Squamous cell carcinoma and adenocarcinoma are the two main types of esophageal cancer. Squamous cell carcinoma makes up about 90% of cases and is usually located in the upper two-thirds of the esophagus. Adenocarcinoma is more common in Western countries and usually arises from Barrett's esophagus in the lower third. Risk factors include tobacco and alcohol use for squamous cell carcinoma and obesity and gastroesophageal reflux for adenocarcinoma. Both types often present with dysphagia and have poor prognosis due to advanced stage at diagnosis.

1. Carcinoma of Esophagus
Lecture 5

2. Carcinoma
• Malignant neoplasms of epithelial cell origin,
derived from any of the three germ layers,
are called carcinomas.
• Most esophageal tumors are
malignant, fewer than 1% are
benign.

3. Carcinoma of esophagus
Two morphologic variants :
Adenocarcinoma and
Squamous cell carcinoma.
• 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.

4. 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.

5. • Barrett esophagus is the only recognized precursor
of esophageal adenocarcinoma. The development
of AC from BE is a multistep
process that unfolds
many years.

6. The degree of dysplasia is the strongest
predictor of the progression to cancer.
Individuals with low –grade dysplasia have
very low rates of progression AC but the
progression to cancer may be 10% or more
per year in individuals with high grade
dysplasia.

7. •Overall, the risk for
developing AC varies from
30-fold to more than
100-fold above normal.

8. • In BE tissue there is increased cell
proliferation, and chromosomal
abnormalities become apparent in high-
grade dysplasia. Mutations in p53
progressively accumulate , and aneuploidy is
commonly found.

9. • Additional genetic abnormalities, such as
alterations in HER-2/NEU and beta catenin,
are present in the carcinomas but there are
no specific markers that precisely identify the
transition from high-grade dysplasia to cancer.

10. Risk of adenocarcinoma
Barrett esophagu
Age- over 60
Sex- more common in men
documented dysplasia
tobacco use,
obesity,
prior radiation therapy.
Obesity
Whites

11. Risk of adenocarcinoma is reduced by
• diets rich in fresh fruits and vegetables.
According to the National Cancer Institute,
"diets high in cruciferous (cabbage,
cauliflower,) and green and yellow vegetables
and fruits are associated with a decreased risk
of esophageal cancer.

12. • Moderate coffee consumption is associated with a
decreased risk.
• According to one Italian study eating pizza more than once
a week .
• Some Helicobacter pylori serotypes are associated
with a decreased risk of adenocarcinoma, perhaps by
causing gastric atrophy and reducing acid reflux (reduced
parietal cells).
• NSAID, particularly aspirin.

13. Epidemiology
• Esophageal adenocarcinoma occurs most
frequently in Caucasians and sevenfold more
common in men.
• Rates being highest in certain developed Western
countries, including the United States, the United
Kingdom, Canada, Australia, the Netherlands, and
Brazil and
• Lowest in Korea, Thailand, Japan, and Ecuador.

14. • In countries where esophageal adenocarcinoma
is more common, the incidence has
increased markedly since 1970, more
rapidly than almost any other cancer. As a
result, esophageal adenocarcinoma, which
represented less than 5% of esophageal cancers
before 1970, now accounts for halfof all
esophageal cancers in the United States.

15. 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.

16. • Microscopically, 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 (similar to those seen
in diffuse gastric cancers) or,
• in rare cases, small poorly differentiated cells
(similar to small-cell carcinoma of the lung).

17. Clinical Features.
Dysphagia,
Odynophagia
Obstruction
progressive weight loss,
Anorexia,
Fatigue,
Weakness,
hematemesis,
chest pain,
Cough

18. • If the disease has spread elsewhere, this
may lead to symptoms related to this:
liver metastasis could cause jaundice and
ascites,
• lung metastasis could cause shortness of
breath, pleural effusions, etc.

19. Diagnosis
• Barium swallow
• CT
• PET
• Endoscopic ultrasound
• Endoscopy
• Biopsy

21. Treatment
• The treatment is determined by the cellular type
of cancer (adenocarcinoma or squamous cell
carcinoma vs other types), the stage of the
disease, the general condition of the patient and
other diseases present. On the whole, adequate
nutrition needs to be assured, and adequate
dental care is vital

22. Treatment
• Surveillance
• Palliation:
• Self-expandable metallic stents
• Endoscopic therapy
• EMR
• Mucosal ablation,
• Nd-YAG laser
• Argon plasma coagulation
• Surgery
• Chemotherapy
• Radiation

23. Follow-up
• Patients are followed up frequently after a
treatment regimen has been completed.
Frequently, other treatments are necessary to
improve symptoms and maximize nutrition.

24. 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.

25. Tylosis with esophageal cancer
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. This is the only genetic syndrome
known to predispose to squamous cell carcinoma of the
esophagus. The risk of developing esophageal cancer is
95% by age 70. The syndrome is inherited in an autosomal
dominant manner. The gene has been mapped to
chromosome 17q25 but has not been identified. The
syndrome is also called nonepidermolytic palmoplantar
keratoderma. The association of tylosis palmoplantaris with
esophageal cancer is called Howel-Evans syndrome.

26. Squamous cell carcinoma
Squamous cell carcinoma
a cancer in which the tumor
cells resemble stratified
squamous epithelium.
90% of esophageal cancer.

27. •Lecture 6

28. Risk factors of SCC of Esophagus
I. Esophageal disorders:
• Long standing esophagitis
• Achalasia
• Plummer-Vinson Syndrome

29. 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.

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

31. 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.

32. V. Age. Over 45
VI. Sex. males four times more frequently than
females.
VII. Poverty
VII. Race- more common in blacks (6 times)
IX. Previous radiation therapy to the
mediastinum.
X. HPV
XI. Coeliac disease

33. • 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.

34. 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.

35. • 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.

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

37. Morphology
•Epithelial dysplasia
•Carcinoma in situ
•Invasive cancer

38. • 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:

39. • 1. Polypoid exophytic masses that protrude
into the lumen.
• 2. Necrotizing cancerous ulceration that extend
deeply and sometimes erode into the respiratory
tree (Pneumonia), aorta (exsanguination)( or elsewhere.
• 3. Diffuse infiltrative neoplasm that cause
thickening and rigidity of the wall and narrowing of
the lumen.

40. • SCC arise about:
• 20% in the cervical& upper thoracic esophagus
50% in the middle third
• 30% in the lower third

41. Regardless of histology,
symptomatic tumors are generally
very large at diagnosis and
have already invaded the esophageal
wall.

42. Clinical Features
• Dysphagia
• Odynophagia
• Obstruction
• Weight loss
• Hemorrhage
• Sepsis

43. 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%.

44. 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.