Use of a standardized diagnostic approach improves the prognostic information of histopathologic factors in pancreatic and periampullary adenocarcinoma

Background: Variability in reported histopathology parameters in operated periampullary adenocarcinomas may affect the prognostic weight of the parameters. Standardized axial sectioning produces a higher incidence of involved margins and also seems to produce a lower relative incidence of pancreatic compared with distal bile duct origin and a higher incidence of involved lymph nodes, compared with non-standardized procedure. The aims of this study were to 1) assess how a previously not described standardized pathology procedure, with longitudinal sectioning along the distal bile duct, affects reported tumour origin, margin status and involved lymph nodes, compared with non-standardized procedure, 2) assess if re-evaluation of microscopic slides affects the prognostic value of margin status and 3) compare the results of this standardized procedure with reported results of other standardized and non-standardized procedures. Methods: One hundred seventy-five consecutive pancreaticoduodenectomy specimens with primary adenocarcinomas, operated during 2001 - 2011 at the University hospitals of Lund and Malmo, Sweden, were re-evaluated histologically, and parameters relevant for classification and prognosis were assessed, with 1 mm as a threshold for involved or uninvolved margins. Follow-up lasted until 31 December 2013. Five-year overall survival (OS) and hazard ratios (HR) were calculated for the margin status stated in the original reports and margin status after re-evaluation. Results: Compared with non-standardized cases (n = 129), standardized cases (n = 46) had more involved lymph nodes in the specimens (median 3 vs 1), a higher fraction of distal bile duct origin (39% vs 21%) and a higher fraction of involved margins (74% vs 47%). The prognostic value of uninvolved margins increased by re-evaluation of slides (p < 0.001) and the adjusted HR for involved margins increased from 1.6 (95% CI 1.1 - 2.4) to 3.3 (95% CI 1.5 - 7.0). Uninvolved margins remained a significant predictor of OS in adjusted analysis. Conclusions: Both the method of sectioning the specimen and the microscopic assessment affect prognostic pathology parameters significantly. The results of the herein described standardized method are similar to the results of other standardized procedures. The 1-mm threshold for involved margins in pancreaticoduodenectomies is relevant for OS, and margin status is an independent prognostic parameter.