Esophageal squamous cell carcinoma (ESCC) is the esophageal cancer that arises from the squamous epithelium lining the esophagus. It is the most common esophageal cancer worldwide, although its incidence has fallen sharply in Western countries during recent decades while adenocarcinoma has risen.
What causes it
The risk factors differ between industrialised and developing countries. In industrialised countries the two strongest are cigarette smoking and excess alcohol use, and they reinforce each other. In developing countries, and in the high-prevalence areas, nutritional and micronutrient deficiencies appear to matter more: deficiencies of vitamin A, C and E, folate, zinc and selenium have all been implicated. Selenium is the best studied of these, and a study found that selenium supplementation reduced the risk of death from ESCC by 17% in people younger than 55 years. Diets rich in vegetables and fruit appear protective — a study found that more than 50 g/day of vegetables or fruit reduced the risk of esophageal cancer by 31% and 22% respectively — and some studies also point to drinking very hot beverages, which can cause thermal injury to the esophageal epithelium.
Long-standing motor disorders of the esophagus, especially achalasia, carry an increased risk of both ESCC and EAC. The risk is about 16-fold during the 1st to 24th year after the diagnosis of achalasia, and it is greater in men. The likely mechanism is stasis of food in the esophagus and the chronic inflammation it produces.
By contrast, obesity and frequent use of NSAIDs seem to be protective against ESCC.
How it develops
ESCC is thought to begin with hyper-proliferative epithelial cells, which give rise to low-grade and then intermediate dysplasia, and finally to the high-grade dysplastic cells that can become cancer.
Several genetic changes carry clinical relevance. Overexpression of cyclin D1, a protein that drives cells through the cell cycle, is associated with a poorer prognosis. Higher expression of VEGF is also associated with a worse prognosis, and amplification of FGFR1 appears to be a negative prognostic factor. Lower p53 and higher p21 or p16 levels are associated with a better prognosis.
Verrucous carcinoma
Verrucous carcinoma of the esophagus is a rare variant of ESCC, with only 30 reported cases, that mostly occurs in middle-aged men. Endoscopically it appears as a papillary or warty lesion, and histologically it shows well-differentiated epithelial cells with hyperkeratosis and only a small column of neoplastic cells.