What is serrated dysplasia in the colon?

Serrated Dysplasia in the Colon: Precancerous Lesions with Significant Clinical Importance

Serrated dysplasia in the colon refers to cytologic dysplasia occurring within serrated polyps, which represents an important precancerous condition that accounts for up to 30% of colorectal cancers through the serrated neoplasia pathway. 1

Types of Serrated Lesions and Dysplasia

Serrated lesions in the colon can be classified into three main categories:

1. Hyperplastic Polyps (HPs)

   • Generally small lesions found in the distal colon
   • Not currently considered precancerous
   • Lack dysplasia

2. Sessile Serrated Lesions/Polyps (SSLs/SSPs)

   • More common in the proximal colon (right side)
   • Typically flat or sessile in shape
   • Have few or no surface blood vessels
   • More difficult to detect at colonoscopy than conventional adenomas
   • Can occur with or without dysplasia:
     • SSLs without cytologic dysplasia - earlier stage
     • SSLs with cytologic dysplasia - more advanced lesion in the polyp-cancer sequence 1

3. Traditional Serrated Adenomas (TSAs)

   • Rare lesions, often found in the left colon
   • Sessile in shape
   • Uniformly dysplastic
   • Often misinterpreted as tubulovillous conventional adenomas due to villous-like growth pattern 1

Molecular and Pathological Features

Serrated lesions with dysplasia have distinct molecular characteristics:

• SSLs have molecular, genetic, and pathological features consistent with being precursor lesions to CpG island methylator phenotype (CIMP+) colorectal cancers 1
• Hypermethylation is a common feature of serrated lesions 1
• SSLs with dysplasia often show BRAF mutations and may progress to microsatellite instability-high (MSI-H) cancers 1, 2
• When dysplasia is present in an SSL, it often appears endoscopically and histologically as a region of conventional adenoma within an otherwise serrated lesion 1

Clinical Significance and Cancer Risk

The clinical importance of serrated dysplasia stems from:

1. Cancer Risk:

   • SSLs with dysplasia are considered to rapidly progress to colorectal cancer compared to non-dysplastic SSLs 2
   • While SSLs show indolent growth before becoming dysplastic (>10-15 years), once dysplasia develops, progression to cancer can be accelerated 2
   • Serrated lesions account for up to 30% of all colorectal cancers 1

2. Detection Challenges:

   • Flat and pale appearance makes detection difficult 3
   • SSLs with dysplasia are often missed during colonoscopy due to their subtle appearance 2
   • They are potent precursors of post-colonoscopy/interval cancers 2

Management Recommendations

Based on current guidelines:

1. For SSLs with dysplasia and TSAs:

   • A one-off colonoscopic surveillance examination should be performed at 3 years after removal 1
   • Complete endoscopic resection is essential 3

2. For SSLs ≥10 mm (even without dysplasia):

   • Surveillance colonoscopy at 3 years is recommended 1

3. For small SSLs (<10 mm) without dysplasia:

   • No clear indication for colonoscopic surveillance unless they meet criteria for serrated polyposis syndrome 1

4. After piecemeal endoscopic mucosal resection of serrated lesions ≥20 mm:

   • Examination of the resection site should be performed within 2-6 months post-resection 1

Special Considerations

Serrated Polyposis Syndrome (SPS)

• Patients meeting WHO criteria for SPS should be offered one to two yearly colonoscopic surveillance due to elevated CRC risk 1
• Consider referral to clinical genetics services or a polyposis registry 1
• Surgery should be considered for patients with SPS who have lesions not amenable to colonoscopic resection 1

Serrated Lesions in Colitis

• Serrated polyps do occur in inflammatory bowel disease (IBD) 1
• Some colitis-associated cancers may arise through the serrated pathway, with activating BRAF mutations identified in approximately 9% of colitis-associated cancers 1
• The relationship between colitic inflammation and the serrated pathway remains unclear 1

Common Pitfalls in Diagnosis and Management

1. Diagnostic Challenges:

   • Poor interobserver agreement between pathologists in differentiating hyperplastic polyps from SSLs 1
   • Clinicians may see widely varying rates of SSLs in pathology reports depending on the pathologist or center 1
   • Traditional serrated adenomas are often misinterpreted as tubulovillous conventional adenomas 1

2. Detection Issues:

   • SSLs are more difficult to detect at colonoscopy than conventional adenomas due to their flat shape and lack of surface blood vessels 1
   • Detection of SSLs is a major deficiency of sigmoidoscopy (as SSLs are predominantly in the proximal colon) and CT colonography (as the lesions tend to be flat) 1

3. Management Errors:

   • Failure to recognize the precancerous potential of serrated lesions with dysplasia
   • Inadequate surveillance intervals for high-risk serrated lesions
   • Incomplete resection of serrated lesions, particularly larger ones

By understanding the nature and significance of serrated dysplasia in the colon, clinicians can better identify, manage, and surveil these important precancerous lesions to reduce colorectal cancer risk.