Background:
Sinonasal mucosal melanoma is a rare and highly aggressive malignant neoplasm with a very unfavorable prognosis. It can exhibit various histological patterns, potentially mimicking other diagnoses. Therefore, complementary immunohistochemical studies are crucial alongside morphological analysis.
We present an unusual case of locally advanced sinonasal melanoma, negative for PS100 and displaying a plasmacytoid morphology with focal aberrant expression of CD138.

A 74-year-old patient experienced epistaxis, decreased visual acuity, and treatment-resistant headaches in August 2022. A brain scan revealed a large tumor in the left nasal fossa. Initial biopsy suggested nasal plasmacytoma based on the presence of disorganized, plasmacytoid cells, CD138 positivity, and PS100 negativity. Radiotherapy was administered, but symptoms worsened. A subsequent scan showed an extensively advanced maxillo-ethmoido-sphenoidal left-sided tissue mass with distant metastases. An initial bone marrow biopsy, cervical adenectomy, and another mass biopsy were performed.

Results:
Received tissue fragments appeared brownish-black.
Histologically, the tumor proliferation comprised large, markedly atypical cells arranged in diffuse sheets, with nuclei exhibiting eccentricity, dense or vesicular chromatin, and prominent nucleoli. Melanin pigments were diffusely present in the cytoplasm.
Immunohistochemical analysis revealed diffuse positive staining for two melanocytic markers, HMB45 and MelanA. PS100 was initially very focally positive on the second biopsy, contrasting with its complete negativity in the medullary and nodal areas. CD138 was negative, avoiding confusion with melanin pigments.
Based on these findings, a diagnosis of melanoma was established.

Discussion and Conclusion:
Mucosal melanoma constitutes 0.3% to 2% of melanomas. Tumors displaying focally melanin pigments with unique histomorphology pose diagnostic challenges. Key melanocytic markers are PS100, HMB45, and MelanA.
In this case, initial and metastatic biopsies were entirely PS100-negative, except for a weak, focal positivity in the later biopsy. Such immunohistochemical profile variations underscore intratumoral immunophenotypic heterogeneity.
The absence of PS100 expression and focal CD138 expression should not lead to diagnostic errors. A comprehensive panel, including at least two plasmacytic and two melanocytic markers, is mandatory for a conclusive diagnosis.

Introduction. Grilling more and more sophisticated dishes is a popular activity. Marshmallows are confectionery products, popular among children and teenagers all over the world, available in many well-known supermarkets ready to be grilled. Grilled marshmallows can be a source of exposure to harmful compounds, including carcinogenic polycyclic aromatic hydrocarbons (PAHs).

Method. The procedure of PAHs formed in marshmallows grilled under different conditions includes the dilution stage with deionized water and liquid—liquid extraction with cyclohexane and solid-phase extraction (SPE on silica gel columns). PAH fractions were initially analyzed via planar chromatography (HPTLC) using densitometry, and PAH concentrations were determined via GC-MS/MS using the selective reaction monitoring (SRM) mode. The authors' designed survey, in relation to the consumption of grilled marshmallows, was also conducted among approximately 300 children and adolescents.

Results. Preliminary results of TLC and GC-MS/MS analysis indicate that "raw" marshmallows do not contain PAHs. However, obtained data suggest a high exposure of young people to carcinogenic PAHs from grilled marshmallows. Carcinogenic BaP was determined in all investigated samples, constituting 36% of total PAH4 content, on average.

Conclusions. The profile of PAH concentrations in extracts isolated from grilled various types of marshmallows was very similar (R>0.8), regardless of the grilling method. The higher concentrations of PAHs were determined in multicolour marshmallows than in white ones. The lack of social awareness in relation to the exposure to carcinogenic substances is frightening.

In recent years, the complex relationship between immune cells and the area around the tumour has become an important factor in how cancer grows and how well treatment works. Regulatory T cells (Tregs), a specific type of CD4+ T cell, are very important for keeping the immune system in balance, but tumours can also use them to weaken the immune system. To improve precision medicine approaches in cancer immunotherapy, we need to know more about the metabolic strategies used by Tregs in the tumour microenvironment. This review looks at the changes that Tregs' metabolism goes through when they enter a tumour, showing how their metabolism is different from that of effector T cells. We look into how Tregs use glycolysis, oxidative phosphorylation, and fatty acid metabolism to help them stay alive and keep other cells from attacking. We also talk about how the metabolism of Treg cells changes in response to environmental cues and immune checkpoint inhibitors. We also talk about what Treg metabolic plasticity means for the development of new strategies in immune metabolism-based precision medicine. In conclusion, this review shows how important it is to understand how Treg cells work in the area around a tumour because it could lead to more personalised and effective cancer immunotherapy. The new information from these studies opens up new ways to treat cancer that might tip the balance in favour of the body's immune system. This could start a new era in the fight against cancer.

Abstract

Purpose: Oral squamous cell carcinoma (OSCC) personifies a worldwide problem for public health. Indeed, squamous cell carcinoma is the most common cancer in the oral cavity and one of the top ten cancers across the globe. According to GLOBOCAN 2020, 264211 new cases of oral cancer were reported, and 125022 individuals died as a result of the disease. Oral cancer had an all-inclusive incidence and mortality rate.

Materials and Methods: An MTT assay was used to assess the proliferation effects of Sanguinarine in oral cancer. A scratch assay was performed using sanguinarine to evaluate the migration effects in oral cancer. To determine the effects of sanguinarine on the characteristics of OSCC colonization, a colony formation assay was performed. In oral cancer, Western blotting was used to measure EMT-attenuating protein expression as well as major pathway protein expression induced by TGF- treatment.

Results: The MTT assay revealed a dose-dependent inhibition of cell proliferation in oral cancer. The results of the scratch assay revealed that sanguinarine played a significant role as a migration impeder in oral cancer. The results of the colony-forming assay demonstrated that sanguinarine has the ability to inhibit the development of colonies. Sanguinarine inhibited cadherin switching in oral cancer based on Western blotting results for EMT-regulating protein expression after TGF- treatment. Furthermore, after TGF treatment, the expression of pathway proteins involved in the EMT process, such as Smad, PI3K/Akt, and MAP kinase, was significantly disguised.

Conclusions: Our findings aided inunderstanding the inhibitoryrole of sanguinarine in OSCC tumorigenesis and its effects on impeding migration and metastasis by following the Smad and PI3K/Akt/MAP kinase pathways.

Background: Tumor metastasis is the leading cause of high mortality in hepatocellular carcinoma (HCC). Moreover, the HCC microenvironment is characterised by high heterogeneity. Single-cell RNA sequencing (scRNA-seq) may aid in determining specific cell clusters that could regulate the immune microenvironment of HCC.

Methods: The scRNA-seq data of 10 HCC samples were collected from the Gene Expression Omnibus (GEO) database GSE124395. Subcluster analyses were conducted to identify malignant hepatocytes. Correlations between key gene expression and clinicopathological data were determined using public databases. Immune cell infiltration analysis was performed and verified by immunohistochemistry and immunofluorescent staining.

Results: Nine malignant hepatocyte clusters with different marker genes and biological functions were identified. C3_Hepatocyte-SERF2 and C6_Hepatocyte-IL13RA2 were mainly involved in the regulation of the immune microenvironment, which was also a significant pathway in regulating HCC metastasis. Key genes in malignant hepatocyte clusters that were associated with HCC metastasis were further screened by LASSO regression analysis. TPI1, a key gene in C6_Hepatocyte-IL13RA2, presented a significant role in regulating the HCC immune microenvironment in the Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases. Moreover, immunohistochemistry analysis demonstrated that TPI1 expression was positively correlated with HCC metastasis and poor prognosis, while it was negatively correlated with CD8⁺ T cell infiltration. The negative correlation between TPI1 expression and CD8⁺ T cell infiltration was further confirmed by immunofluorescence staining.

Conclusion: In summary, a cluster of TPI1⁺ malignant hepatocytes was associated with the suppression of CD8⁺ T cell infiltration and HCC metastasis, providing new insights into novel biomarkers and immunotherapeutic targets for HCC.

Background: There is an ongoing debate over the prognostic value of the number of examined lymph nodes (ELNs) in cases of gastric signet-ring cell cancer (GSRCC). In this study, we sought to evaluate the correlation between the number of ELNs and the prognosis of GSRCC and identify the optimal number of ELNs.

Methods: A total of 1020 patients diagnosed with GSRCC between 2011 and 2018 in the National Cancer Center (NCC) database were identified. Clinicopathological characteristics were retrospectively collected, and the optimal cutoff values of ELNs were calculated using X-tile. The impact of different ELNs on overall survival (OS) was compared using Kaplan‒Meier curves. We used univariate and multivariate Cox and subgroup analyses to explore the relationship between ELNs and OS. Furthermore, nonlinear correlations were investigated using restricted cubic splines (RCSs).

Results: X-tile showed that the optimal cutoff value of ELNs was 22. The 5-year OS was higher for patients with ELNs > 22 (vs. ELNs ≤ 22, 66.9% vs. 74.9%, P = 0.026). Multivariate Cox analyses showed that high ELNs were associated with superior OS (HR=0.56, 95% CI =0.43-0.74, P < 0.001). In subgroup analyses, the significant association between tumor size > 4 cm and TNM III stage was still observed. The RCS regression model showed a U-shaped nonlinear dose–response relationship between ELNs and OS; the inflection point, as well as the lowest risk points, corresponded to 44-52 ELNs.

Conclusion: A U-shaped nonlinear correlation, with inflection points of 44-52 ELNs, between ELNs and prognosis in GSRCC was identified.

Background: Systemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes to systemic inflammatory factors over time are related to short-term and long-term prognosis has not been reported.

Methods: Prospective collection retrospective analysis of 216 GC patients who received NACT in our department from January 2011 to April 2019. Comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups. The endpoints were postoperative complications, recurrence-free survival (RFS), and overall survival (OS).

Results: Finally, Neutrophil-Lymphocyte Ratio (NLR) was the best predictor of the prognosis of the area under the curve (AUC) value compared with other common inflammatory markers and was included in the GBTM analysis. Three trajectories of NLR were obtained, and named the stable group (SG) (n=89), the ascent–descent group (ADG) (n=80) and the continuous descent group (CDG) (n=47). Compared with SG OR=0.333 (95% CI: 0.141-0.788) and ADG OR=0.284 (95% CI: 0.119-0.675), the CDG had significantly higher postoperative serious complications. The risks of tumor recurrence and death in ADG were HR=1.989 (95% CI: 1.157-3.419) and HR=1.830 (95%CI: 1.127-2.969), while for CDG they were HR=2.031 (95% CI: 1.098-3.757) and HR=1.913 (95% CI: 1.092-3.351), respectively. The median RFS and OS of SG were better than those of ADG and CDG (median RFS 81 months vs. 44 and 22 months, and median OS 69 months vs. 41 and 30 months).

Conclusion: There were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.

Background: Globally, over 2 million new cases of lung cancer are diagnosed annually, representing about 11% of all cancers. In males and females, it is the leading cause of cancer-related deaths in 87 and 26 countries, respectively. Only 1% of lung cancer deaths are reported in Africa. In Zimbabwe, lung cancer accounts for less than 4% of annual cancer incidence. Investigating patients for probable lung cancer needs a high index of suspicion by physicians practicing in a high HIV/TB burden country and requires specialized radiology, pathology, surgery and oncology services in diagnosis and treatment. In this setting, the misdiagnosis and/or delayed diagnosis of primary lung cancer is highly probable as Africa goes through the disease burden transitional phase. This study was carried out to determine the prevalence of initial misdiagnosis of primary lung cancer as pulmonary tuberculosis and the resultant time delay in establishing a histological diagnosis.

Methods: A retrospective descriptive study reviewing medical records of patients who presented with pathologically confirmed primary lung cancer from January 2014 to 31 December 2018 was carried out at Parirenyatwa Group of Hospitals Radiotherapy and Oncology Centre. This is the largest cancer treatment centre in Zimbabwe.

Results: A total of 73 patients were eligible for review and males accounted for 58% of all new cases. A pulmonary TB diagnosis in the preceding 12 months before a diagnosis of primary lung cancer was identified in 53% of patients. The median time delay to diagnosis was 8.37 months (range: 1-37 months). Only 11 patients (15.1%) had lung cancer diagnosed within 3 months of the initial presentation to a health care centre. A diagnosis of tuberculosis (TB) is associated with a delay of >7 months in lung cancer diagnosis (p= 0.001). At the time of diagnosis, 77% of patients had stage IV disease.

Conclusion: Most lung cancer patients are initially misdiagnosed as having TB, and this results in a significant time delay to diagnosis. The majority of patients had distant metastases at diagnosis. There is a relationship between the prevalent lung cancer misdiagnosis and the high burden of HIV/TB in Zimbabwe

The prognosis for patients with GBM remains poor and novel therapeutic approaches to address this unmet clinical need are urgently required. In this work we will present our recent efforts to develop compounds to target and tackle gliomas. Furthermore, we will illustrate other approaches that we are following to develop novel theranostic compounds that could be able to target the specific tumor microenvironment.

Cancer immunotherapy and immunology increasingly focuses on antibody development; however, there are multiple ways to re-engage the immune system in assisting with clearing cancer. The Trant Lab at the University of Windsor, Canada is working on three complementary methods (both to each other and to the antibody paradigm) to improve cancer immunotherapeutics. These include the preparation of anticancer vaccines based on modified and stabilized carbohydrates; the development of molecules able to modulate the tumour microenvironment to render it less pleasant for tumour cells, and more favourable for healthy tissue looking to resist tumour invasion and metastasis; and the design of new small molecules to stimulate the invariant natural killer T-cell system. Through cross-fertilization, these disparate disruptive projects inform each other to drive innovation in cancer immunotherapy. This presentation will provide an overview of these methods with a focus on recent results, and a discussion on what needs to be considered in these fields to avoid common pitfalls.