bumps in the road: dirty little secrets of gi tract polyps
TRANSCRIPT
10/21/2019
1
Bumps in the Road:Dirty Little Secrets of Serrated Polyps
Christina A. Arnold, MD
The Ohio State University Wexner Medical Center
Associate Professor
Email: [email protected]
Twitter handle: @CArnold_GI
Select Updates: Reader’s Digest Style
2
Colon Cancer Screening Guidelines
3Rex DK et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017 Jul;112(7):1016-1030.
• Average risk screening:
– Begins at 50y (non-African Americans), 45y (AA)
– Single FDR ≥ 60y with CRC or advanced adenoma
– Colonoscopy is preferred, if normal repeat in 10y
• Increased risk:
– First degree relative (FDR) with CRC or advanced adenoma at age <60y or 2FDR at any age
– Colonoscopy every 5 years
– Begins at 40y or 10y younger than onset of youngest affected relative, whichever is earlier
1
2
3
10/21/2019
2
Serrated Things: Classification, WHO 5th
Hyperplastic polyp
Microvesicular (MVHP)
Goblet cell rich (GCHP)
Mucin poor (MCHP)
Sessile serrated lesion (SSL)
Sessile serrated lesion with dysplasia (SSD)Distinction of “LGD vs HGD not recommended”
Traditional serrated adenoma (TSA)“Report dysplasia when HGD present”
Unclassified serrated adenoma
Serrated Things: Classification, Our Center
Hyperplastic polyp
Microvesicular (MVHP)
Goblet cell rich (GCHP)
Mucin poor (MCHP)
Sessile serrated adenoma/polyp Grade dysplasia when present
Traditional serrated adenoma (TSA)Grade dysplasia when present
Serrated Polyp
Serrated Polyps: Surveillance
**Proximal HP > 1.0 cm should be managed as SSA/P**
Rex et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012 Sep;107(9):1315-29.
4
5
6
10/21/2019
3
The Serrated Neoplasia Pathway
What’s the First Question when Looking at a Tough Serrated Polyp?
Serrated Polyps: Location! Location! Location!
Adapted from Arnold, Lam-Himlin, Montgomery. Atlas of Gastrointestinal Pathology: A Pattern Based Approach to Non-Neoplastic Biopsies
Prolapse
Sessile Serrated Adenoma/Polyp
Hyperplastic polyp
Traditional Serrated Adenoma
7
8
9
10/21/2019
4
Hyperplastic Polyps: The Basics
• Up to 95% of serrated polyps• Distal predominant• Less than 0.5 cm• Proximal HP > 1.0 cm are followed as SSA/P• Histologically defined by
– Surface serrations, stellate lumens, & narrow crypt bases
– Thickened subepithelial collagen table – Endocrine proliferation
• Subtypes:– Microvesicular, Goblet cell-rich, Mucin-poor
Mucin Poor HP
Hyperplastic Polyps: Small Crypt Bases w/o Serrations
Microvesicular HP
Goblet Cell Rich HP
Normal Colon
Mucin Poor HP
Hyperplastic Polyps: Small Crypt Bases w/o Serrations
Microvesicular HP
Goblet Cell Rich HP
Normal Colon
10
11
12
10/21/2019
5
Sessile Serrated Adenoma/Polyp: The Basics
• SSA and SSP are equivalent terms
• Up to 25% of SPs
• Right colon predominant
• Usually > 0.5 cm
• Minimum criteria: 1 unequivocal crypt dilatation– Serrations extend to the dilated crypt base
– Lacks thickened subepithelial collagen table
– Lacks endocrine proliferation
• BRAF mutations, MLH1 methylation, MMR deficient, CIMP, MSI-H (most)
Hyperplastic PolypNormal Colon
The Family of Serrated Polyps
Sessile Serrated Adenoma
Sessile Serrated Adenoma/Polyp: Dilated Crypt Bases with Serrations
**
*
*
13
14
15
10/21/2019
6
Traditional Serrated Adenoma: The Basics
• Less than 2% of all colon polyps
• Distal predominant
• Unique morphology
– Bright pink
– Tennis racquet shaped villi
– Ectopic crypt foci
– Penicillate nuclei
• KRAS or BRAF mutated MMR proficient MSS CRC
Hyperplastic PolypNormal Colon
The Family of Serrated Polyps
Sessile Serrated Adenoma Traditional Serrated Adenoma
Traditional Serrated Adenoma: Bright Pink & Broad Villi
16
17
18
10/21/2019
7
Traditional Serrated Adenoma: Ectopic Crypt Foci
Dirty Little Secret: Real Cases are Really Messy!
• Dysplasia
• Small right colon SPs
• Large left colon SPs
• Concomitant spindly lesions
• Lots of SPS
• Ugly cauterized polyps
Ancillary Tests?
• RNF43
• PTPRK-RSPO3
• Annexin A10
• Ki67
• MUC2
• MUC5AC
• MUC6
• Maspin
• Hes1
• MLH1
• Cathepsin E
• Trefoil factor 1
• BRAF V600E mutation specific antibody VE1
• KRAS
• CIMP
• MUC5AC mucin gene hypomethylation
19
20
21
10/21/2019
8
Describe your comfort-level with dysplastic serrated lesions:
A. I am confident and clear
B. I manage, but could use a refresher
C. I am not sure about these
D. No one is sure about these
Describe your comfort-level with dysplastic serrated lesions:
A. I am confident and clear
B. I manage, but could use a refresher
C. I am not sure about these
D. No one is sure about these
Dysplastic Serrated Polyps:Classification
SSA (assumes NFD)
TSA (assumes NFD)
LGD Cytological Dysplasia
Conventional-Type
Serrated-Type
HGD Cytological Dysplasia
Conventional-Type
Serrated-Type
22
23
24
10/21/2019
9
Dysplastic Serrated Polyps: Classification
SSA (assumes NFD)
TSA (assumes NFD)
LGD Dysplasia
Conventional-Type
Serrated-Type
HGD Dysplasia
Conventional-Type
Serrated-Type
• Dysplastic SSA may progress more quickly
• Serrated dysplasia can be more subtle
• Dysplasia has abrupt transitions
• Dysplasia is a low-power diagnosis
Dysplasia in Serrated Lesions
Serrated Dysplasia can be Subtle
25
26
27
10/21/2019
10
Dirty Little Secret:Dysplasia is Abrupt
SSA, Negative for Dysplasia
Dirty Little Secret:Dysplasia is a Low-Power Diagnosis
SSA w LGD Dysplasia
SSA w Focal HGD Dysplasia SSA w HGD Dysplasia
Dirty Little Secrets:Grading Dysplasia in Serrated Lesions
SSA, Negative for Dysplasia
28
29
30
10/21/2019
11
Dirty Little Secrets:LGD has Preserved Nuclear Polarity
SSA, LGD DysplasiaSSA, Negative for Dysplasia
Dirty Little Secrets:HGD has Loss of Nuclear Polarity
SSA, LGD DysplasiaSSA, Negative for Dysplasia
SSA, HGD Dysplasia
Dirty Little Secrets:Invasion has Single Cells Infiltration or Desmoplasia
SSA, LGD DysplasiaSSA, Negative for Dysplasia
SSA, HGD Dysplasia SSA with Invasion
31
32
33
10/21/2019
12
Diagnosis this small right colon serrated polyp.
A. HP
B. Tubular adenoma
C. SSA/P
D. Prolapse
• Right colon
• 0.15 cm
Diagnosis this small right colon serrated polyp.
A. HP
B. Tubular adenoma
C. SSA/P
D. Prolapse
• Right colon
• 0.15 cm
Dirty Little Secrets:Small Right Serrated Polyps
• Right colon serrated polyps should be SSA/Ps.
• You only need 1 unequivocal dilated crypt for an SSA/P.
• All proximal serrated polyps will be fully excised.
Rex et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012 Sep;107(9):1315-29.
34
35
36
10/21/2019
13
The Small Right Colon Serrated Polyp, Revisited
*
FAQ: What is an “unequivocal dilated crypt?”
FAQ: What is an “unequivocal dilated crypt?”
37
38
39
10/21/2019
14
More Examples of Unequivocal Dilated Crypts of an SSA/P
Diagnosis this equivocal case.
A. HP
B. Tubular adenoma
C. Serrated polyp
D. TSA
• Right colon
• 1.6 cm
Diagnosis this EQUIVOCAL case.
A. HP
B. Tubular adenoma
C. Serrated polyp
D. TSA
• Right colon
• 1.6 cm
40
41
42
10/21/2019
15
Dirty Little Secrets:Equivocal Right Colon Serrated Polyps
• Right colon SPs should be SSA/Ps.
• Proximal SPs > 1.0 are managed as SSA/Ps.
• All proximal SPs should be fully excised.
• Deepers &“SP” helpful for proximal SPs with equivocal histology.
Diagnosis this Large Left Colon Serrated Polyp.
A. HP
B. Tubular adenoma
C. SSA/P
D. Prolapse
• Left colon
• 1.2 cm
43
44
45
10/21/2019
16
Diagnosis this Large Left Colon Serrated Polyp.
A. HP
B. Tubular adenoma
C. SSA/P
D. Prolapse
• Left colon
• 1.2 cm
Dirty Little Secrets:Large Left Colon Serrated Polyps
• Distal SPs should be HP or Prolapse.
• HP helpful features:
– Thickened subepithelial collagen table
– Endocrine proliferation
• Prolapse helpful features:
– Prominent smooth muscle ingrowth
• Distal SSA/P need PERFECT morphology.
• Deepers & “SP” when changes more than expected for prolapse alone.
Distal HP with Prolapse:Prominent Muscle & Squished Crypts
46
47
48
10/21/2019
17
Distal HP with Prolapse:Prominent Muscle & Squished Crypts
Distal HP with Prolapse:Prominent Muscle & Collagen Table
Distal HP with Prolapse:Beware Tangential Sections!
49
50
51
10/21/2019
18
Distal HP with Prolapse:Beware Tangential Sections!
Left Colon (Should be HP)
HP:
- < 0.5 cm
-Prominent subepithelialcollagen & endocrine cells
SP:
-Equivocal morphology, more than typical prolapse
-Deepers & show
SSA:
-Rare at this site
-Perfect morphology
52
53
54
10/21/2019
19
Diagnose the spindly component (EMA+, S100-).
A. Schwann cell hamartoma
B. Perineurioma
C. Prolapse
D. Leiomyoma
Dirty Little Secrets:Perineurioma
• Previously termed “fibroblastic polyp”
• Associated with serrated polyps
• BRAF mutation linked to serrated epithelium
• Reactive: EMA weak, Claudin-1, Glut-1, collagen IV
• NonReactive: S100, SMA
Agaimy et al. Am J Surg Pathol. 2010 Nov;34(11):1663-71; Pai et al. Am J Surg Pathol. 2011Sep;35(9):1373-80; Groisman et al. Am J Surg Pathol. 2013May;37(5):745-51.
Perineurioma:Associated with Serrated Polyps
*
**
*
*
*
55
56
57
10/21/2019
20
Perineurioma:Whorled Cells, Intranuclear Inclusions
Perineurioma:EMA Weakly Reactive
Dirty Little Secrets:Schwann Cell Hamartoma
• Previously termed “neuroma” or “neurofibroma”• Not associated with MEN 2B or NF1 • Not associated with serrated polyps• Reactive: S100• NonReactive: EMA, Claudin-1, GLUT-1, SMA
Gibson JA, Hornick JL. Mucosal Schwann cell "hamartoma": clinicopathologicstudy of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas. Am J Surg Pathol. 2009 May;33(5):781-7.
58
59
60
10/21/2019
21
Schwann Cell Hamartoma:Not Associated with Serrated Polyps
Schwann Cell Hamartoma:S100+, EMA-
Lots of Serrated Polyps:Syndromic Considerations
61
62
63
10/21/2019
22
• Helpful to glance at prior reports for borderline cases• Considerations
– Serrated polyposis– MUTYH-associated polyposis– PTEN Hamartoma Tumor Syndrome (Cowden,
Bannayan-Ruvalcaba-Riley, Proteus)– Peutz-Jeghers – Juvenile Polyposis– Attenuated FAP (if also adenomas)– Hereditary mixed polyposis syndrome with GREM1
duplication– Lynch *NOT* a consideration
Lots of Serrated Polyps:Syndromic Considerations
Serrated Polyposis (SPS)
• WHO Diagnostic Criteria, 5th edition– At least 5 SP proximal to rectum; all ≥ 5mm, ≥ 2 SP ≥
10 mm– > 20 SP distributed throughout the colon, ≥5 proximal
to rectum– Any # proximal SP in a patient with a 1st degree
relative with SPS• Tricks of the trade:
– All serrated polyps count– Count cumulative over multiple colonoscopies
Serrated Polyposis (SPS)
• Up to 50% risk of CRC at time of diagnosis
• Annual endoscopy
– Goal: Clear all proximal SP & left colon SP > 5 mm
• Resection indicated when endoscopy cannot control polyp burden
Snover, WHO, 2010; Rex et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol. 2012 Sep;107(9):1315-29.
64
65
66
10/21/2019
23
Lots of Serrated Polyps: Sample Note
The endoscopic impression of 45 polyps throughout the colon is noted. The corresponding polypectomy specimens consist of hyperplastic polyps, sessile serrated adenomas, and scattered tubular adenomas. Based on the number and distribution of these polyps, consideration of a polyposis syndrome may be worthwhile: serrated polyposis (favored), MUTYH-associated polyposis, PTEN Hamartoma Tumor Syndrome (Cowden, Bannayan-Ruvalcaba-Riley, Proteus), Peutz-Jeghers, Juvenile Polyposis, hereditary mixed polyposis syndrome, and attenuated FAP, among others. Correlation with upper tract endoscopy and a genetic counselor may be worthwhile for further classification.
Ugly Cauterized Polyps!
Dirty Little Secrets of Cauterized Polyps:HP, Thickened Collagen Table &
Endocrine Proliferation
67
68
69
10/21/2019
24
Dirty Little Secrets of Cauterized Polyps:TA, Prominent Apoptotic Bodies
Diagnosis this ugly cauterized polyp.
A. HP
B. TA
C. SSA/P
D. TSA
• Left colon
• 0.4 cm
• Focally prominent collagen table, • No apoptotic bodies• Prominent endocrine cells
• Prominent muscle
Diagnosis this ugly cauterized polyp.
A. HP
B. TA
C. SSA/P
D. Prolapse
• Left colon
• 0.3 cm• Dark elongated nuclei
• No collagen table
• No endocrine cell prominence
• Prominent apoptotic bodies
70
71
72
10/21/2019
25
The Ugly Cauterized Polyp:Reporting Strategy
Burnt Polyp
Secrets Show Deepers
Helpful?
Yes!
Definitive Diagnosis
No!
“Cauterized polyp, favor X”
“Cauterized polyp, NOS”
Thrilling Cases
73
74
75
10/21/2019
26
Dirty Little Secrets:Not every “Lymphoid Aggregate” is Boring
• Take a close peek
• Have a low threshold to show Hematopathology
– Especially if there is a history of bone marrow transplant or lymphoma
Eleview & Orise:Pearls & Pitfalls
• Lifting agents to make sessile lesions polypoid
• Amyloid mimic (Congo Red negative)
• Hyalinized ribbons are a tissue reaction to gel
76
77
78
10/21/2019
27
GI Doc
79
80
81
10/21/2019
28
Merkle Cell Carcinoma involving the Colon
Amyloidosis & Tubular Adenoma
82
83
84
10/21/2019
29
Urothelial Carcinoma Involving the Colon
85
86
87
10/21/2019
30
Dirty Little Secrets:Beware the Suboptimal Biopsy
• Malignant diagnoses lurk in artifacts
• Make sure to check all pieces of tissue
• Red flags include
– Mass/irregular mucosa/rule out cancer
– History of malignancy
• When in doubt, get deepers or repeat bx
Endometrial Adenocarcinoma Involving the Colon
88
89
90
10/21/2019
31
Dirty Little Secrets:Mucosal Colonization can Mimic CRC!
• Have a low-threshold to consider metastasis or direct invasion from elsewhere
• GU and GYN are frequent offenders
• Carcinomas in the small bowel are usually metastasis/direct invasion from elsewhere
• Line diagnosis best to say “Adenocarcinoma”
• Careful note & additional studies helpful
Take-Home Dirty Little Secrets:
• The minimum criteria for SSA/P is 1 unequivocal dilated crypt
• Proximal SP > 1.0 cm are managed as SSA/Ps
• HP exist in the left colon, sigmoid, rectum only
• Left-sided serrated polyps are usually HPs
• Have a low threshold to consider polyposis syndromes
Bumps in the Road:Dirty Little Secrets of Serrated Polyps
Christina A. Arnold, MD
The Ohio State University Wexner Medical Center
Associate Professor
Email: [email protected]
Twitter handle: @CArnold_GI
91
92
93