PATHO 4-3 Diseases of the Esophagus

PATHOLOGY

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 Difficult y in swallowing -  Due to obstruction or motor dysfunction like in  Achalasia or hernia hernia - Usually due to narrowing of lumen (obstruction) 2. Odynophagia - Pain in swallowing - Due to infection or gastric gastric reflux 3. Heartburn - Pain in the retrosternum - Reflux esophagitis 4. Hematemesis 5. Melena

Note: The last two are less common manifestation

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Hallmark – Hallmark – Dysphagia Consists of: 1. Achalasia 2. Hiatal Hernia 3. Laceration 4. Diverticula

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Also known as esophageal esophageal achalasia, esophagosapasm, esophagosapasm, achalasia cardiae, cardiospasm, and esophageal aperistalsis, aperistalsis , esophageal motility disorder Involves the smooth layer of the esophagus esophagus and the LES Due to impaired smooth muscle relaxation Release of NO and VIP from from inhibitory neurons along along with interruption of normal cholinergic signalling  Allows LES to relax Produces functional obstruction of the esophagus esophagus Characterized by the triad of: 1. Incomplete lower lower esophageal esophageal sphincter (LES) relaxation 2. Increased LES tone 3. Aperistalsis Aper istalsis of esophagus Impaired swallowing

 Achalasia

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CONGENITAL ABNORMALITIES  Atresia  

DISORDERS OF MOTOR DYSFUNCTION

Defined as the incomplete development of 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, 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 communication between between two hollow organs Can lead to aspiration, suffocation, pneumonia, severe fluid and electrolyte imbalance  Type C o Most common form esophageal atresia o Fistula which frequently combined with esophageal (90%)  Type E o Least common o Fistula between an intact esophagus & trachea

Note: In the absence of other explanations like cancer or fibrosis Epidemiology: - Incidence rate: 1 every every 100,000 100,000 population/year 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 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

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In infants the immediate response/manifestation is regurgitation of milk and aspiration   So  So when this two are present in newborn infants then considered Esophageal atresia/fistulae and fistula fistula are the most most important important congenita congenitall   Atresia and malformations

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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

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

Sliding Hernia (Axial)        

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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)

Clinical Features: - Progressive dysphagia (classic symptom) - Nocturnal regurgitation -  Aspiration

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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

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) 

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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)

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

Fig. 5. True diverticulum versus Pseudodiverticulum

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UERMMMC Class 2014

Pathology

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PATHOLOGY 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

Clinical Features: - 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

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 

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

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    

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

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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

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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

UERMMMC Class 2014

Pathology 3 | 7

PATHOLOGY 2. B rings - At the squamocolumnar junction of the lower esophagus Insert - Have gastriclecturer cardia-typehere mucosa on their undersurface - Symptom: Episodic dysphagia

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/Etiology: - 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

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

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

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

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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 st  the 1 . 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

UERMMMC Class 2014

Pathology 4 | 7

PATHOLOGY Infectious Esophagitis

Chemical/radiation Esophagitis

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Occur most frequently in those who are immunosuppressed Insert lecturer hereof “full blown: AIDS especially (+) HIV Pxs often indicative  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

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

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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:  10 –30% 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 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 fr om 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

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

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Infected squamous cells becomes larger and multinucleated.  Nuclei show molding? Margination at periphery, “glassy”/empty appearance.  3M’s: M ultinucleation, molding and margination of nuclear chromatin. 3. Cytomegalovirus - Causes shallower, linear ulcers - Characteristic: Nuclear and cytoplasmic inclusions within capillary endothelium and stromal cells

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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 - Velvety red (sometimes pink salmon) appearance - Often multifocal, irregular patches or tongues of tissue - Alternates with residual smooth, pale squamous mucosa - Interfaces with light brown columnar mucosa distally - 2 criteria for t he diagnosis of Barrett esophagus: 1. Endoscopic evidence of abnormal mucosa (columnar epithelium) above the gastroesophageal junction Note: 

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

UERMMMC Class 2014

Pathology 5 | 7

PATHOLOGY 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)

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

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

Classification: 1. Long segment: >3cm of esophagus is involved 2. Short segment: 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 st  metaplasia 1 .

Esophageal Squamous Cell Carcinoma

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

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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 Barret t’s is present is of utmost importance. MOST/ALL adenocarcinomas arising in the esophagos arise from previously existing Barrett’s.

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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

UERMMMC Class 2014

Pathology 6 | 7

PATHOLOGY 4. Genetic predisposition - Long standing celiac disease Insert lecturer here - Ectodemal dysplasia - Tylosis palmaris et plantaris - Racial predisposition - Chromosomal abnormalities: mutations in p53, - p16/INK4 tumor suppressor gene 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

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

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

Fig. 18. Esophageal AdenoCA

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%

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

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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.

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Clinical Features: - 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%

UERMMMC Class 2014

Pathology 7 | 7