Carcinoma of Esophagus

Lecture 5

Esophageal Tumors

Carcinoma is a malignant neoplasm of epithelial cell origin.

Carcinoma- Malignant epithelial tumor

Carcinoma (from the Greek karkinos, or "crab", and -oma, "growth")

Esophageal tumors• Most (> 99%)esophageal tumors are MALIGNANT,

fewer than 1% are benign. • Benign tumors: Squamous cell papilloma,

Adenoma, leiomyoma, lipoma, fibroma, neurofibroma, rhabdomyoma, lymphangioma & hemangioma.

• Malignant tumors: are carcinomas because sarcomas are extremely rare.

Carcinoma of esophagusTwo morphologic variants :

I. Adenocarcinoma <10%

II. Squamous cell carcinoma

>90% scc

• Worldwide, squamous cell carcinoma is more common, but in the United States and other Western countries adenocarcinoma is on the rise.

• A general rule of thumb is that a cancer in the upper two-thirds is a squamous cell carcinoma and one in the lower one-third is an adenocarcinoma.

ADENOCARCINOMA

Adenocarcinoma denotes a lesion in which the neoplastic epithelial cells grow in glandular patterns.

Adenocarcinoma of the esophagus typically arises in a background of Barrett esophagus and long-standing GERD.

Strong association with Barrett Esophagus

Risk of adenocarcinoma

Barrett esophagusAge- over 60 (6th -7th decades)

Sex- more common in MEN (7times)

documented dysplasia tobacco use, obesity, prior radiation therapy.ObesityWhites Risk is reduced by------?

Cruciferous

Vegetables

Fruit

H Pylori

NSAID(Aspirin)CoffeePizza

Barrett esophagus is the only recognized precursor of esophageal adenocarcinoma.

The degree of DYSPLASIA is the strongest predictor of the progression to cancer.

Dysplasia---Carcinoma in situ--Invasive Carcinoma

Morphology Esophageal adenocarcinoma usually occurs in the

distal third of the esophagus and may invade the adjacent gastric cardia. Initially appearing as

flat or raised patches in otherwise intact

mucosa, large nodular masses of 5 cm or more in diameter may develop. Alternatively, tumors may infiltrate diffusely or ulcerate and invade deeply.

Nodular, elevated mass in the lower esophagus

Microscopy of Esophageal Adenocarcinoma

• Barrett esophagus is frequently present adjacent to the tumor.

• Tumors most commonly produce mucin and form glands, often with intestinal-type morphology.

• less frequently tumors are composed of diffusely infiltrative signet-ring cells or,

• in rare cases, small poorly differentiated cells.

Clinical Features. Dysphagia,Odynophagia ( severe pain on swallowing)

Obstruction progressive weight loss, Anorexia,Fatigue,Weakness,hematemesis, chest pain, Cough vomiting.

Diagnosis• Barium swallow• CT• PET• Endoscopic ultrasound• Endoscopy

•Biopsy

Prognosis-Poor-dismal• By the time symptoms appear, the tumor has

usually spread to submucosal lymphatic vessels. As a result of the advanced stage at diagnosis, overall 5-year survival is less than 25%(15%) with most patients dying within the first year of diagnosis.

• In contrast, 5-year survival approximates 80% in the few patients with adenocarcinoma limited to the mucosa or submucosa.

Squamous Cell Carcinoma

SQUAMOUS CELL CARCINOMA

ESOPHAGEAL

Squamous (Epidermoid) cell carcinoma

a cancer in which the tumor cells resemble stratified squamous epithelium.

90% of esophageal cancer.

Risk factors of SCC of Esophagus

I. Esophageal disorders:

• Long standing esophagitis• Achalasia• Plummer-Vinson Syndrome

•Esophageal disorders•Life style or Bad habits•Dietary factors•Genetic predispositionAge, Sex, Poverty, Radiation, Race, HPV, Celiac disease.

II. Life style:

•Alcohol•Tobacco• An important contributing variable is retarded

passage of food through the esophagus, prolonging mucosal exposure to potential carcinogens such

as those contained in tobacco and alcohol beverages.• There is a well-defined predisposing role for chronic

esophagitis, which is often the consequences of alcohol and tobacco use.

III. Dietary Factors• Def. of vit.• Def. of trace metals• Fungal contamination of food stuffs• High content of nitrites/nitrosamines• Frequent consumption of very hot beverages.

IV. Genetic predisposition:

•Tylosis• Abnormalities affecting the p16/INK4

tumor suppressor gene and the epidermal growth factor receptors are frequently present in SCC of the

esophagus. Mutation in p53 in 50% of these tumors.

A genetic disorder characterized by thickening (hyperkeratosis) of the palms and soles, white patches in the mouth (oral leukoplakia), and a very high risk of esophageal cancer.

Nonepidermolytic palmoplantar keratoderma.

Howel-Evans syndrome Autosomal dominant

V. Age. Over 45

VI. Sex. Males 4 times more frequently than

females.

VII. Poverty

VII. Race- more common in BLACKS (6 times)

IX. Previous radiation therapy to the mediastinum.

X. HPVXI. Coeliac disease

• Esophageal squamous cell carcinoma incidence varies up to 180-fold between and within

countries, being more common in rural and

underdeveloped areas.

• The regions with highest incidences are

•Iran, central China, Hong Kong,

Brazil, and South Africa.

Pathogenesis

The majority of esophageal squamous cell carcinomas in Europe and the United States are at least partially attributable to the use of

ALCOHOL AND TOBACCO, which synergize to increase risk.

Pathogenesis of SCC• However, esophageal squamous cell carcinoma is

also common in some regions where alcohol and tobacco use is uncommon. Thus,

• nutritional deficiencies, as well as • polycyclic hydrocarbons, nitrosamines, and • other mutagenic compounds, such as those found

in fungus-contaminated foods, must be considered.

Pathogenesis of SCC

• Human papillomavirus (HPV) infection has also been implicated in esophageal squamous cell carcinoma in high-risk areas but not in low-risk regions.

Pathogenesis of SCC

• The molecular pathogenesis of esophageal squamous cell carcinoma remains

incompletely defined, but loss of several tumor suppressor genes, including p53 and p16/INK4a, is involved.

Clinical Features

• Dysphagia• Odynophagia• Obstruction• Weight loss• Hemorrhage• Sepsis

Morphology• Squamous cell carcinoma begins as an in situ lesion termed

squamous dysplasia.

•Epithelial dysplasia •Carcinoma in situ•Invasive cancer

Morphology• Early overt lesions appears as: small, gray-white,

plaquelike thickenings or elevation of the mucosa..

In months to years these lesions become tumorous, taking one of three forms:

1. Polypoid fungating type (60%): The most common type. Cauliflower-like friable mass protruding into the lumen.

• 2. Ulcerating type (25%): A necrotic ulcer with everted edges that extend deeply and sometimes erode into the respiratory tree (Pneumonia), aorta (exsanguination)( or elsewhere.

• 3. Diffuse infiltrative type (15%): appears as annular, stenosing narrowing of the lumen due to infiltration into the wall of esophagus.

•SCC arise about (locations):• 20% in the cervical& upper thoracic esophagus

50% in the middle third• 30% in the lower third

Morphology• Most squamous cell carcinomas are moderately to

well-differentiated.

Intercellular bridges, Keratinization &Epithelial pearls are commonly seen.

Epithelial nest, Epithelial pearl, Squamous pearlKaratin pearll

Regardless of histology,

symptomatic tumors are generally

very large at diagnosis and have already invaded the esophageal wall.

• Less common histologic variants include• verrucous squamous cell carcinoma,• spindle cell carcinoma, and

• basaloid squamous cell carcinoma

Prognosis- dismal• 5-year survival rates are 75% in individuals with

superficial esophageal carcinoma but much lower in patients with more advanced tumors.

• Lymph node metastases, which are common, are associated with poor prognosis.

• The overall 5-year survival remains a dismal 9%.

Esophageal cancer. A, Adenocarcinoma usually occurs distally and, as in this case, often involves the gastric cardia. B, Squamous cell carcinoma is most

frequently found in the mid-esophagus, where it commonly causes strictures.

Normal Esophagus (Squamous epithelium)

in Barrett's esophagus , the squamous epithelia are replaced by intestinalized metaplastic columnar

epithelia

Barrett's adenocarcinoma with moderate to poor differentiation. Atypic tumor cells form quite irregular tubules and some form solid cord

Esophageal adenocarcinoma organized into back-to-back glands

Squamous cell carcinoma composed of nests of malignant cells that partially recapitulate the organization of squamous

epithelium