The esophagus

Benign tumors and tumor-like lesions

Leiomyomas are the most common benign non-epithelial tumors of the esophagus and are of smooth muscle origin (Postlethwait, 1983; Mutrie et al., 2005). Generally, they occur as a solitary 20–50 mm submucosal mass lesion at the lower one third of the esophagus, bulging into the lumen as a sessile intramural mass or as pedunculated polyps (Geboes, 2002). They may occur in up to 10% of adult esophagi but rarely attain a size to produce symptoms. If they are large they may ulcerate and produce pressure symptoms. Histologically, they are composed of interlacing smooth muscle fascicles with variable fibrosis and appear as a white whorled mass on gross examination (Mutrie et al., 2005).

Squamous cell carcinoma accounts for most esophageal cancers. It occurs in adults over the age of 50 with a male predominance; the male:female ratio is 4:1. There are wide geographical variations in its incidence. Areas of high rate of incidence include Puerto Rico, South Africa, Central Asia, Northern China and Eastern Europe. Low risk areas include most of Western Europe and North America (Crawford, 1999). The major risk factors are alcohol and tobacco (Bahmanyar and Ye, 2006; Hashibe et al., 2007). Human papilloma virus (HPV) has also been implicated as a probable etiological factor in the development of squamous cell carcinoma of the esophagus (Woo and Yoon 1996; Matsha et al., 2007). Dietary and environmental factors have been proposed to increase the risk and nutritional deficiencies act as promoters and potentiators of the tumorigenic effects of environmental carcinogens (Bahmanyar and Ye, 2006). Broad spectrum p53 gene point mutations present in these tumors are related to the effects of methylating nitroso compounds in the diet and in tobacco smoke (Meltzer, 1996; Mandard et al., 1997). Mutations in p16 gene and allelic loss involving other chromosomes are prevalent in these cancers as well, in keeping with the step-wise acquisition and accumulation of genetic alterations which ultimately give rise to cancer (Meltzer, 1996; Fujiki et al., 2002).

Five-year survival with superficial carcinoma is 75% compared with less than 25% in patients with advanced disease (Fletcher et al., 2000). Local and distant recurrence after surgery is common. The important prognostic features in a resection specimen are tumor size, depth of invasion, presence of lymph node metastasis and status of resection margins (Edwards et al., 1989; Lam et al., 1996).

The vast majority of primary esophageal adenocarcinomas arise in the lower esophagus in a background of columnar metaplasia, also known as Barrett’s esophagus, and hence are associated with chronic gastro-esophageal reflux (Haggitt, 1994; Williams et al., 2006; Sayana et al., 2007; De Jonge et al., 2007). Rare adenocarcinomas arising from ectopic gastric mucosa are distinguished by their location in the upper esophagus (Christensen and Sternberg, 1987). Adenocarcinoma arising in the setting of Barrett’s esophagus occurs in patients over 40 years with a median age in their 50s with an increasing incidence in the Western population (Williams et al., 2006; Sayana et al., 2007). Although the exact pathogenesis is unclear, genetic alterations in this disease are well documented.

Barrett’s esophagus is a condition in which the normal stratified squamous epithelium is replaced by metaplastic columnar epithelium that predisposes to the development of esophageal adenocarcinoma (Figures 9.2, 9.3, see color insert) and Figure 9.4 (Haggitt, 1994). Neoplastic progression in Barrett’s esophagus occurs by a multistep process associated with genomic instability and the development of aneuploid cell populations (Ramel et al., 1992). Molecular and immunohistochemical studies have suggested that mutations of the p53 gene accompanied by chromosome 17p allelic loss play an important role in the pathogenesis of the tumor (Fitzgerald, 2005; Sayana et al., 2007). p53 protein over-expression and allelic deletions on chromosome 17p have been shown to be present in some Barrett’s adenocarcinomas (Ramel et al., 1992).

Endoscopically, early cancers appear as flat lesions, while advanced cancers present as large ulcerating, fungating, polypoid or diffusely infiltrating masses (Geboes, 2002). Microscopically, these are mucin-producing glandular tumors with a tubular or papillary appearance exhibiting irregular invasive intestinal type glands lined by cytologically malignant cells (Fletcher et al., 2000). Since most cases arise in a background of Barrett’s esophagus, high grade dysplasia in a background of Barrett’s type metaplastic glandular epithelium is common in the adjacent mucosa (Williams et al., 2006; Sayana et al., 2007).