Desmoplastic reaction (DR) is one of many tumor–host interactions and is associated with the overall survival (OS) of patients with colorectal cancer. However, the clinical significance of DR requires further study in large multicenter cohorts and its predictive value in adjuvant chemotherapy (ACT) response remains unclear. Here, a total of 2,225 patients with colorectal cancer from five independent institutions were divided into primary (N = 1,012 from two centers) and validation (N = 1,213 from three centers) cohorts. DR was classified as immature, middle, or mature depending on the presence of myxoid stroma and hyalinized collagen bundles at the invasive front of the primary tumor. OS among different subgroups were compared, and the correlations of DR type with tumor-infiltrating lymphocytes (TILs) within stroma, tumor stroma ratio (TSR), and Stroma AReactive Invasion Front Areas (SARIFA) were also analyzed. In the primary cohort, patients with mature DR had the highest 5-year survival rate. These findings were confirmed in validation cohort. In addition, for stage II colorectal cancer, patients classified as non-mature DR would benefit from ACT compared with surgery alone. Furthermore, immature and middle DR were more associated with high TSR, less distribution of TILs within stroma and positive SARIFA compared with mature. Taken together, these data suggest that DR is a robust-independent prognostic factor for patients with colorectal cancer. For patients with stage II colorectal cancer, non-mature DR could be a potential marker for recognizing high-risk patients who may benefit from ACT. Significance: DR has the potential to identify patients with high-risk colorectal cancer and predict the efficacy of adjuvant chemotherapy in patients with stage II colorectal cancer. Our findings support reporting DR types as additional pathologic parameters in clinical practice for more precise risk stratification.

Background: Tumor necrosis results from failure to meet the requirement for rapid proliferation of tumor, related to unfavorable prognosis in colorectal cancer (CRC). However, previous studies used traditional microscopes to evaluate necrosis on slides, lacking a simultaneous phase and panoramic view for assessment. Therefore, we proposed a whole-slide images (WSIs)-based method to develop a necrosis score and validated its prognostic value in multicenter cohorts. Methods: Necrosis score was defined as the proportion of necrosis in the tumor area, semi-quantitatively classified into 3-level score groups by the cut-off of 10% and 30% on HE-stained WSIs. 768 patients from two centers were enrolled in this study, divided into a discovery (N = 445) and a validation (N = 323) cohort. The prognostic value of necrosis score was evaluated by Kaplan–Meier curves and the Cox model. Result: Necrosis score was associated with overall survival, with hazard ratio for high vs. low in discovery and validation cohorts being 2.62 (95% confidence interval 1.59–4.32) and 2.51 (1.39–4.52), respectively. The 3-year disease free survival rates of necrosis-low, middle, and high were 83.6%, 80.2%, and 59.8% in discovery cohort, and 86.5%, 84.2%, and 66.5% in validation cohort. In necrosis middle plus high subgroup, there was a trend but no significant difference in overall survival between surgery alone and adjuvant chemotherapy group in stage II CRC (P = .075). Conclusion: As a stable prognostic factor, high-level necrosis evaluated by the proposed method on WSIs was associated with unfavorable outcomes. Additionally, adjuvant chemotherapy provide survival benefits for patients with high necrosis in stage II CRC.

Colorectal cancer (CRC) exhibits high heterogeneity, affecting variable outcomes and response to therapy. Tumor stroma drives progression and immunosuppres

Esophageal ectopic sebaceous gland (EESG) is a rare lesion that can be challenging to differentiate from other upper gastrointestinal endoscopic findings. The origin of EESG remains debated, with hypotheses ranging from embryologic misplacement to metaplasia of esophageal epithelium or glands. The aim of our study is to further investigate the clinicopathological features and pathogenesis of EESG. Our study systematically reviewed 87 cases reported in the literature and analyzed an additional 21 cases from our institution. Demographic data (gender, age), lesion location, endoscopic features, and clinical presentations were summarized. Additionally, immunohistochemical staining for androgen receptor (AR), Kiel 67 (Ki-67), and cytokeratin 14 (CK14) was performed on nine cases. A normality test was conducted to determine whether the age distribution of male and female patients followed a normal distribution. Correlation coefficients and principal component analysis (PCA) were applied to further analyze the characteristics of case onset. The estimated prevalence of EESG was approximately 0.105‰. Lesions were more frequent in males than in females (nearly 2:1 ratio) and predominantly occurred in middle-aged and elderly individuals (mean age: 56.9 years). Most lesions were located in the middle and/or lower esophagus in both genders (99.6% variance explained by PCA). Endoscopically, EESG presented as distinctive “whitehead acne-like” structures with protrusions corresponding to sebaceous duct openings. Immunohistochemistry showed positive AR expression in all cases (9/9, 100%). Ki-67 and CK14 expression patterns indicated a close association between ectopic lesions and the basal layer of the esophageal squamous epithelium. EESG typically presents after puberty with a male predominance. Given that sebaceous glands are androgen-responsive, androgens are likely involved in lesion development. The anatomical proximity of ectopic lesions to the basal layer of the squamous epithelium supports the hypothesis that pubertal androgens may drive aberrant differentiation of basal stem cells toward sebaceous gland lineage.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) play a crucial role in host antitumor processes. High level of TILs is associated with better outcomes for patients. We aim to automatically quantify TILs without any nuclei annotation and further construct an immune score to predict the survival of patients with colorectal cancer. PATIENTS AND METHODS: We developed an artificial intelligence–based pipeline to quantify the level of TILs in hematoxylin-eosin (H&E) images with immunohistochemistry (IHC)–guided nuclei annotation-free auxiliary labels. Patients enrolled in the study were divided into two cohorts (development cohort: n = 557; validation cohort: n = 439). The proposed tumor stroma immune score (TSI score) reflects the immune infiltration in the tumor stroma of patients. RESULTS: A strong correlation of TILs was observed between IHC and H&E images made by consecutive sections staining. Moreover, multivariate analysis confirmed that TSI score was an independent prognostic factor, and the higher TSI score was associated with the better prognosis (development cohort: hazard ratio for high v low 0.54 [95% CI, 0.42 to 0.80], P = .001; validation cohort: 0.68 [95% CI, 0.27 to 0.94], P = .031). The model with TSI score showed a higher C-index (development cohort: 0.700 v 0.679; validation cohort: 0.689 v 0.677). CONCLUSION: IHC images have the value of providing TIL density reference information for spatial corresponding H&E images. TSI score has the ability to predict overall survival.