11: Pathology of Esophageal Cancer

Introduction

Esophageal cancer is a gastrointestinal malignancy that encompasses a range of pathologic entities. Squamous cell carcinomas constitute at least 90% of all cancers worldwide.¹ Adenocarcinoma is the second most common type of cancer. Other types, such as small cell carcinoma and malignant melanoma are rare. The incidence of esophageal adenocarcinoma has increased in the United States from 0.5 to 0.9/100,000 in the 1970s to 3.2 to 4.0/100,000 in the 1980s and 1990s. Although esophageal adenocarcinoma accounted for about 16% of all esophageal cancers among White men in the United States in the mid-1970s, by the late 1990s, this number approached 50%. This increase has been seen across all socioeconomic groups² but has been most pronounced in affluent populations.^3-7 Over the same period of time, there has been a decline in both esophageal squamous cell carcinomas and adenocarcinomas of the distal stomach.^8,9 Barrett esophagus is a metaplastic condition in which normal squamous mucosa of the distal esophagus is transformed into intestinalized columnar epithelium. Barrett esophagus is the established precursor lesion for nearly all esophageal adenocarcinomas.

Squamous Cell Carcinoma and Variants

Squamous cell carcinoma of the esophagus is relatively infrequent in much of Western Europe and North America, but is a major disease for a large proportion of the world's population. About 80% of cases occur within developing countries.¹⁰ In the United States, squamous cell carcinoma continues to represent the most common type of esophageal cancer in African Americans. The highest rates are found in the Asian esophageal cancer belt region, which extends from Turkey to Iran, Iraq and Kazakhstan to Northern China. Squamous cell carcinoma is the most prevalent type of esophageal cancer in this region. However, even within this region, there are sharp gradients of incidence between regions that lie only a few hundred miles apart. In Europe, where the incidence of squamous cell carcinoma is low, pockets of high incidence occur, such as in Normandy and Brittany.¹¹

Etiology and Associations

The etiology of squamous cell carcinoma is most likely multifactorial. Epidemiological studies have provided evidence that causative agents may act synergistically and may differ between geographical regions and between high-risk versus low-risk areas.

Cigarette smoking and alcohol consumption have both been associated with an increased predisposition for esophageal cancer, and the association is stronger with squamous cell carcinoma compared to adenocarcinoma. Smokers are at three to seven times greater risk of developing squamous cell carcinoma compared with the general population.^12-15 There is a statistically higher incidence of esophageal carcinomas among patients who smoke or chew tobacco, and this is equally true for pipe users, cigar, and cigarette smokers.¹⁶ Among combined drinkers and smokers, the risk rises considerably with increased alcohol consumption, compared to increasing tobacco consumption.¹⁵ In the United Kingdom, variations in the rate of esophageal cancer have closely ...