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Colorectal cancer (CRC) epidemiology and pathology Gábor Cserni, MD, PhD, DSc Bács-Kiskun County Teaching Hospital Kecskemét, Hungary
Incidence estimates ‘06 ,[object Object],[object Object],[object Object],[object Object],[object Object],EUROPE EU Ann Oncol 2007;18:531
Mortality ‘06 ,[object Object],[object Object],[object Object],[object Object],[object Object],EUROPE EU Ann Oncol 2007;18:531
ACS 2010 n=72090 n=70480 Estimated deaths: 26580 Estimated deaths: 24790
Risk factors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Molecular pathways ,[object Object],[object Object],[object Object],[object Object],[object Object]
Different pathways ,[object Object],[object Object],[object Object],[object Object]
Based on:  Jass JR. Histopathology 2007;50:113-130. MS: microsatellite; CIMP: CpG island methylator phenotype; TSA: traditional serrated adenoma Ex adenoma,  TIL R>L F>M Neg MSI-H (HNPCC) Ex adenoma, dirty necrosis, tumor budding L>R M>F APC TP53 (KRAS) Neg MSS Ex villous adenoma (kras+) or serrated adenoma L>R M>F KRAS+ Low MSI- L  or  MSS Ex serrated polyps (TSA), serrated, mucinous, HG non-circumscribed, (TIL) R>L F>M BRAF+ High MSI- L  or  MSS Ex serrated polyps (sessile), serrated,  mucinous , HG circumscribed, TIL R>L F>M BRAF+ High MSI-H (sporadic) Morphology Loc M / F Other CIMP MSI / MSS
Phenotype of MSI-H tumors ,[object Object],[object Object],[object Object],[object Object],[object Object]
An example NOS   Mucinous Signet ring cells MSH2 MLH1 TIL
Histological types ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Grade ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Medullary carcinoma MLH1 MSH2
Prognostic factors  (cat I – IIA) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Based on Compton C et al.  Arch Pathol Lab Med 2000
Primary tumor: (c)T & pT ( TNM7 ) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
pT3:  pT3a  (up to 5 mm from the muscularis propria) &  pT3b  (over 5 mm from the muscularis propria) ,[object Object],Bori R et al. Pathol Oncol Res 2009;15:527-32.
Assessment of peritoneal involvement Higher pT4 ration as a result of more precise pathological work-up
Lymph nodes: pN ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Lymph node metastasis vs TD ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Lymph node metastasis vs TD V1 V1 – orcein stain
Lymph node metastasis vs  TD ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The suggested number of LNs to be assessed for a reliable pN0 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
How many LNs? As many as possible ! 8574 T3N0M0 CRC from the SEER database Cserni G,  et al . Is there a minimum number of lymph nodes that should be histologically assessed for a reliable nodal staging of T3N0M0 colorectal carcinomas?  J Surg Oncol  2002; 81:63-69.
Distribution of pN categories at BKMK ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Number of LNs assessed More
Distance from the tumour as qualitative feature Cserni G,  et al .  Distance of lymph nodes from the tumor, an important feature in colorectal  cancer specimens.  Arch Pathol Lab Med  2001; 125:246-249.   Tumour + 1-1 cm 2 cm 2 cm 3 cm 3 cm D  C  B  A  B  C  D   100 cases of CRC  Mean: 17 LN / case
An example A B A B B C C C No fraction D in this specific case
Results ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Cserni G,  et al .  Arch Pathol Lab Med  2001; 125:246-249.
Further testing ,[object Object],[object Object],[object Object],[object Object],Cserni G et al. J Clin Pathol 2011
Sentinel nodes and lymphatic mapping in CRCs ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Unexpected lymph drainage ,[object Object],[object Object],[object Object],[object Object],[object Object],The only positive (only CK+) / 18 LN   Same 2 cases reported in 2 papers
Less success in other series   (11-50 pts, mean 24 pts / series) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Distant metastasis (M –pM) ,[object Object],[object Object],[object Object],[object Object]
Venous invasion ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Cserni G et al., JCP 2010;63(7):575-8.
Suspected VI in muscularis pr NOT VI! Unsuspected VI in submucosa VI!
 
Resection margins ,[object Object],[object Object],Quirke P, Morris E. Histopathology 2007;50:103-12. Mucinous carcinoma CRM involvement: Local R1 resection (R2 if identified  macroscopically
Quality of surgery  (TME) ,[object Object],[object Object],[object Object],[object Object]
[object Object]
G 3 – Good quality - mesorectal plane (complete TME)
G 1 – Poor quality - muscular plane (incomplete TME)
Tumor regression  grade (TRG) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Jacob C et al. J Pathol 2004;204:562-8.
Predictive factors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Predictive factors ,[object Object],K-ras plays a central role in the downstream regulatory  processes of the EGFR  signaling pathway. Activating mutations abolish  the GTP-ase activity required for inactivation.
THE END

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BALKAN MCO 2011 - V. Gregorc - Epidemiology, pathology and molecular biology

  • 1. Colorectal cancer (CRC) epidemiology and pathology Gábor Cserni, MD, PhD, DSc Bács-Kiskun County Teaching Hospital Kecskemét, Hungary
  • 2.
  • 3.
  • 4. ACS 2010 n=72090 n=70480 Estimated deaths: 26580 Estimated deaths: 24790
  • 5.
  • 6.
  • 7.
  • 8. Based on: Jass JR. Histopathology 2007;50:113-130. MS: microsatellite; CIMP: CpG island methylator phenotype; TSA: traditional serrated adenoma Ex adenoma, TIL R>L F>M Neg MSI-H (HNPCC) Ex adenoma, dirty necrosis, tumor budding L>R M>F APC TP53 (KRAS) Neg MSS Ex villous adenoma (kras+) or serrated adenoma L>R M>F KRAS+ Low MSI- L or MSS Ex serrated polyps (TSA), serrated, mucinous, HG non-circumscribed, (TIL) R>L F>M BRAF+ High MSI- L or MSS Ex serrated polyps (sessile), serrated, mucinous , HG circumscribed, TIL R>L F>M BRAF+ High MSI-H (sporadic) Morphology Loc M / F Other CIMP MSI / MSS
  • 9.
  • 10. An example NOS Mucinous Signet ring cells MSH2 MLH1 TIL
  • 11.
  • 12.
  • 14.
  • 15.
  • 16.
  • 17. Assessment of peritoneal involvement Higher pT4 ration as a result of more precise pathological work-up
  • 18.
  • 19.
  • 20. Lymph node metastasis vs TD V1 V1 – orcein stain
  • 21.
  • 22.
  • 23. How many LNs? As many as possible ! 8574 T3N0M0 CRC from the SEER database Cserni G, et al . Is there a minimum number of lymph nodes that should be histologically assessed for a reliable nodal staging of T3N0M0 colorectal carcinomas? J Surg Oncol 2002; 81:63-69.
  • 24.
  • 25. Distance from the tumour as qualitative feature Cserni G, et al . Distance of lymph nodes from the tumor, an important feature in colorectal cancer specimens. Arch Pathol Lab Med 2001; 125:246-249. Tumour + 1-1 cm 2 cm 2 cm 3 cm 3 cm D C B A B C D 100 cases of CRC Mean: 17 LN / case
  • 26. An example A B A B B C C C No fraction D in this specific case
  • 27.
  • 28.
  • 29.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34. Suspected VI in muscularis pr NOT VI! Unsuspected VI in submucosa VI!
  • 35.  
  • 36.
  • 37.
  • 38.
  • 39. G 3 – Good quality - mesorectal plane (complete TME)
  • 40. G 1 – Poor quality - muscular plane (incomplete TME)
  • 41.
  • 42.
  • 43.