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Assessment of
Adenomas
Geraint Williams
Pathology Department
Cardiff University
The great majority of lesions in the
Screening Programme are small
adenomas and hyperplastic polyps
Recognising adenomas
Categorising adenomas
Invasion
Completeness of Excision
Serrated lesions
Recognising adenomas
Categorising adenomas
Invasion
Completeness of Excision
Serrated lesions
Size
Villousness
Dysplasia
Frequency of Carcinoma in
Adenomas
< 1 cm
1479
1.3%
1-2 cm
580
9.5%
> 2 cm
430
46.0%
Muto et al 1975
Frequency of Carcinoma in
Adenomas
tubular
1875
4.7%
tubulovillous
380
22.4%
villous
234
41.9%
Muto et al 1975
Frequency of Carcinoma in
Adenomas
mild dysplasia
1734
5.7%
moderate dysplasia
549
18.0%
severe dysplasia
223
34.5%
Muto et al 1975
High Risk (‘Advanced’)
Adenomas
> 1 cm
villous component
severe dysplasia
As long as there is no invasive
malignancy and excision is
complete No worries!
Rectosigmoid Adenoma Follow-Up
1618 patients followed for a mean of 14 years
after removal of rectosigmoid adenomas:
49 (3%) developed colorectal cancer:
14 rectal SIR 1.2 (CI 0.7-2.1)
(11/14 had incompletely excised adenomas)
35 colonic SIR 2.1 (CI 1.5-3.0)
Atkin et al 1992
Risk of Subsequent Colon Cancer
tubular
1
mild
1.3
tubulovillous 3.8
moderate
3.4
villous
5.0
severe
3.3
<1 cm
1.5
1 tumour
1.7
1-2 cm
2.2
>2 tumours 4.8
>2 cm
5.9
Risk of Subsequent Colon Cancer
Patients
Cancers
SIR
Low Risk Adenomas
Single
Multiple
Total
712
64
776
4
0
4
0.6
0
0.5
High Risk Adenomas
Single
Multiple
Total
683
159
842
20
11
31
2.9
6.6
3.6
Advanced Adenoma Patients
> 1 cm
villous component
severe dysplasia
multiple polyps
Risk of Advanced Neoplasia 5.5yrs
No neoplasia
Tubular Adenoma <10mm
1-2
3+
Tubular Adenoma >10mm
Villous Adenoma
High Grade Dysplasia
Carcinoma
Patients
298
622
496
126
123
81
46
23
Ad Neo
7
38
23
15
19
13
8
8
RR
1
2.56
1.92
5.01
6.40
6.05
6.87
13.56
Lieberman et al 2007
Even if there is no invasive malignancy
and excision is complete Grading of dysplasia and assessment
of villousness in adenomas that are
<10mm will govern surveillance
So we’ve got to try hard to get it
right!
Grading Dysplasia in 2189
Adenomas at 13 Centres
min
max
median
mild
29%
88%
42%
moderate
10%
67%
43%
1%
24%
4%
severe
Low grade and high grade
High Grade Dysplasia
Expected in <5% of all adenomas
Equates to ‘intramucosal adenocarcinoma’
Involves more than 1-2 glands
High Grade Dysplasia
Recognition based primarily on ARCHITECTURE:
COMPLEX glandular crowding and irregularity
PROMINENT budding
CRIBRIFORM ‘back-to-back’ glands
INTRALUMINAL papillary tufting
Low power diagnosis - epithelium is thick, blue,
disorganised and ‘dirty’
High Grade Dysplasia
CYTOLOGY:
Loss of polarity and nuclear stratification
Markedly enlarged nuclei
Atypical mitoses
Prominent apoptosis
Usually more than one of these
Histology of 2206 Adenomas at
13 Centres
min
max
median
62%
93%
84%
tubulovillous
6%
37%
15%
villous
0%
6%
1%
tubular
Reproducibility of Identifying
Villousness
– 3 observers
– Overall agreement
61%
Jensen et al 1995
Tubulovillous Adenomas
The 20% Rule
Neoplastic Villi
Classical
Palmate
Foreshortened
May have prominent low grade mucinous
epithelium
Flat Adenomas
–
–
–
–
–
–
thickness does not exceed twice that of
adjacent mucosa
more often right sided
usually small (<1cm) with tubular growth
pattern
more often high grade dysplasia
40% contain carcinoma
uncommon because no chromoendoscopy
Muto et al 1985
National Polyp Study
• 1418 patients
• Complete colonoscopy with removal of
adenomas
• No special attempt to identify flat adenomas
• Follow up colonoscopy, mean 5.9 years
• 97% clinical follow up, 80% colonoscopies
• 8401 patient years
National Polyp Study
• 90% reduction in colorectal cancer
incidence
• all five colorectal cancers found on
follow-up were polypoid
Macroscopic Examination &
Trimming of Polyps
• Size - to nearest millimetre in formalin
fixed specimen (whole polyps)
• Polypoid lesions
•
•
•
•
Fixed intact
Bisect through stalk if <10mm
If larger, trim to leave central intact stalk
At least three levels of stalk
• Sessile lesions pinned out and all-embedded
after inking margins
Serrated Lesions
Hyperplastic polyp
Serrated adenoma
Mixed polyp
Sessile serrated polyp
Serrated carcinoma
Hyperplastic Polyps
• Formerly metaplastic polyps
• Left > right
• Male > female
• Infolded epithelial tufts and enlarged goblet
cells
• No dysplasia
• Failure of anoikis (shedding of mature cells)
Ki-67
Hyperplastic Polyp
Increase in frequency with age
17 times commoner in colons with carcinoma
Similar dietary and lifestyle risk factors to CRC
K-ras mutation common
Clonal
Monocryptal?
Serrated Adenoma
Dysplasia by definition
Eosinophilic cytoplasm
Pseudostratified, ‘pencillate’ nuclei
May be tubular, tubulovillous or villous
Invade to give serrated carcinoma
Longacre & Fenoglio-Preiser 1990
‘Traditional’ Serrated adenoma (TSA)
Mixed Polyps
Collision between hyperplastic polyp and
adenoma
Dysplasia in Hyperplastic Polyp
Longacre & Fenoglio-Preiser 1990
Sessile Serrated Polyp
(Adenoma)
• Serrated polyps with unusual architectural
features
• No conventional dysplasia but may have
‘nuclear atypia’ or ‘hypermucinous’ change
• Right colon
• Females > males
• Large sessile, poorly defined
Torlakovic & Snover 1996
Sessile serrated polyp
Serrated Adenocarcinoma
• Serrated, mucinous or
trabecular growth pattern
• Abundant eosinophilic
cytoplasm
• Chromatin condensation
• Preserved polarity
• No necrosis
Tuppurainen K et al 2005 J Pathol 207: 285-94
Tuppurainen K et al 2005 J Pathol 207: 285-94
Serrated Neoplasia
Microsatellite instability
DNA methylation
MLH1 inactivation
BRAF mutation
Baker K et al J Clin Pathol 2004; 57: 1089
BRAF mutation
•
•
•
•
•
•
•
•
Typical adenomas
Typical hyperplastic polyps
Sessile serrated adenomas
Traditional serrated adenomas
Mixed Polyps
HNPCC cancers
All colorectal cancers
MSI-high non-HNPCC cancers
0%
19-78%
75-78%
20-66%
57-89%
0%
15%
76%
Serrated Neoplasia Pathway
Proximal hyperplastic polyp
Sessile serrated polyp
Serrated adenoma
MSI-high, methylation-rich non-HNPCC
“serrated” carcinoma (50% mucinous)
Higuchi T & Jass JR 2004 J Clin Pathol 57: 682
1250 Polyps at Colonoscopy
Polyp
Dysplasia
%
Adenoma Tubular
Tubulovillous
Villous
+
+
+
55
15
1
Serrated Hyperplastic
polyps
Sessile Serrated Polyp
Mixed Polyp
Serrated Adenoma
+
+
24.5
2.5
0.8
1.2
NBCSP
Hyperplastic polyp
Serrated adenoma
Mixed polyp
Sessile serrated polyp
Serrated carcinoma