Definition/General
Introduction:
Colorectal tubulovillous adenoma is a mixed adenomatous polyp combining features of both tubular and villous adenomas
Contains 25-75% villous architecture
Represents 15-20% of all colorectal adenomas
Higher malignant potential than pure tubular adenomas.
Origin:
Arises from colonic epithelium through adenoma-carcinoma sequence
Develops from aberrant crypt foci
Results from accumulation of genetic mutations
Shows progressive architectural complexity and dysplasia
Part of adenomatous polyposis spectrum.
Classification:
Classified by architectural pattern: >75% tubular (tubular adenoma)
25-75% villous (tubulovillous adenoma)
>75% villous (villous adenoma)
Dysplasia grading: Low-grade dysplasia (mild/moderate)
High-grade dysplasia (severe/carcinoma in situ).
Epidemiology:
Peak incidence in 6th-7th decades
Male predominance (2:1 ratio)
More common in left-sided colon
Associated with Western lifestyle
Indian population shows increasing incidence with dietary changes.
Clinical Features
Presentation:
Often asymptomatic (detected on screening)
Rectal bleeding (most common symptom)
Change in bowel habits
Mucus discharge
Tenesmus (rectal lesions)
Large polyps may cause obstruction.
Symptoms:
Bright red bleeding per rectum (50-60% cases)
Mucoid diarrhea (large villous component)
Abdominal pain (cramping)
Iron deficiency anemia (chronic bleeding)
Hypokalemia (massive villous adenomas).
Risk Factors:
Age >50 years
Western diet (high fat, low fiber)
Obesity
Smoking
Alcohol consumption
Family history of colorectal cancer
Inflammatory bowel disease.
Screening:
Colonoscopy (gold standard)
Fecal occult blood testing
CT colonography
Flexible sigmoidoscopy
Fecal immunochemical test (FIT)
Multitarget stool DNA test.
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Gross Description
Appearance:
Pedunculated or sessile polyp
Velvety surface (villous areas)
Lobulated contour
Red-pink to tan coloration
Friable consistency
May show surface erosions.
Characteristics:
Cauliflower-like appearance
Soft, friable consistency
Cut surface shows complex architecture
Papillary projections visible
Areas of induration (high-grade dysplasia)
Surface ulceration possible.
Size Location:
Size typically 1-5 cm (larger than tubular)
Sigmoid colon (most common site)
Rectum (second most common)
Left-sided predominance
Usually solitary
Multiple adenomas in polyposis syndromes.
Multifocality:
Usually solitary (sporadic cases)
Multiple adenomas (20-30% cases)
Synchronous carcinomas (5% cases)
Metachronous lesions (surveillance needed)
FAP association (numerous polyps).
Microscopic Description
Histological Features:
Mixed tubular and villous architecture
Finger-like villous projections
Dysplastic epithelium lining surface and crypts
Lamina propria core in villi
Inflammatory infiltrate in stroma
Surface maturation may be lost.
Cellular Characteristics:
Columnar epithelial cells with loss of polarity
Nuclear stratification (pseudostratification)
Hyperchromatic nuclei
Increased nuclear-cytoplasmic ratio
Mitotic figures above crypt base
Mucin depletion in dysplastic areas.
Architectural Patterns:
Tubular component: branched crypts with rounded profiles
Villous component: finger-like projections with fibrovascular cores
Complex crypts with budding
Back-to-back glands (high-grade dysplasia)
Cribriform pattern may develop.
Grading Criteria:
Low-grade dysplasia: mild architectural distortion, nuclear changes confined to lower 2/3 of crypt
High-grade dysplasia: severe architectural complexity, nuclear changes extending to surface
Loss of surface maturation
Carcinoma in situ (intramucosal carcinoma).
Immunohistochemistry
Positive Markers:
CDX2 (intestinal differentiation)
CK20 (colonic epithelium)
CEA (apical staining, normal)
p53 (may be positive in high-grade dysplasia)
Ki-67 (proliferation marker).
Negative Markers:
CK7 (usually negative)
TTF-1 (negative)
p53 (wild-type staining in low-grade)
Chromogranin A (unless neuroendocrine differentiation)
Vimentin (negative in epithelium).
Diagnostic Utility:
CDX2 positivity confirms intestinal origin
p53 staining pattern helps assess dysplasia grade
Ki-67 index reflects proliferative activity
β-catenin may show nuclear accumulation
CK20 pattern maintains polarity.
Molecular Subtypes:
Microsatellite stable (most common)
Microsatellite unstable (Lynch syndrome)
CpG island methylator phenotype (CIMP)
Traditional adenoma pathway (APC mutations)
Serrated pathway (rare in tubulovillous).
Molecular/Genetic
Genetic Mutations:
APC gene mutations (60-80% cases)
KRAS mutations (40-50% cases)
TP53 mutations (high-grade dysplasia)
PIK3CA mutations (20-30% cases)
SMAD4 mutations (advanced lesions).
Molecular Markers:
Wnt pathway activation (β-catenin nuclear localization)
p53 accumulation (mutation-dependent)
EGFR overexpression
Loss of 18q (SMAD4 region)
Chromosomal instability (CIN pathway).
Prognostic Significance:
Size >1 cm increases malignancy risk
Villous component >25% higher risk
High-grade dysplasia significant risk factor
TP53 mutations indicate progression risk
Complete excision curative for benign adenomas.
Therapeutic Targets:
Endoscopic resection (treatment of choice)
Surgical resection (large lesions, malignancy)
COX-2 inhibitors (prevention, controversial)
Surveillance colonoscopy (monitoring)
Polypectomy with clear margins.
Differential Diagnosis
Similar Entities:
Tubular adenoma (<25% villous component)
Villous adenoma (>75% villous component)
Serrated adenoma (serrated architecture)
Adenocarcinoma (invasive component)
Inflammatory polyp (reactive).
Distinguishing Features:
Tubulovillous adenoma: 25-75% villous architecture
Tubulovillous adenoma: Mixed pattern
Tubular adenoma: <25% villous
Villous adenoma: >75% villous
Serrated adenoma: Serrated crypts
Adenocarcinoma: Stromal invasion.
Diagnostic Challenges:
Distinguishing high-grade dysplasia from adenocarcinoma (basement membrane integrity)
Assessing completeness of excision
Quantifying villous component percentage
Identifying focus of invasion
Adequate sampling essential.
Rare Variants:
Adenoma with mixed differentiation
Adenoma with neuroendocrine cells
Adenoma with squamous differentiation
Adenoma in inflammatory bowel disease
Flat adenoma (lateral spreading tumor).
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
Tubulovillous Adenoma
Location
Location: [anatomical site in colon/rectum]
Architectural Features
Shows mixed tubular and villous architecture with [X]% villous component. Finger-like villous projections with fibrovascular cores present.
Dysplasia Grade
Dysplasia: [Low-grade/High-grade] dysplasia
Size and Extent
Size: [X] cm, [pedunculated/sessile] polyp
Margin Assessment
Excision margins: [Complete/Incomplete] - [distance to nearest margin] mm
Special Features
Surface ulceration: [Present/Absent]. Adenomatous tissue extends to: [specify level]
Final Diagnosis
Colorectal Tubulovillous Adenoma with [low-grade/high-grade] dysplasia