Horses out of the barn: pancreatic ductal adenocarcinoma frequently extends beyond the grossly visible tumour, requiring microscopic rectification for accurate T-staging

Abstract

Aims Accurate determination of tumour size is critical for pT staging in pancreatic ductal adenocarcinoma (PDAC), yet gross measurement alone often underestimates the true tumour extent because of the tumour's ill-defined and infiltrative nature. This study aimed to evaluate the diagnostic and prognostic value of incorporating microscopic rectification into tumour size assessment in PDAC.Methods and results A total of 342 therapy-na & iuml;ve pancreatoduodenectomies were analysed using a grossing protocol that includes separate sampling of anterior and posterior soft tissues via the 'orange-peeling' technique to retrieve lymph nodes and document soft tissue involvement. Peripancreatic soft tissue involvement was present in 91% of cases, and isolated microscopic foci distant from the main mass in 48%. Of the 266 tumours grossly classified as pT1/T2 (<= 4 cm), 39 (14%) showed carcinoma in both anterior and posterior soft tissues, and were reclassified as pT3. This subset showed significantly worse survival (P = 0.04) and higher nodal positivity (87% versus 69%, P = 0.02) than the remaining pT2 cases, comparable to conventional pT3 tumours (86%, P = 0.77). Multivariable Cox regression adjusted for age, sex, nodal status, margin, and lymphovascular/perineural invasion confirmed the survival disadvantage of this subgroup. Reclassification yielded a more balanced distribution of T categories (pT2 66% -> 52%, pT3 22% -> 34%) and modestly improved prognostic discrimination (C-index: 0.592 versus 0.574).Conclusions This study elucidates that PDAC frequently extends beyond the visible mass ('horses out of the barn' phenomenon); peripancreatic soft tissue involvement is common, and gross size often underestimates the true tumour extent, making microscopic correction crucial. Approximately one in six pT1/T2 tumours (<= 4 cm) shows carcinoma in both anterior and posterior soft tissues and behave like pT3 in outcomes and nodal status. Therefore, gross-micro rectification is essential to avoid understaging, particularly for T2 tumours. The orange-peeling protocol should classify tumours with foci in both anterior and posterior soft tissues as pT3, while other approaches may employ mapping techniques to enable microscopic reconstruction and biologically accurate staging.