Laurențiu Augustus Barbu, Liliana Cercelaru, Valeriu Şurlin, Stelian Ştefăniţă Mogoantă, Tiberiu Ștefăniță Țenea Cojan, D. Marinescu, Nicolae-Dragoș Mărgăritescu, Liviu Vasile
Background: Small bowel tumors are rare and biologically diverse, and prognostic assessment remains difficult, particularly regarding proliferative markers such as Ki-67 and tumor size. Objective: To evaluate the clinicopathological and immunohistochemical characteristics of small bowel tumors and explore factors associated with malignancy. Methods: A retrospective analysis of 61 surgically treated primary small bowel tumors (2020–2024) was performed using WHO 2019/2022 and AJCC 8th criteria. Immunohistochemistry included CD117, DOG1, CD34, SMA, and Ki-67. Results: Adenocarcinomas were most frequent (52.5%), followed by GISTs (26.2%) and NETs (9.8%). CD117 and DOG1 were expressed in 93.8% of GISTs, confirming high diagnostic specificity. The median Ki-67 index was 8%, significantly higher in non-GIST tumors (p = 0.004). Tumor size correlated moderately with Ki-67 (ρ = 0.42, p = 0.018). In this exploratory model, tumor size > 5 cm (p = 0.03) and Ki-67 > 10% (p = 0.04) were associated with malignancy. Conclusions: Tumor size and Ki-67 were associated with malignancy in this exploratory multivariable analysis, but these findings should be interpreted with caution due to limited follow-up and sample imbalance. Combined with CD117/DOG1 profiling, they enhance diagnostic accuracy and may inform diagnostic assessment; however, prognostic implications require outcome-based studies.