with the novel peptide PIP-2, which blocks NOX2 activation (via inhibition of Ca2+-independent phospholipase A2, aiPLA2), significant abrogation of ROS was observed. Endothelial inflammation and cell death were also significantly blunted.
The endothelium is activated during COVID-19 via cytokine storm-driven NOX2-ROS activation, which causes a pro-inflammatory phenotype. The concept of endothelial NOX2-ROS production as a unifying pathophysiological axis in COVID-19 raises the possibility of using PIP-2 to maintain vascular health.
Update on Sinonasal Tract Malignancies Gubbiotti, Maria A; Livolsi, Virginia; Montone, Kathleen T
Archives of pathology & laboratory medicine,
2023-Mar-15, 2023-03-15, 20230315
Journal Article
Recenzirano
Odprti dostop
Sinonasal tract malignancies are rare cancers with frequent morphologic overlap. Given the similar histologic profiles seen in many of these entities, they often present a diagnostic challenge to the ...practicing pathologist.
To provide a streamlined algorithm using histologic clues, immunohistochemical profiles, and molecular assays to aid in diagnosis of these lesions.
Sources were the World Health Organization Tumor Classification, literature review, and institutional experience.
Although many sinonasal tract malignancies show similar histology, distinct immunohistochemical and molecular profiles can help parse out differences, thereby facilitating diagnosis for the pathologist.
PDF
