This document discusses various types of colorectal polyps and polyposis syndromes. It begins by defining different types of colorectal polyps based on size, attachment, cellular architecture, and histological appearance. Larger polyps have a higher likelihood of harboring cancer. The main polyposis syndromes discussed are familial adenomatous polyposis (FAP), hereditary non-polyposis colorectal cancer (HNPCC), Peutz-Jeghers syndrome, and juvenile polyposis syndrome. FAP is characterized by hundreds of colonic polyps and a 100% risk of colon cancer. Management involves prophylactic colectomy and surveillance of other organs for extracol
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polyposis syndromes
1. Department Of General And Minimal Invasive Surgery .
“POLYPOSIS SYNDROMES IN
COLORECTUM”
Presenter: Dr. Muzzain Iqbal Khateeb.
Moderator: Dr. Fazl .Q .Parray.
Postgraduate Seminar Presentation
2. A colorectal polyp is any mass
projecting into the lumen of the
bowel.
Polyps are further categorized
according to
i. Size.
ii. Character of their attachment
to bowel wall.
iii. Cellular architecture.
iv. Histological appearance.
3. POLYPS WITH LARGER MASS HAVE
GREATER VOLUME OF NEOPLASTIC
CELLS ,HENCE A HIGHER
LIKELIYHOOD OF HARBORING
CANCER.
POLYP SIZE(mm)
<5
6-15
16-25
16-36
37-42
>42
NUMBER
5137
3581
1069
516
219
677
% WITH INVASIVE
CARCINOMA
0
2.2
18.6
42.8
63.9
78.9
4. Depending upon attachment to
bowel wall, polyps can be
1) Pedunculated:
with stalk
2) Sessile: without
stalk
Note: the way in which polyp is attached to the wall does not accurately predict
the presence verses absence of invasive malignancy.
6. Adenomatous polyps:
Are common
These lesions are dysplastic, so should
be treated as premalignant.
Based on extent to which dysplastic
epithelium is organized these can be
7. 1)Tubular:
Found any where in
colon.
Approx 65%-85% of all
adenomatous polyps.
Most often
pedunculated.
Have less atypia,
associated with
malignancy in only 5%
of cases.
Pedunculated tubular
adenoma
9. 3)Villous: most commonly occur in the
rectal area.
Least common about 5%-10%.
Most often sessile.
Generally have severe atypia or
dysplasia, may harbour cancer in
up to 40%.
They tend to be larger than the
other two types.
1 cm sessile villous
adenoma of the sigmoid
colon.
10. Associated with the highest morbidity and
mortality rates of all polyps.
Can cause hyper secretory syndromes :
hypokalemia and profuse mucous discharge
Can harbor carcinoma in situ or invasive
carcinoma more frequently than other
adenomas.
11. Clinical presentation and
natural history of Adenomas
Adenomas are generally asymptomatic
and are most often detected by colon
cancer screening tests.
Small adenomas do not typically bleed
Advanced adenomas are more likely to
bleed and cause a positive fecal occult
blood test.
12. Advanced pathologic risk factors
Adenomatous polyps >1 cm in diameter
Adenomatous polyps with high-grade
dysplasia
Adenomatous polyps with >25 percent
villous histology
13. Adenoma carcinoma
sequence
Peak incidence for
discovery of benign
colorectal polyp is 50
yrs an development of
colorectal cancer is
60yrs:
s/o 10 yrs span for
progression of
adenomatous polyp to
cancer
14. Haggits and colleagues have proposed classification for polyps
containing cancer acc to depth of invasion as:
Level 0: Carcinoma does not invade the
muscularis mucosa (ca –in-situ)
Level 1: carcinoma invades head of
pedunculated polyp(invades through
muscularis mucosae)
Level 2:invasion into neck
Level 3:invasion into stalk
Level 4:invasion into base.(invades
submucosa)
By defination ,all sessile polyps with
invasive carcinoma are level 4.
15.
16. Depth of submucosal invasion in sessile
malignant polyps.
Sm1: invasion into upper third
Sm2: invasion into middle third
Sm3:invasion into lower third.
20. 1.Familial adenomatous polyposis (FAP)
Prototypical hereditary
polyposis syndrome.
Autosomal dominant.
Frequency about
1:10,000.
Account for about 1% of
all colorectal cancers.
21. The APC gene:
The adenomatous polyposis coli (APC) gene is a
tumour suppressor gene located on chromosome
5q21.
Mutation in APC gene is genetic basis attributed to
a truncating mutation in the germ-line APC gene.
The gene expression is 100% in patients with the
mutation.
GENETICS
22. The presentation and severity
of disease is related to the site
of the APC gene mutation.
Proximal APC mutations
(proximal to codon 1249)
produce a milder attenuated
phenotype with sparse
polyposis.
APC mutations between
codons 1250 and 1330 present
with tremendous degrees of
polyposis.
23. APC is universally expressed but mRNA is found in
particularly high levels in normal colonic mucosa
Weighs 300-KDa: found in cytoplasm
APC binds and down regulates cytoplasmic b-catenin,
preventing its translocation to nucleus.
Abnormal APC protein fails to do this, so that b-
catenin is free to enter the nucleus and form a
complex which results in specific transcription of cell
cycle stimulating DNA sequences, and hence
proliferation.
The APC protein
24. Common expression of syndrome is:
Multiple colonic polyps(>100)
Polyps start after age 10–20, cancer in
100% at age 40.
All patients will develop cancer of colon
if left untreated.
26. Gastric polyp :mostly are fundic gland
hyperplasia and have limited malignant
potential.
Duodenal polyp: adenomatous thus
premalignant.
Duodenal cancer and desmoid disease are major
sources of morbidity and mortality.
Increased risk of adenocarcinoma in the
periampullary region in 3–10% of patients
27. Interesting marker is
CHRPE( congenital
hypertrophy of retinal
pigment cells).
It is a patchy fundus
discoloration.
Detected by indirect
ophthalmoscopy in 75% of
patients.
31. Gardner syndrome (GS)
Characterized by
Colonic adenomatous polyposis
Osteomas: usually present in skull, mandible,
and tibia
They are virtually always benign.
Soft tissue tumours like epidermoid cysts,
fibromas, desmoid tumors.
32. Desmoid tumors can
present in the
retroperitoneum and
abdominal wall of affected
patients
These tumors seldom
metastasize but are often
locally invasive, and direct
invasion of the mesenteric
vessels, ureters, or walls of
the small intestine can
result in death.
36. MYH POLYPOSIS
An autosomal recessive form of FAP.
Caused by mutation in the MutY homolog
(MYH) gene.
Individuals have fewer than 100 polyps
Colonic microadenomas and duodenal adenomas
are present.
Diagnosis is considered in families where
No APC mutation have been identified
The mode of inheritance is not clearly autosomal dominant
Polyp numbers are low.
37. Attenuated familial adenomatous polyposis
(AFAP).
Approximately 25% of FAP patients remain without
an identified APC mutation
Have lower polyp number(1-50)
Later age at diagnosis
Tendency to spare the rectum.
Lower extra colonic manifestations.
38. Diagnosis
Genetic testing:
DNA from an individual with FAP is analysed to identify
a mutation in APC, which is successful in about 80% of
cases.
Failure to detect an APC mutation does not exclude a
diagnosis of FAP, and may occur for a variety of reasons
including gene deletion AND some missense mutation.
39. Polyposis registries
Aim: to provide counseling, support and clinical services for
families with FAP.
This includes
i. Thorough pedigree analysis and identification of at-risk
family
ii. Members, who are offered clinical surveillance and genetic
testing so that those affected can be offered prophylactic
surgery
Studies suggest that the introduction of registries, together
with the use of prophylactic surgery, has led to increased life
expectancy and a dramatic reduction in the incidence of
colorectal cancer in FAP
40. Surveillance
Colonoscopy every 12 months starting at around
age 10 to 12 and continuing until age 35 to 40 if
negative.
Flexible proctosigmoidoscopy at age 10-12 year;
repeat every 1-2 yr until age 35; after age 35 repeat
every 3 yr
Upper GI endoscopy every 1-3 yr starting when
polyps first identified
41. Familial Adenomatous Polyposis (FAP)
SCREENING
RECOMMENDATIONS
Colorectal cancer 100% Colonoscopy annually, beginning
age 10-12 yr
Duodenal or
periampullary cancer
5%-10% Upper GI endoscopy every 1-3 yr,
beginning age 20-25 yr
Pancreatic cancer 2% Possible periodic abdominal
ultrasound
Thyroid cancer 2% Annual thyroid examination
Gastric cancer <1% Upper GI endoscopy as for
duodenal and periampullary
Central nervous system
cancer
<1% Annual physical examination
42. Management of large bowel
Once FAP has been diagnosed, the aim is to
perform prophylactic surgery
Patients with severe polyposis or those people
who are symptomatic, should have surgery as soon
as possible.
In those individuals with milder disease, it can
usually be delayed until a convenient time family.
In these circumstances, annual colonoscopy is
recommended to monitor disease.
43. Choice of operation
The surgical options for the management of this
condition are
Proctocolectomy with end ileostomy (with or without
ileal pouch)
Colectomy with ileoanal anastamosis
Proctocolectomy with ileal pouch anal anastamosis
(IPAA).
44. Because few patients desire a permanent
ileostomy, proctocolectomy with end
ileostomy is rarely done.
In most cases, however, the choice is between
colectomy with IRA or proctocolectomy with
ileoanal pouch (IPAA) .
Surgical treatment of patients with FAP is
directed at removal of all affected colonic and
rectal mucosa.
45. Restorative proctocolectomy with
IPAA has become the most
commonly recommended
operation.
The procedure is usually
accompanied by a distal rectal
mucosectomy to ensure that all
premalignant colonic mucosa is
removed, and the IPAA is fashioned
between the ileal pouch and the
dentate line of the anal canal.
46. An alternative approach is total abdominal
colectomy with ileorectal anastomosis: has
certain advantages.
Technically a simpler operation to perform
Pelvic dissection is avoided.
Theoretically less risk for anastomotic leak from the relatively simple
ileorectal anastomosis
An additional argument : sulindac and celecoxib have been observed to
cause the regression of adenomatous polyps in some patients with FAP.
The disadvantages are that the rectum remains
at high risk for the formation of new
precancerous polyps 12-29% after 20-25 years
47. Patients with Gardner syndrome
require surgical treatment of
Cutaneous cysts
Symptomatic dental anomalies and osteomas
Biopsy and resection for malignancies, including
hepatoblastoma, thyroid carcinoma, osteocarcinoma,
gastric carcinoma, periampullary carcinoma, and biliary
tract carcinoma
Liver transplantation may be required in patients with
hepatoblastoma
Patients with Turcot syndrome require
surgical intervention for diagnosis and management of
CNS lesions, gastric lesions and hepatic lesions.
48. Postop surveillance
After IRA, the retained rectum should be examined
using a flexible sigmoidoscope, every 6–12 months.
Polyps larger than 5 mm should be removed
If severe dysplasia or uncontrolled polyposis develops,
completion proctectomy with or without ileoanal
pouch formation is indicated.
In patients who have had IPAA, the pouch should be
examined by flexible endoscopy annually, and a careful
digital examination of the anorectal transition zone
should be performed.
49. Chemoprevention
Have reduced the number and size of colorectal
adenomas
THESE ARE
i. (NSAID) –sulindac
ii. The COX-2 inhibitor celecoxib
50. 2.Hereditary non-polyposis colon cancer
(HNPCC)
HNPCC is the most frequently occurring
hereditary colorectal cancer syndrome
Autosomal dominant.
It also known as Lynch I and II syndromes.
The Lynch I variants describe patients with
predominantly colorectal cancer at a young age
Lynch II: those with both colorectal and
extracolonic cancers.
51. Accounts for 3–5% of all colorectal cancers with
predominance of mucinous or poorly differentiated
(signet cell) adenocarcinoma
Despite its name, these cancers typically arise
from colonic polyps, but a diffuse polyposis is not
present.
The penetrance of the HNPCC predisposition is
high and results in an 80–85% lifetime risk of
colorectal cancer and a 40–50% risk of
endometrial cancer
52. Characterized by an early onset of colorectal
cancers predominantly but not exclusively on
the right side of the colon with synchronous and
metachronous cancers.
HNPCC patients are at increased risk of
developing extracolonic malignancies :
• Cancer of the small bowel
• Stomach
• Hepatobiliary tract
• Urinary tract
• Ovary
• Brain
53. Mutations in Mismatch repair
genes (MMR ) result in the
HNPCC syndrome (including
hMLH1, hMSH2, hMSH3,
hPMS1, hPMS2, and hMSH6)
Mutations in hMSH2 or hMLH1
account for more than 90% of
cases.
These mutations produce
microsatellite instability which
result in errors in S phase when
DNA is newly synthesized and
copied.
Patients with hMSH2 mutation
tend to develop extracolonic
cancers, in particular endometrial
cancer, as compared with hMLH1
mutation carriers.
54. To facilitate the clinical diagnosis of HNPCC,
the International Collaborative Group on
HNPCC (ICG-HNPCC) proposed the
Amsterdam Criteria in 1990.
55. Amsterdam Criteria I (1990)
At least three relatives with colorectal cancer,
one of whom should be a first-degree relative
of the other two.
At least two successive generations should be
affected.
At least one colorectal cancer should be
diagnosed before the age 50 years.
56. Colorectal cancer cannot be
considered an obligate requisite to
define HNPCC , Amsterdam
Criteria II, which now better weigh
extra colonic manifestations as part of
the family history came into
considration.
57. Amsterdam Criteria II (1999)
There should be at least three relatives with HNPCC-associated cancer
(colorectal cancer, cancer of the endometrium, small bowel, and ureter),
of which one should be a first-degree relative of the other two.
At least two successive generations should be affected.
At least one colorectal cancer should be diagnosed before the age 50
years.
59. Revised Bethesda Guidelines (2002) for Testing
Colorectal Tumours for MSI
Criterion Comment
Colorectal cancer diagnosed in a patient less
than 50 years of age
Presence of synchronous, metachronous
colorectal cancer, or other HNPCC-associated
tumor, regardless of age
Stomach, ovarian, pancreas, ureter and renal
pelvis, biliary tract, and brain, sebaceous
gland adenomas and keratoacanthomas, and
small bowel
Colorectal cancer with MSI-high histology
diagnosed in a patient less than 60 years of
age
Tumor infiltrating lymphocytes, Crohn's-like
lymphocytic reaction, mucinous/signet-ring
differentiation, or medullary growth pattern
Colorectal cancer diagnosed in at least on
first-degree relative with an HNPCC-related
tumor diagnosed under age 50
Colorectal cancer diagnosed in two or more
first or second-degree relatives with HNPCC-
related tumors, regardless of age.
60. The mainstay of the diagnosis of HNPCC is a
detailed family history.
20% of newly discovered cases of HNPCC are
caused by spontaneous germline mutations, so a
family history may not accurately reflect the
genetic nature of the syndrome.
Colorectal cancer, or an HNPCC-related cancer,
arising in a person younger than 50 years should
raise the suspicion of this syndrome.
61. Surveillance
Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
Colorectal cancer 80% Colonoscopy, every 2 yr
beginning age 20 yr, annually
after age 40 yr or 10 years
younger than earliest case in
family
Endometrial cancer 40%-60% Pelvic exam, transvaginal
ultrasound, endometrial
aspirate every 1-2 yr, beginning
age 25-35 yr
Upper urinary tract cancer 4%-10% Ultrasound and urinalysis
every 1-2 yr; start at age 30-35
yr
Gallbladder and biliary
cancer
2%-18% No recommendation
Central nervous system
cancer
<5% No recommendation
Small bowel cancer <5% No recommendation
62. MANAGEMENT
When colon cancer is detected in a patient
with HNPCC, an abdominal colectomy and
ileorectal anastomosis is the procedure of
choice.
If the patient is a woman with no further plans
for childbearing, prophylactic total abdominal
hysterectomy and bilateral salpingo-
oophorectomy are recommended.
The rectum remains at risk for development
of cancer, and annual proctoscopic
examinations are mandatory after abdominal
colectomy.
63. Other forms of cancer associated with HNPCC
are treated according to the same criteria as in
nonhereditary cases.
The role of prophylactic colectomy for patients
with HNPCC has been considered in some
instances, but this concept has not received
universal acceptance.
It is an interesting but well-documented fact
that the prognosis is better for cancer patients
with HNPCC than for non-HNPCC patients
with cancer of the same stage.
64. 3.Peutz-Jeghers syndrome.
Autosomal dominant syndrome
The combination of
hamartomatous polyps of the
intestinal tract
Germline defects in the tumor
suppressor serine/threonine
kinase 11 (STK11) gene are
implicated in this rare disease.
65. Symptoms include:
GI bleeding
Intussusception
Rectal prolapse
Nasal polyposis (chronic sinusitis) Pigmented macules on the
lips and digits
Gynecomastia
The most common location of Peutz-Jeghers polyps is in
the upper gastrointestinal tract, specifically the upper
jejunum.
66. There is also an increased risk for extraintestinal
malignancies including
cancer of the breast
ovary
Cervix
fallopian tubes
Thyroid
Lung
Gallbladder
bile ducts
pancreas
testicles.
67. Mucocutaneous
hyperpigmentation
presents as dark blue
to dark brown
mucocutaneous
macules around the
mouth, eyes, and
nostrils, in the
perianal area, on the
buccal mucosa, and
on the fingers
68. PJS Diagnostic Criteria (WHO, 2010)
1.3 or more histologically confirmed PJ polyps, or
2. Any number of PJ polyps with a family history of
PJS,
3.Characteristic prominent mucocutaneous
pigmentation with a family history of PJS, or
4.Any number of PJ polyps and characteristic
prominent mucocutaneous pigmentation.
70. Peutz-Jeghers Syndrome surveillance
Upper GI endoscopy 2 yearly.
Small bowel radiography 2 yearly.
Colonoscopy every 2 yr.
Ultrasound.
Haemoglobin levels annually.
Gynaecologic examination, cervical
smear, and pelvic ultrasound annually.
71. Clinical breast exam and mammography at age
25 yr.
Clinical testicular exam and testicular
ultrasound in males with feminizing features.
Nasal endoscopy :to exclude the presence of
nasal polyps.
Potassium titanyl phosphate (KTP) laser has
been used to treat mucocutaneous melanosis of
the lips and hands in a patient with PJS
72. 4.Juvenile polyposis syndrome (JPS)
Most common hamartomatous syndrome
Inherited as an autosomal dominant trait.
A germ-line mutation in the SMAD-4 gene
(18q21) accounts for approximately 50% of
the reported cases of the syndrome.
The term "juvenile" refers to the type of
polyp, not the age of onset of polyps.
73. Characterized by predisposition for
hamartomatous polyps in the (GI) tract,
specifically in the stomach, small intestine,
colon, and rectum.
The average age of onset is approximately 18
years.
Associated with congenital birth defects (15%-
20%) of patients including malrotation,
hydrocephalus, cardiac lesions, Meckel's
diverticulum, and mesenteric lymphangioma
74. Although the diagnostic criteria
for juvenile polyposis syndrome
are somewhat controversial, the
most commonly used criteria
include
i. 3 or more juvenile polyps of the
colon,
ii. polyposis involving the entire
gastrointestinal tract,
iii. or any number of polyps in a
member of a family with a
known history of juvenile
polyps.
JUVENILE POLYP
75. In infancy, patients may present with acute or
chronic gastrointestinal bleeding,
intussusception, rectal prolapse, or a protein-
losing enteropathy.
In adulthood, patients commonly present with
either acute or chronic gastrointestinal blood
loss.
Polyps are located most frequently in the recto
sigmoid region.
76. Some individuals may only have four or five
polyps over their lifetimes, whereas others in
the same family may have over a hundred.
Most juvenile polyps are benign; however,
malignant transformation can occur.
Estimates of developing GI cancers in families
with JPS range from 9-50%.
78. 5.Cowden syndrome
Also known as multiple hamartoma-
neoplasia syndrome.
It is an autosomal dominant condition
Complete penetrance by the age 20.
Germ-line mutations in the PTEN tumor
suppressor gene located at 10q22.
Polyps arise more commonly from
ectodermal rather than endodermal
elements.
79. 80% of patients present with benign tumor
of the hair shaft.
CNS is the second most involved system,
with approx 40% having macrocephaly.
The majority of patients with Cowden's
disease suffer from benign thyroid or breast
disease- projected lifetime risk of 10% for
thyroid cancer and of 30–50% for breast
cancer.
80. Cowden's Disease
Annual physical exam with special
attention to thyroid
Mammography at age 30 or 5 yr
before earliest breast cancer case in
the family
81. 6.Hyperplastic polyposis syndrome
Hyperplastic polyps are found commonly in
the large bowel, predominantly in the rectum
and sigmoid.
Because of their small size, hyperplastic
polyps rarely cause symptoms.
However, large or multiple hyperplastic polyps
occasionally can be responsible for
gastrointestinal symptoms.
82. HPS is a rare condition
Characterized by numerous hyperplastic
polyps throughout the large bowel that give
the mucosa a "studded" look.
The endoscopic and radiologic appearance
of the mucosal abnormalities closely
resembles FAP, but hyperplastic polyposis
is not heritable and does not have any
extraintestinal manifestations.
83. 7.Hereditary mixed polyposis
syndrome
Mode of inheritance is unknown.
The syndrome is characterized by atypical juvenile
polyps, polyps containing mixed histology, or
multiple polyps of more than one histologic type in
an individual.
Neurofibromatosis type 1 (NF1)
Individuals with NF1 may exhibit multiple
intestinal polypoid neurofibromas or
ganglioneuromas in the small bowel, stomach, and
colon
84. 7.Cronkite-Canada syndrome
Characterized by diffuse hamartomatous
polyposis
The polyps are Ectodermal abnormalities such
as alopecia, onychodystrophy, and skin
hyperpigmentation.
The syndrome can be distinguished by the
diffuse distribution of polyps throughout the
entire gastrointestinal tract with exception of
the esophagus, which is spared.
85. Symptoms include diarrhea, weight loss, nausea,
vomiting, and anorexia, as well as paresthesias,
seizures, and tetany related to electrolyte
abnormalities.
Cancer occurs in the stomach, colon, and rectum, but
it remains controversial whether polyps in Cronkite-
Canada syndrome possess malignant potential.
As many as 15% of patients with Cronkite-Canada
syndrome have a malignant tumor at the time of
diagnosis
86. 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
87. 8.Bannayan-Riley-Ruvalcaba Syndrome
Rare autosomal dominant condition
Includes two other syndromes, both of which, like
Cowden's disease, are associated with genetic
alterations in the PTEN gene on chromosome 10q23 ,
may be considered a variant of juvenile polyposis coli.
No increased risk of colorectal carcinoma, other
gastrointestinal malignancies, or extraintestinal
malignancy has been documented in these patients.
88. It is characterized by
hamartomatous polyps of the gastrointestinal tract
macrocephaly
mental retardation,
delayed psychomotor development
lipid storage myopathy,
Hashimoto's thyroiditis,
hyperpigmentation of the skin of the penis.
89. Research testing of PTEN gene
available
No known published
recommendations for screening
90. Gorlin syndrome (GS),
Also termed nevoid basal cell carcinoma syndrome
commonly presents with
Hamartomatous gastric polyps,
Palmar pits,
Short metacarpals,
Odontogenic keratocysts,
Intracranial calcifications,
Skeletal malformations,
Neoplasia (basal cellcarcinoma, ovarian carcinoma, medulloblastoma).
(GS) may present in infancy with congenital hydrocephalus, cleft lip and palate, lung
cysts, rib and vertebral anomalies, and palmar pits.
Children with GS may present with symptoms of medulloblastoma when younger
than 5 years.
Dental anomalies and basal cell carcinoma can appear in adolescents.
91. Patients with GS may require surgical
management for the following:
Craniofacial lesions (cleft lip and palate, jaw cysts,
other mandibular lesions)
Abdominal masses (mesenteric cysts, lymphatic
cysts, ovarian fibromas)
Diagnostic and therapeutic interventions for
potential neoplasia within the CNS
(medulloblastoma), skin (basal cell carcinoma),
jaw (fibrosarcoma), ovaries (fibrosarcoma), and
endometrium (adenocarcinoma)