malignant polyp Daily Challenges in Digestive Endoscopy for Endoscopists and Endoscopy Nurses BSGIE Annual Meeting 18/09/2014 Mechelen

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Plan Incidental finding of a malignant polyp 1. What is a polyp malignant? 2. Role of the pathologist and the endoscopist 3. Quantitative and qualitative risk assessment 4. How to decide what to do? Hubert Piessevaux, MD PhD Anne Jouret-Mourin, MD PhD Brussels, Belgium Malignant or not? What is a malignant polyp? A malignant (pedunculated, sessile or flat) polyp is defined as a lesion that endoscopically appears like an adenoma but histologically contains invasive adenocarcinoma extended into but not beyond the submucosa We use the term of adenocarcinoma when the neoplasm has invaded the submucosa A desmoplastic stromal reaction is virtually always present Capable of metastasis 3 4 1

In contrast: Malignant or not? An intra mucosal carcinoma breaks the basal membrane and invades the lamina propria but does not reach the muscularis mucosae (ptis) Metastasis has never been reported from colonic intra mucosal carcinoma Therefore, intra mucosal carcinomas should not be regarded as malignant polyps 5 6 The role of the pathologist: The role of the endoscopist: Not only to propose a correct diagnosis Not to resect lesions that have high probability of (deep) submucosal invasion. But also provide crucial information for the therapy: In case of large or suspicious lesions to provide the pathologist with an optimal specimen: Is the lesion completely excised? If possible, complete en bloc resection What is the risk for lymph nodes metastasis? Adequate orientation of the polyp 7 8 2

Pitt pattern NICE IV V-i V-n Kudo, Endoscopy 2001 Hayashi, Gastrointest Endosc 2013 9 10 Technical issues Pohl, Gastroenterology 2013 11 12 3

Importance of technique and operator! How to evaluate completeness of excision? Correct gross examination is crucial Importance of the orientation 13 14 The majority of polyps are sessile Haggitt classification: levels of submucosal invasion Level 1: submucosal invasion (head) Level 2: submucosal invasion (neck): low risk of lymph node mets (<3%) Level 3: submucosal invasion (stalk) Level 4: same submucosal invasion pedunculated or sessile: high risk Robert, Clin Gastroenterol Hepatol 2007; Haggitt Gastroenterology 1985 15 16 4

Pedunculated vs. flat lesions Quantitative risk assessment Grade of vertical submucosal invasion (depth Y) Sm1 = less than 0.5mm from the mm, superficial third Sm 2= 0.5 to 1mm, middle third Sm3= over 1mm, deepest third sm3 : high risk for metastases Ueno : > 2000µm 17.1 % Grade of horizontal submucosal invasion (width X) < 2mm of the tumoral width 2 3mm of the tumoral width > 4 mm of the tumoral width > 4mm high risk for metastases Ueno : > 4mm 18.2 % Ueno, Gastroenterology 2004 17 Kikuchi R Dis Colon Rectum 1995 Ueno, Gastroenterology 2004 18 Qualitative measures Relation between margin and recurrence Tumour differentiation Well or moderately differentiated: favourable Poorly differentiated or mucinous: unfavourable Margin Negative: favourable (but until which distance?) Positive including in cautery: unfavourable Lymphatic invasion: unfavourable Tumour budding, cribriform features: unfavourable Ueno, Gastroenterology 2004 19 20 5

Daily Challenges in Digestive Endoscopy BSGIE Annual Meeting 18/09/2014 Mechelen Lymphatic invasion Budding Not commonly seen Tumour budding is defined as an isolated single cancer cell or a cluster composed of fewer than 5 cancer cells Inter observer variability : retraction artefact can mimic lymphatic invasion Independent predictor of lymph node metastasis* Lymphatic invasion without other unfavourable pathologic features : rare Immunohistochemistry : D2 40 increases detection (more than 2 fold) Choi, Dis Colon Rectum 2009 21 22 Pseudo invasion Summary of unfavourable features Glands arranged in a smooth rounded nest or «bolus» lobular configuration Displaced glands have rounded contours and lobular configuration Herniated neoplastic tubules surrounded by lamina propria Glands invested by lamina propria with inflammatory cells, sometimes hemosiderin Incomplete resection Submucosal invasion Tumour less than 1 mm from the deep cauterized margin Differentiation : Grade III (poorly differentiated) Presence of lympho vascular invasion 24 23 6

Combination of qualitative and quantitative risk factors for nodal metastases Integration of clinical, endoscopic and pathologic features Yoshii, Clin Gastroenterol Hepatol 2014 25 26 To help you decide: 32/2020 (1.6%) 35/1744 (2.0%) Tjandra, Colorectal Dis 2006 27 28 7

What if you decide to operate? Ask you surgeon to perform an extensive lymphadenectomy! TME or even Abdomino perineal resection if needed. What if you decide not to operate? No evidence in the literature of the benefit of adjuvant (Radio )chemotherapy in this setting Follow up should focus on extra mucosal disease: CT MRI EUS Conclusion Evaluate before it is too late: Use the endoscopic tools (NBI, pit pattern, lift sign, ) to determine before cutting if it is reasonable to do so! Do not cut if you are not sure to be able to remove the lesion totally If possible remove en bloc for optimal pathological assessment Important features in the pathology report for clinical decision making: Horizontal and vertical measure of submucosal infiltration in sessile polyp Haggitt level and measure of distance between deepest infiltration and coagulated margin in pedunculated polyp Lymphatic invasion Venous invasion Differentiation Budding Quirke, Endoscopy 2012 29 30 8