pathology of tumours of the lower gastrointestinal

tract

Dr Simon CrossAcademic Unit of Pathology

University of Sheffield

adenomas

colorectal cancer

0

1,000

2,000

3,000

4,000

0-4

5-9

10-1

4

15-1

9

20-2

4

25-2

9

30-3

4

35-3

9

40-4

4

45-4

9

50-5

4

55-5

9

60-6

4

65-6

9

70-7

4

75-7

9

80-8

4

85+

Age at diagnosis

Nu

mb

er

of

cases

0

200

400

600

Ra

te p

er

10

0,0

00

po

pu

lati

on

Male cases

Female cases

Male rates

Female rates

New cases and age-specific incidence rates - bowel cancer, UK 2005

3

Incidence rates - world regions, 2002 estimates

0 5 10 15 20 25 30 35 40 45 50

Middle Africa

South-central Asia

Northern Africa

Western Africa

Eastern Africa

Central America

Melanesia

Western Asia

Southern Africa

South-Eastern Asia

China

Polynesia

Caribbean

Micronesia

South America

Eastern Asia

Central & Eastern Europe

Southern Europe

Northern Europe

Western Europe

Northern America

Australia/New Zealand

Rate per 100,000 population

Males

Females

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

1975

1977

1979

1981

1983

1985

1987

1989

1991

1993

1995

1997

1999

2001

2003

2005

Year of diagnosis/death

Rate

per

100,0

00 p

op

ula

tio

n

Incidence males Incidence females

Mortality males Mortality females

Incidence and mortality rates - colorectal cancer, Great Britain, 1975-2005

5

who gets colorectal cancer?

normal epithelium

dysplastic epithelium

normalepithelium

adenomacolorectal

adenocarcinoma

familial adenomatous

polyposis

Polyps

nucleus

nuclear membrane

DNA

cytoplasmapcGSK

betacatenin

apcGSK

betacatenin

apcGSK

betacatenin

apc

apcGSK

betacatenin

epithelialproliferation

adenoma

apcGSK

betacatenin

apcGSK

betacatenin

apcGSK

betacatenin

apcGSK

betacatenin

epithelialproliferation

adenoma

hereditary nonpolyposis colorectal cancer

HNPCC

DNA repairprotein gene

DNA repairprotein gene1st hit

2nd hit

no DNA repair protein produced

reasons for identifying HNPCC cancers

• risk of further cancers in index patient and relatives

• possible implications for therapy– tolerance of 5-FU etc.– do not recognise DNA damage– apoptosis not activated

macroscopic features of colorectal cancer

31

Figure 1.1: Percentage distribution of cases by site within the large bowel, England 1997-2000

38%

colorectal cancer - microscopic

• adenocarcinoma

colorectal cancerstaging & prognosis

Posterior view of total

mesorectal excision of

rectal cancer

Anterior view of total

mesorectal excision of

rectal cancer

Transverse slices of

specimen Rectal cancer

Rectal cancerInvolved lymph node

resection marginscolon

mesentery

resection coding

• R0 - tumour completely excised locally• R1 - microscopic involvement of margin by

tumour• R2 - macroscopic involvement of margin by

tumour

prognosis and circumferential resection margin (CRM)

• CRM +ve 20% 5 year survival with 85% risk of local recurrence

• CRM –ve 75% 5 year survival with 10% risk of local recurrence

why stage?

mucosamuscularis mucosa

submucosa

muscularis propria

lymph nodes

high tie lymph node

Dukes’ pTispN0

Dukes’ A pT1pN0 Dukes’ A pT1pN0

Dukes’ A pT2pN0 Dukes’ B pT3pN0

Dukes’ B pT3pN0 Dukes’ C1 pT3pN1

Dukes’ C1 pT3pN1 Dukes’ C2 pT3pN2

Dukes’ A pT2 Dukes’ B pT3

mucosa

submucosa

muscularis propria

lymph nodes

serosal/peritoneal surface

Dukes’ B pT3 Dukes’ B pT4

Dukes’ B pT4 Dukes’ B pT4

Dukes’ B pT4

Dukes’ stage and prognosis

• A 95% 5 year survival• B 75% 5 year survival• C 35% 5 year survival• D 25% 5 year survival

normalepithelium adenoma

colorectaladenocarcinoma

metastaticcolorectal

adenocarcinoma

endoscopic resection

surgical resection

chemotherapy palliative care

prevention