Chapter 17: GIT- Esophageal Tumors

Question 1

Two morphologic variants comprise the majority of esophageal cancers:

Answer 1

• 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.

The potential
reasons for these increases are discussed below

Question 2

Adenocarcinoma of the esophagus typically arises in a background of what?

Answer 2

• Barrett esophagus and
• long-standing GERD.

Question 3

Risk of adenocarcinoma is greater in those with what?

Answer 3

documented dysplasia

and is further increased by:

• tobacco use,
• obesity, and
• prior radiation therapy. [9]

Question 4

Conversely, risk of adenocarcinoma is reduced by what?

Answer 4

• diets rich in fresh fruits and vegetables.
• Some Helicobacter pylori serotypes are associated with a decreased risk of adenocarcinoma, perhaps by causing gastric atrophy and reducing acid reflux.

Question 5

How does Helicobacter pylori serotypes are associated with a decreased risk of adenocarcinoma of the esophagus?

Answer 5

perhaps by causing gastric atrophy and reducing acid reflux.

Question 6

Esophageal adenocarcinoma occurs most frequently where?

Answer 6

• iCaucasians and
• shows a strong gender bias, being sevenfold more common in men.

However, the incidence varies 60-fold worldwide,

with 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.

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 half of all esophageal cancers in the United
States.

Question 7

What is the pathogenesis of Esophageal Adenocarcinoma?

Answer 7

Molecular studies suggest that the progression of Barrett esophagus to adenocarcinoma
occurs over an extended period through the stepwise acquisition of genetic and epigenetic
changes.

This model is supported by the observation that epithelial clones identified in
nondysplastic Barrett metaplasia persist and accumulate mutations during progression to
dysplasia and invasive carcinoma.

Chromosomal abnormalities and mutation or overexpression of p53 are present at early stages of esophageal adenocarcinoma.

Additional genetic changes
include amplification of c-ERB-B2, cyclin D1, and cyclin E genes; mutation of the retinoblastoma
tumor suppressor gene; and allelic loss of the cyclindependent kinase inhibitor p16/INK4a.

In
other instances p16/INK4a is epigenetically silenced by hypermethylation.

Increased epithelial
expression of tumor necrosis factor (TNF)- and nuclear factor (NF)-κB–dependent genes
suggests that inflammation may also contribute to neoplastic progression.

Question 8

Esophageal adenocarcinoma usually occurs where?

Answer 8

in the distal third of the esophagus and may invade the adjacent gastric cardia ( Fig. 17-9A ).

Question 9

What is the appearance of Esophageal Adenocarcinoma?

Answer 9

• Initially appearing as flat or raised patches in otherwise intact mucosa,
• large masses of 5 cm or more in diameter may develop.
• Alternatively, tumors may infiltrate diffusely or ulcerate and invade deeply.

Question 10

What is the appearance of Esophageal Adenocarcinoma microscopically?

Answer 10

• Microscopically, Barrett esophagus is frequently present adjacent to the tumor.
• Tumors most commonly produce mucin and form glands ( Fig. 17-10A ), 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).

Question 11

Answer 11

FIGURE 17-9 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

Question 12

Answer 12

FIGURE 17-10 Esophageal cancer.

• A, Esophageal adenocarcinoma organized into backto- back glands.
• B, Squamous cell carcinoma composed of nests of malignant cells that partially recapitulate the organization of squamous epithelium

Question 13

What are the clinical features of Esophageal Adenocarcinoma?

Answer 13

Although esophageal adenocarcinomas are occasionally discovered in evaluation of GERD or
surveillance of Barrett esophagus, they more commonly present with:

• pain or
• difficulty in swallowing,
• progressive weight loss,
• hematemesis,
• chest pain, or
• vomiting.

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%.

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

Question 14

Esophageal squamous cell carcinoma occurs in what age and gender?

Answer 14

In the United States, esophageal squamous cell carcinoma occurs in:

• adults over age 45 and
• affects males four times more frequently than females. [10]

Question 15

What are Risk factors of Esophageal Squamous carcinoma?

Answer 15

• alcohol and
• tobacco use,
• poverty, c
• austic esophageal injury,
• achalasia,
• tylosis,
• Plummer-Vinson syndrome,
• and frequent consumption of very hot beverages. [9]

Question 16

To what race is Esophageal Squamous Carcinoma more common?

Answer 16

It is nearly sixfold more common in African- Americans than Caucasians, a striking risk disparity that reflects differences in rates of alcohol and tobacco use as well as other poorly understood factors. [11]

Question 17

Previous radiation therapy to
the mediastinum also predisposes individuals to esophageal carcinoma, typically 10 or more
years after exposure

T or F

Answer 17

True

Question 18

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

Question 19

What is the etiology of Esophageal Squamous Carcinoma?

Answer 19

• 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.
• 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 funguscontaminated foods, must be considered.
• Human papillomavirus (HPV) infection has also been implicated in esophageal squamous cell carcinoma in high-risk areas but not in low-riskregions. [12]

Question 20

What is the molecular pathogenesis of Esophageal Squamous Carcinoma?

Answer 20

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.

Question 21

What is the difference between Esophageal Adenocarcinoma vs Sq Cell Carcinoma in relation to location?

Answer 21

In contrast to adenocarcinoma, half of squamous cell carcinomas occur in the middle third of the esophagus (see Fig. 17-9B ).

Question 22

Squamous cell carcinoma begins as what?

Answer 22

an in situ lesion termed squamous dysplasia (this lesion is referred to as intraepithelial
neoplasia or carcinoma in situ at other sites).

Question 23

What is the morphology of the ofEsophageal Squamous Carcinoma?

Answer 23

• Early lesions appear as small, gray-white, plaque-like thickenings.
• Over months to years they grow into tumor masses that may be polypoid or exophytic and protrude into and obstruct the lumen.
• Other tumors are either ulcerated or diffusely infiltrative lesions that spread within the esophageal wall and cause thickening, rigidity, and luminal narrowing. These may invade surrounding structures including the respiratory tree, causing pneumonia; the aorta, causing catastrophic exsanguination; or the mediastinum and pericardium.

Question 24

Most squamous cell carcinomas are what type of dirrentiation?

Answer 24

moderately to well-differentiated (see Fig. 17-10B ).

Question 25

What are the less common histologic variants of Esophageal Squamous Carcinoma?

Answer 25

Less common histologic variants include:

• verrucous squamous cell carcinoma,
• spindle cellvcarcinoma, and
• basaloid squamous cell carcinoma.

Question 26

Regardly of histoly in Esophageal Sq Cell Carcinoma what is the presentation of the tumoat diagnosis ?

Answer 26

Regardless of histology, symptomatic

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

The rich submucosal lymphatic network promotes circumferential and longitudinal spread, and intramural tumor nodules may be present several centimeters away from the principal mass.

The sites of lymph node metastases vary with tumor location:

• cancers in the upper third of the esophagus favor cervical lymph nodes;
• those in the middle third favor mediastinal, paratracheal, and tracheobronchial nodes; and
• those in the lower third spread to gastric and celiac nodes.

Question 27

What is the clinical course of Esophageal Sq Cell Carcinoma?

Answer 27

insidious

Question 28

What are the signs and symptoms of Esophageal Sq Cell Carcinoma?

Answer 28

• ultimately produces dysphagia,
• odynophagia (pain on swallowing),
• and obstruction.

Patients subconsciously adjust

to the progressively increasing obstruction by altering their diet from solid to liquid foods.

• *Extreme weight loss and debilitation result from both impaired nutrition and effects of the tumor
  itself. **

Hemorrhage and sepsis may accompany tumor ulceration.

Occasionally, the first
symptoms are caused by aspiration of food via a tracheoesophageal fistula.

Question 29

What is the prognosis of Esophageal Sq Cell Carcinoma?

Answer 29

Increased prevalence of endoscopic screening has led to earlier detection of esophageal
squamous cell carcinoma.

This is critical, because 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%.

Question 30

Other malignancies of the esophagus include what?

Answer 30

• unusual forms of adenocarcinoma,
• undifferentiated carcinoma,
• carcinoid tumor,
• melanoma,
• lymphoma, and
• sarcoma.

Question 31

Benign tumors of the esophagus are generally oriigns of what?

Answer 31

mesenchymal in origin and arise within the

esophageal wall.

Question 32

What are the other uncommon tumors of the esophagus?

Answer 32

• Tumors of smooth muscle origin
  
  • leiomyomas, are most common;
  • fibromas,
  • lipomas,
  • hemangiomas,
  • neurofibromas, and
  • lymphangiomas also occur.
• Some benign tumors take the form of mucosal polyps. These are usually composed of fibrous and vascular tissue, or adipose tissue, and are known as fibrovascular polyps or pedunculated lipomas, respectively.
• Squamous papillomas are sessile lesions with a central core of connective tissue and a hyperplastic papilliform squamous mucosa.
• Uncommonly, papillomas are associated with HPV infection, in which case the term condyloma applies.
• In rare instances a mass of inflamed granulation tissue, growing either as an inflammatory polyp or an infiltrative mass in the wall of the esophagus, may resemble a malignant lesion. These benign lesions are called inflammatory pseudotumors.