Introduction: A mass in the salivary gland region often presents a diagnostic challenge with regard to its site of origin (salivary versus nonsalivary), benign or malignant nature, and tissue-specific diagnosis. The present study describes the utility of fine-needle aspiration (FNA) cytology in the diagnosis of these lesions. Subjects and Methods: Over a 6-year period (January 1994 to December 1999), 712 patients aged between 6 months and 91 years (median, 37 years) were subjected to FNA of swellings in their salivary gland regions. Male:female ratio was 1.28:1. The swellings were mostly located in the parotid (323 cases), submandibular (343 cases), and upper cervical region (27 cases). Swellings of oral (5 cases) and sublingual (2 cases) sites were rare. The lesions diagnosed by FNA cytology were compared among the major salivary glands. Cytologic diagnoses were correlated with histology in 45 cases. Results: Benign nonneoplastic lesions were the most common (73%), followed by neoplasms (20%), and those with atypical cytology (1%). Cytologic material was inadequate in 6% cases. Parotid gland region was involved more frequently by neoplasms (27.1%) than the submandibular gland region (13.7%, p < 0.0001). Inflammatory processes affected the submandibular gland region more commonly (42.0%) than the parotid (32.6%, p = 0.0164). Pleomorphic adenoma was the most common neoplasm (61.5%), followed by Warthin’s tumor (12.6%). Malignancies accounted for 10.5% of neoplasms. Frequency of involvement of parotid by Warthin’s tumor (16.7%) was significantly higher than that of submandibular gland (2.3%, p = 0.0191). However, the submandibular gland was more commonly affected by malignancy than the parotid gland (p = 0.0003). Sensitivity, specificity, and diagnostic accuracy of FNA cytology for all neoplastic lesions of the salivary gland were 94.6, 75.0, and 91.1%, respectively. The corresponding figures for malignancies were 60.0, 95.0, and 91.1%, respectively. Conclusion: FNA cytology is very useful for the diagnosis of salivary gland lesions. However, sampling and interpretation errors may occur. The low specificity for the diagnosis of neoplasms as a whole and the poor sensitivity for malignancies found in our study can be attributed to the relatively small number of benign nonneoplastic and malignancy cases with available histopathologic diagnoses.

Despite recent advances in colorectal cancer (CRC) treatment, a large proportion of patients show limited responses to therapies, especially in advanced stages. There is an urgent need to identify prognostic biomarkers and/or therapeutic targets in advanced stages, aiming to improve the efficacy of current treatments. We aimed to determine prognostic biomarkers in tumor tissue and circulation of CRC patients, with a special focus on T cell exhaustion markers. We found that mRNA levels of PD-1, TIM-3, CTLA-4, TIGIT, CD160, CD244, KLRG1, TOX2, TOX3, Ki-67, and PRDM1 were elevated in CRC tumor tissues. We also investigated differences in gene expression between early and advanced disease stages. We found that TOX and potentially TIM-3, CTLA-4, VISTA, TIGIT, KLRG1, TOX2, SIRT1, Ki-67, and Helios mRNA levels in tumor tissue were elevated in advanced disease stages, suggesting their potential roles in CRC progression. In contrast, PD-1 and CD160 levels in tumor tissue were downregulated in advanced stages. In the circulation of CRC patients, mRNA levels of PD-1, VISTA and LAG-3 were higher than those of healthy individuals. Moreover, in circulation, PD-1, CTLA-4 and TIGIT mRNA levels were reduced in advanced stages. Interestingly, levels of PD-1 in both tumor tissue and circulation were reduced in advanced stages, suggesting that targeting PD-1 in patients with advanced stages could be less effective. Altogether, these findings suggest some potential T cell exhaustion markers that could be utilized as prognostic biomarkers and/or therapeutic targets for CRC. However, further investigations and validations in larger cohorts are required to confirm these findings.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

BackgroundCytotoxic CD8+ T cell-mediated response is the most important arm of adaptive immunity, which dictates the capacity of the host immune response in eradicating tumor cells. Due to tumor intrinsic and/or extrinsic factors, the density and function of CD8+ tumor-infiltrating lymphocytes (TILs) could be compromised, leading to poor prognosis and survival.MethodsUsing RNA-Seq, transcriptomes of sorted CD3+CD8+ TILs from treatment-naïve colorectal cancer (CRC) patients at advanced stages (III and IV) were compared with those from patients with early stages (I and II). A signature referred to as ‘poor prognosis CD8 gene signature (ppCD8sig)’ was identified and analyzed in The Cancer Genome Atlas CRC dataset. Scores for the ppCD8sig were calculated and classified as high, intermediate and low, and its prognostic significance was assessed using multivariate analysis and Cox proportional hazard model. Densities of CD3+ and CD8+ T cell infiltration in tumors from patients with high and low ppCD8sig scores were assessed by flow cytometry and immunostaining.ResultsGenes related to epigenetic regulation and response to hypoxia were upregulated in CD8+ TILs from patients with advanced stages, while genes related to T cell activation, cell proliferation and cell cycle were downregulated. Patients with high ppCD8sig score had poorer disease-specific survival (DSS) and shorter progression-free interval (PFI). The ppCD8sig was an independent prognostic indicator for DSS (HR 1.83, 95% CI 1.40 to 2.38, p<0.0001) and PFI (HR 1.42, 95% CI 1.04 to 1.93, p=0.026). Additionally, patients with high ppCD8sig score were more likely to have advanced stages (χ2 p<0.0001) and residual disease after primary therapy (χ2 p=0.046). Patients with high ppCD8sig score had reduced levels of CD3+ and CD8+ TILs and low Immunoscores (IS), compared to patients with low ppCD8sig score.ConclusionsOur data provided insights into the altered regulation of biological mechanisms and signaling pathways in CD8+ TILs during CRC progression, and revealed a gene signature as an independent prognostic indicator. Patients with high ppCD8sig score had lower levels of TILs and low IS. These data further confirm the prognostic value of the identified ppCD8sig and potentially highlight its clinical relevance.

Highlights Exotic tropical infection in migrant populations. Intriguing history. Enigmatic taxonomy. Challenging management.