Definition/General
Introduction:
Colorectal villous adenoma is a benign epithelial neoplasm composed of dysplastic epithelium with >75% villous architecture
Represents 10-15% of all adenomatous polyps
Shows highest malignant potential among adenomas
Associated with significant secretory activity and electrolyte imbalance.
Origin:
Arises from colonic surface epithelium
Results from APC gene mutations and subsequent genetic alterations
Shows monoclonal proliferation
Demonstrates villous morphogenetic program
Associated with Wnt pathway activation.
Classification:
WHO classification: Villous adenoma (>75% villous architecture)
Tubulovillous adenoma (25-75% villous)
Dysplasia grading: Low-grade dysplasia
High-grade dysplasia (more common than tubular)
Carcinoma in situ included in high-grade.
Epidemiology:
Peak incidence in 6th-8th decades (older than tubular)
Male predominance
More common in rectosigmoid region
Larger size at presentation (mean 3-4 cm)
Higher malignancy rate (20-30% vs 5% tubular)
Secretory symptoms common.
Clinical Features
Presentation:
Mucoid diarrhea (characteristic)
Rectal bleeding
Electrolyte imbalance (hypokalemia)
Dehydration
Palpable rectal mass
Change in bowel habits
McKittrick-Wheelock syndrome (severe secretory).
Symptoms:
Profuse mucoid diarrhea (up to 3L/day)
Hypokalemia and weakness
Hyponatremia
Dehydration and prerenal azotemia
Rectal bleeding
Tenesmus
Abdominal cramping.
Risk Factors:
Advanced age (>60 years)
Male gender
Personal history of adenomas
Family history of colorectal cancer
Familial adenomatous polyposis
High-fat diet
Smoking.
Screening:
Colonoscopy with polypectomy
Careful histological examination
Complete excision mandatory
Surveillance colonoscopy
Electrolyte monitoring
Family screening if syndromic.
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Gross Description
Appearance:
Large, sessile polyp (usually >2 cm)
Velvety, cauliflower-like surface
Frond-like projections
Broad-based attachment
Soft, friable consistency
Pink to red coloration.
Characteristics:
Villous surface architecture visible grossly
Lobulated appearance
May show focal induration (suggests malignancy)
Friable surface bleeds easily
Mucin production visible.
Size Location:
Size typically 2-8 cm (larger than tubular)
Rectosigmoid region most common (60%)
Cecum second most common
Sessile morphology predominant
Broad-based attachment.
Multifocality:
Usually solitary
Synchronous adenomas in 30% cases
Associated with higher adenoma burden
Metachronous development common
FAP association in some cases.
Microscopic Description
Histological Features:
Villous architecture predominant (>75%)
Finger-like projections lined by dysplastic epithelium
Dysplastic epithelium throughout
Surface maturation often lost
High-grade dysplasia more common
Basement membrane intact.
Cellular Characteristics:
Tall columnar epithelial cells
Enlarged, hyperchromatic nuclei
Nuclear pseudostratification
Reduced mucin content
Increased mitotic activity
Loss of nuclear polarity in high-grade areas.
Architectural Patterns:
Villous fronds with central fibrovascular cores
Surface epithelial dysplasia
Cribriform pattern in high-grade areas
Back-to-back glands
Complex branching
Papillary infoldings.
Grading Criteria:
Low-grade dysplasia: preserved polarity, mild-moderate atypia
High-grade dysplasia: loss of polarity, severe atypia, cribriform architecture
More likely high-grade than tubular adenomas
Invasion assessment challenging in villous architecture.
Immunohistochemistry
Positive Markers:
β-catenin nuclear accumulation (Wnt pathway)
CDX2 positive (intestinal differentiation)
CK20 positive
Ki-67 increased proliferation
p53 positive in high-grade dysplasia.
Negative Markers:
CK7 typically negative
TTF-1 negative
Chromogranin negative
Synaptophysin negative
Smooth muscle markers negative.
Diagnostic Utility:
β-catenin confirms Wnt pathway activation
p53 accumulation indicates progression
Ki-67 shows proliferative activity
Mismatch repair proteins for Lynch syndrome screening
CDX2 confirms intestinal phenotype.
Molecular Subtypes:
Chromosomal instability pathway (majority)
Microsatellite instability (Lynch syndrome)
CIMP-high phenotype possible
Traditional adenoma pathway.
Molecular/Genetic
Genetic Mutations:
APC mutations (90% cases)
KRAS mutations (40-50%)
PIK3CA mutations (20%)
TP53 mutations (progression to carcinoma)
SMAD4 mutations
Loss of 18q.
Molecular Markers:
Wnt pathway activation
RAS-MAPK signaling
PI3K-AKT pathway
TGF-β pathway disruption
p53 pathway alterations.
Prognostic Significance:
Size >3 cm high malignancy risk
Villous architecture independent risk factor
High-grade dysplasia indicates progression
Sessile morphology difficult complete excision
Recurrence risk if incompletely excised.
Therapeutic Targets:
Complete surgical excision
Endoscopic mucosal resection for large lesions
Transanal excision for rectal lesions
Segmental resection if malignancy suspected
Close surveillance mandatory.
Differential Diagnosis
Similar Entities:
Tubulovillous adenoma - mixed architecture (25-75% villous)
Invasive adenocarcinoma - stromal invasion present
Serrated adenoma - serrated architecture
Hyperplastic polyp - no dysplasia
Inflammatory polyp - reactive changes.
Distinguishing Features:
Tubulovillous adenoma: <75% villous component, mixed architecture
Adenocarcinoma: desmoplastic stroma, invasion beyond muscularis mucosae
Serrated adenoma: saw-tooth pattern, eosinophilic cells
Hyperplastic polyp: surface maturation, no dysplasia.
Diagnostic Challenges:
Assessing invasion in villous architecture
Pseudoinvasion vs true invasion
High-grade dysplasia vs invasive carcinoma
Tangential sectioning artifacts
Incomplete sampling of large lesions.
Rare Variants:
Villous adenoma with focal carcinoma
Secretory villous adenoma (McKittrick-Wheelock syndrome)
Mixed adenoma with villous component
Flat villous 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
Colorectal polypectomy, [size] cm, sessile morphology
Diagnosis
Villous adenoma with [low-grade/high-grade] dysplasia
Classification
Adenomatous polyp, villous type (>75% villous architecture)
Histological Features
Shows predominantly villous architecture with dysplastic epithelium. [Grade] dysplasia present throughout.
Architecture
Villous: [%], Tubular: [%]
Invasion Assessment
No evidence of invasive carcinoma. Basement membrane intact.
Margins
Margins: [involved/uninvolved with adenoma]
Recommendations
Close surveillance colonoscopy in 3 months if completely excised, sooner if margins involved
Final Diagnosis
Villous adenoma with [grade] dysplasia, [completely/incompletely] excised