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M1b Other distant metastasis

Stage IVB

Any T

Any N

M1b

1 {1, 66}. This classification applies only to carcinomas.

2A help desk for specific questions about the TNM classification is available at http://tnm.uicc.org.

Squamous cell carcinoma of the oesophagus

H.E. Gabbert T. Shimoda P. Hainaut

Y. Nakamura J.K. Field H. Inoue

Definition

Squamous cell carcinoma (SCC) of the oesophagus is a malignant epithelial tumour with squamous cell differentiation, microscopically characterised by keratinocyte-like cells with intercellular bridges and/or keratinization.

ICD-O Code 8070/3

Epidemiology

Squamous cell carcinoma of the oesophagus shows great geographical diversity in incidence, mortality and sex ratio. In Western countries, the age-standardized annual incidence in most areas does not exceed 5 per 100,000 population in males and 1 in females. There are, however, several well-defined high-risk areas, e.g. Normandy and Calvados in North-West France, and Northern Italy where incidence may be as high as 30 per 100,000 population in males and 2 in females {1020, 1331}. This type of cancer is much more frequent in Eastern countries and in many developing countries. Regions with very high incidence rates have been identified in Iran, Central China, South Africa and Southern Brazil. In the city of Zhengzhou, capital of Henan province in China, the mortality rate exceeds 100 per 100,000 population in males and 50 in females {1116, 2191}.

In both high-risk and low-risk regions, this cancer is exceedingly rare before the age of 30 and the median age is around 65 in both males and females. Recent changes in the distribution pattern in France indicate that the rate of SCC has increased steadily in low-risk areas, particularly among females, whereas there may be a slight decrease in high-risk areas. In the United States, a search in hospitalisation records of military veterans indicates that SCC is 2-3 times more frequent among blacks than among Asians, Whites or Native Americans {453}.

Aetiology

Tobacco and alcohol. In Western countries, nearly 90% of the risk of SCC can be attributed to tobacco and alcohol. Each of these factors influences the risk of oesophageal cancer in a different way. With regard to the consumption of tobacco, a moderate intake during a long period carries a higher risk than a high intake during a shorter period, whereas the reverse is true for alcohol. Both factors combined show a multiplicative effect, even at low alcohol intake. In high-risk areas of North-West France and Northern Italy, local drinking customs may partially explain the excess incidence of SCC {523, 1020}. In Japanese alcoholics, a polymorphism in ALDH2, the gene encoding aldehyde dehydrogenase 2, has been shown to be significantly associated with several cancers of the upper digestive tract, including squamous cell cancer. This observation suggests a role for acetaldehyde, one of the main carcinogenic metabolites of alcohol in the development of oesophageal carcinoma {2177}.

Nutrition. Risk factors other than tobacco and alcohol play significant roles in other regions of the world. In high-risk areas of China, a deficiency in certain trace elements and the consumption of pickled or mouldy foods (which are potential sources of nitrosamines) have been suggested.

Hot beverages. Worldwide, one of the most common risk factors appears to be the consumption of burning-hot beverages (such as Mate tea in South America) which cause thermal injury leading to chronic oesophagitis and then to precan-cerous lesions {1116, 2191, 387}. HPV. Conflicting reports have proposed a role for infectious agents, including human papillomavirus (HPV) infection. Although HPV DNA is consistently detected in 20 to 40% of SCC in high-risk areas of China, it is generally absent in the cancers arising in Western countries {954, 679}.

Fig. 1.01 Worldwide annual incidence (per 100,000) of oesophageal cancer in Fig. 1.02 Squamous cell carcinoma of the oesophagus. Age-standardized incidence males. Numbers on the map indicate regional average values. rates per 100,000 and proportions (%) due to alcohol and tobacco (dark-blue).

Fig. 1.03 Macroscopic images of squamous cell carcinoma (SCC) of the oesophagus. A Flat superficial type. B Lugol iodine staining of the specimen illustrated in A. C Polypoid SCC. D Longitudinal sections of carcinoma illustrated in C. E Deeply invasive polypoid SCC. F Longitudinal sections of carcinoma illustrated in E.

Fig. 1.03 Macroscopic images of squamous cell carcinoma (SCC) of the oesophagus. A Flat superficial type. B Lugol iodine staining of the specimen illustrated in A. C Polypoid SCC. D Longitudinal sections of carcinoma illustrated in C. E Deeply invasive polypoid SCC. F Longitudinal sections of carcinoma illustrated in E.

Associations between achalasia, Plum-mer-Vinson syndrome, coeliac disease and tylosis (focal nonepidermolytic palmoplanar keratoderma) with oeso-phageal cancer have also been described.

Localization

Oesophageal SCC is located predominantly in the middle and the lower third of the oesophagus, only 10-15% being situated in the upper third {1055}.

Clinical features

Symptoms and signs

The most common symptoms of advanced oesophageal cancer are dys-phagia, weight loss, retrosternal or epigastric pain, and regurgitation caused by narrowing of the oesophageal lumen by tumour growth {606}. Superficial SCC usually has no specific symptoms but sometimes causes a tingling sensation, and is, therefore, often detected incidentally during upper gastrointestinal endoscopy {464, 1874}.

Endoscopy and vital staining

Superficial oesophageal cancer is commonly observed as a slight elevation or shallow depression on the mucosal surface, which is a minor morphological change compared to that of advanced cancer. Macroscopically, three types can be distinguished: flat, polypoid and ulcerated. Chromoendoscopy utilizing toluidine blue or Lugol iodine spray may be of value {465, 481}. Toluidine blue, a metachromat-ic stain from the thiazine group, has a particular affinity for RNA and DNA, and stains areas that are richer in nuclei than the normal mucosa. Lugol solution reacts specifically with glycogen in the normal squamous epithelium, whereas precan-cerous and cancerous lesions, but also inflamed areas and gastric heterotopia, are not stained. However, the superficial extension of carcinomas confined to the mucosa can not be clearly recognized by simple endoscopy.

Endoscopic ultrasonography

Endoscopic ultrasonography is used to evaluate both depth of tumour infiltration and para-oesophageal lymph node involvement in early and advanced stages of the disease {1509, 1935}. For the evaluation of the depth of infiltration, high frequency endoscopic ultrasono-graphy may be used {1302}. In general,

Fig. 1.04 Catheter probe ultrasonograph of a squamous cell carcinoma, presenting as hypoechoic lesion (arrow).

oesophageal carcinoma presents on endosonography as a circumscribed or diffuse wall thickening with a predominantly echo-poor or echo-inhomoge-neous pattern. As a result of tumour penetration through the wall and into surrounding structures, the endosono-graphic wall layers are destroyed.

Computed tomography (CT) and magnetic resonance imaging (MRI)

In advanced carcinomas, CT and MRI give information on local and systemic spread of SCC. Tumour growth is characterized as swelling of the oesophageal wall, with or without direct invasion to surrounding organs {1518}. Cervical, abdominal and mediastinal node enlargement is recorded. Three-dimensional CT or MRI images may be presented as virtual endoscopy, effectively demonstrating T2-T4 lesions, but not T1 lesions.

Macroscopy

The gross appearance varies according to whether it is detected in an early or an advanced stage of the disease. Among early SCC, polypoid, plaque-like, depressed and occult lesions have been described {161, 2183}. For the macroscopic classification of advanced oeso-phageal SCC, Ming {1236} has proposed three major patterns: fungating, ulcerative, and infiltrating. The fungating pattern is characterized by a predominantly exophytic growth, whereas in the ulcerative pattern, the tumour growth is predominantly intramural, with a central ulceration and elevated ulcer edges. The infiltrative pattern, which is the least common one, also shows a predominantly intramural growth, but causes only a small mucosal defect. Similar types of macroscopic growth patterns have been defined in the classification of the Japanese Society for Esophageal Diseases {58}.

Tumour spread and staging

For the staging of SCC, the TNM system (tumour, node, metastasis) established by the International Union Against Cancer (UICC) is the most widely used system. Its usefulness in the planning of treatment and in the prediction of prognosis has been validated {1104, 895, 66, 1, 772}.

Superficial oesophageal carcinoma.

When the tumour is confined to the mucosa or the submucosa, the term superficial oesophageal carcinoma is used irrespective of the presence of regional lymph node metastases {58, 161}. In China and in Japan, the term early oesophageal carcinoma is often used defining a carcinoma that invades no deeper than the submucosa but has not metastasised {609}. In several studies from Japan, superficial carcinomas accounted for 10-20% of all resected carcinomas, whereas in Western countries

Fig. 1.05 A Endoscopic view of a superficial squa-mous cell carcinoma presenting as a large nodule (CA) in a zone of erosion. B After spraying of 2% iodine solution, the superficial extent of the tumour becomes visible as unstained light yellow area (CA, arrows).

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