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PATHOLOGY DISEASES OF THE ESOPHAGUS Dr. Janet L. Dy November 17, 2011
PATHOLOGY
DISEASES OF THE ESOPHAGUS
Dr. Janet L. Dy
November 17, 2011

DISEASES OF THE ESOPHAGUS

Diseases of the esophagus tend to produce similar symptoms which include:

1.

Dysphagia

- Difficulty in swallowing

- Due to obstruction or motor dysfunction like in Achalasia or hernia

- Usually due to narrowing of lumen (obstruction)

2.

Odynophagia

- Pain in swallowing

- Due to infection or gastric reflux

3.

Heartburn

- Pain in the retrosternum

- Reflux esophagitis

4.

Hematemesis

5.

Melena

Note:

The last two are less common manifestation

CONGENITAL ABNORMALITIES

Atresia

Defined as the incomplete development of the esophagus

Thin, non-canalized cord replaces a segment of esophagus, causing a mechanical obstruction

Occurs most commonly at or near the tracheal bifurcation

Usually associated with a fistula

Also associated with congenital heart defects, genitourinary malformations, neurologic diseases

Stenosis

o

Incomplete form of atresia

o

Lumen is markedly reduced in calibre as a result of fibrous thickening Partial or complete obstruction

Fistulae

Abnormal communication between two hollow organs

Can lead to aspiration, suffocation, pneumonia, severe fluid and electrolyte imbalance

Type C

o

Most common form

o

Fistula which frequently combined with esophageal atresia

(90%)

Type E

o

Least common

o

Fistula between an intact esophagus & trachea

o Fistula between an intact esophagus & trachea Note:  In infants the immediate response/manifestation

Note:

In infants the immediate response/manifestation is regurgitation of milk and aspiration So when this two are present in newborn infants then considered Esophageal atresia/fistulae

Atresia and fistula are the most important congenital malformations

DISORDERS OF MOTOR DYSFUNCTION

Hallmark Dysphagia

Consists of:

1. Achalasia

2. Hiatal Hernia

3. Laceration

4. Diverticula

Achalasia

Also known as esophageal achalasia, esophagosapasm,

achalasia cardiae, cardiospasm, and esophageal aperistalsis, esophageal motility disorder

Involves the smooth layer of the esophagus and the LES

Due to impaired smooth muscle relaxation

Release of NO and VIP from inhibitory neurons along with interruption of normal cholinergic signalling Allows LES to relax

Produces functional obstruction of the esophagus

Characterized by the triad of:

1. Incomplete lower esophageal sphincter (LES) relaxation

2. Increased LES tone

3. Aperistalsis of esophagus Impaired swallowing

Note:

In the absence of other explanations like cancer or fibrosis

Epidemiology:

- Incidence rate: 1 every 100,000 population/year

- Sex: F:M = 1:1

-

Age: 25-60

Types:

1. Primary Achalasia

Idiopathic

Degenerative changes in neural innervations (either intrinsic, within extraesophageal vagus nerve or dorsal motor nucleus of vagus)

Loss of intrinsic inhibitory innervations (NO, VIP) and

myenteric ganglion cells

2. Secondary Achalasia

May arise in Chagas disease in which Trypanosoma cruzi causes destruction of the myenteric plexus, failure of peristalsis and esophageal dilatation

May also developed from polio as a result of destruction of dorsal motor nuclei from the diabetic autonomic neuropathy

Achalasia-like Diseases

- May be caused by diabetic neuropathy, malignancy, amyloidosis, sarcoidosis, polio, surgical ablation

amyloidosis, sarcoidosis, polio, surgical ablation Fig. 2. This figure is an example of Megaloesophagus: There

Fig. 2. This figure is an example of Megaloesophagus: There is progressive dilatation (that is why MEGALO) at oral end because food stays in this are due to constricted LES or Aperistalsis of esophagus thus obstructions. Take note that as it approaches the LES, it is progressively narrowed

SECTION B

UERMMMC Class 2014

Pathology

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Pathophysiology:

- Disrupted innervations results in loss of neuromuscular coordination and muscle tone at the lower end of the esophagus Decreased peristalsis and relaxation of LE

Morphology:

A. Gross:

- Progressive dilatation of esophagus above the level of LES

- Distal end is narrowed while the proximal end is dilated (Bird’s beak appearance diagnostic in achalasia)

- Wall: may present with normal, thin, or thick

- May present with + or mucosal changes

B. Histology:

- Absence of ganglion cells

- Inflammation on myenteric plexus area

Clinical Features:

-

Progressive dysphagia (classic symptom)

-

Nocturnal regurgitation

-

Aspiration

- Nocturnal regurgitation - Aspiration Fig. 3. Bird’s beak appearance of LES in radiographic

Fig. 3. Bird’s beak appearance of LES in radiographic image. By the look of the x- ray, it is obvious that LES is constricted, thus no food passages Dysphagia is manifested (classic symptom) It is confirmatory diagnosis using Barium Enema (BE) and Manometry.

Complications:

- 5% of cases progress to squamous carcinoma

- Candida esophagitis

- Lower esophageal diverticula

- Aspiration pneumonia

- Airway obstruction

Notes:

Regurgitation occurs at night time because by the end of the day not all food is conveyed to the stomach thus leading to accumulation of food. Note that the undigested

form of food is regurgitated.

Bird;s beak: Diagnostic for achalasia

Hiatal Hernia (Diaphragmatic Hernia)

A congenital defect due to incomplete formation of the diaphragm which allows the abdominal viscera to herniate into the thoracic cavity

Very common

Females > Males

Incidence increases with age

Separation of diaphragmatic crura and widening of muscular crura and esophageal wall

Associated with reflux esophagitis

Etiology: Unknown ;

The stomach moves into thorax

2 Types:

1. Sliding Hernia (Axial)

2. Rolling/Paraesophageal Hernia (Non-Axial)

Sliding Hernia (Axial)

95 % of cases

This is the more common type of hernia

GEJ moves above the diaphragm together with some of the stomach (cardia and fundus)

Stomach herniates through the diaphragmatic opening through which the LE normally passes

Creates a bell shaped dilatation of protruding stomach

Developed from muscle weakness

Common symptoms in sliding reflux are esophagitis (aggravated by bending forward, supine position, and obesity) and reflux of gastric contents

Reflux esophagitis are sometimes present.

Sliding hiatal hernias develop from muscle weakening in the esophageal hiatus.

Rolling/Paraesophageal Hernia (Non-axial)

When a part of the stomach (usually the greater curvature) herniates through the esophageal hiatus and lies beside the esophagus, without movement of the GEJ

Developed from an anatomic defect when stomach is not properly anchored

Paraesophageal hernia is less common, but is more cause for concern

Esophagus and stomach stay in their normal locations, but part of the stomach squeezes through the hiatus, landing it next to the esophagus.

Symptom is usually a vague epigastric pain

Although you can have this type of hernia without any symptoms, the danger is that the stomach can become "strangled," or have its blood supply shut off.

There is no reflux esophagitis unlike in sliding hernia

 There is no reflux esophagitis unlike in sliding hernia Fig. 4. Examples of Hiatal Hernia

Fig. 4. Examples of Hiatal Hernia

Diverticula

True diverticulum Blind outpouching of the alimentary

tract, lined by mucosa, communicates with the lumen, and includes all 3 layers of the bowel wall (mucosa, submucosa, muscularis)

Outpouching of esophagus in areas of muscular weakness brought about by increase intraluminal pressure o Meckel diverticulum

Most common type and is found in the ileum

Formed by the failure of involution of vitelline duct (connects lumen of developing gut to yolk sac)

Rule of 2s (REMEMBER this)

1. Occur in 2% of population

2. 2 feet from ileocecal valve

3. 2 inches long

4. Symptomatic by age 2

Pseudodiverticulum lack true muscularis and is formed due to weakness of the esophageal wall and/or increase in esophageal wall stress

esophageal wall and/or increase in esophageal wall stress Fig. 5. True diverticulum versus Pseudodiverticulum SECTION

Fig. 5. True diverticulum versus Pseudodiverticulum

SECTION B

UERMMMC Class 2014

Pathology

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Types of Esophageal Diverticula:

1. Zenker / Paraesophageal diverticulum

Insert lecturer here

- More common, esophago-pharyngeal junction, often

large

- Associated with esophago-pharyngeal motor

dysfunction

- May accumulate significant amounts of food, producing a mass and symptoms that include regurgitation in episodic

- Causes dysphagia

2. Traction diverticulum

- Midpoint of the esophagus

- Less common

- Rarely collect food

- Tuberculous lymphadenitis

3. Epiphrenic diverticulum

- Just above the LES

- No dysphagia (different from Zenker)

- May manifest nocturnal regurgitation of massive amount of fluid.

Note:

Regurgitation in Zenker diverticulum are episodic. As food particles pass some may fall in the pocket. Slowly the pocket fills up with food Symptom: Regurgitation

the pocket fills up with food  Symptom: Regurgitation Fig. 6. Types of esophageal diverticula Lacerations

Fig. 6. Types of esophageal diverticula

Lacerations (Mallory-Weiss tears)

Longitudinal tears at the gastro-esophageal junction

Associated with severe retching or vomiting secondary to acute alcohol intoxication

retching or vomiting secondary to acute alcohol intoxication Fig. 7. Take note of the black arrows.

Fig. 7. Take note of the black arrows. These are the MW tears. Remember it is longitudinal tears along esophagus. If not treated immediately, a lot of blood will be out to our system via hematenesis or blood in our stool. May lead to Boerhave syndrome. Treatment can be medication like vasoconstrictor drugs or balloon is inserted. S: stomach, E: Esophagus

Pathogenesis:

- Failure of reflex LES relaxation and the refluxing gastric contents suddenly overwhelm the contraction of the musculature of gastric inlet Cause the esophageal wall to stretch and tear

Morphology:

- Linear, irregular lacerations Longitudinally oriented Range in length from mm to several cm

- Usually cross the E-G junction

- May also be in proximal gastric mucosa

Clinical Features:

PATHOLOGY

- Mallory Weiss syndrome (superficial lacerations)

Healing tends to be rapid and complete

Surgical intervention no generally required

Represents up to 5-10% of upper gastrosintestinal

bleeding (UGIB) which often presents as hematemesis

- Boerhaave syndrome

Complication of Mallory Weiss syndrome

Characterized by distal esophageal rupture, perforation and mediastinitis

Occurs rarely and a catastrophic event

Requires surgical intervention

and a catastrophic event  Requires surgical intervention Fig. 8. Boerhave syndrome.Probe = Area of perforation.

Fig. 8. Boerhave syndrome.Probe = Area of perforation. There are also sign of ulceration

Notes:

Most of the time tear is superficial; one tear involves entire

mucosa Perforation, rupture, secondary to acute inflammation

Normal: Reflex relaxation of the GE musculature precedes the antiperistaltic contractile wave associated with vomiting

ESOPHAGEAL OBSTRUCTION

Esophageal Stenosis

Fibrous thickening of esophageal submucosa with atrophy of muscularis layer

Most often due to inflammation and scarring

Progressive dysphagia

Causes:

1. Chronic gastroesophageal reflux

2. Irradiation

3. Caustic injury

4. Scleroderma

Note: Mostly acquired

Esophageal Webs

Ledge-like , circumferential mucosal protrusions into the lumen in the upper esophagus

Episodic dysphagia (partial occlusion)

Semicircumferential, eccentric lesions protruding less than 5 mm with a thickness of 2-4 mm

Composed of fibrovascular connective tissue and overlying epithelium

Unknown pathogenesis

Frequently encountered in women over age 40

Main symptom is dysphagia associated with incompletely chewed food

Paterson-Brown-Kelly / Plummer-Vinson syndrome

1. Upper esophageal webs

2. Iron-deficiency anemia

3. Atrophic glossitis

4. Cheilosis

5. Post-cricoid Esophageal Ca

Esophageal Rings/Schatzki Rings

Circumferential mucosal protrusions in the distal esophagus.

Similar to webs but are thicker and circumferential

Types according to location:

1. A rings

- Above the gastroesophageal (squamocolumnar junction)

- Covered by squamous mucosa

SECTION B

UERMMMC Class 2014

Pathology

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2. B rings

- At the squamocolumnar junction of the lower esophagus

- Have gastric cardia-type mucosa on their undersurface

- Symptom: Episodic dysphagia

Insert lecturer here

ESOPHAGEAL VARICES

Tortuous dilated veins at the distal esophagus and proximal stomach

Portal hypertension Most common cause

Found in 90% of cirrhotic patients

Formation of collaterals in the lower esophagus when the portal blood flow is shunted into the plexus of esophageal subepithelial and submucosal veins

Pathogenesis:

- Portal HTN Development of collateral channels (where portal and caval systems communicate) Lead to development of a congested subepithelial and submucosal venous plexus within distal esophagus

Note:

THREE common areas of portal/caval anastomoses

- Hepatic schistosomiasis is the second most common cause

- Net effect:

Irregular protrusion of the overlying mucosa in the lumen Thus high risk for bleeding when food pass the lumen’

Morphology:

- Appear as tortuous dilated veins lying primarily within the submucosa of distal esophagus and proximal stomach

- Collapse in absence of blood flow

- Rupture results in hemorrhage into the lumen or esophageal wall

Clinical Features:

- Often asymptomatic until they rupture causing massive hematemesis and hemorrhage which is a medical emergency

- Contributing factors that lead to rupture:

a. Inflammatory erosion of thinned overlying mucosa

b. Increased tension in progressively dilated veins

c. Increased vascular hydrostatic pressure associated with vomiting

- 40-50% fatality rate in the first bleeding episode

- Fatal hemorrhage is the most feared consequence

ESOPHAGITIS

Heartburn is the common symptom among the different types

Causes:

1. Chemical (alcohol, acids, alkalis, smoking, pill, chemotherapy)

2. Physical (hot fluids, radiation, prolonged intubation)

3. Biological

- Infectious agents (especially in debilitated or immunosuppressed individuals)

4. GERD

- Most frequent cause of esophagitis

Reflux Esophagitis (aka GERD)

Gastro-esophageal reflux disease

Most common cause of esophagitis

Normal protective mechanisms against acid-peptic juice action:

1. Submucosal glands secrete mucin and bicarbonate

2. Constant LES tone prevents reflux of acid gastric contents

Pathogenesis/Etiology:

PATHOLOGY

- Reflux of gastric acid is central to the development of injury

- Decrease anti-reflux mechanism ( secondary to hypothyroidism, CNS depressants, alcohol, tobacco, pregnancy) Pregnancy Increase intrabdominal pressure Reflux of gastric contents

- Sliding hiatal hernia

- Delayed gastric emptying, increase gastric volume

- Acid peptic juice action in esophageal mucosa

- Bile reflux

Acid peptic juice action in esophageal mucosa - Bile reflux Fig. 9. Nonspecific findings: Hyperemia and

Fig. 9. Nonspecific findings: Hyperemia and edema. Long standing: may develop ulcers Bleeding

Morphology:

- Morphologic changes depend on the cause, duration, & severity of exposure to injury

A. Gross:

- Esophagus appears red and hemorrhagic with linear ulcers obliterating the z-line (simple hyperemia May be the only alteration)

B. Histology:

- 3 important features:

Presence of inflammatory cells: Eosinophils (early finding ), neutrophils (severe injury ) or lymphocytes in the epithelial mucosa Basal zone hyperplasia exceeding 20 % of epithelial thickness Part where reserve cells are found Thickening of the epithelium with increase in the height of the vascular papillae of the lamina propria, to greater than 50% of the thickness of the epithelium

to greater than 50% of the thickness of the epithelium Fig. 10. L : Early Reflux
to greater than 50% of the thickness of the epithelium Fig. 10. L : Early Reflux

Fig. 10. L: Early Reflux Esophagitis, eosinophils is appreciated (black arrow) R: Severe Reflux Esophagitis, being infiltrated by neutrophils

Note:

These 3 features may not all be present, only 1 or 2 may be observed. Regarding the inflammatory cells the eosiniphils are the 1 st . Presence of neutrophils indicates severity

Clinical Features:

- Dysphagia and heartburn are the most common symptoms

- Less frequent regurgitation of sour-tasting gastric contents

- Severity of symptoms not closely related to degree of histologic damage Increase with disease duration Complications:

- Bleeding

- Ulceration

- Hematemesis

- Melena

- Strictures

- Barrett’s Esophagus Most important complication, especially from long standing reflux esophagitis Treatment:

- Proton pump inhibitors or H 2 histamine receptor antagonists

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UERMMMC Class 2014

Pathology

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Infectious Esophagitis

Occur most frequently in those who are immunosuppressed

Insert lecturer here

especially (+) HIV Pxs often indicative of “full blown: AIDS

Bacterial esophagitis occurs 10-15%

1. Candida esophagitis

- Found in 20 % among adults

- Associated with disturbance in the normal GI flora

- Associated with conditions of reduced host resistance, immunodeficiency and malignancies

- Surface proliferation in the absence of epithelial invasion is not considered infection (colonization )

- Epithelial invasion by fungi accompanied by an inflammatory tissue reaction

- Many are asymptomatic

- Characterized by adherent, gray-white pseudomembranes

- Composed of densely matted fungal hyphae and inflammatory cells

of densely matted fungal hyphae and inflammatory cells Fig. 11. Image shows Candida esophagitis. You can

Fig. 11. Image shows Candida esophagitis. You can see the fungal masses along the esophagus (blue arrow) creamy white-yellow patches of fungal masses.

(blue arrow) creamy white-yellow patches of fungal masses. Fig. 12. Histologic image of Candida esophagitis: to

Fig. 12. Histologic image of Candida esophagitis: to be sure that esophagitis is due to fungal infection then hyphae or fungal elements must be appreciated in the slide that came from fungal masses from previous picture.

Epidemiology:

- Seen in 50 % of AIDS patient

- Seen in other immunodeficient states (leukemia, lymphoma, chemotherapy, steroid therapy, hereditary immunodeficient states , diabetes mellitus, severe debilitation, elderly )

2. Herpes simplex virus

- Causes punched out-ulcers

- Nuclear viral inclusions within a rim of degenerating epithelial cells at the margin of the ulcer

of degenerating epithelial cells at the margin of the ulcer Fig. 13. Shows viral esophagitis, in
of degenerating epithelial cells at the margin of the ulcer Fig. 13. Shows viral esophagitis, in

Fig. 13. Shows viral esophagitis, in the left picture, you can see the tan-brown base lesion as the arrow pointed. This can cause punched out ulcers once it is remove from the mucosa; the right picture just show histologic characteristic of a viral infected cell. It is large multinucleated with inclusion bodies

PATHOLOGY

Chemical/radiation Esophagitis

Damage in stratified squamous mucosa by a variety of irritants

Implicated agents: Alcohol, corrosive acids or alkali, (suicidal attempt ) , detergents , excessive hot fluid , heavy smoking

Cytotoxic anticancer treatment

Radiation

Generally only causes self limited pain, particulary dysphagia

Morphologic:

- Dense infiltrates of neutrophils are present in most cases; may be absent following injury induced by chemicals (outright necrosis)

- Esophageal irradiation: intimal proliferation and luminal narrowing of submucosal and mural blood vessels.

- Final common pathway for all

Severe acute inflammation

Superficial mucosal necrosis and ulceration

Formation of granulation tissues

Late stage: Fibrosis

Clinical features:

- Uncomplicated ingestion: Acute oral burns, pain, and dysphagia

- Complications:

1030% with scar and stricture formation

Acute dysphagia

Acute respiratory compromise

Laryngeal edema, tracheitis and pneumonitis

Esophageal perforation

Septicemia, mediastinitis, peritonitis, empyema

Hemorrhage

BARRETT’S ESOPHAGUS

Etiology:

- Complication of long standing G-E reflux with replacement of distal squamous by metaplastic columnar epithelium containing goblet cells

- Presence of GOBLET CELLS in the esophageal mucosa is DIAGNOSTIC

- Characterized by intestinal metaplasia within the esophageal squamous mucosa

- Occurs in 5-15%

- Greatest concern: Increased risk of esophageal carcinoma (precursor to malignancy), however, most do not develop esophageal tumors)

Notes:

This condition was initially thought to represent a congenitally short esophagus. Results from alteration in the different program of stem cells This patient have long history of heartburn and other reflux symptoms like “sinisikmura”

Pathogenesis:

- Increased exposure to gastric acid Reflux esophagitis Erosion and ulceration Stimulation of pluripotential stem cells in the basal layer Intestinal metaplasia

Morphology:

- Located in the G-E junction

Note:

- Velvety red (sometimes pink salmon) appearance

Infected squamous cells becomes larger and

- Often multifocal, irregular patches or tongues of tissue

multinucleated.

- Alternates with residual smooth, pale squamous mucosa

Nuclei show molding? Margination at periphery,

- Interfaces with light brown columnar mucosa distally

“glassy”/empty appearance.

- 2 criteria for the diagnosis of Barrett esophagus:

3M’s: Multinucleation, molding and margination of nuclear chromatin.

1.

Endoscopic evidence of abnormal mucosa (columnar epithelium) above the gastroesophageal junction

3. Cytomegalovirus

- Causes shallower, linear ulcers

- Characteristic: Nuclear and cytoplasmic inclusions within capillary endothelium and stromal cells

Note:

Helps to prevent misdiagnosis if metaplastic goblet cells within the cardiac are included in the biopsy

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2. Histologically documented intestinal metaplasia

- Goblet cells (have distinct mucous vacuoles)

Insert lecturer here

Define intestinal metaplasia

Necessary for diagnosis of Barrett esophagus

Note:

Simple yet important: when the gross images are pale red like in esophagus or maybe oral mucosa -> strat. Squamous epith; but if it is velvety red or pink salmon like most of our visceral GI organs then it is simple columnar epith. That is why when you see pink salmon patches in esophagus, then it may be Barrett’s Esophagus due to metaplasia. (kasi nga dapat strat. Squamous ang esophagus, e naging columnar kaya metaplasia)

Squamous ang esophagus, e naging columnar kaya metaplasia) Fig. 14. L : Normal. R : BE;
Squamous ang esophagus, e naging columnar kaya metaplasia) Fig. 14. L : Normal. R : BE;

Fig. 14. L: Normal. R: BE; So as previously discussed, in the left there is smooth delineated boundary between the two organs Normal. Unlike the right picture; there are already infiltrates of patchy velvety red lesion in the esophagus thus intestinal metaplasia thus BE

lesion in the esophagus thus intestinal metaplasia thus BE Fig. 15. B: note presence of goblet

Fig. 15. B: note presence of goblet cells (red arrow; top right shows basal zone hyperplasia A: Normal GEJ

Classification:

1. Long segment: >3cm of esophagus is involved

2. Short segment: <3 cm of esophagus is involved

Dysplasia in Barrett’s Esophagus

- Low grade dysplasia

- High grade dysplasia

Note:

Present in both grades: inc. epithelial proliferation w/ atypical mitoses and nuclear hyperchromasia, irreg. clumped chromatin, inc. N:C ratio and failure of epith.cells to mature High grade More severe changes If high grade dysplasia is present in biopsy specimen, there is 70% chance of AdenoCA present Precursor to malignancy

Clinical Features:

- Only identified through endoscopy and biopsy, prompted by GERD symptoms

- Symptoms are related to reflux esophagitis Single risk factor to development of adenoCA

Complications:

- Ulceration

- Hemorrhage

- Stricture

- Dysplasia

- Development of adenocarcinoma Dysplasia is the single determinant

PATHOLOGY

Note:

Periodic surveillance (endoscopy with biopsy) for detection of dysplasia should be undertaken, as the incidence of adenocarcinoma in Barrett's is 30x that of the general population Searching for dysplasia when Barrett’s is present is of utmost importance. MOST/ALL adenocarcinomas arising in the esophagos arise from previously existing Barrett’s.

ESOPHAGEAL TUMORS

1. Benign tumors - Uncommon/mesenchymal origin

1. Squamous papilloma

2. Leiomyoma , fibroma, hemangioma

3. Fibrovascular polyps

4. Inflammatory pseudo-tumors

2. Malignant tumors Epithelial in nature

1. Squamous cell carcinoma

2. Adenocarcinoma

3. Melanocarcinoma

4. Leiomyosarcoma

Esophageal carcinoma statistics:

o 6 % of GIT cancers

o 90 % of esophageal Ca are Squamous cell carcinoma (worldwide stats)

o In US , Adeno CA incidence > SCCA

Notes:

The very best way to classify ALL tumors of a major organ is to remember BASIC HISTOLOGY. You do NOT need to memorize a stupid list from a pathology lecture, just remember an organ’s native cells! (Dr. Dy’s notes in the

PPT)

Dr. Dy’s notes above is correct! Example, skin, normally lined by strat. Squamous cell, of course when it begins to produce neoplastic cells Become Squamous Cell CA, not Skin AdenoCA. Same goes with Esophagus, highly it will be SCCA UNLESS! It undergoes intestinal metaplasia like Barrett’s esophagus thus prone to become Esophageal AdenoCA. Gets?

Another classic info: worldwide Esophageal SCCA incidence > AdenoCA except in US, why? They always use Aspirin which can cause ulcer Reflux problem Barrett’s Esophagus AdenoCA. Kaya impossible magkaka Esophageal AdenoCA ka w/o having intestinal

metaplasia 1 st .

Esophageal Squamous Cell Carcinoma

Affects males more (2:1 to 20:1)

Affects African-Americans (blacks) than Caucasians (whites)

More common in rural and underdeveloped areas

Regions with highest incidences: Iran, central China, Hong Kong, Brazil, South Africa

Etiopathogenesis:

- Molecular pathogenesis of esophageal SCC remains incompletely defined

1. Dietary

- Def of Vit (A, C, Riboflavin, B12 )

- Def of trace metals (zinc , molybdenum )

- Fungal contamination of food (mutagenic compounds)

- High nitrites/nitrosamines content

2. Lifestyle

- Alcohol

- Tobacco

- Urban environment

3. Esophageal disorders

- Chronic esophagitis , HPV infection

- Achalasia

- Plummer-Vinson syndrome Triad of esophageal web, Fe deficiencies and glossitis

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4. Genetic predisposition

- Long standing celiac disease

- Ectodemal dysplasia

- Tylosis palmaris et plantaris

- Racial predisposition

- Chromosomal abnormalities: mutations in p53,

- p16/INK4 tumor suppressor gene

Insert lecturer here

Note:

Etiopathogenesis is multifactorial ranging from nutritional deficiencies as well as carcinogenic compounds like nitosamines and others like from fungal. Alcohol and tobacco synergize to increase risk. Environment and diet contribute synergistically, modified by genetic factors.

Morphology:

- Begins as an in situ lesion termed squamous dysplasia

- early lesions appear as small, gray-white, plaque-like thickenings

- SCCs may invade the respiratory tree, aorta, mediastinum, or pericardium

- Half occur in the middle third of the esophagus

- Morphologic patterns :

Exophytic 60 %

Flat/ diffusely infiltrative - 15 %

Excavated / ulcerated 25 %

- Location :

Upper third 20 % (linked to PV synd.elderly women)

Middle third 50 %

Lower third 30 %

Most SCC moderately to well-differentiated

Epithelial dysplasia Regional lymph node spread is early and common

Rich submucosal lymphatic network promotes circumferential and longitudinal spread

Spread-transmural invasion

Sites of lymph node metastases vary with tumor location

o

Cancers in upper third of esophagus favor cervical lymph nodes

o

Cancers in middle third favor mediastinal, paratracheal, tracheobronchial nodes

o

Cancers in lower third favor gastric and celiac nodes

Cancers in lower third favor gastric and celiac nodes Fig. 16 L : well-differentiated, keratin pearls?
Cancers in lower third favor gastric and celiac nodes Fig. 16 L : well-differentiated, keratin pearls?

Fig. 16 L: well-differentiated, keratin pearls? Formation, solid nest infiltrating stroma,intracellular bridges indicates it originated from squamous? R: moderately differentiated

Clinical Features:

- Dysphagia, odynophagia (pain on swallowing), obstruction, extreme weight loss, debilitations

- Hemorrhage and sepsis may accompany tumor ulceration

- Prognosis is poor

- Overall 5 year survival = 9%

Note:

Overall is 9%, this may be d/t very early spread of the neoplasm because of rich lymphatic network, another reason would be the absence of serosa thus less barrier.

PATHOLOGY

Esophageal Adenocarcinoma

Usually involves the lower third of the esophagus

Commonly arises from metaplastic columnar epithelium (i.e. Barrett’s esophagus)

May also arise from heterotropic gastric mucosa or from submucosal glands

It is one of the most significant complications of barrett’s esophagus

Risk is reduced by diets rich in fruits and vegetables

Epidemiology:

- Most frequent among Caucasians

- 7-fold more common in men

- Usually seen between the ages of 40 and 60

- Incidence of adenocarcinoma in Barrett's esophagus is probably less than 5-10% but is really unknown because the true incidence of Barrett's is not known

because the true incidence of Barrett's is not known Fig. 17. T he transition of a

Fig. 17. The transition of a normally squamous esophageal mucosa to a glandular or “intestinal” type of a mucosa is called BARRETT’S

Pathogenesis:

- Progression of Barrett esophagus to adenocarcinoma occurs over an extended period through the stepwise acquisition of genetic and epigenetic changes

- The evolution of esophageal adenocarcinoma:

Reflux esophagitis Metaplastic Barrett's esophageal mucosa Glandular epithelial dysplasia AdenoCA

Morphology:

- Occur almost exclusively in the distal third of the esophagus

- May invade the adjacent gastric cardia

- May infiltrate diffusely or ulcerate and invade deeply

- First appears as a thickened plaque-like white mucosa

- Larger lesions form white, exophytic, polypoid masses

- Tumors may infiltrate diffusely or ulcerate and invade deeply

- May be multifocal

diffusely or ulcerate and invade deeply - May be multifocal Fig. 18. Esophageal AdenoCA Microscopic Features:

Fig. 18. Esophageal AdenoCA

Microscopic Features:

- Microscopically indistinguishable from gastric adeno Ca

- Majority are moderate to well differentiated intestinal type

- Most commonly produce mucin and form glands

- Minority with signet ring type

- Prognosis for both types is poor

with signet ring type - Prognosis for both types is poor Clinical Features: - Commonly present

Clinical Features:

type - Prognosis for both types is poor Clinical Features: - Commonly present with pain or

- Commonly present with pain or difficulty in swallowing, progressive weight loss,

- Hematemesis, chest pain, vomiting

- When symptoms appear, tumor has usually spread to submucosal lymphatic vessels.

- In advanced stages, overall 5-yr survival is less than 25%

SECTION B

UERMMMC Class 2014

Pathology

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