Colorectal polyps - med.alexu.edu.eg

Colorectal polyps

• Visible protrusion above

the surface of the

surrounding normal

large bowel mucosa

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)

Yes

Tubulovillous adenoma(25-75% villous tissue)

Villous adenoma(75-100% villous tissue)

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





Lymphoid

Inflammatory


Yes



Hamartomatous polyposis syndromes

• Juvenile polyps

• Peutz-Jeghers polyps

• Cronkhite-Canada syndrome

Juvenile polyposis

• Juvenile polyposis syndrome

(JPS) is a hereditary condition

that is characterized by the

presence of hamartomatous

polyps in the digestive tract.

Juvenile polyposis

• Incidence: 1 in 100,000 persons

• Autosomal dominant

• Mutation of SMAD4 gene on

chromosome 18

Juvenile polyposis

• The term “juvenile polyposis”

refers to the type of polyp

(juvenile polyp) that is found

after examination of the polyp

under a microscope, not the age

at which people are diagnosed

with JPS.

• Presence of around 5 to more

than 100 juvenile polyps in the

GI tract

Juvenile polyposis

• Most juvenile polyps are noncancerous, but there

is an increased risk of cancer of the digestive tract,

such as stomach, small intestine, colon,

and rectum cancers, in families with JPS.

• Colon cancer risk 50%

• Pancreatic cancer

https://www.cancer.net/node/19645




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%

Peutz-Jeghers syndrome

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%

Cronkhite-Canada syndrome

• Gastrointestinal hamartomatous polyposis that lead to• Diarrhea,

• Weight loss and

• Abdominal pain

• Extra-intestinal manifestations• Alopecia,

• Cutaneous hyperpigmentation,

• Onycho-dystrophy

Cronkhite-Canada syndrome

• Five-year mortality rates as high as 55 percent have been reported with most deaths due to • gastrointestinal bleeding,

• sepsis, and

• congestive heart failure.

• Treatment has included nutritional support, corticosteroids, acid suppression, and antibiotics





Lymphoid

Inflammatory


Yes



Lymphoid polyps

Mucosal nodularity in representing lymphoid hyperplasia





Lymphoid

Inflammatory


Yes



Inflammatory polyps/ pseudopolyps

• These lesions develop as by-products of the ulcers that penetrate into the submucosa, leaving islands of adjacent regenerative mucosa.

• Although most common in ulcerative colitis, inflammatory polyps may also be seen in Crohn's disease, ischemia, and other ulcerative conditions of the colon.

Inflammatory polyps/ pseudopolyps





Lymphoid

Inflammatory


Yes



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

Regardless of aetiology, most CRC arise from adenomas

Adenoma CRC

10 years

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

Familial adenomatous polyposis (FAP)

• 1% of all CRC

• Present in about 1 in

8000 births


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 geneadenoma-carcinoma sequence

Loeb 1991

Mechanisms of Carcinogenesis in FAP

Genotype vs. phenotype

Clinical

Presentation

Extracolonic

manifestations

Affected part of gene

Cell adhesion and structural

molecules

Extracolonic manifestations

• Congenital hypertrophy of retinal

pigmented epithelium (CHRPE)

• Osteomas, desmoid tumours,

epidermoid cysts (Gardner’s

syndrome)

• CNS malignancies including

medulloblastoma and glioblastoma

(Turcot’s syndrome)

• Duodenal, hepatobiliary-pancreatic,

thyroid tumours

CHRPE

Gardner’s syndrome

Desmoid 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

Mutation

Protein truncation test

DNA sequencing

Genetic testsEndoscopy

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

• Upper GIT Endoscopy every 1-3 years is also recommended to

evaluate for upper GI adenomas

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


• 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

78%

43%

19% 18%

10% 9%

0%

20%

40%

60%

80%

100%

Colorectal Endometrial Stomach Biliary tract Urinary tract Ovarian

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


• 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


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

Average Risk Individuals

No Symptoms

Age 50

No risk factors

Current RecommendationsAverage Risk

*Preferred strategy by ACG

Test Interval (years)

FOBT Yearly

Sigmoidoscopy Every 5

FOBT + Sigmoidoscopy Yearly, every 5

Colonoscopy Every 10*

Barium enema Every 5

Approach to Colon Cancer TestingAsymptomatic

Men and Women

Age < 50 yr

No family Hx

No Screening

HNPCC or FAP

Genetic Counseling

1 first-degree

60 yrs

Average-risk

screening,

starting age 40

YES family Hx

2 or more first-degree or

1 first-degree < 60 yrs

Colonoscopy every

5 yrs, starting age 40

Age 50 yr

NO family Hx

Average Screening

Management of colorectal polypsFactors Affecting

Location: colon or rectum

Number: solitary or multiple

Morphology: pedunculated or sessile

Histology: benign or malignant

Management of colorectal polyps

Excision

Pedunculated

Colonoscopic polypectomy usually possible (Snaring)

Rectal Ca Local excision – Latest Fashion Transanal approaches

• Transanal Endoscopic Microsurgery (TEM)• Developed for lesions out of reach from transanal approach

• Can be used for benign lesions above the peritoneal reflection

• Favourable T1 lesions have equivalent local recurrence and 5yr survival cf radical surgery

• Unfavourable T1 lesions have higher local recurrence (10-15%)

• TEM + XRT on T2 have local recurrence (25-46%)


Excision

Sessile

• Colonoscopic polypectomy if possible

• (larger polyps may require piecemeal removal)

• 5-8 snaring excision

• > 8 removal of affected segment segmental colectomy

• Endoscopic removable not possible operative removal

• Colon: colectomy


Excision

Sessile

• 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)


Definitive Mx (histology)

Benign

Surveillance

colonoscopy

Malignant

Depends on histological characteristics

Radical Surgery

Malignant PolypFactors determining need of radical surgery

Histology

• Poorly differentiated

• Margin <2mm

• Stalk invasion

• Lymphovascular invasion

Increase risk of recurrence and LN 2o

Standard surgical treatment

Restorative proctocolectomy with ileal pouch-anal anastomosis

Suitable for most patients with FAP

TPC IPIAA

IPIAA

Total colectomy Ileorectal anastmosis

Other surgical options

Total colectomy with

ileorectal anastomosis

(IRA)

Proctocolectomy with ileostomy

Attenuated FAP

low rectal cancers

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

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

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Colorectal polyps - med.alexu.edu.eg