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8/9/2019 Polyps and Polyposis
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Colorectal polyps and
polyposis syndromes
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Colorectal polyps
• visible protrusion
above the surface of
the surrounding
normal large bowel
mucosa
• Detected by
endoscopy or by DCBE
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Classication of colorectalpolyps
Histologicalclassication
Polyp type Malignant potential
on!neoplastic Hyperplastic o
Hamartomatous
"#uvenile$ Peut%!&eghers'
(ymphoid
)n*ammatory
eoplastic "adenoma' +ubular adenoma",!-./ villous tissue'
0es
+ubulovillousadenoma
"-.!1./ villous tissue'
2illous adenoma"1.!3,,/ villous tissue'
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Hyperplastic polyps
• Ma#ority of non!neoplastic polyps
• Prevalence rates of -,!45/ "autopsy
and screening colonoscopy studies'
• Predominantly located in the distal
colon and rectum
• 6enerally small "7,8.cm' in si%e
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9denomas : facts andgures
• 1,/ of all colorectal polyps
• )ncrease with age "44/ of population by .,yr$ and in .,/ by 1,yr'
• 1,/ located in the left colon
• 1,/ are solitary "4,/ synchronous'
• 1,/ are small "73cm in si%e'
• 1/ have severe dysplasia$ 4!./ have invasive cancer
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9denoma!carcinomase;uence
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=actors determining ris> of malignanttransformation within adenomas
High ris> (ow ris>
(arge si%e " ?38.cm' @mall si%e " 73cm'
@essile or *at Pedunculated
@evere dysplasia Mild dysplasia
2illous architecture +ubular architecture
Polyposis syndrome "multiple polyps' @ingle polyp
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Percent of adenomas containinginvasive cancer by si%e and histology
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Malignant colorectal polyp
• Polyp that contains invasive cancer
• Malignant cells that have invadedthrough the mucularis mucosa into the
submucosa
mm
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Management of colorectal polyps "3'
=actors
Location: colon or rectum
Morphology: pedunculated or sessile
Histology: benign or malignant
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Management of colorectal polyps "-'
EAcision
Pedunculated
Colonoscopic polypectomy usually possible
@essile
Colonoscopic polypectomy if possible "larger polyps may re;uire piecemeal removal'
Endoscopic removable not possible operative removal
• Colon colectomy
•
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Management of colorectal polyps "4'
Denitive MA "histology'
Benign
@urveillance
colonoscopy
Malignant
Depends onhistological
characteristics
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@urveillance after polypectomyBenign polyps
Characteristics of polypseAt =
colonoscopy
small rectal hyperplasic polyps "Faverage ris>' 3, years
one or two small "73cm' tubular adenomas .!3, years
4 to 3, adenomas$ or adenoma G 3cm$ or villous features$ or
high!grade dysplasia4 years
?3, adenomas 74 years
sessile adenomas removed piecemeal -! months
6uidelines for colonoscopy surveillance after polypectomy a consensus
update by the @ Multi!@ociety +as> =orce on Colorectal Cancer and the
9merican Cancer @ociet -,,
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Malignant Polyp=actors determining need of radical
surgeryHistology
• Poorly diIerentiated
• Margin 7-mm
• @tal> invasion
• (ymphovascular invasion
)ncrease ris> of recurrence and ( -o
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=amilial Colorectal Cancer
@yndromes
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=amilial adenomatous polyposis"=9P'
• 3/ of all C
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=9P
• ?3,, adenomas
• Patients develop adenomas
by the mean age of 3
years$ and Ces -,!4, years to
develop C
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Molecular genetics of =9P
• Caused by mutations of 9PC gene "tumour suppressor gene' on chromosome
.;-3
• Encodes for a protein$ which functions in cell adhesion and signal transduction
• Mutations will result in truncated protein and aIect cell growth
9PC t >
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9PC as gate>eeper geneadenoma!carcinoma
se;uence
Loeb 1991
Mechanisms of Carcinogenesis
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Mechanisms of Carcinogenesisin =9P
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6enotype vs8 phenotype
ClinicalPresentation
Extracolonic
manifestations
Affected part of gene
Cell adhesion and structural
molecules
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EAtracolonic manifestations
• Congenital hypertrophy of retinalpigmented epithelium "CH
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6ardnerLs syndrome
Desmoid
Chest broma
Mandibular osteoma @>ull osteoma
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9ttenuated =9P "9=9P'
• 2ariant of =9P
• 73,, adenomas
• (ate age!of!onset "adenomas at 55 C
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Cancer ris>s in =9P
Cancer Cancer ris>s
Colon Near 100%
Duodenal or periampullary .!3,/
Pancreatic 9bout -/
+hyroid 9bout -/
6astric 9bout ,8./
C@$ usually cerebellarmedulloblastoma "+urcotOs
syndrome'73/
Hepatoblastoma 38/ of children 7. years of age
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Diagnosis of =9P
Mutation
Protein truncation test
D9 se;uencing
6enetic testsEndoscopy
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@creening of =9P
• Genetic screening of family members for 9PC mutations
• Annual fexible sigmoioscopy beginning at age 3,!3-
until age 5,$ then every 4!. years
!"# polyposis is present$ colectomy shoul be consiere
• G& every 3!4 years is also recommended to evaluate
for upper 6) adenomas
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Prophylactic colectomy for=9P
• +he aim of surgical treatment of =9P is to
intervene in the adenoma!carcinoma se;uence by
removing the adenomas before the
transformation to malignancy occurs
=9P C
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+iming of surgery
Clinical presentation +iming of surgery
9symptomatic patient with
modest number of small
adenomas
9ble to wait for a few years for
surgery$ as long as colonoscopic
surveillance is performed yearly
@ymptomatic patient with large
number of adenomasEarly surgery
@uspicious of C
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@tandard surgical treatment
'estorati(e proctocolectomy )ith ileal pouch*analanastomosis
@uitable for most patients with=9P
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ther surgical options
+otal colectomy )ith ileorectal
anastomosis ,"'A-.roctocolectomy )ith ileostomy
9ttenuated =9P
low rectal cancers
poor sphincters
Desmoid tumors
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Medical treatment of =9P• @ulindac "@9)D' and celecoAib "CQ!- inhibitor' shown to
control and reduce the number of colorectal adenomas in =9P
• ot denitive treatment
• +empori%ing treatment "eg when surgery needs to be delayed'
• May control pouch and rectal polyposis after initial
prophylactic surgery
Hereditary nonpolyposis
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Hereditary nonpolyposiscolorectal cancer "HPCC'
Dr8 98 @8 Rarthin and the rst
HPCC pedigree$ Sthe family
6L 3JK.
Dr8 Henry (ynch rst described the term
Scancer family syndromeL in 3K "later
renamed as (ynch syndrome and
HPCC'
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HPCC
• -!./ of all Ces only 4!. years todevelop C
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HPCC (ynch syndromes
(ynch syndrome ) (ynch syndrome ))
Early onset of C
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HPCC related eAtracolonictumors
Endometrial cancer is the most common eAtracolonic malignancy
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Diagnosis 9msterdamcriteria 3
Due to lac> of phenotypic mar>ers li>e polyps
Diagnosis is based on family history of C
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Diagnosis 9msterdamcriteria -
Same as Amsterdam 1 but
includes all HNPCC
related tumors
Molecular genetics of
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Molecular genetics ofHPCC
HPCC is caused by mutations of
&NA mismatch repair ,MM'- genes
Survey NA forreplication errors
Molecular genetics of
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Molecular genetics ofHPCC
• Mutations of these MM< genes will result in replication errors during
D9 synthesis ,microsatellite instability- leading to acceleration o#
genetic mutations
• HPCC patients develop adenomas at the same rate as the general
population
• nce these adenomas develop$ however$ defective D9 repair ensues
and mismatches accumulates
• +hus$ it ta>es only 4!. years to develop C
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Molecular genetics ofHPCC
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Demonstration of M@)
MicrosatelliteMar>ers
9mplify by Polymerase Chain
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M@@ +umor
D2S123D17S250BAT 25BAT 26
D5S346
NORMA
L
MUCOS
A
TUMOR
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M@) +umor
NORMA
L
TUMOR
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Microsatellite
instability testing
egative
@top
)mmunohistochemistry
M(H3
M@H-@e;uence M(H3 o protein
@e;uence M@H- o protein
ormal
@top
Positive
HPCCMutation detection for M(H3 and M@H-
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@creening of HPCC
• Colonoscopy every - years starting at ages -,!-.
or
. years younger than the earliest diagnosis of C
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@urgical treatment ofHPCC
• +otal colectomy with ileorectal anastomosis
•
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Hamartomatous polyposissyndromes
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Peut%!&eghers syndrome
• )ncidence 3 in -,,$,,, persons
9utosomal dominant
• Mutations of the @+U33 gene onchromosome 3K
• Characteri%ed by perioral
pigmentations and hamartomatous polyps throughout the 6) tract
• G" an non*G" cancers are common
@ite of polyps =re;uency
@tomach 4J/
@mall bowel 1J/
Colon 5-/
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Cancer ris> in P!& syndrome
6) cancers Cancer ris>s
Colon 4K/
Pancreatic 4/
@tomach -K/
@mall bowel 34/
Esophagus ,8./on!6) cancers Cancer ris>s
Breast .5/
varian -3/
terine K/
@eA cord tumour with annular tubules"@C+9+' -,/ become malignant
@ertoli cell tumour 3,!-,/ become malignant
(ung 3./
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&uvenile polyposis
• Presence of ≥3, #uvenile polyps in
the 6) tract
• )ncidence 3 in 3,,$,,, persons
• 9utosomal dominant
• Mutation of @M9D5 gene on
chromosome 3J
• Polyps are most commonly found
in colon
• Colon cancer ris> .,/
• of gastric$ duodenal$ and
pancreatic cancers
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