What is a papilloma of the esophagus?

What is a Papilloma of the Esophagus?

An esophageal squamous papilloma is a rare benign tumor of the esophagus, typically appearing as a small, exophytic growth with papillary projections, often detected incidentally during endoscopy, and is presumed to be associated with human papillomavirus (HPV) infection in approximately 46-50% of cases. 1, 2

Clinical Characteristics

Epidemiology and Presentation:

• Esophageal squamous papillomas occur in approximately 0.26-0.35% of patients undergoing upper endoscopy 1, 3
• The lesions affect both sexes relatively equally, with a mean age of presentation around 45 years 1
• Most papillomas (approximately 90%) are solitary lesions, though multifocal presentations occur in a minority of cases 1
• The vast majority are asymptomatic and discovered incidentally during esophagogastroduodenoscopy performed for other indications 4, 5
• Larger papillomas may rarely cause dysphagia, odynophagia, or bleeding 4

Anatomic Distribution:

• Papillomas are most commonly located in the middle and upper portions of the intrathoracic esophagus 1
• This distinct localization differs from reflux esophagitis (which affects the lower esophagus), suggesting that papillomas are not caused by hiatus hernia or gastroesophageal reflux 1

Endoscopic and Histologic Features

Macroscopic Appearance:

• Papillomas appear as exophytic, sessile, or pedunculated growths with papillary projections 2
• They can appear pink or white depending on the degree of keratinization 2
• Most lesions are only a few millimeters in size, though larger lesions (up to 8 mm) have been reported 4

Microscopic Features:

• Histologically characterized by squamous epithelium with papillary architecture and fibrovascular cores 2
• May demonstrate koilocytes (cells with perinuclear halos), which are suggestive of HPV infection 2

HPV Association and Oncogenic Potential

Viral Etiology:

• HPV DNA can be detected in approximately 46-50% of esophageal papillomas using PCR techniques 1, 2
• When HPV is detected, high-risk oncogenic genotypes (particularly HPV 16 and 18) predominate 1
• Low-risk HPV genotypes 6 and 11 are also commonly detected 2

Malignant Transformation Risk:

• The malignant potential of esophageal papillomas remains controversial and appears to be very low 1, 3, 6
• Direct transformation of papilloma to carcinoma has not been definitively documented in most series 1
• Synchronous esophageal squamous cell carcinoma occurs rarely (approximately 1.3% in one large series) 1
• Papillomas harboring high-risk HPV genotypes may carry increased risk for dysplasia, particularly in immunosuppressed individuals 2, 7
• The identical anatomic localization of papillomas and squamous cell carcinoma in the esophagus suggests potentially shared etiology (HPV infection), though causality remains unproven 1

Important Caveat: Unlike anogenital condylomata (where dysplasia and malignant transformation are well-documented), esophageal papillomas appear to behave in a more benign fashion 3, 6

Management Approach

Diagnostic Workup:

• Complete endoscopic removal with histological examination is recommended for definitive diagnosis and to exclude dysplasia or malignancy 7, 5, 6
• Small papillomas (few millimeters) can be removed with standard biopsy forceps 1, 4
• Larger lesions require endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) techniques 1, 4
• HPV testing via PCR should be considered, particularly for multifocal lesions or in immunosuppressed patients 1, 6

Treatment Strategy:

• Surgical excision (endoscopic resection) is the standard of care to ensure complete removal of infected epithelium at the base and to rule out dysplasia 2, 7
• Complete excision minimizes recurrence risk, which is uncommon (reported in <1% of cases when completely removed) 1, 4
• Incomplete removal may lead to recurrence due to residual infected epithelium 2

Surveillance Recommendations:

• For small, solitary, non-dysplastic papillomas that are completely excised, routine long-term surveillance may not be necessary 6
• Multifocal lesions, high-risk HPV-positive cases, or lesions in immunosuppressed patients warrant closer endoscopic follow-up 6, 7
• Follow-up endoscopy at 6-12 months is reasonable for higher-risk presentations to assess for recurrence 4, 6
• No standardized surveillance protocol currently exists, and practice varies by institution 6

Differential Diagnosis

Key Distinctions:

• Must be differentiated from verrucous carcinoma (carcinoma verrucosum), which can have similar papillary architecture but demonstrates invasive features 1
• Condyloma acuminatum can appear similar but typically occurs in younger patients and is more commonly associated with sexual transmission 2
• Verruca vulgaris is uncommon in the esophagus and typically shows prominent hyperkeratosis 2

Clinical Pitfalls

• Do not assume all papillary esophageal lesions are benign—histological confirmation is mandatory 5
• Incomplete excision may lead to recurrence, so ensure removal includes the base of the lesion 2
• In immunosuppressed patients, maintain higher suspicion for dysplasia and consider more aggressive surveillance 2, 7
• The presence of high-risk HPV does not definitively predict malignant transformation, but warrants closer monitoring 1, 6