Benign esophageal neoplasms

Benign esophageal neoplasms are uncommon lesions that arise from the esophageal wall. Predominant types include esophageal leiomyomas, gastrointestinal stromal tumors (GISTs), squamous papillomas, and inflammatory or fibrovascular polyps. Clinical presentation varies with tumor type and size; patients may be asymptomatic or experience dysphagia and symptoms consistent with gastroesophageal reflux disease (GERD). Diagnosis typically involves endoscopic evaluation with tissue biopsy for histopathologic confirmation. Treatment generally consists of tumor resection or endoscopic ablation, depending on lesion characteristics and patient factors.

Other benign esophageal tumors include:

• GIST
• Schwannoma
• Lymphangioma
• Hemangioma
• Granular cell tumor
• Glomus tumor
• Lipoma
• Adenoma

Diagnosis of benign esophageal neoplasm initially requires endoscopic evaluation. Tissue biopsy is usually needed in most cases for definitive diagnosis.

Endoscopic evaluation ^[1]

• Endoscopy (e.g., EGD)
  • Initial evaluation of esophageal lesions
  • May be supplemented with advanced imaging techniques (e.g., virtual chromoendoscopy, Lugol iodine staining)
• Endoscopic ultrasound (EUS) to further characterize lesions, particularly subepithelial lesions
• Other imaging modalities (e.g., barium swallow, CT, MRI) may be considered.

Tissue biopsy ^[1]

• Biopsy for definitive diagnosis and to differentiate from malignant lesions
  • Methods may include EUS-guided tissue acquisition (e.g., FNB, FNA) or mucosal incision-assisted biopsy (MIAB).
• Histopathology and special testing on the acquired tissue
  • Histologic evaluation to confirm the diagnosis
  • Immunohistochemistry (IHC) to differentiate between tumor types (e.g., leiomyoma vs. GIST)
  • Specialized molecular testing as indicated
    • MDM2 testing to exclude liposarcoma in suspected fibrovascular polyps
    • HPV testing (e.g., PCR, in situ hybridization) for esophageal squamous papillomas

Definition

An esophageal leiomyoma is a slow-growing, rare mesenchymal tumor that arises from the smooth muscle cells of the muscularis mucosae or muscularis propria (more common) layer of the esophageal wall. ^[1][2]

Epidemiology

• Most common benign esophageal tumor ^[1]
• Incidence: 0.005–5.1% ^[2]
• Age: most often between 20–50 years ^[2]
• Sex: ♂ > ♀ (approx. 2:1 ratio) ^[2]
• Locationof tumor within the esophagus
  • Lower third: 50–60% ^[2]
  • Middle third: 30–40% ^[2]
  • Upper third: 10% ^[2]

Etiology

• Unclear

Clinical features ^[1][2]

• Usually asymptomatic
• Symptoms typically occur with larger tumors (> 5 cm).
  • Dysphagia
  • Chest pain or retrosternal discomfort
  • Heartburn and regurgitation
  • Respiratory symptoms due to airway compression (rare), e.g., cough, dyspnea, sudden asphyxial death

Diagnosis ^[1][2][6]

Diagnosis consists of EUS to characterize the lesion, followed by tissue acquisition in the case of diagnostic uncertainty or if malignancy is suspected.

• Endoscopic ultrasound
  • Obtained to characterize subepithelial lesions
  • Findings are nonspecific and show a well-circumscribed, homogeneous, hypoechoic mass ^[1][2]
• Tissue biopsy
  • Indicated for definitive diagnosis
  • Method:
    • EUS-guided fine-needle biopsy or fine-needle aspiration with rapid on-site evaluation
    • Mucosal incision-assisted biopsy (alternative)
  • Histopathology: hypocellular neoplasm with spindle cells, no mitotic activity or nuclear atypia ^[1]
  • Immunohistochemistry (confirmatory): positive SMA and desmin, negative CD34 and CD117 ^[1][2]
• Additional studies: may be considered for a comprehensive evaluation
  • Barium swallow: findings of esophageal lumen with smooth-surfaced, crescent-shaped filling defect with sharp angles relative to the normal esophageal wall
  • CT or MRI: typically show a well-marginated, smooth, homogeneous mass

Management

General principles ^[2][7]

• Management depends on tumor size, location, symptoms, and comorbidities.
• Asymptomatic, small, confirmed leiomyoma does not require resection or routine surveillance.
• Tumor resection with enucleation is the preferred surgical method.
• Minimally invasive techniques are preferred over open thoracotomy.

Endoscopic and surgical therapy ^[2]

• Indications for resection ^[7]
  • Presence of symptoms (e.g., dysphagia, chest pain)
  • Tumor size > 5 cm
• Therapeutic options ^[6]
  • Endoscopic resection (e.g., submucosal tunneling endoscopic resection)
  • Thoracoscopic resection (e.g., via video-assisted thoracoscopic surgery or robotic-assisted thoracoscopic surgery)
  • Open thoracotomy or laparotomy: for giant, complex, or encircling tumors

Postprocedural complications ^[2]

• GERD
• Mucosal injury or perforation
• Anastomotic leak (following resection)
• Pseudodiverticulum

Definition

An esophageal fibrovascular polyp is an intraluminal, benign esophageal tumor consisting of adipose and fibrous tissue, typically featuring a vascular stalk. ^[1]

Epidemiology

• Most common intraluminal benign esophageal tumor ^[1]
• Usually located near cricopharyngeus muscle ^[3]

Etiology

Esophageal fibrovascular polyps develop in response to inflammation. ^[1]

Clinical features

• Symptomatic when the polyp is large ^[3]
• Dysphagia
• Tumor regurgitation may cause airway compromise and asphyxiation (rare) ^[1]

Diagnosis ^[1][3]

Diagnosis can be made by clinical presentation alone (e.g., regurgitation of the tumor, asphyxiation). Visualization on endoscopy provides diagnostic confirmation.

• Endoscopic ultrasound: heterogeneous appearance; doppler reveals vascularity within the stalk. ^[1]
• Tissue biopsy
  • Tissue is typically analyzed after resection.
  • MDM2 testing should be performed to exclude liposarcoma.
  • Histopathology: dense or loose fibrous tissue along with adipose tissue and vascular structures, enveloped by normal squamous epithelium ^[3]
• Additional studies
  • CT with oral contrast: intraluminal lesion surrounded by a thin rim of contrast
  • MRI: heterogeneous hyperintensity seen on T2 or iso- to hypo-intensity seen on T1-weight imaging
  • PET scan: FDG avidity

Differential diagnoses ^[1]

• Liposarcoma
• Other benign esophageal neoplasms

Management ^[1][3]

Surgical resection (typically via esophagotomy) is recommendeddue to the potential for airway compromise.

Definition ^[4]

• Esophageal squamous papilloma (ESP): a benign, rare epithelial lesion of the esophagus; typically a solitary exophytic lesion
• Esophageal squamous papillomatosis: extensive esophageal involvement of squamous papilloma lesions, with a higher risk for malignant transformation

Epidemiology ^[4]

• Prevalence: 0.01%–0.45% in patients undergoing esophagogastroduodenoscopy (EGD) ^[4]
• Median age at diagnosis: 49–52 years ^[4]
• Findings on sex and race are variable.

Etiology ^[4]

The exact pathogenesis remains uncertain, but two main hypotheses have been proposed.

• Chronic mucosal irritation
  • GERD
  • Mechanical trauma (e.g., from sclerotherapy or stents)
  • Alcohol and/or tobacco use
• Human papillomavirus (HPV) infection
  • HPV DNA detected in 10–80% of ESPs. ^[4]
  • Both low-risk and high-risk HPV genotypes have been identified.

Clinical features ^[4]

• Esophageal squamous papilloma
  • Usually asymptomatic
  • Nonspecific symptoms due to underlying condition (e.g., clinical features of GERD)
• Esophageal squamous papillomatosis
  • Frequently symptomatic
  • Dysphagia (most common)
  • Weight loss
  • Heartburn
  • Epigastric discomfort
  • Indigestion

Diagnosis ^[1][4]

ESP is typically discovered incidentally during EGD. Histologic confirmation is required for definitive diagnosis.

• Endoscopy
  • EGD
    • Typically found in middle and distal thirds of esophagus (rarely diffuse)
    • Usually small (2–6 mm), rarely > 10 mm
    • Solitary lesion in ESP; multiple clustered lesions in esophageal papillomatosis
    • Exophytic, wart-like growth with whitish-pink appearance and demarcated margins
    • Vessel seen crossing beneath the surface on advanced techniques (e.g., narrow-band imaging)
  • EUS: findings of noninvasive, homogeneous, hypoechoic lesion
• Tissue biopsy
  • Indications
    • Confirmation of ESP or esophageal papillomatosis
    • To exclude squamous cell carcinoma
  • Histopathology
    • Squamous epithelium with finger-like projections over a fibrovascular core
    • Occasional presence of koilocytes in HPV-related conditions
  • HPV testing
    • Obtained to determine underlying cause
    • PCR and in situ hybridization: used to detect viral DNA in esophageal tissue
    • p16 immunohistochemistry is not a reliable surrogate marker for HPV in esophageal tissue.

Differential diagnosis

• Esophageal squamous cell carcinoma
• Other benign esophageal polyps

Management ^[4]

General principles

• Complete removal of the lesion should be performed when feasible.
• Histopathologic evaluation of the resected specimen is essential to exclude dysplasia or carcinoma.
• Otolaryngologic assessment should be considered to rule out synchronous laryngeal or tracheal involvement in cases of extensive or recurrent disease.

Endoscopic therapy

• Esophageal squamous papilloma
  • Small lesions (≤ 5 mm): removal with biopsy forceps
  • Larger lesions (> 5 mm): endoscopic mucosal resection (EMR) or snare polypectomy
  • Suspicion for squamous cell carcinoma: endoscopic submucosal dissection (ESD)
• Esophageal squamous papillomatosis
  • Ablative therapies (e.g., radiofrequency ablation, argon plasma coagulation)
  • Localized or suspicious lesions may be treated with EMR or ESD.

Surgical therapy ^[4]

Esophagectomy may be indicated for papillomatosis with malignant transformation or in cases of failed endoscopic therapy.

Follow-up and surveillance ^[4]

• Recurrence after treatment
  • Recurrence of solitary, nondysplastic ESPs after complete resection is rare.
  • Recurrence of esophageal papillomatosis is more common.
• Surveillance strategies should be individualized based on patient risk factors.
• Routine surveillance may not be required for small, nondysplastic, HPV-negative lesions that have been completely removed.
• Consider endoscopic monitoring in patients with:
  • Large lesions
  • High-risk HPV positivity
  • Dysplasia or superficial carcinoma

Prognosis ^[4]

• ESP and papillomatosis are generally considered benign lesions.
• Risk for malignant transformation to esophageal squamous cell carcinoma in:
  • Esophageal papillomatosis
  • Association with high-risk HPV infection
  • Presence of dysplasia

Definition ^[1]

Esophageal inflammatory or hyperplastic polyp, also known as inflammatory pseudotumor, is a benign polypoid lesion of the esophagus.

Etiology ^[5][8]

• GERD
• Barrett esophagus
• Esophagitis (e.g., medication induced, infection)
• Iatrogenic (e.g., polypectomy sites, photodynamic therapy)

Clinical features ^[5]

• Typically asymptomatic
• Symptoms of underlying condition (e.g., clinical features of GERD)
• Extremely rare: symptoms of luminal obstruction or GI bleed if the polyp is large

Diagnosis ^[1]

The diagnosis is made based on histological findings since it is indistinguishable from other subepithelial lesions on endoscopy and EUS.

• EGD and EUS: homogeneous mass that is either hypoechoic or hyperechoic with indistinct margins.
• Tissue biopsy (confirmatory): reactive fibroblasts with an inflammatory infiltrate and blood vessels

Management ^[1]

Endoscopic resection is often a viable treatment option.