BALKAN MCO 2011 - G. Cserni - Epidemiology and pathology

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]

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]

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.

BALKAN MCO 2011 - G. Cserni - Epidemiology and pathology

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BALKAN MCO 2011 - G. Cserni - Epidemiology and pathology