Modern Pathology (2017) 30, 104–112 104 © 2017 USCAP, Inc All rights reserved 0893-3952/17 $32.00 Diagnosis of T1 colorectal cancer in pedunculated polyps in daily clinical practice: a multicenter study Yara Backes1, Leon MG Moons1, Marco R Novelli2, Jeroen D van Bergeijk3, John N Groen4, Tom CJ Seerden5, Matthijs P Schwartz6, Wouter H de Vos tot Nederveen Cappel7, Bernhard WM Spanier8, Joost MJ Geesing9, Koen Kessels10, Marjon Kerkhof11, Peter D Siersema1,12, G Johan A Offerhaus13, Anya N Milne14 and Miangela M Lacle13 (on behalf of the Dutch T1 Colorectal Cancer Working Group) 1Department of Gastroenterology & Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands; 2Department of Histopathology, University College Hospital, London, UK; 3Department of Gastroenterology & Hepatology, Gelderse Vallei, Ede, The Netherlands; 4Department of Gastroenterology & Hepatology, Sint Jansdal, Harderwijk, The Netherlands; 5Department of Gastroenterology & Hepatology, Amphia Hospital, Breda, The Netherlands; 6Department of Gastroenterology & Hepatology, Meander Medical Center, Amersfoort, The Netherlands; 7Department of Gastroenterology & Hepatology, Zwolle, The Netherlands; 8Department of Gastroenterology & Hepatology, Arnhem, The Netherlands; 9Department of Gastroenterology & Hepatology, Diakonessenhuis, Utrecht, The Netherlands; 10Department of Gastroenterology & Hepatology, Flevo Hospital, Almere, The Netherlands; 11Department of Gastroenterology & Hepatology, Groene Hart Hospital, Gouda, The Netherlands; 12Department of Gastroenterology and Hematology, Radboud University Medical Center, Nijmegen, The Netherlands; 13Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands and 14Department of Pathology, Diakonessenhuis, Utrecht, The Netherlands T1 colorectal cancer can be mimicked by pseudo-invasion in pedunculated polyps. British guidelines are currently one of the few which recommend diagnostic confirmation of T1 colorectal cancer by a second pathologist. The aim of this study was to provide insights into the accuracy of histological diagnosis of pedunculated T1 colorectal cancer in daily clinical practice. A sample of 128 cases diagnosed as pedunculated T1 colorectal cancer between 2000 and 2014 from 10 Dutch hospitals was selected for histological review. Firstly, two Dutch expert gastrointestinal pathologists reviewed all hematoxylin-eosin stained slides. In 20 cases the diagnosis T1 colorectal cancer was not confirmed (20/128; 16%). The discordant cases were subsequently discussed with a third Dutch gastrointestinal pathologist and a consensus diagnosis was agreed. The revised diagnoses were pseudo-invasion in 10 cases (10/128; 8%), high-grade dysplasia in 4 cases (4/128; 3%), and equivocal in 6 cases (6/128; 5%). To further validate the consensus diagnosis, the discordant cases were reviewed by an independent expert pathologist from the United Kingdom. A total of 39 cases were reviewed blindly including the 20 cases with a revised diagnosis and 19 control cases where the Dutch expert panel agreed with the original reporting pathologists diagnosis. In 19 of the 20 cases with a revised diagnosis the British pathologist agreed that T1 colorectal cancer could not be confirmed. Additionally, amongst the 19 control cases the British pathologist was unable to confirm T1 colorectal cancer in a further 4 cases and was equivocal in 3 cases. In conclusion, both generalist and expert pathologists experience diagnostic difficulty distinguishing pseudo-invasion and high-grade dysplasia from T1 colorectal cancer. In order to prevent overtreatment, review of the histology of pedunculated T1 colorectal cancers by a second pathologist should be considered with discussion of these cases at a multidisciplinary meeting. Modern Pathology (2017) 30, 104–112; doi:10.1038/modpathol.2016.165; published online 7 October 2016 Correspondence: Dr MM Lacle, MD, PhD, Pathology, University Population-based colorectal cancer screening pro- Medical Center Utrecht, PO Box 85500, Heidelberglaan 100, grams have been widely introduced in Western Utrecht 3508 GA, The Netherlands. countries.1,2 The four main difficulties in the E-mail: [email protected] Received 15 June 2016; revised 5 August 2016; accepted 8 August pathology of the screening program have been 2016; published online 7 October 2016 reported to be the recognition of serrated lesions, a www.modernpathology.org Pedunculated T1 colorectal cancer Y Backes et al 105 biopsy diagnosis of malignancy, determining risk submucosa. Patients with hereditary predisposition features in T1 colorectal cancer, and the recognition for colorectal cancer, inflammatory bowel disease, of pseudo-invasion.3,4 The latter, also called epithe- synchronous advanced colorectal cancer, non-cancer lial misplacement or pseudo-carcinomatous inva- related death within one year after treatment, and sion, has been advocated to be the pathologic non-pedunculated or unknown morphology were diagnostic conundrum of the screening program excluded. Patient and polyp characteristics were with important consequences.4 In contrast to T1 collected. In addition, follow-up data were collected colorectal cancer, pseudo-invasion is a benign con- in order to correlate the diagnosis after review to the dition that lacks metastatic potential. Therefore, outcome during follow-up. inadequate recognition can lead to over diagnosis A sample of cases was selected for histological and the subsequent risk of surgical overtreatment of review. Selection was based on inclusion in another benign lesions.4 study (not published yet). For that study, the Pseudo-invasion was first described in 1973 by hematoxylin-eosin stained slides of all pedunculated Muto et al.5 It is a phenomenon in which cancer is T1 colorectal cancer cases with either lymph node mimicked in a benign lesion by misplacement of metastasis or recurrent cancer were collected from epithelium from the mucosa to the submucosa, and the participating hospitals. In addition, hematoxylin- rarely even in the muscularis propria.6,7 As it is eosin stained slides of matched pedunculated T1 mostly seen in pedunculated polyps located in the colorectal cancer cases without lymph node metas- sigmoid colon, it is hypothesized that it is caused by tasis or recurrent cancer were collected from the tension and shear forces leading to mucosal pro- same hospitals. Matching was performed based on lapse, microtrauma, and subsequent breaks in the type of treatment and polyp location using the muscularis mucosae.8–10 Pedunculated sigmoidal method of incidence density sampling. Collection polyps are exposed to enhanced trauma due to the of the slides and matching was performed by two narrow lumen in which solid feces passes, the curves independent researchers who were not involved in the sigmoid colon makes and the relatively loosely the review process (YB and LM). Slides were attached mucosa. These forces can result in epithe- scrambled by the same two researchers before lial necrosis and subsequent hemorrhage, which can pathology review, so that the participating patholo- be identified by hemosiderin deposition. gists remained fully blinded. The United Kingdom guideline on colorectal This study was approved by the Medical Ethics cancer screening is currently one of the few that Review Committee of the University Medical Center recommends diagnostic confirmation of T1 color- Utrecht (approval for data-collection, reference ectal cancer by a second pathologist.3,11 This number: 15–487; approval for histological review, recommendation is not yet widely followed by other reference number 15–716). The study was performed guidelines, as it is currently unknown on what scale in accordance with the Helsinki Declaration. All misclassification takes place in daily clinical prac- patients’ data were coded and anonymity of patients tice. The aim of this study was to provide insights in was guaranteed. the diagnostic accuracy and reproducibility of the histological diagnosis of pedunculated T1 colorectal cancers in daily clinical practice, by review of the Pathology Review original histological diagnosis by pathologists with special expertize in gastrointestinal pathology. Three pathologists from the Netherlands (ML, AM, and JO) and a pathologist from the United Kingdom (MN) participated in this study, all with special expertize in gastrointestinal pathology. All patholo- Materials and methods gists were blinded to the clinical characteristics (ie, Study Population and Sample Collection patient and polyp characteristics) and clinical out- come (ie, lymph node metastasis or recurrent cancer This study was conducted in a sub-cohort of the T1 during follow-up). In order to guarantee the same colorectal cancer registration cohort, initiated by the setting for the original pathologists and the pathol- Dutch T1 Colorectal Cancer Working Group. This ogists that performed the review, all available collaboration initiative consists of 10 hospitals, hematoxylin-eosin stained slides were provided for including 9 non-academic and 1 academic hospital. reading; no additional deeper sections were All patients with T1 colorectal cancer diagnosed performed. between 2000 and 2014 in these hospitals were A flowchart of the study design is presented in identified using the Netherlands Cancer Registry. Figure 1. First, all slides on which the local The electronic medical records of all patients were pathologist diagnosed T1 colorectal cancer were reviewed. Only cases in which the local pathologist mutually