Programmed death-ligand 1 (PD-L1) on tumor cells, including Hodgkin and Reed–Sternberg (HRS) cells in classical Hodgkin’s lymphoma (cHL), suppresses immune responses in the tumor immune microenvironment (TME). We analyzed PD-L1 expression in macrophages and HRS cells of 98 cHL cases and correlated the findings with clinicopathological features, overall survival (OS), and progression-free survival (PFS). Epstein–Barr virus (EBV) was detected by in situ hybridization for EBV-encoded RNA. Ten high-power fields were evaluated to count the total number of macrophages and PD-L1+ macrophages, and to calculate PD-L1 histoscore (H-score) in HRS cells. EBV-positive cHL was found in 22.5% of patients. The median H-score was 80 (range 0–300). Bulky disease was associated with a lower number of PD-L1+ macrophages, and extranodal disease with a higher number (p = 0.05). EBV-positive cHL showed a higher PD-L1 H-score in HRS cells and a greater number of PD-L1⁺ macrophages (p = 0.005); both of these features, along with the proportion of PD-L1⁺ macrophages, were associated with shorter PFS and OS (p < 0.001). High PD-L1 expression in HRS and macrophages may be linked to worse clinical outcomes.

Background/Objectives: Advanced gastric cancer usually has an unfavorable prognosis. Stroma AReactive Invasion Front Area (SARIFA) is a newly recognized biomarker of aggressiveness, easily recognized as five tumor cells in direct contact with adipocytes in perigastric, submucosal, and perivascular adipose tissue. We investigated this phenomenon and correlated it with other pathohistological variables. Material and Methods: The sample includes 102 Croatian patients with locally advanced gastric cancer, who underwent total gastrectomy/lymphadenectomy between 2012–2018 and in 2023 at University Hospital Split, Croatia, and had pathological stage pT3 or pT4. Representative histological specimens were analyzed for SARIFA, and results were compared with other variables and overall survival. External validation and gene expression analysis of CD36 and FABP4 were performed using the TCGA-STAD cohort. Results: SARIFA was significantly associated with positive pN status (p = 0.009) and perineural invasion (p = 0.043). Patients with SARIFA had a more than fivefold increased risk of nodal involvement (OR = 6.35; 95% CI: 1.35–29.84; p = 0.019). Lymphovascular invasion (LVI) was associated with nodal disease (OR = 4.39; 95% CI: 1.194–16.143; p = 0.026), and SARIFA was marginally associated (OR = 4.886; 95% CI: 0.985–24.241; p = 0.052). Patients who had both LVI and SARIFA had a higher proportion of affected lymph nodes (p = 0.009). SARIFA status did not significantly affect overall survival. Gene expression analysis showed a significant increase in CD36 expression, while FABP4 expression was elevated but not statistically significant, in SARIFA-positive cases. Conclusions: SARIFA could be used as a marker for invasiveness and further investigated due to its predictive potential.

Patients with laryngeal squamous cell carcinoma (LSCC) often develop other malignancies, most commonly second primary lung cancer (SPLC). This study aimed to estimate the incidence of SPLC in LSCC patients and evaluate whether pulmonary nodules on baseline thoracic computed tomography (CT) predict SPLC development. In this single-center retrospective cohort study, 243 patients with LSCC diagnosed from 2017 to 2024 at the University Hospital of Split, Croatia, were followed, of whom 26 (10.7%) developed SPLC. The median time from LSCC to SPLC diagnosis was approximately 1.2 years. Patients with LSCC had an approximately eightfold higher risk of developing an SPLC than the general population (standardized incidence ratio [SIR] 8.40; 95% confidence interval [CI] 5.48–12.30). Pulmonary nodules at diagnosis were the only predictor associated with the development of an SPLC (hazard ratio [HR] 2.37; 95% CI 1.09–5.13; p = 0.029), although this association weakened and lost significance when the analysis was restricted to metachronous tumors (HR 1.84; 95% CI 0.71–4.77; p = 0.207). Metachronous tumors were predominantly squamous cell carcinomas (83.3%), whereas adenocarcinoma was the most common histological type among synchronous tumors (50.0%; p = 0.022). Patients with SPLC had a shorter overall survival than those without it (median 5.4 vs. 8.0 years; log-rank p = 0.016). The presence of pulmonary nodules at LSCC diagnosis was associated with a higher risk of SPLC. However, these findings originate from a single center, and further studies are needed to determine whether stratification based on initial radiological findings can improve early detection of SPLC in patients with LSCC.