Original Article: PDF OnlyTumor-Insular Complex in Neoadjuvant Treated Pancreatic Ductal Adenocarcinoma Is Associated With Higher Residual TumorGonzález, Iván A. MD*; Kang, Liang-I MD, PhD*; Williams, Gregory A. MA†; Liu, Jingxia MS, PhD‡; DeNardo, David G. PhD*,§; Hawkins, William G. MD†; Chatterjee, Deyali MD*Author Information *Department of Pathology and Immunology †Department of Surgery, Division of HPB and GI Surgery ‡Department of Surgery, Division of Public Health §Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO W.G.H., D.G.D., G.A.W., and J.L. are supported by the SPORE Grant 5P50CA196510-02. L.-I.K. supported by NIH 5T32EB021955. REDCap supported by Clinical and Translational Science Award (CTSA) Grant (UL1 TR000448) and Siteman Comprehensive Cancer Center and NCI Cancer Center Support Grant P30 CA091842. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Deyali Chatterjee, MD, Department of Pathology and Immunology, Washington University School of Medicine, Room 3419, 425 South Euclid Avenue, Campus Box 8118, Saint Louis, MO 63110 (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: February 19, 2020 - Volume Publish Ahead of Print - Issue - doi: 10.1097/PAS.0000000000001454 Buy PAP Metrics Abstract The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a vital role in treatment response, and therefore, patient survival. We and others have observed an intimate association of neoplastic ductal cells with non-neoplastic islet cells, recapitulating the ductoinsular complex. We define this phenomenon as tumor-insular complex (TIC). Herein, we describe the clinicopathologic characteristics of TIC in neoadjuvant treated PDAC cases for the first time. We retrospectively reviewed the pathology of 105 cases of neoadjuvant treated PDAC resected at our institution. TIC was noted in 35 cases (33.3%), the mean tumor bed size was 2.7±1.0 cm, mean percentage of residual tumor 40±28% and mean Residual Tumor Index (RTI) (an index previously established as a prognostic parameter by our group) was 1.1±1.0. TIC was significantly associated with perineural invasion (P=0.001), higher tumor bed size (P=0.007), percentage of residual tumor (P=0.009), RTI (P=0.001), ypT stage (P=0.045), and poor treatment response, grouped by a previously established criteria (P=0.010). Using our prior binary reported prognostic cutoff for RTI of ≤0.35 and >0.35, TIC was associated with a RTI >0.35 (P=0.002). Moreover, patients who did not receive neoadjuvant radiation were associated with a higher frequency of TIC (P=0.003). In this cohort, RTI but not TIC was also shown to be a significant independent prognosticator for recurrence-free survival and overall survival on multivariate analysis. In conclusion, TIC is significantly associated with a more aggressive neoplasm which shows a poor treatment response. Further studies will be needed to better understand the tumor biology of TICs. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.