Early colorectal cancer Quality and rules for a good pathology report Histoprognostic factors
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1 Early colorectal cancer Quality and rules for a good pathology report Histoprognostic factors Frédéric Bibeau, MD, PhD Pathology department Biopathology unit Institut du Cancer de Montpellier France
2 Quality and rules of a good pathology report Simple but rigourous
3 Useful histopronostic factors Early colorectal cancer (CRC)
4 Useful histopronostic factors Micrometastatic disease Adjuvant chemotherapy
5 Useful histopronostic factors Content - Tumour - Depth of invasion - Distant extension - Margins
6 Useful histopronostic factors - Tumour - Depth of invasion - Distant extension - Margins
7 Colorectal cancer (CRC): heterogeneous disease Different histologic types
8 CRC histologic types 90% Lieberkühnian Mucinous micropapillary adenosquamous Signet ring cells Serrated Small cells Medullary Adenocarcinoma Carcinoma
9 MSI histologic features Tumour Microenvironment Mucinous Crohn-like reaction Signet ring cells Medullary Lymphocytic infiltrate CD3+
10 CRC grading Low grade (well, moderatly differenciated) High grade (low, indifferenciated) modulation according to MSI status
11 Useful histopronostic factors - Tumour - Depth of invasion - Distant extension - Margins
12 ptnm classification MUCOSA Muscularis Muscosae --> SUB-MUCOSA MUSCULARIS SUB-SEROSA --> SEROSA --> pt Tis T1 T2 T3 T4 pn pm N0 : no positive lymph node (LN) N1 : 3 positive LN N2 : 4 positive LN M0 : No distant metastasis M1 : Distant metastasis TNM UICC th Classification Organe infiltration and / or visceral peritoneal perforation
13 ptnm classification MUCOSA Muscularis Muscosae --> SUB-MUCOSA MUSCULARIS SUB-SEROSA --> SEROSA --> pt Tis T1 T2 T3 T4 pn pm N0 : no positive lymph node (LN) N1 : 3 positive LN N2 : 4 positive LN M0 : No distant metastasis M1 : Distant metastasis TNM UICC th Classification Organe infiltration and / or visceral peritoneal perforation
14 Serosal involvement Gross examination +++
15 Serosal involvement pt4a 7 th TNM UICC 2009 classification Frankel et al. Mod Pathol 2015
16 Serosal involvement Deeper block levels pt4a 7 th TNM UICC 2009 classification Frankel et al. Mod Pathol 2015
17 Serosal involvement pt4a 7 th TNM UICC 2009 classification Frankel et al. Mod Pathol 2015
18 Invasion front Expansive Infiltrative Svrcek et al. Cancero Dig. 2012
19 Tumour budding Invasion front Wang LM, Am J Surg Path 2009
20 Tumour budding Which method? Lugli et al. Br J cancer 2012
21 Immune adaptative microenvironment Galon et al. Cancer Res 2007
22 Prognostic impact of immune response
23 Immune infiltrate evaluation Which method? Which markers? Intra and peri-tumoral? Linear quantification? Pagès et al., New Engl J Med 2005 Allard et al. Diagnostic Pathology 2014
24 Pronostic impact of the immune response - Treatment for particular stage II? - No treatment for certain stage III? Not enough data in 2016 (May 20 th )
25 Pronostic impact of the immune response - Treatment for particular stage II? - No treatment for certain stage III? But new data at 2016 ASCO (June 5 th )
26 Useful histopronostic factors - Tumour - Depth of invasion - Distant extension - Margins
27 ptnm classification MUCOSA Muscularis Muscosae --> SUB-MUCOSA MUSCULARIS SUB-SEROSA --> SEROSA --> pt Tis T1 T2 T3 T4 pn N0 : no positive lymph node (LN) N1 : 3 positive LN N2 : 4 positive LN N+ Organe infiltration and / or visceral peritoneal perforation pm M0 : No distant metastasis M1 : Distant metastasis Adjuvant chemotherapy TNM UICC th Classification
28 Distant extension: lymph nodes Recommendations > 12 But Goldstein et al. Am J Surg Pathol 2002
29 Distant extension: lymph nodes Gross examination +++ No magic number! More = better
30 Distant extension: lymph nodes Tougeron et al. Modern Path 2009.
31 Distant extension : tumour deposits Nx N0 N1 N2 N1a N1b N1c N2a N2b Statut ganglionnaire non évaluable No positive regional lymph node Metastase(s) in 1-3 regional lymph node(s) 1 positive lymph node 2-3 positive regional lymph node Tumour deposits, satellites, in the sub-serosa or peri-rectal or peri-colic non peritonised tissue, without regional metastatic lymph node 4 or more positive regional lymph nodes 4-6 regional positive lymph nodes 7 regional positive lymph nodes TNM UICC th Classification
32 Distant extension : tumour deposits TNM 5 th edition TNM 6 th edition TNM 7 th edition >3 mm Lymph node Smooth shape Lymph node No residual lymph node Tumour deposit Frankel et al. Mod Pathol 2015
33 Distant extension : tumour deposits Pericolic or -rectal tissu location Puppa et al. Modern Pathol 2007
34 Impact of «tumour deposits» (N1c) P< Jin et al. Am J Surg Path 2014
35 Impact of «tumour deposits» (N1c) P= Jin et al. Am J Surg Path 2014
36 Distant extension : tumour deposits Recommendations for interprétation (F.A.Q*) - N1c only if negative lymph node - No N1c if positive lymph node - Do not add tumour deposits to positive lymph node - Do not modify T stage *Frequently Asked Question
37 Distant extension : tumour deposits Nx N0 N1 N2 N1a N1b N1c N2a N2b Statut ganglionnaire non évaluable No positive regional lymph node Metastase(s) in 1-3 regional lymph node(s) 1 positive lymph node 2-3 positive regional lymph node Tumour deposits, satellites, in the sub-serosa or peri-rectal or peri-colic non peritonised tissu without regional metastatic lymph node 4 or more positive regional lymph nodes 4-6 regional positive lymph nodes 7 regional positive lymph nodes TNM UICC th Classification Clinical trials
38 Distant extension : VELIPI* Lymphatic invasion Venous invasion Perineural invasion Harris et al, Am J Surg Path 2008 Mori et al. Histopathology 2009 Liebig et al J Clin Oncol 2010 *Venous emboli and lymphatic and perineural invasion
39 Extra-mural venous invasion 30%: frequent underestimation? Nagtegaal et al. histopathology 2015
40 Perineural invasion OS DFS CSS Knijn et al. Am J Surg Path 2015
41 Useful histopronostic factors - Tumour - Depth of invasion - Distant extension - Margins
42 Margins Distal ans proximal very rarely positive
43 Useful histopronostic factors - Tumour - Depth of invasion - Distant extension - Margins
44 Molecular profile Microsatellite instability (15%) Immunohistochemistry Molecular biology Normal DNA MSI tumour Less or supplementary nucleotides Favorable prognosis in CCR stage II
45 Molecular profile Impact of KRAS et BRAF mutations Poor prognosis in stage III CRC (MSS)* Not used as prognostic factors in 2016 Stratification for clinical trials? MSI, RAS, BRAF status for all CRC, tomorrow? *Taieb et al JAMA Oncol 2016
46 Useful histopronostic factors for treatment Early CRC in ptnm - Grade - VELIPI - MSI
47 Useful histopronostic factors for treatment Early CRC in 2016 Stage III - ptnm N+ (including N1c= tumour dep.) adjuvant CT - Grade - VELIPI - MSI
48 Useful histopronostic factors for treatment Early CRC in 2016 Stage II - ptnm N0 pt4 (serosa +), <12 N - Grade high (poor differenciation) - VELIPI + - MSI - Adjuvant CT (Multidisciplinary team discussion)
49 Pathology report key elements OMS Histologic type Differenciation (Grade) Extension - Tumour (pt) - Lymph node (pn) Margins - Distal/proximal - Circumferential (Rectum) Lymphatics Veins Nerves Vasculo-lymphatic and perineural invasions
50 Translationnal research
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