pathology of colorectal Flashcards

1
Q

risk factors for colorectal cancer?

A

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

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2
Q

origin of colon cancer?

A

•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

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3
Q

adenomas

A

• 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)

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4
Q

molecular for colon cancer

A
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5
Q

frequency of carcinoma in adenomas

A

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

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6
Q

hiogh risk adenomas

A

> 1 cm
villous component
severe dysplasia
multiple polyps

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7
Q

flexible sigmoidoscopic screening

A

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

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8
Q

flat adenomas

A

– 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

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9
Q

TNM stagin

A

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

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10
Q

cetuximab

A

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)

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11
Q

familial adenomatous polyposis

A

Inherited APC mutation
Autosomal dominant
Duodenal adenomas and
carcinomas
Mesenteric fibromatosis
Osteomas
Thyroid carcinoma
Brain tumours
Hepatoblastomas

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12
Q

MutYH associated polyposis

A

Inherited defect of Base excision repair
Autosomal recessive
High frequency of G>T mutations
Mimics FAP

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13
Q

colorectal cancer

A

Sporadic

Inherited
• Familial Adenomatous Polyposis 1%
• MutYH Associated Polyposis 1%
• Hereditary Non-Polyposis CRC 2-5%

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14
Q

HNPCC

A

• 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

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15
Q

amsterdam criteria

A

• 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

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16
Q

hnpcc colorectal tumors

A
  • Right-sided
  • Poorly differentiated
  • Mucinous differentiation
  • Prominent lymphoid response
  • Microsatellite instability
17
Q

sporadic colorctal cancer with MSI

A

Hypermethylation (silencing) of MLH1
Different molecular pathogenesis from
majority of colorectal cancers
More often right sided, mucinous
Often have serrated morphology
Better prognosis
May not respond to conventional 5-FU
based chemotherapy

18
Q

peutz jeghers syndrome

A

• Rare, autosomal dominant, STK11 mutation
• Polyps throughout G-I tract
– Intussusception or obstriction
• Mucosal melanin pigmentation
• Increased tumour risk in pancreas, breast,
lung, ovary uterus, GI tract

19
Q

juvenile polyposis

A

– Autosomal dominant (SMAD4/DPC4)
– Polyps predominantly in colorectum
– Increased risk of colorectal, gastric,
duodenal, biliary tree and pancreas
tumours

– > 5 juvenile polyps in colorectum
OR
– Juvenile polyps throughout GI tract
OR
– Any number of juvenile polyps with a
family history of juvenile polyposis

20
Q

hyperplastic polyps

A

• Common, especially left colon & rectum
• Benign
• Elongated and dilated crypts
• Serrated appearance
• Large right sided lesions may be associated
with carcinoma

21
Q

national colorectal cancer screening in england

A

– 60-69 yrs (started in 2006)
– Primary test: FOB (no dietary restriction
and rehydration of sample) every 2 years
– Follow-up: Colonoscopy (with Double
Contrast Barium Enema if incomplete)
– Moving to screen up to 75 years
– One off flexible sigmoidoscopy at 55 years
– Rollout date awaited

– Invitation by mail from GP, with test kit
– Collect specimens from 3 consecutive
bowel motions onto cards
– Cards returned to Screening Centre
– Patients requiring investigation attend
Assessment Clinics at nearest Cancer
Units

22
Q

bowek cancer wales

A

• Current age range 60-71 years age (50y-75y aim)
• FOB kits sent in post every 2 years
• 15% quoted decrease in mortality
• 56% uptake so far
• 425 cancers and 3033 adenomas detected
• No current plans in Wales for flexible
sigmoidoscopy

23
Q
A