Gi Pathology, Lecture 1: Esophagus

Front 1

CONGENITAL ANOMALIES AND MALFORMATIONS

Back 1

Fistulas
Webs and rings and diverticula

Front 2

CONGENITAL ANOMALIES AND MALFORMATIONS
Fistulas

Back 2

Three types of ________________s are recognized. In the most common form (approximately 90%), the upper part of the esophagus ends in a blind pouch, whereas the inferior portion connects to the trachea (Fig. 1). The inability to swallow leads to regurgitation and occasionally to aspiration. In the fetal stage it can result in hydramnios. Aspiration is an unavoidable complication of the second type of ________________ in which the upper segment of the esophagus drains directly into the trachea and the lower segment constitutes the blind sack (Figure 2). The least common type is the H type ________________. A continuous esophagus connects laterally to the trachea (fig 3). Surgical correction is necessary for almost all ________________s.

Front 3

CONGENITAL ANOMALIES AND MALFORMATIONS
Webs and rings and diverticula

Back 3

Esophageal webs
Schatzki’s ring
Diverticula

Front 4

Esophageal webs

Back 4

thin mucosal membranes that reduce the diameter of the esophageal lumen. They can be single or multiple and affect any part of the esophagus. In the Plummer-Vinson (or Patterson-Kelly) syndrome, _________ are associated with mucosal lesions and iron deficiency anemia. Approximately 90% occur in women and there is an increased risk of esophageal carcinoma. The prevalence of this disease has declined significantly in recent years, likely due to improved diet.

Front 5

Schatzki’s ring

Back 5

a discrete circumferential constriction of the distal esophagus that occurs at the squamo-columnar junction. The rings, which are of unknown etiology, can be seen in up to 10% of radiological studies. However, only a minority of these are symptomatic. Histologically, the lesion consists of fibrous tissue without inflammation. It is covered by squamous epithelium proximally, and by glandular mucosa distally (squamo-columnar junction).

Front 6

Diverticula
Three distinctive forms of diverticula occur in the esophagus at the upper third, mid-esophagus and immediately above the diaphragm (epiphrenic), respectively:

Back 6

1. Zenker’s diverticulum
2. Traction diverticulum:
3. Epiphrenic diverticulum:

Front 7

MOTOR DISORDERS (ACHALASIA)

Back 7

Achalasia
Primary achalasia
Secondary achalasia

Front 8

MOTOR DISORDERS (ACHALASIA)
Achalasia
(the lack of "chalasis", i.e., relaxation)

Back 8

the failure of the lower esophageal sphincter (LES) to relax with swallowing, usually accompanied by the absence of peristalsis in the body of the esophagus. Most cases (approx. 90%) of ________ are idiopathic (primary). Secondary cases are due to diseases that affect either the structure or function of the esophageal myenteric plexus or muscularis propria.

Front 9

MOTOR DISORDERS (ACHALASIA)
Primary achalasia

Back 9

believed to develop as a consequence of an autoimmune response developing in genetically disposed individuals. There are familial cases and the disease is often associated with the Class II HLA antigen DQw1. It is suspected that immune destruction of the ganglion cells leads to the inability to induce relaxation of the LES. Disappearance or reduction in the number of ganglion cells is a cardinal feature of ________. The esophagus is dilated and the wall is of normal thickness or shows compensatory muscular hypertrophy.

In addition to dysphagia, patients often experience regurgitation. Aspiration of the contents can lead to pneumonia. The most dreaded complication is the development of squamous carcinoma, which occurs in approximately 5% of the patients. Successful treatment by myotomy unfortunately leads to reflux.

Front 10

MOTOR DISORDERS (ACHALASIA)
Secondary achalasia

Back 10

seen in patients with scleroderma or also, classically, with Chagas’ disease, in which the parasite Trypanosoma cruzi is directly responsible for the destruction of the ganglion cells.

Front 11

HIATAL HERNIAS

Back 11

the protrusion of an organ or tissue through an abnormal opening
In the ___________, the stomach protrudes through the esophageal hiatus; hence, _________. There are two types of _________: sliding hernias, which account for approximately 90% of cases, and paraesophageal hernias.

Front 12

HIATAL HERNIAS
sliding hernias

Back 12

the proximal part of the stomach (cardia) moves upward through the diaphragmatic hiatus to reside in the thoracic cavity.

Front 13

HIATAL HERNIAS
paraesophageal hernias

Back 13

the LES remains below the diaphragm, but a portion of the fundus extends above the diaphragm

Front 14

Typical symptoms attributed to hiatal hernia include

Back 14

heartburn and regurgitation, usually exacerbated in the recumbent position. Complications can occur secondary to reflux. Paraesophageal hernias can become strangulated or obstructed, or rarely, the entire stomach can protrude through into the chest.

Front 15

ESOPHAGEAL VARICES

Back 15

Two thirds of patients with portal hypertension due to cirrhosis, particularly alcohol-induced, develop _________. The_______ are asymptomatic until rupture and massive hematemesis occur. This initial episode is lethal in up to 40% of patients. These are very hard to treat. Gross examination of the esophagus may not reveal any lesions due to the collapse of the involved veins. Dilated submucosal vessels, covered by a thin layer of mucosa, are seen on histological examination

Front 16

ESOPHAGEAL VARICES
Mallory-Weiss tears

Back 16

vertical linear lacerations of the lower esophagus and proximal stomach, usually occurring in the setting of alcoholism, due to severe retching/vomiting.
However, many cases occur in essentially normal patients without a history of retching.
Profuse bleeding (hematemesis) can occur.

Front 17

ESOPHAGEAL VARICES
Boerhaave syndrome

Back 17

Spontaneous rupture of the esophagus due to vomiting

Front 18

ESOPHAGITIS

Back 18

Inflammation (usually acute) of the esophagus

Front 19

ESOPHAGITIS
4 Categories:

Back 19

1. Reflux esophagitis
2. Infectious esophagitis
a. Viral
b. Fungal
3. Esophagitis due to chemical and physical agents
4. Esophagitis associated with systemic diseases
a. Epidermolysis bullosa
b. Pemphigoid
c. Graft vs. host disease

Front 20

ESOPHAGITIS
Infectious esophagitis

Back 20

Its occurrence is largely limited to patients with variable degrees of immunosuppression due to chemotherapy for neoplastic disease, immunosuppressive drugs for organ transplantation or AIDS.

- Candida albicans is the most common fungal etiology.

- Herpes simplex virus infection is a common visceral manifestation of infection in patients with hematologic malignancies (leukemia/lymphoma).

- Cytomegalovirus esophagitis is common in AIDS as part of systemic infection.

Front 21

ESOPHAGITIS
Chemical and radiation esophagitis

Back 21

due to accidental poisoning with household cleaners. In adults it often follows failed suicide attempts. The injuries due to alkaline agents are transmural and characterized by marked inflammation, saponification of the cell membrane lipids, and vascular thrombosis. Acids usually produce a more superficial coagulative necrosis with sloughing and scabbing. Perforation, strictures and esophageal cancer are known complications of ________ esophagitis

Front 22

ESOPHAGITIS
Esophagitis from systemic disease

Back 22

Involvement of the esophagus as part of multi-system or systemic diseases occurs and is probably best thought of as those that involve the mucosa (lots of primary skin disorders) such as erythema multiforme, Behcet’s syndrome, pemphigus vulgaris and bullous pemphigoid, and graft versus host disease. The other group involves the wall such as amyloidosis and scleroderma. They can cause dysphagia, obstruction, or motor abnormalities depending on the type

Front 23

ESOPHAGITIS
Reflux esophagitis

Back 23

is the consequence of regurgitation of gastrointestinal contents into the esophagus. Whereas mild and occasional _______ is considered physiologic, prolonged exposure of the squamous mucosa to acid, pepsin, or bile will elicit a progressive response and increasingly severe injury. The main cause of _______ is an inappropriate function of the LES. Hiatal hernia, certain foods (chocolate, alcohol, fatty foods), drugs (morphine, diazepam), and pregnancy among others are associated with lower LES pressure

Front 24

Infectious esophagitis
Candida albicans

Back 24

he most common fungal etiology. The lesions vary from small white plaques on the mucosa to confluent pseudomembranes to shallow ulcers. Removal of the plaques often leads to ulceration. Invasion of the submucosa can lead to fungemia, but this is rare.

Front 25

Infectious esophagitis
Herpes simplex virus infection

Back 25

a common visceral manifestation of infection in patients with hematologic malignancies (leukemia/lymphoma). The lesions are painful (odynophagia) and can present as vesicles, erosions or plaques. The typical intranuclear inclusions are identified in epithelial cells. These patients usually have systemic infection.

Front 26

Infectious esophagitis
Cytomegalovirus esophagitis

Back 26

common in AIDS as part of systemic infection. Ulcers, similar to those seen in Herpetic esophagitis, are present, and the typical viral inclusions are seen in endothelial cells lining small blood vessels and usually not in the epithelial cells.

Front 27

Unequivocal evidence of reflux (Gastroesophageal reflux disease; GERD)

Back 27

Peptic ulceration and replacement of the squamous mucosa by columnar (glandular epithelium)

Front 28

Complications of Esophagitis

Back 28

- Severe inflammation or injury to the esophagus can erode through the wall with periesophageal spread of contents
- Mediastinitis (inflammation or infection of the mediastinal soft tissue
- There can also be fibrosis from the injury with narrowing of the lumen (stricture formation)

Front 29

Mucosal Injury Progression Model

Back 29

(Injury – Metaplasia – Dysplasia – Neoplasia)

Front 30

Mucosal Injury Progression Model
Barrett's esophagus

Back 30

Substitution of the mature squamous epithelium by mature glandular epithelium (aka metaplasia: where one type of tissue is replaced by another in an attempt to adapt to changing conditions – in this case, exposure to gastric acid and enzymes)

Front 31

Typical symptoms associated with GERD

Back 31

heartburn, dysphagia, regurgitation, nocturnal cough or even asthma.

Front 32

Typical Complications associated with GERD

Back 32

Complications include strictures and dysplasia where regeneration and toxic injury result in genetic damage to the epithelial precursor cells – mutations, deletions, aneuploidy, etc.

Some of these can lead to loss of growth controls and differentiation so that cells proliferate too much and develop an abnormal morphology that we can detect under the microscope.

With continued proliferation and genetic damage, these cells can eventually develop the ability to invade the underlying tissue, form masses, and spread – neoplasia or adenocarcinoma – the final step of the model

Front 33

NEOPLASIA

Back 33

Epithelial tumors
Mesenchymal Tumors
Other tumors:
Malignant Melanoma

Front 34

NEOPLASIA
Epithelial tumors

Back 34

Benign
- Squamous papilloma

Malignant (6% of carcinomas of the GI tract)
- Squamous cell carcinoma
- Adenocarcinoma
- Small cell carcinoma

Front 35

NEOPLASIA
Mesenchymal Tumors

Back 35

Benign
# Leiomyoma
# Granular cell tumor
Malignant
# Leiomyosarcoma
# Gastrointestinal stromal tumor (rare)

Front 36

NEOPLASIA
Epithelial tumors
Adenocarcinoma

Back 36

Most (>95%) __________ of the esophagus arise in patients with Barrett’s esophagus. The adjacent mucosa frequently shows dysplastic changes. Dysplasia of the glandular mucosa is thought to represent a precancerous change of the glandular epithelium, and its presence in Barrett’s esophagus prompts closer surveillance. Resection is recommended if high grade dysplasia is seen in more than one biopsy even if cancer has not yet developed. Low grade dysplasia requires periodic endoscopic examination.
The macroscopic appearance of the adenocarcinomas is similar to that of SCC – fungating, nodular, or plaque-like with wall thickening - but with polypoid lesions being more common. A more varied appearance is seen at the microscopic level, tumors ranging from well-differentiated, gland-forming adenocarcinomas, to poorly differentiated tumors with individual cells and signet ring cells.

Front 37

NEOPLASIA
Epithelial tumors
Small Cell Carcinoma (SCC)

Back 37

A disease of the adult population, ______ is most common in males (3:1 M to F ratio) over the age of 50. There are significant geographical differences in distribution, with high incidence seen in areas of China, Iran, India, Chile and Scandinavian countries. Diet and nutritional deficiencies, alcohol and tobacco consumption are believed to be responsible. Preexisting conditions associated with _____ include achalasia, chemical esophagitis, and Plummer-Vinson syndrome

Dysphagia is the most common presenting symptom, and unfortunately, one that indicates the presence of a large tumor and advanced disease. Hoarseness (due to nerve involvement) and cachexia are signs of advanced, unresectable disease.

________________ can arise in any part of the esophagus but is most common in the middle third followed by the lower third and upper third, respectively. Histologically, most ________________s are moderately differentiated and some will exhibit keratinization. Carcinoma in-situ can be seen in adjacent mucosa.

Front 38

Common Risk Factors for Esophageal Cancers
Squamous cell carcinoma

Back 38

60 to 70 years of age
Achalasia
Alcohol abuse
African American
High-starch diet without fruits and vegetables
Lye ingestion
Male
Plummer-Vinson syndrome
Previous head and neck squamous cell carcinoma
Radiation therapy
Smoking

Front 39

Common Risk Factors for Esophageal Cancers
Adenocarcinoma

Back 39

50 to 60 years of age
Barrett's esophagus
Gastroesophageal reflux disease
Hiatal hernia
Male
Caucasian

Front 40

Esophageal Cancers
Spread/Prognosis

Back 40

first involving regional lymph nodes, gastric and celiac for tumors in the lower third, and mediastinal lymph nodes for middle third tumors. Liver and lung metastasis occur late in the disease course. Regardless of the histologic type, the survival for esophageal cancer is around 20-30% at five years

Front 41

NEOPLASIA
Mesenchymal Tumors
Leiomyoma

Back 41

The most common mesenchymal tumor of the esophagus. Most develop in the muscularis propria of the lower or middle third of the esophagus. Common symptoms at presentation are dysphagia and retrosternal pain. The tumors are well circumscribed and composed of mature smooth muscle. The malignant counterpart, ________sarcoma, is rare.

Front 42

NEOPLASIA
Mesenchymal Tumors
Granular cell tumor

Back 42

__________ are derived from the Schwann cells investing peripheral nerves. These tumors are usually incidental findings at endoscopy and present as submucosal, non-ulcerated lesions. They are almost invariably benign, and complete resection is rarely necessary.