As macroscopic appearance represents tumor microenvironment, it may also reflect the biological and clinicopathological characteristics of a cancer. The aim of the study was to evaluate the clinicopathological significance of the gross appearance of pancreatic ductal adenocarcinoma (PDA). We investigated fresh macroscopic features in 352 cases of PDA and their clinicopathological significance. Three unique gross features were found: a honeycomb-like appearance (diffusely distributed microcysts and interstitial fibrotic thickening), macroscopic necrosis, and a tube/branching structure (apparent small cylindrical or linear structure). A honeycomb-like appearance was present in 24 cases (6.8 %) and significantly associated with low serum CA19-9 level and well-differentiated adenocarcinoma. Macroscopic necrosis was present in 235 cases (66.8 %) and significantly correlated with tumor size, nodal metastasis, nerve plexus invasion, no adjuvant chemotherapy, and distant recurrence. The presence of macroscopic necrosis was significantly associated with shorter disease-specific survival (DSS) and disease-free survival (DFS). The presence of larger areas of necrosis (≥2 mm) was closely associated with shorter survival. A tube/branching structure was found in 179 cases (50.9 %), which was correlated with larger tumor size and no adjuvant chemotherapy and macroscopic necrosis. The presence of a tube/branching structure was significantly associated with shorter DSS and DFS. Multivariate survival analyses showed that the presence of tube/branching structures was an independent negative prognostic factor in patients having PDA. We suggest that the gross appearance of PDA reflects clinicopathological characteristics and may be useful in predicting prognosis.
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