Definition/General
Introduction:
Sessile serrated adenoma (SSA) is a precancerous serrated polyp characterized by architectural abnormalities and malignant potential through the serrated pathway
Represents 15-20% of all colorectal polyps
Shows distinct molecular pathway (BRAF mutations, CIMP-high)
Associated with interval cancers and microsatellite instability.
Origin:
Arises from colonic surface epithelium through serrated pathway
Results from BRAF mutations and oncogene-induced senescence
Shows CpG island methylator phenotype
Demonstrates crypt architectural distortion
Associated with MLH1 methylation in progression.
Classification:
WHO 2019: Sessile serrated lesion (SSL) without dysplasia
SSL with dysplasia
Former terms: Sessile serrated adenoma
Sessile serrated polyp
Distinguished from hyperplastic polyps and traditional serrated adenomas.
Epidemiology:
Peak incidence in 5th-6th decades
Female predominance (2:1)
More common in right colon (cecum, ascending)
Increasing recognition with improved criteria
Associated with synchronous lesions
Flat morphology makes detection difficult.
Clinical Features
Presentation:
Asymptomatic in most cases
Detected on screening colonoscopy
Subtle endoscopic appearance
Flat or slightly raised
Mucus cap covering surface
Right-sided location
Associated with interval cancers.
Symptoms:
Usually asymptomatic
Rectal bleeding rare
Change in bowel habits uncommon
Abdominal pain not typical
Iron deficiency anemia rare
Detected incidentally on colonoscopy.
Risk Factors:
Age >40 years
Female gender
Smoking
Obesity
Serrated polyposis syndrome
Family history of serrated lesions
Western diet
Sedentary lifestyle.
Screening:
High-quality colonoscopy
Chromoendoscopy improves detection
Virtual chromoendoscopy
Adequate bowel preparation
Slow withdrawal technique
Right colon inspection.
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Gross Description
Appearance:
Flat or sessile polyp
Subtle elevation
Mucus cap may be present
Pale or pink coloration
Smooth surface
Indistinct margins.
Characteristics:
Difficult to visualize endoscopically
Flat morphology predominant
May appear as mucosal fold
Mucin production visible
No obvious dysplastic features grossly.
Size Location:
Size typically 0.5-2 cm
Right colon predominance (70%)
Cecum and ascending colon most common
Sessile morphology
Flat configuration.
Multifocality:
Multiple lesions common (serrated polyposis syndrome)
Synchronous polyps in 60% cases
Field effect in serrated pathway
Associated with interval cancers.
Microscopic Description
Histological Features:
Serrated crypt architecture with saw-tooth pattern
Horizontal crypt orientation at base
Dilated crypt bases
Inverted T or L-shaped crypts
Prominent serrations extending to crypt base
Architectural distortion.
Cellular Characteristics:
Columnar epithelial cells with abundant cytoplasm
Eosinophilic cytoplasm
Vesicular nuclei
Prominent nucleoli
Decreased mucin
Surface maturation usually preserved.
Architectural Patterns:
Boot-shaped crypts
Horizontal growth at muscularis mucosae
Crypt dilation and branching
Serrated surface and deep crypts
Asymmetric proliferation.
Grading Criteria:
SSL without dysplasia: architectural abnormalities only
SSL with dysplasia: superimposed conventional or serrated dysplasia
Minimal deviation from hyperplastic polyps required for diagnosis.
Immunohistochemistry
Positive Markers:
Ki-67 shows expanded proliferative zone
CK20 pattern altered (surface positive in abnormal areas)
MLH1 retained (usually)
CDX2 positive
β-catenin membranous pattern.
Negative Markers:
p53 wild-type pattern usually
MLH1 loss only in advanced lesions
Chromogranin negative
Synaptophysin negative.
Diagnostic Utility:
Ki-67 helps identify architectural abnormalities
CK20 pattern supports serrated morphology
MLH1 loss indicates progression risk
β-catenin remains membranous (unlike conventional adenomas).
Molecular Subtypes:
CIMP-high phenotype
BRAF-mutated (90% cases)
Microsatellite stable initially
May develop MSI with MLH1 loss.
Molecular/Genetic
Genetic Mutations:
BRAF V600E mutations (90% cases)
CpG island hypermethylation
MLH1 promoter methylation (progression)
KRAS mutations rare (mutually exclusive with BRAF)
PIK3CA mutations occasionally.
Molecular Markers:
CIMP-high status
Oncogene-induced senescence
p16 methylation
MGMT methylation
Epigenetic instability.
Prognostic Significance:
BRAF mutations indicate serrated pathway
CIMP-high associated with progression
MLH1 methylation leads to MSI cancers
Right-sided location poorer prognosis cancers
Interval cancer risk.
Therapeutic Targets:
Complete excision mandatory
Surveillance interval 3 years
Assessment for serrated polyposis syndrome
Family screening
BRAF inhibitors (experimental).
Differential Diagnosis
Similar Entities:
Hyperplastic polyp - no architectural distortion, smaller
Traditional serrated adenoma - surface eosinophilia, different morphology
Conventional adenoma - tubular architecture, APC mutations
Mixed polyp - components of both
Inflammatory polyp - ulceration, reactive changes.
Distinguishing Features:
Hyperplastic polyp: straight crypts, surface serrations only, <5mm
Traditional serrated adenoma: eosinophilic surface, KRAS mutations
Conventional adenoma: nuclear β-catenin, APC pathway
Mixed polyp: both conventional and serrated areas.
Diagnostic Challenges:
Minimal architectural distortion
Distinction from hyperplastic polyps
Tangential sectioning
Sampling adequacy
Mixed lesions.
Rare Variants:
SSL with conventional dysplasia
SSL with serrated dysplasia
Giant SSL (>2cm)
SSL with carcinoma
Serrated polyposis syndrome.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Colorectal polypectomy, [size] cm, right colon
Diagnosis
Sessile serrated lesion [with/without] dysplasia
Classification
Serrated polyp, sessile serrated type
Histological Features
Shows serrated architecture with crypt dilation and horizontal growth pattern. [Dysplasia present/absent].
Architectural Features
Boot-shaped crypts: present, Horizontal orientation: present, Crypt dilation: present
Dysplasia Assessment
Dysplasia: [absent/conventional type/serrated type]
Margins
Polyp appears completely excised
Recommendations
Surveillance colonoscopy in 3 years. Assess for serrated polyposis syndrome if multiple lesions.
Final Diagnosis
Sessile serrated lesion [with/without] dysplasia, completely excised