Seeds of invasion in a field of immunity inside the tumor microenvironment: an H&E-based evaluation of stromal TIL density and tumor budding in colorectal carcinoma

Abstract Background Colorectal carcinoma (CRC) is a major cause of cancer-related morbidity and mortality worldwide. Stromal tumor-infiltrating lymphocytes (TILs), an important component of the tumor microenvironment, have emerged as potential modulators of tumor behavior. Their relationship with tumor budding and other histopathological indicators of aggressiveness remains incompletely understood. The objectives of the study were to evaluate the association between stromal TIL density and clinicopathological parameters, including tumor budding and metastatic indicators, in colorectal carcinoma. Materials and methods This retrospective study included 35 histologically confirmed cases of colorectal carcinoma. Resection specimens were examined on routine H&E-stained sections. Stromal TILs were assessed according to the International Immuno-Oncology Biomarker Working Group guidelines and categorized as low (< 50%) or high (≥ 50%) density, a threshold applied for descriptive dichotomization in this exploratory cohort in the absence of a cut-off specifically validated for colorectal carcinoma. Tumor budding was assessed at the invasive front according to International Tumor Budding Consensus Conference (ITBCC) 2016 criteria. Associations between TIL density and clinicopathological variables, including tumor grade, stage, nodal status, lymphovascular invasion (LVI), perineural invasion (PNI), depth of invasion, tumor side, and tumor budding, were analyzed using Fisher’s exact test. A p-value < 0.05 was considered statistically significant. Results The mean patient age was 50.2 years. Most tumors were moderately differentiated adenocarcinomas and predominantly right-sided. Stromal TIL density was low (< 50%) in 22 cases (62.9%) and high (≥ 50%) in 13 cases (37.1%). High stromal TIL density showed significant associations with lower tumor grade, absence of lymphovascular invasion, absence of perineural invasion, and lower tumor budding on univariate analysis. Conclusion In this small, single-institution cohort, high stromal TIL density was associated with less aggressive histopathological features, including lower tumor grade and reduced tumor budding, lymphovascular invasion and perineural invasion. H&E-based assessment of stromal TILs may represent a simple, reproducible morphological parameter warranting further validation as an adjunct marker of tumor aggressiveness in CRC, pending confirmation in larger, prospective, multi-institutional cohorts with outcome data.