Colonic polyps

• Polyp : A protuberance into the lumen above the surrounding

colonic mucosa.

• Colon polyps are usually asymptomatic but may ulcerate and

bleed, cause tenesmus if in the rectum, and, when very large,
produce intestinal obstruction.

• Colonic polyps may be neoplastic (eg, adenomas) or non-

neoplastic (eg, inflammatory polyps).
• ADENOMATOUS POLYPS
• — Adenomas are the most prevalent neoplastic polyps in the
colon.
• Epidemiology and risk factors
• Approximately two-thirds of all colonic polyps are adenomas.

• 30 to 50 percent of colons with one adenoma will contain at

least one other synchronous adenoma.

• Increasing age is a risk factor for the development of colonic

adenomas and is associated with the development of high-
grade dysplasia within an adenoma, independent of size and
histology.

• Advancing age is also a risk factor for right-sided polyps.

• Increased body mass index (BMI)
• Lack of physical activity
• Male gender
• Clinical presentation and natural history

• Adenomas are generally asymptomatic and are most often detected

by colon cancer screening tests.
• Bleeding
• Tenesmus
• Obstruction

• The risk of progression to cancer is higher for advanced adenomas

(adenoma with high-grade dysplasia, >10 mm in size, or a villous
component).
• The proportion of adenomas showing advanced histologic
features increases with polyp size from approximately 1 to 2
percent in small adenomas (<5 mm) to 7 to 12 percent for
medium-sized adenomas (5 to 10 mm) and 20 to 30 percent for
large adenomas (>1 cm).
• Endoscopic features and classification
• The majority of adenomas (60 to 75 percent) are less than 1
cm at endoscopy.

• Based on their gross appearance, adenomas may be

pedunculated, sessile, flat, depressed, or excavated.
• Sessile – In a sessile polypoid lesion, the base and the top of
the lesion have the same diameter.
• Pedunculated – In pedunculated polyp the base is narrow.
A mucosal stalk is interposed between the polyp and the wall.
• Flat – Flat lesions are defined as those with a height less than
one-half the diameter of the lesion.
• Depressed – In depressed lesions the entire thickness of the
mucosa in the lesion is often less than that of the adjacent
mucosa.
• Histologic features
• Adenomas are characterized as tubular, villous, or a mixture of
the two.

• An advanced adenoma is defined as adenomas ≥10 mm in size

or with villous components or high-grade dysplasia.
• Some degree of dysplasia exists in all adenomas. Based on the degree of
dysplasia, polyps are classified as having:
●Low-grade dysplasia
●High-grade dysplasia

High-grade dysplasia (synonymous with intraepithelial carcinoma)

represents an intermediate step in the progression from a low-grade
dysplasia to cancer.

The term is applied to lesions that are confined to the epithelial layer of
crypts and lack invasion through the basement membrane into the lamina
propria.

As there are no lymphatic vessels in the lamina propria, lesions with high
grade dysplasia are not associated with metastasis
• SESSILE SERRATED LESIONS
• Sessile serrated lesions are a heterogenous group of polyps
with variable malignant potential.

• They include hyperplastic polyps, traditional serrated adenomas,

and sessile serrated polyps (SSPs; with and without cytologic
dysplasia).
• Risk of cancer – SSP frequently exhibit dysplasia.

• Risk factors for a synchronous advanced adenoma in patients

with SSPs include SSP/A size ≥10 mm, location in the proximal
colon, and the presence of dysplasia.
• Hyperplastic polyps
• Hyperplastic polyps are the most common non-neoplastic
polyps in the colon.

• They are typically located in the rectosigmoid and are less than
5 mm in size.
• Risk of cancer – Small rectosigmoid hyperplastic polyps do not
appear to increase the risk of colorectal cancer.
• Inflammatory pseudopolyps
• Inflammatory pseudopolyps are irregularly shaped islands of
residual intact colonic mucosa that are the result of the mucosal
ulceration and regeneration that occurs in response to localized
or diffuse inflammation (eg, ulcerative colitis or Crohn disease).
• Risk of malignancy – Inflammatory pseudopolyps do not
undergo neoplastic transformation.

• Management – Inflammatory pseudopolyps do not require

excision unless they cause symptoms (eg, bleeding,
obstruction). Treatment is directed at the underlying cause of
inflammation.
• HAMARTOMATOUS POLYPS
• Hamartomatous polyps are made up of tissue elements that
are normally found at that site but are growing in a disorganized
mass.
• Juvenile polyposis syndrome (JPS) is an autosomal dominant
condition characterized by multiple hamartomatous polyps
throughout the gastrointestinal tract.

• Individuals with JPS are at increased risk for colorectal and

gastric cancer.
• Peutz-Jeghers polyps
• The Peutz-Jeghers polyp is a hamartomatous lesion of
glandular epithelium
• The Peutz-Jeghers polyp is usually, but not always, associated
with the Peutz-Jeghers syndrome (PJS), due to STK11
mutations.

• Peutz-Jeghers polyps should be resected. The polyps are

usually benign, but may grow progressively and produce
symptoms or undergo malignant transformation.

• Patients with PJS are at increased risk of both gastrointestinal

(gastric, small bowel, colon, pancreas) and nongastrointestinal
cancers including breast cancer.
Colorectal cancers
• To date, most guidelines have suggested initiating screening at
the age of 50 unless individuals have inflammatory bowel
disease, a history of abdominal radiation, a positive family
history, or a predisposing inherited syndrome.

• However, in 2021, given the rising incidence in younger adults,

the United States issued an updated recommendation to initiate
screening at age 45 in all adults.
• CLINICAL PRESENTATION
• — Patients with CRC may present in three ways:

• Suspicious symptoms and/or signs

• Asymptomatic individuals discovered by routine screening

• Emergency admission with intestinal obstruction, perforation, or

rarely, an acute gastrointestinal bleed.
• Symptoms from the local tumor
• — Typical symptoms/signs associated with CRC include
hematochezia or melena, abdominal pain, otherwise
unexplained iron deficiency anemia, and/or a change in bowel
habits.

• Less common presenting symptoms include abdominal

distention, and/or nausea and vomiting, which may be
indicators of obstruction.
• Obstructive symptoms are more common with cancers that encircle
the bowel, producing the so-called (apple-core) description as seen
most classically on barium enema, which is now rarely used.

• Among symptomatic patients, clinical manifestations also differ

depending on tumor location:

• A change in bowel habits is a more common presenting symptom for

left-sided than right-sided CRCs.

• Fecal contents are liquid in the proximal colon and the lumen caliber
is larger, and CRCs are therefore less likely to be associated with
obstructive symptoms, including colicky pain.
• Hematochezia is more often caused by rectosigmoid than right-sided
colon cancer.

• Iron deficiency anemia from unrecognized blood loss is more common

with right-sided CRCs. Cecal and ascending colon tumors have a fourfold
higher mean daily blood loss (approximately 9 mL/day) than tumors at
other colonic sites.

• Abdominal pain can occur with tumors arising at all sites; it can be caused
by a partial obstruction, peritoneal dissemination, or intestinal perforation
leading to generalized peritonitis.

• Rectal cancer can cause tenesmus, rectal pain, and diminished caliber of
stools.
• Role of fecal immunochemical test to triage patients with
symptoms
• — Given the limitations to timely colonoscopy in many health
care settings and the nonspecific nature of most colorectal
(cancer) symptoms, there is emerging interest in using fecal
immunochemical tests for occult blood (FIT) using a low
threshold of fecal hemoglobin to maximize sensitivity in order
to stratify symptomatic patients who need more urgent
diagnostic colonoscopy.
• This approach is supported by a meta-analysis which concluded
that at the lower limit of detection of fecal hemoglobin (≥2
microg/g feces), the summary sensitivity was 97 percent, and
the negative predictive value was no lower than 98 percent,
regardless of the CRC prevalence.

• These data suggest that a single quantitative FIT test can

adequately exclude CRC in symptomatic patients and allow
prioritization of colonoscopy resources, or at least stratification
for relative urgency on waiting lists.

• However, this approach is not widespread in North America

where colonoscopy is readily available.
• Because the venous drainage of the intestinal tract is via the
portal system, the first site of hematogenous dissemination is
usually the liver, followed by the lungs, bone, and many other
sites, including the brain.

• Tumors arising in the distal rectum may metastasize initially to

the lungs rather than liver because the inferior rectal vein drains
into the inferior vena cava rather than into the portal venous
system.
• Screening and Diagnosis
• OB
• FIT
• Colonoscopy
• Rectosigmoidoscopy
• Barium study

• — The diagnosis of a CRC is made by histologic examination of a biopsy

that is usually obtained during lower gastrointestinal tract endoscopy or
from a surgical specimen.

• Histopathologically, the majority of cancers arising in the colon and

rectum are adenocarcinomas.
• Colonoscopy
• — Colonoscopy is the most accurate diagnostic test for CRC,
since it can localize and biopsy lesions throughout the large
bowel, detect synchronous neoplasms, and remove polyps.
• Flexible sigmoidoscopy
• — Over the last 50 years, a gradual shift toward right-sided or
proximal colon cancers has been observed both in the United
States and internationally, with the greatest increase in
incidence in cecal primaries.

• Because of this, and because of the high frequency of

synchronous CRCs, flexible sigmoidoscopy is generally not
considered to be an adequate diagnostic study for a patient
suspected of having a CRC, unless a palpable mass is felt in the
rectum.
Computed tomography colonography

— CT colonography (also called virtual colonoscopy or CT

colography) provides a computer-simulated endoluminal
perspective of the air-filled distended colon.

• CT colonography requires a mechanical bowel preparation that

is similar to that needed for barium enema, since stool can
simulate polyps.

• colonoscopy remains the gold standard for investigation of

symptoms suggestive of CRC. CT colonography is preferred
over barium enema where access to colonoscopy is limited.
• Laboratory tests
• — Although CRC is often associated with iron deficiency
anemia, its absence does not reliably exclude the disease.

• Tumor markers
• — A variety of serum markers have been associated with CRC,
particularly carcinoembryonic antigen (CEA).

• However, all these markers, including CEA, have a low

diagnostic ability to detect primary CRC due to significant
overlap with benign disease and low sensitivity for early stage
disease.
• Neither serum CEA nor any other marker, including CA 19-9,
should be used as a screening or diagnostic test for CRC.
• However, CEA levels do have value in the prognosis and follow-
up of patients with diagnosed CRC:

• Elevated preoperative CEA levels that do not normalize

following surgical resection imply the presence of persistent
disease and the need for further evaluation.

• A rising CEA level after surgical resection implies recurrent

disease and should prompt follow-up radiologic imaging.
RISK FACTORS
• Age and early onset colorectal cancer
• Age is a major risk factor for sporadic CRC.

• Hereditary CRC syndromes

• Familial adenomatous polyposis (FAP) and Lynch syndrome

(hereditary nonpolyposis colorectal cancer [HNPCC])
Adenomatous polyposis syndromes
• FAP — Familial adenomatous polyposis (FAP) and its variants (Gardner
syndrome, Turcot syndrome, and attenuated familial adenomatous
polyposis [AFAP]) account for less than 1 percent of CRCs.

• In typical FAP, numerous colonic adenomas appear during childhood.

• Symptoms appear at an average age of approximately 16 years and

colonic cancer occurs in 90 percent of untreated individuals by age 45.

• AFAP carries a high risk of colon cancer (though its magnitude is not as
well defined), but is characterized by fewer adenomas and an older
average age of cancer diagnosis of 54 years.
• FAP is caused by germline mutations in the adenomatous
polyposis coli (APC) gene which is located on chromosome 5.

• The same gene is involved in the attenuated form of FAP, but the
sites of the APC gene mutations are different.
• Lynch syndrome
— Lynch syndrome or HNPCC is an autosomal-dominant
syndrome that is more common than FAP and accounts for
approximately 3 percent of all colonic adenocarcinomas.

Lynch syndrome can be suspected on the basis of a strong family

history of CRC, endometrial, and other cancers.
• The term Lynch syndrome is now commonly reserved for
families who have been genetically determined to have a
disease-causing defect in one of the DNA mismatch repair
(MMR) genes, most commonly hMLH1, hMSH2, hMSH6, or
hPMS2.
• Lynch syndrome CRCs have impaired DNA MMR, are
hypermutable, and are microsatellite unstable.
• Early age of onset, right sided, mucinous, poorly differentiated
tumours
• Extracolonic cancers are very common in Lynch syndrome:
• endometrial carcinoma
• ovary,
• stomach,
• small bowel,
• hepatobiliary system,
• brain
• renal pelvis or ureter,
• breast
• prostate.
• Personal or family history of sporadic CRCs or adenomatous
polyps

• — Patients with a personal history of CRC or adenomatous

polyps of the colon are at risk for the future development of
colon cancer.
• A personal history of large (>1 cm) adenomatous polyps and
polyps with villous or tubulovillous histology or with high-grade
dysplasia also increases the risk of CRC, particularly if multiple.

• Having a single affected first-degree relative (parent, sibling, or

child) with CRC increases the risk approximately twofold over
that of the general population.

Risk is further increased if two first, or one first and one or more
first or second-degree relatives on either side of the family have
colon cancer, or if a first-degree relative is diagnosed below 50
years of age.
Inflammatory bowel disease
• Ulcerative colitis
• There is a well-documented association between chronic
ulcerative colitis and colonic neoplasia, with the extent, duration,
and activity of disease being the primary determinants.
• Crohn disease
• Although there are much less data, it appears that pancolitis
due to Crohn disease is associated with a similar RR of colon
malignancy as extensive ulcerative colitis, although the data are
less consistent.
• Abdominopelvic radiation
• Cystic fibrosis
• Age
• The rising incidence of early onset CRC, particularly among those in
the 40 to 49 year old age group, has prompted at least two groups to
lower the recommended age of first screening.

• Race and gender

• African Americans have the highest CRC rates of all ethnic groups in
the United States.
• CRC mortality is approximately 25 percent higher in males than in
females, and both colonic adenomas and CRCs appear to have a more
proximal distribution in females, particularly in postmenopausal women.
• Acromegaly
• Renal transplantation
• — Renal transplantation, in association with long-term
immunosuppression, has been linked with increased CRC risk.

• Obesity
• — Obesity is a risk factor for CRC. The excess risk associated
with obesity is reduced after bariatric surgery, with at least one
report suggesting that CRC rates approximate those in the general
population within five or six years of surgery.
• Diabetes mellitus and insulin resistance
• One possible explanation linking diabetes to CRC is hyperinsulinemia,
because insulin is an important growth factor for colonic mucosal cells
and stimulates colonic tumor cells.

• Red and processed meat

• Although the data are not entirely consistent, long-term consumption of
red meat or processed meats appears to be associated with an increased
risk of CRC, particularly for left-sided tumors.

• High temperature cooking (eg, barbecuing, pan-frying) has been implicated

as contributing to risk, perhaps by the production of polyaromatic
hydrocarbons and other carcinogens produced from proteins in the
charring process.
• Tobacco
• — Cigarette smoking has been associated with increased
incidence and mortality from CRC.

• Alcohol

• Use of androgen deprivation therapy

• Cholecystectomy

• Other risk factors

• The presence of coronary heart disease
• Ureterocolic anastomoses
• endometrial cancer
• Several bacterial and viral agents (eg, Streptococcus bovis,
Helicobacter pylori, JC virus, human papilloma virus [HPV],
Fusobacterium, colonization of the gut by pathogenic strains of
E. coli, and decreased diversity of the gut bacterial microbiome)
have been proposed as risk factors for CRC.
• PROTECTIVE FACTORS
• Physical activity
• Diet
• diet high in fruits and vegetables
• Fiber
• Folic acid
• Vitamin B6 (pyridoxine)
• Calcium and dairy products
• Vitamin D
• Magnesium
• Garlic
• Fish consumption
• Coffee intake
• Aspirin and NSAIDs

• Regular use of aspirin and other NSAIDs is associated with a 20

to 40 percent reduction in the risk of colonic adenomas and
CRC in individuals at average risk.

• Hormone therapy in females

• Statins
• Bisphosphonates
• Angiotensin II inhibition
• Recommended evaluation for routine surveillance of colon
cancer survivors:
• Physical examination
• CEA
• CT of the chest- abdominal-pelvic
• Colonoscopy