pathology of colorectal Flashcards
risk factors for colorectal cancer?
Major risk factor is DIET
•Red meat versus vegetables and fish
•Rapid „Westernisation‟ diet in countries - > big colon cancer incidence increase
•Low rates in Africa
•High rates in USA and Europe
•Incidence is going up, mortality going down
•Survival rates more than doubled since 70s
•Vast majority that survive 5 years are cured
origin of colon cancer?
•Lesions in colon:
Non-neoplastic (such as inflammatory polyps)
Benign but potentially pre-malignant (adenomas)
Malignant (such as adenocarcinomas)
Colon cancer arise from ADENOMAS, via a number of genetic mutations and steps, altering essentially normal epithelium to frankly invasive colon cancer in a proportion of cases
adenomas
• Adenomas – alterations in the nuclei, with cell
proliferation, excess mitotic activity, apoptosis->
DYSPLASIA (potentially pre-malignant)
• -mild/moderate/severe dysplasia
• Excess proliferation->mass protruding into lumen
Polyp
Tubular architecture – “test tubes” appearances
Villous architecture – frondy, frilly appearances
Tubulo-villous architecture – admixture of both
Polyps can be attached via stalk (pedunculated)
Polyps without a stalk (sessile)
molecular for colon cancer
frequency of carcinoma in adenomas
mild dysplasia 1734 5.7%
moderate dysplasia 549 18.0%
severe dysplasia 223 34.5%
Mild/Moderate=Low Grade Dysplasia
Severe dysplasia=High Grade Dysplasia
hiogh risk adenomas
> 1 cm
villous component
severe dysplasia
multiple polyps
flexible sigmoidoscopic screening
Once only, 55-64 yrs
170,000 subjects in 14 centres, randomly allocated
Small polyps removed
Colonoscopy for high risk polyps:
• more than 2 adenomas
• > 1cm
• villous histology
• severe dysplasia
flat adenomas
– more often right sided
– usually small (<1cm) with tubular growth
pattern
– K-ras mutation unusual
– higher proliferative fraction
– more often high grade dysplasia
– 40% contain carcinoma
TNM stagin
T1 Tumour invades submucosa
T2 Tumour invades muscularis propria
T3 Tumour penetrates muscularis propria into
subserosa or pericolic/perirectal tissues
T4 Tumour invades adjacent structures and/or
perforates visceral peritoneum
N0 No lymph node metastasis
N1 Metastasis in 1-3 regional lymph nodes
N2 Metastasis in 4 or more regional lymph nodes
M0 No distant metastasis
M1 Distant metastasis present
cetuximab
Cetuximab - antibody to Epidermal Growth
Factor Receptor
Given to patients whose tumours do not have
RAS mutations
KRAS mutations respond very poorly (40%
of colon cancers)
familial adenomatous polyposis
Inherited APC mutation
Autosomal dominant
Duodenal adenomas and
carcinomas
Mesenteric fibromatosis
Osteomas
Thyroid carcinoma
Brain tumours
Hepatoblastomas
MutYH associated polyposis
Inherited defect of Base excision repair
Autosomal recessive
High frequency of G>T mutations
Mimics FAP
colorectal cancer
Sporadic
Inherited
• Familial Adenomatous Polyposis 1%
• MutYH Associated Polyposis 1%
• Hereditary Non-Polyposis CRC 2-5%
HNPCC
• Mutation in mismatch repair gene (MMR)
– Family of DNA repair genes
– MLH1, MSH2, MSH6, PMS2
• Multiple colorectal adenomas and carcinomas
appearing at early age (40+)
• Adenoma - carcinoma sequence probably
accelerated
• Other tumours
– Endometrium, stomach, bladder, pancreas, brain,
skin
amsterdam criteria
• 3 relatives with CRC or HNPCC related
cancer, one a 1st degree relative of the
other two
• Cases that span at least 2 generations
• At least one CRC diagnosed <50yrs