Background: To implement the new marker in clinical practice, reliability assessment, validation, and standardization of utilization must be applied. This study evaluated the reliability of tumor-infiltrating lymphocytes (TILs) and tumor-stroma ratio (TSR) assessment through conventional microscopy by comparing observers’ estimations. Methods: Intratumoral and tumor-front stromal TILs, and TSR, were assessed by three pathologists using 86 CRC HE slides. TSR and TILs were categorized using one and four different proposed cutoff systems, respectively, and agreement was assessed using the intraclass coefficient (ICC) and Cohen’s kappa statistics. Pairwise evaluation of agreement was performed using the Fleiss kappa statistic and the concordance rate and it was visualized by Bland–Altman plots. To investigate the association between biomarkers and patient data, Pearson’s correlation analysis was applied. Results: For the evaluation of intratumoral stromal TILs, ICC of 0.505 (95% CI: 0.35–0.64) was obtained, kappa values were in the range of 0.21 to 0.38, and concordance rates in the range of 0.61 to 0.72. For the evaluation of tumor-front TILs, ICC was 0.52 (95% CI: 0.32–0.67), the overall kappa value ranged from 0.24 to 0.30, and the concordance rate ranged from 0.66 to 0.72. For estimating the TSR, the ICC was 0.48 (95% CI: 0.35–0.60), the kappa value was 0.49 and the concordance rate was 0.76. We observed a significant correlation between tumor grade and the median of TSR (0.29 (95% CI: 0.032–0.51), p-value = 0.03). Conclusions: The agreement between pathologists in estimating these markers corresponds to poor-to-moderate agreement; implementing immune scores in daily practice requires more concentration in inter-observer agreements.

Background: To implement the new marker in clinical practice, reliability assessment, validation, and standardization of utilization must be applied. This study evaluated the reliability of TILs and TSR assessment through conventional microscopy by comparing observers’ estimations. Methods: Intratumoral and tumor-front stromal TILs, and TSR were assessed by three pathologists using 86 HE slides CRC. TSR and TILs were categorized using one and four different proposed cut-off systems, respectively and agreement was assessed using the intraclass coefficient (ICC) and Cohen’s kappa statistics. Pairwise evaluation of agreement was performed using the Fliess Kappa statistic and the concordance rate and it was visualized by Bland-Altman plots. Results: For the evaluation of intratumoral stromal TILs, ICC of 0.505 (95% CI:0.35-0.64) was obtained, Kappa values were in the range of 0.21 to 0.38, and concordance rates in the range of 0.61 to 0.72. For the evaluation of tumor-front TILs, ICC was 0.52 (95% CI:0.32 - 0.67), the overall kappa value ranged from 0.24 to 0.30, and the concordance rate ranged from 0.66 to 0.72. For estimating the TSR, the ICC was 0.48 (95% CI:0.35 - 0.60), the kappa value was 0.49 and the concordance rate was 0.76. Conclusion: The agreement between pathologists in estimating these markers corresponds to poor to the moderate agreement, however, implementing immune scores in daily practice requires more concentration in inter-observer agreements.

Doctor Joseph Désiré Tholozan was a French physician who became the special physician of Nassereddin Shah, King of Persia (Iran) in the 19th century. He studied lots of topics in the field of epidemiology of infectious diseases. His efforts led to the discovery of the main vector of Iranian tick-born relapsing fever, Ornithodoros tholozani. He was also one of the pioneers of the Iranian Sanitary Council, whose efforts led to the foundation of the Ministry of Health of Iran a few decades later. This paper is a brief review of his biography and his roles in promoting health in Iran in the 19th century.

Background: Inter-observer variability among pathologists' reports has been a significant challenge in the diagnosis of diseases, especially cancers. Designing a grading system with minimal inter-observer variability can help achieve more accurate diagnoses. Objectives: We aimed to determine whether the grading system proposed by Cheng and colleagues (Cheng’s grading system) can improve inter-observer variability among pathologists in grading urothelial cancer, compared with the World Health Organization (WHO) grading system (2004/2016). Methods: Four pathologists examined all slides of bladder biopsy samples diagnosed as urothelial carcinoma, available in the archives of Imam Reza Hospital, Mashhad, Iran, from 2019 to 2022. Each pathologist reported the tumor grade based on both grading systems, independently of previous answers or the reports of their colleagues. Results: Of 132 samples, the majority were from men (84.1%); the mean age of patients was 66.56±11.31 years. For low and high grades of the WHO system and grade II in Cheng’s grading system, κ = 0.602; agreement was lower for grade III (κ = 0.439) and higher for grade IV (κ = 0.690) compared with the WHO grading system. There was significant agreement among the pathologists in all tumor characteristics, with excellent agreement for stromal invasion (κ = 0.790) and muscular invasion (κ = 0.884), fair to good agreement for WHO 2004/2016 grading (κ = 0.602) and Cheng’s grading (κ = 0.574) overall, and poor agreement for tumor heterogeneity (κ = 0.360). Conclusions: Both grading systems demonstrated favorable agreement among pathologists, without significant differences between the two systems. These results confirm the appropriateness of both grading systems.

Doctor Badri Teymourtash (1908‒1995) was among the first Iranian lady dentists. She was one of the founders of Mashhad Dental School and one of the pioneers of modern dentistry in Iran. This paper takes a glance at the story of the life of this academic woman with its ebbs and flows.