Villous adenoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: Adenomatous polyps; VA; TVA

Overview

Villous adenoma (also known as adenomatous polyp) is a type of polyp that grows in the gastrointestinal tract; it occurs most commonly in the colon. Villous adenoma may result in malignant (cancerous) transformation. Villous adenoma was first discovered by Helwig in 1946. According to the World Health Organization, villous adenoma may be classified into tubular, tubulovillous, and villous (most common) subtypes. Villous adenoma arises from epithelial tissue, which is normally part of the lining of the colon. The estimated risk of malignant transformation among villous adenomas is between 15% and 25%. Genes associated with the development of villous adenoma include APC, TP53, K-ras, and BAT-26. The prevalence of villous adenoma is approximately 3.5 per 100,000 individuals worldwide. The most potent risk factors in the development of villous adenoma include familial syndromes such as Turcot syndrome, juvenile polyposis syndrome, and Cowden disease). Surgical removal is the mainstay of therapy for villous adenoma. Exploratory colonoscopy and cautery snare is the most common approach to the diagnosis and treatment of villous adenoma. Effective measures for the primary prevention of villous adenoma include periodic screening of patients with family history of familial adenomatous polyposis. Secondary prevention strategies include annual occult blood test and colonoscopy every ten years for patients above the age of 50.

Historical Perspective

Villous adenoma was first discovered by Helwig in 1946.

Classification

Villous adenoma may be classified into 3 subtypes according to histological appearance:

• Tubular
• Tubulovillous
• Villous

Villous adenoma can be classified into 4 types according to the gross appearance.

• Flat
• Sessile
• Pedunculated
• Depressed

Pathophysiology

Pathogenesis

• The pathogenesis of villous adenoma is characterized by overgrowth of epithelial tissue with glandular characteristics.
• Dysplastic changes are present in the adenomas.
• Low grade or high-grade dysplasia, which indicates the level of maturation of the epithelium determines the progression of the adenoma.
• The cytological features of low-grade dysplasia include crowded, pseudo-stratification to early stratification of spindled or elongated nuclei which occupy the basal half of the cytoplasm.
• Pleomorphism and atypical mitoses are absent in low grade dysplasia.
• The crypts maintain a resemblance to normal colon, without significant crowding, cribriform, or complex forms.
• High-grade dysplasia cytologically has increased nucleus to cytoplasm ratio, more significant loss of polarity, more "open" appearing nuclei with increasingly prominent nucleoli.
• Other features which distinguish a high grade from low-grade dysplasia include significant pleomorphism, rounded nuclei, atypical mitoses, and significant loss of polarity.
• Cribriform and crowding, back-to-back glands indicate high-grade dysplasia and are important architectural features to aid in differentiating cases of low vs. high-grade dysplasia.
• The progression of adenoma-to-carcinoma can also occur with activation of oncogenes and inactivation of tumor suppressor genes.
• Multiple genetic mutations result in the transition from normal mucosa to adenoma to severe dysplasia and finally to carcinoma.
• The K-ras oncogene, inactivation of tumor suppressor genes, the APC gene, on 5q, have important roles in adenoma formation.
• On gross pathology, characteristic findings of villous adenoma include:
  • Polypoid or sessile mass
  • Cauliflower-like in appearance\
• On microscopic histopathological analysis, characteristic findings of villous adenoma include:
  • Nuclear changes at the surface of the mucosa
  • Cigar-shaped (elongated) nucleus (length:width > 3:1) with nuclear hyperchromasia
  • Large round nuclei
  • Nuclear crowding
  • Positive Ki-67

Causes

Villous adenomas are commonly idiopathic. The most common known cause of villous adenoma is familial adenomatous polyposis.

Differentiating Villous Adenoma from Other Diseases

Villous adenoma must be differentiated from other diseases that cause abnormal growth of tissue projecting from a mucous membrane such as:

• Colorectal cancer
• Inflammatory fibroid polyp

Epidemiology and Demographics

Prevalence

The prevalence of villous adenoma is approximately 3.5 per 100,000 individuals worldwide. The prevalence of adenomas increases with age.

Age

Patients of all age groups may develop villous adenoma.

Gender

Males are more commonly affected with villous adenoma than females.

Race

Villous adenoma more commonly affects caucasians.

Risk Factors

Common risk factors in the development of villous adenoma include:

• Familial adenomatous polyposis
• Peutz–Jeghers syndrome
• Turcot syndrome
• Juvenile polyposis syndrome
• Cowden disease
• Bannayan–Riley–Ruvalcaba syndrome (Bannayan-Zonana syndrome)
• Gardner's syndrome

Natural History, Complications and Prognosis

Natural History

The majority of patients with villous adenoma remain asymptomatic for years. Early clinical features may include flatulence, bloating, and abdominal pain. If left untreated, patients with villous adenoma may progress to develop colorectal cancer.

Complications

Common complications of villous adenoma include:

• Bleeding
• Obstruction
• Bowel torsion

Prognosis

The prognosis of villous adenoma is generally good and the 5-year mortality is approximately 89%. Prognosis becomes poorer with malignant transformation of the lesion. The estimated risk of malignant transformation of villous adenoma is from 15% to 20%.

Diagnosis

Symptoms

Villous adenoma is commonly asymptomatic. Villous adenoma symptoms are often non-specific. Symptoms of villous adenoma may include:

• Flatulence
• Abdominal pain
• Constipation
• Diarrhea
• Cramping
• Pencil-thin stools

Physical Examination

Patients with villous adenoma commonly appear well. Physical examination findings are often non-specific. Physical examination may demonstrate:

• Bright red blood on digital rectal examination
• Rectal mass

Laboratory Findings

There are no specific laboratory findings associated with villous adenoma. In some cases, patients with villous adenoma may demonstrate positive fecal occult blood test or hypokalemia.

Other diagnostic studies

Colonoscopy is the diagnostic modality of choice for villous adenoma. On colonoscopy, characteristic findings of villous adenoma include:

• A sessile polyp
• Size can range from 0.5 cm to 5 cm

Alternative imaging studies include:

• CT colonography
• Video capsule endoscopy (less specific)

Treatment

Medical Therapy

There is no medical therapy for villous adenoma; the mainstay of therapy is surgical removal.

Surgery

Surgical removal is the mainstay of therapy for villous adenoma. Colonoscopy is both diagnostic and therapeutic. Cautery snare in conjunction with exploratory colonoscopy is the most common approach to both the diagnosis and treatment of villous adenoma.

Prevention

Primary Prevention

Effective measures for the primary prevention of villous adenoma include periodic screening for patients with family history of familial adenomatous polyposis.

Secondary Prevention

Secondary prevention strategies include annual occult blood test and colonoscopy every ten years for patients above the age of 50.