Definition/General

Introduction:
-Traditional serrated adenoma (TSA) is a distinctive adenomatous polyp characterized by serrated crypt architecture and conventional dysplasia
-Represents 1-5% of all colorectal adenomas
-Shows unique morphologic features combining serration with adenomatous dysplasia
-Higher malignant potential than hyperplastic polyps.
Origin:
-Arises through the serrated pathway of carcinogenesis
-Originates from hyperplastic polyps or sessile serrated adenomas
-Develops conventional adenomatous dysplasia secondarily
-Shows CpG island methylation
-May progress to microsatellite unstable carcinomas.
Classification:
-Part of serrated polyp spectrum
-Distinct from hyperplastic polyps (no dysplasia)
-Different from sessile serrated adenomas (architectural distortion pattern)
-Shows conventional dysplasia unlike other serrated lesions
-WHO classification recognizes as separate entity.
Epidemiology:
-Peak incidence in 6th-7th decades
-Slight female predominance
-More common in left-sided colon
-Associated with smoking and alcohol
-Indian population data limited but increasing recognition.

Clinical Features

Presentation:
-Often asymptomatic (screening detection)
-Rectal bleeding (most common symptom)
-Change in bowel habits
-Abdominal discomfort
-Mucus passage
-Large polyps may cause obstruction.
Symptoms:
-Bright red bleeding per rectum (40-50% cases)
-Altered bowel habits
-Crampy abdominal pain
-Mucoid stools
-Tenesmus (rectal lesions)
-Iron deficiency anemia (chronic bleeding).
Risk Factors:
-Age >50 years
-Smoking (strong association)
-Alcohol consumption
-Western diet
-Obesity
-Female gender
-Family history of colorectal cancer.
Screening:
-Colonoscopy (gold standard)
-High-definition endoscopy (better detection)
-Chromoendoscopy (enhanced visualization)
-Narrow band imaging
-CT colonography (limited sensitivity).

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Gross Description

Appearance:
-Sessile or pedunculated polyp
-Mamillated surface
-Pink to red coloration
-Friable consistency
-Serrated contour visible grossly
-May show surface erosions.
Characteristics:
-Irregular, mamillated surface
-Soft consistency
-Cut surface shows complex architecture
-Cystic spaces may be present
-Areas of induration (high-grade dysplasia)
-Well-demarcated from surrounding mucosa.
Size Location:
-Size typically 0.5-3 cm
-Left-sided colon predominance
-Rectosigmoid (most common)
-Descending colon (second most common)
-Usually solitary
-Rarely multiple.
Multifocality:
-Usually solitary (>90% cases)
-Rarely multiple (<10% cases)
-Synchronous adenomas possible
-Associated with other serrated lesions
-No polyposis syndrome association.

Microscopic Description

Histological Features:
-Serrated crypt architecture throughout the polyp
-Conventional adenomatous dysplasia
-Eosinophilic cytoplasm (distinctive feature)
-Complex crypt branching
-Surface serration prominent
-Lamina propria inflammation common.
Cellular Characteristics:
-Columnar cells with abundant eosinophilic cytoplasm
-Pencillate nuclei (elongated, hyperchromatic)
-Nuclear stratification
-Mitotic figures above crypt base
-Mucin depletion in dysplastic areas
-Goblet cell decrease.
Architectural Patterns:
-Serrated crypts with saw-tooth appearance
-Complex crypt architecture
-Villiform surface (may be present)
-Crypt branching and budding
-Infolding pattern
-Surface maturation loss in high-grade areas.
Grading Criteria:
-Low-grade dysplasia: mild architectural complexity, nuclear changes limited
-High-grade dysplasia: severe architectural distortion, marked nuclear atypia
-Loss of surface maturation
-Cribriform pattern (high-grade)
-Back-to-back crypts.

Immunohistochemistry

Positive Markers:
-CDX2 (intestinal differentiation)
-CK20 (colonocyte marker)
-p53 (may accumulate in high-grade dysplasia)
-Ki-67 (increased proliferation)
-MLH1 (may be lost).
Negative Markers:
-CK7 (usually negative)
-TTF-1 (negative)
-Chromogranin A (negative unless neuroendocrine cells)
-MLH1 (lost in subset)
-MGMT (may be lost).
Diagnostic Utility:
-CDX2 positivity confirms colonic origin
-CK20 pattern shows surface-to-crypt gradient
-p53 staining assesses dysplasia grade
-MLH1 loss suggests hypermethylation
-Ki-67 reflects proliferative activity.
Molecular Subtypes:
-BRAF-mutated (majority of cases)
-CpG island methylator phenotype (CIMP-high)
-MLH1 hypermethylation (subset)
-Microsatellite unstable (progression)
-Serrated pathway carcinogenesis.

Molecular/Genetic

Genetic Mutations:
-BRAF mutations (60-80% cases)
-KRAS mutations (rare, <10% cases)
-PIK3CA mutations (subset)
-APC mutations (rare)
-TP53 mutations (high-grade dysplasia).
Molecular Markers:
-CpG island hypermethylation (CIMP phenotype)
-MLH1 promoter methylation
-MGMT methylation
-Microsatellite instability (progression to carcinoma)
-Chromosomal stability (early lesions).
Prognostic Significance:
-Size >1 cm increases malignancy risk
-High-grade dysplasia significant risk factor
-BRAF mutations associated with progression
-MLH1 loss predicts microsatellite instability
-Complete excision generally curative.
Therapeutic Targets:
-Endoscopic resection (treatment of choice)
-Complete excision essential
-Surveillance colonoscopy (shorter intervals)
-BRAF inhibitors (research setting)
-Methylation status guides prognosis.

Differential Diagnosis

Similar Entities:
-Hyperplastic polyp (no dysplasia)
-Sessile serrated adenoma (different architecture)
-Conventional adenoma (no serration)
-Mixed polyp (both patterns)
-Adenocarcinoma (invasive).
Distinguishing Features:
-Traditional serrated adenoma: Serration + conventional dysplasia
-Hyperplastic polyp: Serration, no dysplasia
-Sessile serrated adenoma: Architectural distortion, subtle dysplasia
-Conventional adenoma: No serration
-Mixed polyp: Separate areas of different patterns.
Diagnostic Challenges:
-Distinguishing from hyperplastic polyps (dysplasia assessment)
-Differentiating from sessile serrated adenomas (architectural criteria)
-Recognizing high-grade dysplasia
-Assessing completeness of excision
-Adequate sampling essential.
Rare Variants:
-Traditional serrated adenoma with high-grade dysplasia
-Mixed serrated-conventional adenoma
-Traditional serrated adenoma with invasive carcinoma
-Flat serrated adenoma
-Giant traditional serrated adenoma.

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

[specimen type], measuring [size] cm in greatest dimension

Diagnosis

Traditional Serrated Adenoma

Location

Location: [anatomical site in colon/rectum]

Architectural Features

Shows serrated crypt architecture throughout with conventional adenomatous dysplasia. Crypts display saw-tooth serrated pattern.

Cellular Features

Columnar cells with abundant eosinophilic cytoplasm and pencillate nuclei. Nuclear stratification present.

Dysplasia Grade

Dysplasia: [Low-grade/High-grade] conventional adenomatous dysplasia

Size and Extent

Size: [X] cm, [pedunculated/sessile] polyp

Margin Assessment

Excision margins: [Complete/Incomplete] - [distance to nearest margin] mm

Final Diagnosis

Colorectal Traditional Serrated Adenoma with [low-grade/high-grade] dysplasia