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Bumps in the Road:Dirty Little Secrets of Serrated Polyps

Christina A. Arnold, MD

The Ohio State University Wexner Medical Center

Associate Professor

Email: Christina.Arnold@osumc.edu

Twitter handle: @CArnold_GI

Select Updates: Reader’s Digest Style

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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

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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.

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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The Small Right Colon Serrated Polyp, Revisited

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FAQ: What is an “unequivocal dilated crypt?”

FAQ: What is an “unequivocal dilated crypt?”

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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

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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

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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

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Distal HP with Prolapse:Prominent Muscle & Squished Crypts

Distal HP with Prolapse:Prominent Muscle & Collagen Table

Distal HP with Prolapse:Beware Tangential Sections!

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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

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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

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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.

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Schwann Cell Hamartoma:Not Associated with Serrated Polyps

Schwann Cell Hamartoma:S100+, EMA-

Lots of Serrated Polyps:Syndromic Considerations

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• 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.

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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

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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

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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

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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

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GI Doc

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Merkle Cell Carcinoma involving the Colon

Amyloidosis & Tubular Adenoma

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Urothelial Carcinoma Involving the Colon

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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

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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: Christina.Arnold@osumc.edu

Twitter handle: @CArnold_GI

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