Reappraisal of Grading in Intestinal-Type Sinonasal Adenocarcinoma: Tumor Budding as an Independent Prognostic Parameter

Since sinonasal intestinal-type adenocarcinomas (ITAC) show resemblance to colorectal adenocarcinomas, we aimed to investigate novel prognostic factors of outcome, with particular focus on the role of tumor budding (TB). Retrospective clinico-pathological single-institution study on consecutive ITAC patients between 1996 and 2020. Histopathological parameters including conventional subtypes and TB features (low, intermediate, high) were evaluated with the aid of pancytokeratin (AE1/AE3) immunohistochemical staining. Parameters were correlated to clinical data and outcome. A total of 31 ITAC patients were included. Overall, 19/31 patients (61.3%) presented with stage III/IV disease. Presence of lymph node or distant metastases was rare (1/31 patient, 3.2%). Treatment protocols consisted of tumor resection in 30/31 patients (96.8%) and primary radiochemotherapy in 1/31 patient (3.2%). Adjuvant radiation therapy was conducted in 20/30 surgically treated patients (66.7%). The 3- and 5-year overall survival (OS) was 83.9% and 78.3% and the 3- and 5-years disease-specific survival (DSS) 83.7% % and 78.5%, respectively. The presence of intermediate/high TB (defined as ≥ 5 buds) was associated with both, worse DSS (log rank p = 0.03) and OS (log rank p = 0.006). No patient with low TB revealed progressive disease or died of the disease. No association between TB and tumor stage or conventional tumor subtype was found. Tumor budding seems to be an independent prognostic factor of worse outcome in ITAC.