Neoplastic Disease of the Esophagus

Raised Lesions

Schwannomas are rare benign tumors derived from Schwann cells in the peripheral nerves. Microscopically, they are diagnosed by lymphoid cuffing, nuclear atypia, and the presence of spindle-shaped cells. Rarely do they cause dysphagia, and malignant schwannomas are highly unusual. Small lesions may be enucleated and larger ones may be surgically resected.

Lymphangiomas arise from lymphatic tissue malformations. They are rare in the esophagus, occurring most frequently in patients younger than 2 years of age. Endoscopy reveals translucent yellow compressible mass structures less than 0.5 cm. Biopsy may be negative, as they are submucosal, but EUS is diagnostic. Histology reveals dilated endothelial cavities with eosinophilic material lined by flat endothelial cells. Treatment is with observation unless they grow to 4 to 5 cm. They are resected by band-assisted mucosectomy, endoscopic submucosal dissection (ESD), or by using a CO ₂ laser.

Esophageal hemangiomas occur in 0.04% of autopsies. Most are cavernous and rarely involve capillary lesions. Usually they occur alone, but multiple lesions are seen in disorders such as Osler-Weber-Rendu disease, Klippel-Trénaunay syndrome, or congenital blue rubber bleb nevus syndrome. They are found incidentally on endoscopy and are nodular, soft, and bluish-red; they blanch when compressed. These lesions have been confused with Kaposi sarcoma. Rarely, they may bleed or cause dysphagia, which is the only reason to resect them endoscopically or surgically.

Fibrovascular polyps arise from nodular mucosa and take up 0.5% to 1.0% of all benign esophageal lesions; most are located proximally and 75% occur in men. They are most common in the upper esophagus and are usually attached to the cricopharyngeus. They are a conglomerate of fibrous, vascular, and adipose tissues with a squamous epithelium. Histologically they are inclusive of different fibromas, fibrolipomas, myomas, and lipomas. They are rare, accounting for 0.5% to 1% of all benign esophageal lesions. Fibrovascular polyps rarely cause symptoms of dysphagia, chronic cough, nausea, and vomiting. They can grow to 20 cm and prolapse into the larynx, causing airway obstruction. Gastric prolapse can result in ulceration and bleeding. If fibrovascular polyps are symptomatic, they are removed. They usually have stalks that are vascular and can be detected by EUS. Lesions can be removed endoscopically if an Endoloop is used to ligate the nutrient vessels.

Approximately 10% of granular cell tumors arise in the gastrointestinal (GI) tract; the esophagus is involved in 65% of such cases. Granular cell tumors of the esophagus are rare, occurring in 0.033% of all individuals at endoscopy and composing 1% of benign esophageal tumors. Approximately 60% of those affected are men. Endoscopic exam reveals sessile yellowish-white lesions with normal mucosa with a thick consistency. Of all, 90% are solitary with histologically large polygonal cells containing eosinophilic granules. They are believed to be of neural origin, as they resemble Schwann cells under electron microscopy and are positive for S100 protein. Deeper tunneling biopsies are needed to diagnose these deeper lesions. The larger the lesion, the faster the growth and the higher the malignant potential. Lesions of 4 cm and greater compose all of the 4% of malignant lesions that demonstrate infiltrative growth. These lesions must therefore be removed, which is usually possible with the techniques of classic biopsy, endoscopic mucosal resection or submucosal tunnel endoscopic.

Esophageal adenomas usually arise in segments of Barrett esophagus. They are dysplastic, polypoid, or nodular lesions that may reach 1.5 cm and may be multiple. They may be found in conjunction with esophageal adenocarcinoma; therefore adjacent areas must be biopsied along with narrow-band imaging and chromoendoscopy. If surrounding Barrett is detected, patients are treated as having Barrett esophagus with dysplasia. If there is no Barrett, lesions smaller than 1 cm are removed endoscopically and those greater than 1 cm with high-grade dysplasia (HGD) undergo mucosal resection or surgery.

Inflammatory fibroid polyps are composed of many lesions with reactive blood vessels, fibroblasts, and inflammatory cells such as hamartomas, inflammatory pseudopolyps, and eosinophilic granulomas. They are extremely rare, at 3 per million cases, and less likely to be found in the esophagus than any other section of the intestine. They are believed to be caused by acid reflux.

Inflammatory fibroid polyps are benign, incidentally found, reactive and inflammatory, with a connective tissue stroma and eosinophilic infiltrate. They occasionally cause dysphagia and hemorrhage and may grow to 9 cm, at which point endoscopic snare removal or surgery is warranted.

Esophageal papillomas are rare, with an incidence up to 0.04%, benign epithelial with microscopic fingerlike projections of squamous cells, connective tissue, and blood vessels. The cause of these lesions is unknown but believed to be an underlying inflammatory condition. Approximately 70% are located in the distal third of the esophagus and associated with reflux, esophagitis, or mechanical manipulation. Substances such as benzopyrene and nitrosamines may be a cause as well. Human papillomavirus (HPV) is associated in up 5% to 46% of cases and may be a cause. Sexual transmission may be the route of spread, as serotypes 6 and 11 are commonly found in the human oropharynx and genital tract. HPV is documented to be associated with cancer of the larynx and cervix. HPV is also involved with esophageal squamous cell carcinoma, along with papillomas. Malignant transformation related to HPV infection has not been proven.

Esophageal papilloma is most common in individuals in their 50s, with a mostly equal gender frequency. Most lesions are solitary, but rarely up to 10 are found. Endoscopy reveals small whitish-pink wartlike exophytic projections with a differential diagnosis of verrucous squamous cell carcinoma, granulation tissue, and papillary leukoplakia. Papillomas are found more frequently in patients with tylosis, acanthosis nigricans, and Goltz syndrome. Large lesions can cause dysphagia, but most may be endoscopically resected with forceps when they are 1 cm or less in size; mucosal resection can be performed when they are larger.

Flat Lesions

Heterotopic sebaceous glands are found in ectodermal tissues such as the genitalia, parotid gland, palms, soles, eyelashes, lips, mouth, and tongue; they are rare in the esophagus. They are unlikely congenital, resulting from heterotopic mucosa or reactive metaplasia of the esophagus. Endoscopy reveals yellowish-gray plaquelike lesions occurring in clusters of up to 100 in one area. Histology reveals groups of sebaceous cells in the lamina propria. Lesions may be observed as they have no malignant potential.

Glycogen acanthosis occurs in 3.5% to 15% of all endoscopies and 30% of barium esophagrams. There are multiple round protrusions 2 to 15 mm in size in the midesophagus. The pathogenesis is unclear but has been associated with Cowden disease. Most lesions present in patients in their 40s and 50s, mainly in men, and increase in number and frequency with age. Endoscopic mucosal biopsies reveal plaques of hyperplastic squamous epithelium with glycogen in the cells.

Esophageal parakeratosis on endoscopy appears as whitish membranous linear plaques. Histologically they manifest epithelial acanthosis, basal hyperplasia, and parakeratosis covered by nonnucleated squamous cells. Esophageal parakeratosis has been associated with esophageal and head and neck carcinoma but is not premalignant and represents 40% of new squamous cell cancers (SCCs) of the head and neck. It is also associated with submucosal fibrosis in smokers and betel nut chewers.

Esophagitis dissecans superficialis is a rare condition involving sloughing of mucosal epithelium and characterized by tubular casts within the esophageal lumen. It occurs with pemphigus vulgaris in 5% of patients or as a complication of rigid endoscopy with esophageal dilation, ingestion of oral bisphosphonates, and celiac disease.

An esophageal inlet patch is heterotopic gastric mucosa of the upper esophagus (HGMUE) occurring with a prevalence of 5% of adults by autopsy and 11% at endoscopy. These lesions are most commonly found in individuals their 50s and are most often located in the proximal 3 cm of the esophagus. Patches range from 2 mm to 4.5 cm in size and can occur alone or be multiple. They are red, velvety, and flat but rarely raised or polypoid. Microscopically they have fundic-type of gastric mucosa with some parietal cells and evidence of an inflammatory infiltrate.

The origin of the esophageal inlet patch is unclear; it is unknown whether they develop from “heterotopic” gastric mucosa or are embryonic. They are frequently found in children and their prevalence does not increase with age. Immunohistochemical analysis reveals that the cells are reactive to glucagon, which is an embryonic finding that is not noted in mature gastric cells. Controversy exists as to their origin, which may be the failure to replace the columnar lining of the esophagus with squamous epithelium during maturation as well as the belief that inlet patches are more similar to Barrett mucosa, which has been believed to be an acquired lesion. Trauma to the lining with rehealing by squamous mucosa has also been suggested.

Clinical problems have been attributed to the inlet patches by association. Tracheoesophageal fistula has occurred at the site of an inlet patch secondary to acid production with perforation. Patients with strictures, rings, and webs that have a patch frequently have dysphagia. Patches have been suggested as a cause of Plummer-Vinson syndrome. Helicobacter pylori grows in the patch in 19% to 73% of those that are H. pylori –positive in the stomach, indicating that the esophagus may be a reservoir. Barrett esophagus has been found in the distal esophagus of 20% of individuals with a patch. Esophageal and laryngeal adenocarcinoma has been found arising from inlet patches in the upper esophagus. Symptoms of globus, cough, and laryngopharyngeal reflux have been associated with patches, and improvement in globus symptoms has occurred after argon plasma ablation. Diagnosis is made on endoscopic visualization and confirmed by biopsy. Patches are benign and are treated only if symptomatic. Risk factors for malignancy are unclear. Endoscopic ablation and treatment a PPI can result in replacement with squamous mucosa.

Cystic Lesions

Cystic lesions of the esophagus occur in 1 in 8200 patients and most commonly are bronchogenic or originate from the GI tract. Bronchogenic cysts are lined by columnar cells and contain a milky-white substance, smooth muscle, hyaline cartilage, and seromucous glands. Enterogenous cysts are lined with columnar, bowel, or cuboidal cells or gastric mucosa and contain green mucus. They occur secondary to abnormal embryonal budding; they are located periesophageally or may be intrapulmonary and average 4 cm in size. Endoscopy and barium esophagraphy reveal protruding masses with normal mucosa, but EUS must be performed to confirm their presence. If dysphagia is present from a large cyst, surgical resection is indicated. These lesions do not have malignant potential.

Duplication cysts are congenital and are found in 1 in 8000 live births. They are rarely found in the esophagus, where they are located within the esophageal wall and are covered by two muscle layers covered by squamous epithelium. The cysts contain gastric mucosa in 33% of cases but they may also contain pancreatic mucosa. They are usually located to the right side of the esophagus. There is no cyst-esophageal communication in 80%, but 20% are parallel with esophagus and do communicate. They usually cause symptoms, resulting in 80% being diagnosed in patients younger than 2 years of age. Compression of adjacent structures causes dysphagia in 70%, epigastric pain in 20%, and mediastinal pain in 10% as well as respiratory symptoms and occasional hematemesis. Symptoms are an indication for surgical resection. Malignancy is rare.