Inflammatory and Hyperplastic Polyps

Inflammatory polyps are the most common type of benign, squamous esophageal polyp. They occur primarily in men at the lower esophageal junction and usually are associated with gastroesophageal reflux disease (GERD).^2–4 Inflammatory polyps represent an exaggerated response to mucosal injury. Some are exuberant, healed ulcer sites. Inflammatory polyps may also develop proximal to the gastroesophageal junction, where they are often associated with mucosal injury caused by embedded pills, infection, or surgical anastomoses.⁵

Histologically, inflammatory polyps often have a smooth, rounded surface and consist of irregular tongues of squamous epithelium that extend deeply within an inflamed lamina propria (Fig. 19.1). Although controversial, some investigators think these polyps represent an endophytic type of squamous papilloma.⁶ Human papillomavirus (HPV) was identified in 33% of these polyps by polymerase chain reaction analysis in a study by Odze and colleagues.⁶ HPV was postulated to be a promoter of epithelial growth in mucosa that had been damaged by other irritants such as GERD.⁶

At the level of the gastroesophageal junction, hyperplastic polyps composed primarily of gastric hyperplastic foveolar epithelium, with or without hyperplastic and regenerative-appearing squamous epithelium, can develop, presumably as a result of chronic mucosal injury.⁵ These gastroesophageal junction polyps have been most often reported in the clinical gastroenterology or radiology literature.⁷ Hyperplastic polyps at the gastroesophageal junction may be associated with a short or ultrashort Barrett’s esophagus (33% of cases), and they have less inflammation compared with those arising in a non-Barrett’s setting.⁸

Squamous Papilloma

Squamous papillomas are the other main type of squamous polyp of the esophagus (see Chapter 24).⁹ They are the most common benign tumor of the esophagus.^1,6 In an upper gastrointestinal (GI) screening study from Korea, squamous papillomas were detected in 0.31% of patients.⁹ Other studies suggest that these lesions are underdiagnosed.

Two or three main histologic patterns have been described: exophytic, endophytic, and spiked.⁶ The exophytic type is more common. On endoscopy, these lesions have a cauliflower-like appearance. Histologic examination of the exophytic type reveals finger-like squamous papillae overlying fibrovascular cores of lamina propria (Fig. 19.2). The squamous epithelium may have features of koilocytosis, but it usually lacks the large, hyperchromatic nuclei and binucleation typical of human papillomavirus (HPV)–infected cervical epithelium. Exophytic squamous papillomas occur most frequently in the distal esophagus, but they also occur in the middle and upper esophagus. HPV is associated with as many as 78% of these squamous papillomas.^6,10

The endophytic type of papilloma has a round, smooth surface and an inverted papillomatous appearance. Some investigators think they are inflammatory polyps. Spiked squamous papillomas have a verrucous appearance, a corrugated surface, hyperkeratosis, and a prominent granular cell layer. This is the least common form of squamous papilloma. Forty percent of spiked papillomas were shown to harbor HPV in one study.⁶ Ratoosh and co-workers described a 60-year-old woman who had a large, verrucous lesion of the distal esophagus and multiple warts on her distal fingertips.¹¹ HPV-45 DNA sequences were identified in the fingertip and esophageal verrucous lesions, suggesting autoinoculation of the finger wart HPV virus to the esophagus.¹¹

Squamous papillomas are benign. Rarely, large squamous papillomas have undergone malignant degeneration.¹² However, whether these lesions represent de novo carcinomas or true malignant degeneration of a squamous papilloma is unknown.

Heterotopia

Several types of esophageal heterotopias rarely manifest as polypoid lesions on endoscopy (see Chapter 24). Heterotopias occur in 10% of the general population and usually consist of gastric heterotopia, although thyroid, parathyroid, and ectopic sebaceous tissues have been described.¹³ Gastric heterotopias in the esophagus usually contain glands and foveolar epithelium (82% of cases) and are thought to be congenital in origin.¹⁴ Heterotopias are often found in the proximal esophagus and may be called an inlet patch on endoscopy.

Glycogenic Acanthosis

Small, plaquelike or nodule-like lesions can occur in patients with prominent glycogenic acanthosis. It represents focal nodular thickening of the squamous mucosa with cells that contain prominent intracytoplasmic glycogen. Endoscopically, the lesions can resemble squamous papillomas. Patients with Cowden syndrome or tuberous sclerosis may have numerous polypoid areas of glycogenic acanthosis, and this finding always raises the possibility of one of these diagnoses.^15,16

Adenomas

True adenomas of the esophagus are rare (see Chapter 24). Most commonly, they develop from the submucosal gland or duct system and show a mixture of tubal, cystic, and papillary growth patterns that are similar to those of intraductal papillomas of the breast or sialadenoma papilliferum of the salivary glands. Most of these tumors are benign, but rare cases of malignant transformation have been described.

Polypoid Dysplasia in Barrett’s Esophagus

Most so-called adenomas reported in the earlier literature are instead polypoid areas of dysplasia arising in Barrett’s esophagus (Fig. 19.3) (see Chapter 24). In one series, dysplasia was polypoid in 2% of a series of Barrett’s patients with dysplasia.

Grossly, they resemble colonic adenomas, which led investigators to label them as adenomas. However, polypoid dysplasia arising in Barrett’s esophagus has clinical, pathologic, and molecular features similar to those of flat dysplasia and should not be considered benign lesions that can be excised without further follow-up. In one study, all adenoma-like polypoid areas of dysplasia in Barrett’s esophagus were associated with carcinoma. Because the term adenoma often implies a relatively benign natural history, we recommend that this term for dysplastic lesions be replaced with polypoid dysplasia arising in Barrett’s esophagus.^17,18

Spindle Cell Carcinoma

Spindle cell carcinoma (also referred to as carcinosarcoma, pseudosarcoma, polypoid carcinoma, sarcomatoid carcinoma, and spindle cell variant of squamous cell carcinoma) is a rare type of malignant tumor that represents 2% of all esophageal carcinomas (see Chapter 24).^19,20 Spindle cell carcinomas are bulky, intraluminal masses with exophytic growth that most often develop in the middle portion of the esophagus of middle-aged to elderly men (80%).^21,22 The most common presenting symptom is dysphagia, followed by weight loss and pain.²¹

Typical radiologic features include a dilated esophagus expanded by a polypoid, bulky mass with a smooth or scalloped margin. The classic radiologic appearance has been referred to as a cupola sign.^20,22 Histologic examination of these tumors reveals a biphasic growth pattern, showing areas of carcinoma (well, moderately, or poorly differentiated) and areas of malignant, undifferentiated spindle cells.

The epithelial origin of spindle cells has been confirmed by immunohistochemistry, electron micrographic studies, and genetic studies that have shown similar TP53 mutations in the sarcomatous and carcinomatous components.^1,23,24 The mesenchymal component may show liposarcoma, rhabdomyosarcoma, leiomyosarcoma, chondrosarcoma, or osteosarcoma differentiation. Many previously reported primary soft tissue sarcomas of the esophagus probably instead represent spindle cell carcinomas with a predominant undifferentiated soft tissue sarcoma component. The carcinomatous component is usually squamous, but rarely it can have adenocarcinomatous elements (Fig. 19.4).²⁵