Colorectal polyps and

polyposis syndromes

Colorectal polyps
visible protrusion
above the surface of
the surrounding
normal large bowel
mucosa

Detected by
endoscopy or by DCBE

Classification of colorectal
polyps
Histological
classification

Polyp type

Malignant potential

Non-neoplastic

Hyperplastic

No

Hamartomatous
(juvenile, Peutz-Jeghers)

Lymphoid
Inflammatory
Neoplastic (adenoma)

Tubular adenoma
(0-25% villous tissue)

Tubulovillous
adenoma
(25-75% villous tissue)

Villous adenoma
(75-100% villous tissue)

Yes

Hyperplastic polyps
Majority of non-neoplastic polyps

Prevalence rates of 20-34% (autopsy

and screening colonoscopy studies)

Predominantly located in the distal

colon and rectum

Generally small (<0.5cm) in size

Adenomas facts and

figures
70% of all colorectal polyps

Increase with age (33% of population by 50yr, and in 50% by 70yr)

70% located in the left colon

70% are solitary (30% synchronous)

70% are small (<1cm in size)

7% have severe dysplasia, 3-5% have invasive cancer

Adenoma-carcinoma
sequence
10 years

Adenoma

CRC

Regardless of aetiology, most CRC arise from adenomas

Factors determining risk of malignant

transformation within adenomas
High risk

Low risk

Large size ( >1.5cm)

Small size ( <1cm)

Sessile or flat

Pedunculated

Severe dysplasia

Mild dysplasia

Villous architecture

Tubular architecture

Polyposis syndrome (multiple polyps)

Single polyp

Percent of adenomas containing

invasive cancer by size and histology

Malignant colorectal polyp

Polyp that contains invasive cancer
Malignant cells that have invaded
through the mucularis mucosa into the
submucosa

mm

Management of colorectal polyps (1)

Factors
Location: colon or rectum
Morphology: pedunculated or sessile

Histology: benign or malignant

Management of colorectal polyps (2)

Excision
Pedunculated
Colonoscopic polypectomy usually possible

Sessile
Colonoscopic polypectomy if possible (larger polyps may require piecemeal removal)

Endoscopic removable not possible operative removal

Colon: colectomy
Rectum: staged with EUS or MRI
Benign / Early malignant (T1No) : Transanal local excision or TEMS (may need further
radical surgery)
Other malignant : radical excision (APR /anterior resection)

Management of colorectal polyps (3)

Definitive Mx (histology)
Benign

Malignant
Depends on
histological
characteristics

Surveillance
colonoscopy

Radical Surgery

Surveillance after polypectomy

Benign polyps
Characteristics of polyps

Next FU
colonoscopy

small rectal hyperplasic polyps (=average risk)

10 years

one or two small (<1cm) tubular adenomas

5-10 years

3 to 10 adenomas, or adenoma 1cm, or villous features, or

high-grade dysplasia

3 years

>10 adenomas

<3 years

sessile adenomas removed piecemeal

2-6 months

Guidelines for colonoscopy surveillance after polypectomy: a consensus

update by the US Multi-Society Task Force on Colorectal Cancer and the
American Cancer Society (2006)

Malignant Polyp
Factors determining need of radical
surgery
Histology
Poorly differentiated
Margin <2mm
Stalk invasion
Lymphovascular invasion

Increase risk of recurrence and LN 2o

Familial Colorectal Cancer

Syndromes

Familial adenomatous polyposis

(FAP)
1% of all CRC
Present in about 1
in 8000 births
Autosomal
dominant with near
100% penetrance

FAP
>100 adenomas
Patients develop adenomas
by the mean age of 16
years, and CRC by 39 years
Adenomas form early, but it
takes 20-30 years to
develop CRC from
adenomas
Disease of abnormal
tumour initiation

Molecular genetics of FAP

Caused by mutations of APC gene (tumour suppressor gene) on chromosome

5q21

Encodes for a protein, which functions in cell adhesion and signal transduction

Mutations will result in truncated protein and affect cell growth

APC as gatekeeper gene

adenoma-carcinoma
sequence

Loeb 1991

Mechanisms of Carcinogenesis
in FAP

Genotype vs. phenotype

Affected part of gene

Clinical
Presentation
Extracolonic
manifestations

Cell adhesion and structural

molecules

Extracolonic manifestations
Congenital hypertrophy of retinal
pigmented epithelium (CHRPE)

Osteomas, desmoid tumours,

epidermoid cysts (Gardners syndrome)

CNS malignancies including

medulloblastoma and glioblastoma
(Turcots syndrome)

Duodenal, hepatobiliary-pancreatic,
thyroid tumours

CHRPE

Gardners syndrome

Desmoi
d

Chest fibroma

Mandibular osteoma

Skull osteoma

Attenuated FAP (AFAP)

Variant of FAP
<100 adenomas
Late age-of-onset (adenomas at 44; CRC at 56)
Proximal distribution of adenomas
*Colonoscopy for surveillance
*Infrequent involvement of the rectum supports
the role
of total colectomy and IRA

Cancer risks in FAP

Cancer

Cancer risks

Colon

Near 100%

Duodenal or periampullary

5-10%

Pancreatic

About 2%

Thyroid

About 2%

Gastric

About 0.5%

CNS, usually cerebellar

medulloblastoma (Turcot's
syndrome)

<1%

Hepatoblastoma

1.6% of children <5 years of age

Diagnosis of FAP
Endoscopy

Genetic tests

Mutation
Protein truncation test

DNA sequencing

Screening of FAP
Genetic screening of family members for APC mutations

Annual flexible sigmoidoscopy beginning at age 10-12

until age 40, then every 3-5 years

*If polyposis is present, colectomy should be considered

OGD every 1-3 years is also recommended to evaluate

for upper GI adenomas

Prophylactic colectomy for

FAP

FAP

CRC

The aim of surgical treatment of FAP is to

intervene in the adenoma-carcinoma sequence by
removing the adenomas before the
transformation to malignancy occurs

Timing of surgery
Clinical presentation

Timing of surgery

Asymptomatic patient with

modest number of small
adenomas

Able to wait for a few years for

surgery, as long as colonoscopic
surveillance is performed yearly

Symptomatic patient with large

number of adenomas

Early surgery

Suspicious of CRC

Very early/urgent surgery

Standard surgical treatment

Restorative proctocolectomy with ileal pouch-anal
anastomosis

Suitable for most patients with

FAP

Other surgical options

Total colectomy with ileorectal
anastomosis (IRA)

Proctocolectomy with ileostomy

low rectal cancers

Attenuated FAP

poor sphincters
Desmoid tumors

Medical treatment of FAP?

Sulindac (NSAID) and celecoxib (COX-2 inhibitor) shown to

control and reduce the number of colorectal adenomas in FAP

Not definitive treatment

Temporizing treatment (eg when surgery needs to be delayed)

May control pouch and rectal polyposis after initial

prophylactic surgery

Hereditary nonpolyposis
colorectal cancer (HNPCC)

Dr. A. S. Warthin and the first

HNPCC pedigree, the family
G 1895

Dr. Henry Lynch first described the term

cancer family syndrome in 1966 (later
renamed as Lynch syndrome and
HNPCC)

HNPCC
2-5% of all CRC

Autosomal dominant

70-80% penetrance

It takes only 3-5 years to

develop CRC from adenomas
Accelerated progression

HNPCC: Lynch syndromes

Lynch syndrome I

Lynch syndrome II

Early onset of CRC (40-45 years)

Features of Lynch Syndrome I +

extracolonic malignancies

Predominantly proximal to the

splenic flexure (60-70%)

*Gastric, small bowel,

hepatobiliary, endometrial,
ovarian, ureteral and renal
tumours

Increase frequency of synchronous

and metachronous lesions (33%)

HNPCC related extracolonic

tumors

Endometrial cancer is the most common extracolonic malignancy

Diagnosis: Amsterdam
criteria 1
Due to lack of phenotypic markers like polyps
Diagnosis is based on family history of CRC
only

1. One member less than 50 years of age

2. Two involved generations
3. Three family members affected, one of whom is a

first-degree relative of the other two

Diagnosis: Amsterdam
criteria 2

Same as Amsterdam 1 but

includes all HNPCC
related tumors

Molecular genetics of
HNPCC
HNPCC is caused by mutations of
DNA mismatch repair (MMR) genes

Survey DNA for

replication errors

Molecular genetics of
HNPCC
Mutations of these MMR genes will result in replication errors during
DNA synthesis (microsatellite instability) leading to acceleration of
genetic mutations

HNPCC patients develop adenomas at the same rate as the general

population

Once these adenomas develop, however, defective DNA repair ensues

and mismatches accumulates

Thus, it takes only 3-5 years to develop CRC from adenomas

Molecular genetics of
HNPCC

Demonstration of MSI
DNA Normal
Tissue

DNA Tumor Tissue

Microsatellite
Markers
Amplify by Polymerase Chain
Reaction
Compare normal and tumor profiles of
amplified microsatellite on gel to detect
genetic mutations in these
microsatellites

MSS Tumor
BAT 26
D5S346
NORMA
L
MUCOS
A
TUMOR

BAT 25 D17S250

D2S123

MSI Tumor

NORMA
L

TUMOR

HNPCC:
Mutation detection for MLH1 and MSH2
Microsatellite
instability testing

Negative:
Stop?

Positive

Immunohistochemistry
MLH1

Sequence MLH1

No protein

Sequence MSH2

No protein

MSH2

Normal
Stop?

Screening of HNPCC
Colonoscopy every 2 years starting at ages 20-25
or
5 years younger than the earliest diagnosis of CRC
whichever is earlier until 40yr , and then annually

Flexible sigmoidoscopy is not acceptable, due to the proximal

location of tumours

Transvaginal US and endometrial aspiration annually starting at

ages 25-35 years are also recommended

Surgical treatment of
HNPCC
Total colectomy with ileorectal anastomosis

Restorative proctocolectomy with ileal pouch-anal anastomosis

Segmental colectomy not recommended because of high rate

of metachronous CRC

TAHBSO for endometrial cancer

Hamartomatous polyposis
syndromes

Peutz-Jeghers syndrome
Incidence: 1 in 200,000 persons
Autosomal dominant

Mutations of the STK11 gene on

chromosome 19

Characterized by perioral
pigmentations and hamartomatous
polyps throughout the GI tract

GI and non-GI cancers are common

Site of polyps

Frequency

Stomach

38%

Small bowel

78%

Colon

42%

Rectum

28%

Cancer risk in P-J syndrome

GI cancers

Cancer risks

Colon

39%

Pancreatic

36%

Stomach

29%

Small bowel

13%

Esophagus

0.5%

Non-GI cancers

Cancer risks

Breast

54%

Ovarian

21%

Uterine

9%

Sex cord tumour with annular tubules

(SCTAT)

20% become malignant

Sertoli cell tumour

10-20% become malignant

Lung

15%

Juvenile polyposis

Presence of 10 juvenile polyps in

the GI tract

Incidence: 1 in 100,000 persons

Autosomal dominant

Mutation of SMAD4 gene on

chromosome 18

Polyps are most commonly found

in colon

Colon cancer risk 50%

Risk of gastric, duodenal, and

pancreatic cancers