pathology of the gastrointestinal tract ismail matalka,mrcpath department of pathology jordan...

PATHOLOGY OF THE PATHOLOGY OF THE GASTROINTESTINAL GASTROINTESTINAL

TRACTTRACT

PATHOLOGY OF THE PATHOLOGY OF THE GASTROINTESTINAL GASTROINTESTINAL

TRACTTRACT

Ismail Matalka ,MRCPathIsmail Matalka ,MRCPath

Department of PathologyDepartment of Pathology

Jordan University of Science & Jordan University of Science & TechnologyTechnology

Irbid - JordanIrbid - Jordan

THE ALIMENTARY (DIGESTIVE) SYSTEMTHE ALIMENTARY (DIGESTIVE) SYSTEM

Oral cavity (including salivary glands)Oral cavity (including salivary glands) EsophagusEsophagus StomachStomach Small intestineSmall intestine ColonColon AppendixAppendix LiverLiver Biliary tractBiliary tract PancreasPancreas

ANATOMY & HISTOLOGY OFANATOMY & HISTOLOGY OF

THE ORAL CAVITYTHE ORAL CAVITY AnatomyAnatomy

– Orifice to digestive & respiratory tractsOrifice to digestive & respiratory tracts– Lips, buccal mucosa, tongue, soft & hard Lips, buccal mucosa, tongue, soft & hard

palatepalate– Teeth & periodontal tissueTeeth & periodontal tissue

HistologyHistology– Lined by nonkeratinized squamous epitheliumLined by nonkeratinized squamous epithelium– Minor salivary glands & sebaceous glands in Minor salivary glands & sebaceous glands in

lips & buccal mucosalips & buccal mucosa– Lymphoid tissueLymphoid tissue

DISEASES OF THEDISEASES OF THE

ORAL CAVITYORAL CAVITY Congenital anomalies, e.g. cleft lip & cleft Congenital anomalies, e.g. cleft lip & cleft

palate, macroglossia, branchial cleft cystspalate, macroglossia, branchial cleft cysts Inflammations: Aphthous ulcers, Herpes Inflammations: Aphthous ulcers, Herpes

stomatitis, Candidiasis ...stomatitis, Candidiasis ... Pre-malignant lesions: leukoplakia, Pre-malignant lesions: leukoplakia,

erythroplasiaerythroplasia Tumors: Squamous cell carcinomaTumors: Squamous cell carcinoma Salivary gland inflammationsSalivary gland inflammations Salivary gland tumorsSalivary gland tumors

ULCERATIVE & INFLAMMATULCERATIVE & INFLAMMATORY LESIONS OF THE ORAL CAVITYORY LESIONS OF THE ORAL CAVITY

APHTHOUS ULCERS (CANKER SORES)APHTHOUS ULCERS (CANKER SORES) Extremely common, up to 40% of populationExtremely common, up to 40% of population Single or multiple shallow fibrin-coated Single or multiple shallow fibrin-coated

painful ulcers of oral mucosa, usually <1 cm, painful ulcers of oral mucosa, usually <1 cm, may coalescemay coalesce

Unknown etiology (?viruses, hypersensitivity)Unknown etiology (?viruses, hypersensitivity) Triggered by stress, fever, menstruation, Triggered by stress, fever, menstruation,

pregnancy, certain foods; may be familial pregnancy, certain foods; may be familial May be associated with inflammatory bowel May be associated with inflammatory bowel

disease & Behcet syndromedisease & Behcet syndrome Self limiting in a few weeksSelf limiting in a few weeks


HERPETIC STOMATITISHERPETIC STOMATITIS HSV I>>II; person to person transmissionHSV I>>II; person to person transmission After primary infection it is usually asymptomatic After primary infection it is usually asymptomatic

but virus will persist in ganglia in dormant statebut virus will persist in ganglia in dormant state Reactivation: fever, sun or cold exposure, URTI, ..Reactivation: fever, sun or cold exposure, URTI, .. Herpes labialis: cold sores or fever blistersHerpes labialis: cold sores or fever blisters

»Vesicular lesion, edema, degeneration of Vesicular lesion, edema, degeneration of epidermisepidermis

»Tzanck test: intranuclear inclusions & giant Tzanck test: intranuclear inclusions & giant cellscells

In immunocompromised: virulent dissiminated In immunocompromised: virulent dissiminated infection: gingivostomatitis, encephalitis ...infection: gingivostomatitis, encephalitis ...


FUNGAL INFECTIONSFUNGAL INFECTIONS Candida albicans is part of normal flora (30-40%)Candida albicans is part of normal flora (30-40%) Oral candidiasis (moniliasis, thrush): common in:Oral candidiasis (moniliasis, thrush): common in:

»Diabetes mellitusDiabetes mellitus»AnemiaAnemia»Antibiotic or glucocorticoid RxAntibiotic or glucocorticoid Rx» Immunodeficiencies & debilitating diseasesImmunodeficiencies & debilitating diseases

Soft white cheese-like plaquesSoft white cheese-like plaques Minimal- marked ulceration with inflammatory Minimal- marked ulceration with inflammatory

exudate and fungal microorganisms exudate and fungal microorganisms (pseudohyphae)(pseudohyphae)

In vulnerable patients, disease may spreadIn vulnerable patients, disease may spread


ACQUIRED IMMUNODEFICIENCY ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)SYNDROME (AIDS)

HIV infection is associated with different lesions HIV infection is associated with different lesions in the oral cavityin the oral cavity– CandidiasisCandidiasis– Herpetic vesiclesHerpetic vesicles– Other oppurtunistic infectionsOther oppurtunistic infections– KaposiKaposi’’s sarcoma: multifocal vascular tumor, present s sarcoma: multifocal vascular tumor, present

in 25% of AIDS patients; HSV8in 25% of AIDS patients; HSV8– Hairy leukoplakia: white patches with hairy surface:Hairy leukoplakia: white patches with hairy surface:

» caused by EBVcaused by EBV» rare, but seen mainly in AIDS rare, but seen mainly in AIDS » histology shows acanthosis, hyperkeratosishistology shows acanthosis, hyperkeratosis

PRE-MALIGNANT LESIONS OF THE ORAL CAVITYPRE-MALIGNANT LESIONS OF THE ORAL CAVITY

LEUKOPLAKIALEUKOPLAKIA A clinical term used to describe a whitish well- A clinical term used to describe a whitish well-

defined mucosal patch or plaque caused by defined mucosal patch or plaque caused by epidermal thickening or hyperkeratosisepidermal thickening or hyperkeratosis

Older men; associated with tobacco, chronic friction Older men; associated with tobacco, chronic friction (dentures), alcohol & irritant foods; HPV link(dentures), alcohol & irritant foods; HPV link

Microscopically, they vary from hyperkeratosis Microscopically, they vary from hyperkeratosis without dysplasia to mild to severe dysplasia or CISwithout dysplasia to mild to severe dysplasia or CIS

Only histologic examination distinguishes these Only histologic examination distinguishes these changeschanges

3-6% transform into squamous cell carcinoma3-6% transform into squamous cell carcinoma

PRE-MALIGNANT LESIONS OF THE ORAL CAVITYPRE-MALIGNANT LESIONS OF THE ORAL CAVITY

ERYTHROPLAKIAERYTHROPLAKIA Red velvety areas which may remain level with or Red velvety areas which may remain level with or

slightly depressed in relation to surrounding slightly depressed in relation to surrounding mucosamucosa

Greater tendency for epithelial cell atypia and Greater tendency for epithelial cell atypia and marked dysplasia than leukoplakiamarked dysplasia than leukoplakia

Hyperkeratosis is less frequent; red color is due Hyperkeratosis is less frequent; red color is due to intense inflammation and vascular congestionto intense inflammation and vascular congestion

Higher risk (50%) of malignant transformation (the Higher risk (50%) of malignant transformation (the risk corresponds to the degree of atypia)risk corresponds to the degree of atypia)

Erythroleukoplakia: speckled leukoplakia; mixture Erythroleukoplakia: speckled leukoplakia; mixture of erythroplasia and leukoplakia of erythroplasia and leukoplakia

MALIGNANT TUMORS OF THE ORAL CAVITYMALIGNANT TUMORS OF THE ORAL CAVITY

SQUAMOUS CELL CARCINOMASQUAMOUS CELL CARCINOMA Represent 90% of oral cavity malignancies (3% of all Represent 90% of oral cavity malignancies (3% of all

malignant tumors); M>Fmalignant tumors); M>F Lip>ant. floor of mouth>tongue>palateLip>ant. floor of mouth>tongue>palate Etiology: smoking, smokeless tobacco, protracted irritation Etiology: smoking, smokeless tobacco, protracted irritation

(e.g. dentures), chronic dental & oral infections, sunlight, (e.g. dentures), chronic dental & oral infections, sunlight, heat, alcohol, atrophy, HPVheat, alcohol, atrophy, HPV

Plaque, mucosal thickening or ulcerPlaque, mucosal thickening or ulcer Invasive &/or in situ carcinoma; well differentiated to Invasive &/or in situ carcinoma; well differentiated to

undifferentiatedundifferentiated Spread to local LN (submandibular, high jugularSpread to local LN (submandibular, high jugular……)) Px: depends on location (e.g. lip), gradePx: depends on location (e.g. lip), grade , , stagestage 50% lead to death in 5 years ;overall 5 YS without L.N mets 50% lead to death in 5 years ;overall 5 YS without L.N mets

is 40% after chemo & radio ;and 20% with L.N mets is 40% after chemo & radio ;and 20% with L.N mets

DISEASES OF THEDISEASES OF THESALIVARY GLANDSSALIVARY GLANDS

InflammationInflammation– Viral sialadenitisViral sialadenitis– Bacterial sialadenitisBacterial sialadenitis– Autoimmune sialadenitisAutoimmune sialadenitis– SialolithiasisSialolithiasis

TumorsTumors– BenignBenign

» Pleomorhpic adnoma (mixed tumor)Pleomorhpic adnoma (mixed tumor)» WarthinWarthin’’s tumors tumor

– MalignantMalignant» Carcinoma ex-pleomorphic adenomaCarcinoma ex-pleomorphic adenoma» Mucoepidermoid carcinomaMucoepidermoid carcinoma» Adenoid cystic carcinomaAdenoid cystic carcinoma

MickuliczMickulicz’’s syndromes syndrome

INFLAMMATIONS OF THE SALIVARY GLANDSINFLAMMATIONS OF THE SALIVARY GLANDS VIRAL SIALADENITISVIRAL SIALADENITIS

Most common cause is mumps, which usually Most common cause is mumps, which usually affects the parotid gland (epidemic parotitis) affects the parotid gland (epidemic parotitis)

70% bilateral parotid; 20% unilateral; 10% others70% bilateral parotid; 20% unilateral; 10% others Mumps is an acute contagious childhood diseaseMumps is an acute contagious childhood disease Paramyxovirus, acquired by respiratory dropletsParamyxovirus, acquired by respiratory droplets Usually self limited, but may lead to Usually self limited, but may lead to

complications, which are commoner in adults:complications, which are commoner in adults:– PancreatitisPancreatitis– Orchitis: usually unilateral; rarely leads to Orchitis: usually unilateral; rarely leads to

infertilityinfertility– CNS inflammation: rare but seriousCNS inflammation: rare but serious

INFLAMMATIONS OF THE SALIVARY GLANDSINFLAMMATIONS OF THE SALIVARY GLANDS

AUTOIMMUNE SIALADENITISAUTOIMMUNE SIALADENITIS SjogrenSjogren’’s syndrome: inflammation of salivary s syndrome: inflammation of salivary

glands & mucus-secreting glands of nasal glands & mucus-secreting glands of nasal mucosa (resulting in dry mouth ormucosa (resulting in dry mouth or xerostomia xerostomia) ) and lacrimal glands (resulting in dry eyes or and lacrimal glands (resulting in dry eyes or keratoconjunctivitis siccakeratoconjunctivitis sicca))

90% are females; parotid enlargment in 50%90% are females; parotid enlargment in 50% May be primary or secondary (60%) to othe May be primary or secondary (60%) to othe

autoimmune disease (RA, SLE, polymyositis ..)autoimmune disease (RA, SLE, polymyositis ..) Lymphocytic infiltration & fibrosisLymphocytic infiltration & fibrosis RF, ANAs +/-; anti-ribonucleoprotein SS-A & B RF, ANAs +/-; anti-ribonucleoprotein SS-A & B

AbsAbs High risk to develop lymphomasHigh risk to develop lymphomas

INFLAMMATIONS OF THE SALIVARY GLANDSINFLAMMATIONS OF THE SALIVARY GLANDSSIALOLITHIASIS & NONSPECIFIC SIALOLITHIASIS & NONSPECIFIC

SIALADENITISSIALADENITIS BacterialBacterial Secondary to ductal obstruction by stones Secondary to ductal obstruction by stones

(sialolithiasis) in major excretory duct(sialolithiasis) in major excretory duct Usually unilateralUsually unilateral Pathogenesis: impacted food debris & Pathogenesis: impacted food debris &

edema around orifice following injuryedema around orifice following injury Ductal dilatation, periductal inflammation, Ductal dilatation, periductal inflammation,

secondary bacterial invasion & suppurationsecondary bacterial invasion & suppuration Predisposing factors: Hx of major surgery, Predisposing factors: Hx of major surgery,

dehydration, long-term phenothiazines Rxdehydration, long-term phenothiazines Rx

SALIVERAY GLANDSSALIVERAY GLANDS

TUMORSTUMORS Relatively uncommon; 2% of tumors in humansRelatively uncommon; 2% of tumors in humans 80% of tumors occur in parotid gland80% of tumors occur in parotid gland Equal M:F ratio; all ages [6th - 7th decade] Equal M:F ratio; all ages [6th - 7th decade] Most of these neoplasms are benign: 70-80% of Most of these neoplasms are benign: 70-80% of

parotid tumors and only 50% of submaxillary parotid tumors and only 50% of submaxillary tumorstumors

c/o: mass at angle of jawc/o: mass at angle of jaw Wide histologic variationsWide histologic variations

– Benign: Pleomorphic adenoma, WarthinBenign: Pleomorphic adenoma, Warthin’’s tumors tumor– Malignant: Carcinoma ex-pleomorphic adenoma, Malignant: Carcinoma ex-pleomorphic adenoma,

mucoepidermoid carcinoma, adenoid cystic mucoepidermoid carcinoma, adenoid cystic carcinomacarcinoma

TUMORS OF THE SALIVARY GLANDSTUMORS OF THE SALIVARY GLANDS

PLEOMORPHIC ADENOMAPLEOMORPHIC ADENOMA aka: mixed tumor: Most common tumor (65-aka: mixed tumor: Most common tumor (65-

80%) of the salivary glands80%) of the salivary glands Slowly growing well-demarcated, mostly Slowly growing well-demarcated, mostly

arising from superficial parotidarising from superficial parotid Pathology: heterogeneous histology with Pathology: heterogeneous histology with

epithelial elements, myxoid stroma, often epithelial elements, myxoid stroma, often containing chondroid foci or, rarely, bonecontaining chondroid foci or, rarely, bone

Px: recurrence after surgery: 10%Px: recurrence after surgery: 10% Malignant transformation: 15% in parotid, 40% Malignant transformation: 15% in parotid, 40%

in submandibular glandin submandibular gland

TUMORS OF THE SALIVARY GLANDSTUMORS OF THE SALIVARY GLANDS

WARTHIN’S TUMORWARTHIN’S TUMOR aka: Papillary cystadenoma lymphomatosumaka: Papillary cystadenoma lymphomatosum Benign slowly growing tumorsBenign slowly growing tumors 5-10% of all parotid tumors; extremely rare in 5-10% of all parotid tumors; extremely rare in

other salivery glandsother salivery glands Pathology: composed of cystic spaces lined Pathology: composed of cystic spaces lined

by tall columnar cells overlying abundant by tall columnar cells overlying abundant lymphoid tissuelymphoid tissue

Histogenesis: vestigial embryonic remnnants Histogenesis: vestigial embryonic remnnants of branchial cleft origin?of branchial cleft origin?

Rx: cured by surgical excisionRx: cured by surgical excision

PATHOLOGY OF THE SALIVARY GLANDSPATHOLOGY OF THE SALIVARY GLANDS

MICKULICZ’S SYNDROMEMICKULICZ’S SYNDROME Combination of salivary and lacrimal Combination of salivary and lacrimal

glands enlargement with xerostomiaglands enlargement with xerostomia May be due to many causes:May be due to many causes:

– SarcoidosisSarcoidosis

– Leukemia/lymphomaLeukemia/lymphoma

– SjogrenSjogren’’s syndromes syndrome

THE ALIMENTARY (DIGESTIVE) SYSTEMTHE ALIMENTARY (DIGESTIVE) SYSTEM

Oral cavity (including salivary glands)Oral cavity (including salivary glands) EsophagusEsophagus StomachStomach Small intestineSmall intestine ColonColon AppendixAppendix LiverLiver Biliary tractBiliary tract PancreasPancreas

DISEASES OFDISEASES OF THE ESOPHAGUSTHE ESOPHAGUS

Congenital anatomic disordersCongenital anatomic disorders– Agenesis, atresia, fistula, stenosisAgenesis, atresia, fistula, stenosis

Acquired anatomic/motor disordersAcquired anatomic/motor disorders– Stenosis, webs & rings, HH, achalasia, ...Stenosis, webs & rings, HH, achalasia, ...

InflammationsInflammations– Reflux esophagitisReflux esophagitis

BarrettBarrett’’s esophagus s esophagus Vascular diseasesVascular diseases TumorsTumors

CLINICAL FEATURES OFCLINICAL FEATURES OF DISEASES OF THE ESOPHAGUSDISEASES OF THE ESOPHAGUS

Different esophageal diseases share a limited number Different esophageal diseases share a limited number of symptoms:of symptoms:– Dysphagia: difficulty in swallowingDysphagia: difficulty in swallowing

» deranged esophageal motor functionderanged esophageal motor function» narrowing or obstruction of lumennarrowing or obstruction of lumen

– Heartburn: retrosternal burning painHeartburn: retrosternal burning pain» regurgitation of gastric contentsregurgitation of gastric contents

– Hematemesis: vomiting of bloodHematemesis: vomiting of blood– Melena: blood in stoolsMelena: blood in stools

» severe inflammation, ulceration or lacerationsevere inflammation, ulceration or laceration– Respiratory symptoms: dyspnea, cough,..Respiratory symptoms: dyspnea, cough,..

» aspirationaspiration

PATHOLOGY OF THE ESOPHAGUSPATHOLOGY OF THE ESOPHAGUS CONGENITAL ANATOMIC DISORDERSCONGENITAL ANATOMIC DISORDERS

Present at birth with vomiting, aspiration Present at birth with vomiting, aspiration (pneumonia, asphyxia), gastric distention(pneumonia, asphyxia), gastric distention

Agenesis:Agenesis: absence of esophagus. Very rare absence of esophagus. Very rare Atresia:Atresia: failure of development of a segment of failure of development of a segment of

esophagus, which is replaced by a thin non-esophagus, which is replaced by a thin non-canalized cord (absence of lumen) with formation canalized cord (absence of lumen) with formation of upper & lower pouches; associated with of upper & lower pouches; associated with tracheo-esophageal fistulatracheo-esophageal fistula

Stenosis:Stenosis: developmental defect resulting in partial developmental defect resulting in partial obstruction or narrowing of the esophageal lumenobstruction or narrowing of the esophageal lumen

Rx: Urgent medical & surgical interventionRx: Urgent medical & surgical intervention

PATHOLOGY OF THE ESOPHAGUSPATHOLOGY OF THE ESOPHAGUS

ACQUIRED ANATOMIC DISORDERSACQUIRED ANATOMIC DISORDERS

StenosisStenosis : : caustic strictures ,post-surgical ,inflammatory,caustic strictures ,post-surgical ,inflammatory,

tumours , autoimmune diseases ( Scleroderma ) .tumours , autoimmune diseases ( Scleroderma ) .

Webs & RingsWebs & Rings : Mucosal webs or mucosal and submucosal : Mucosal webs or mucosal and submucosal

concentric ring partially occluding the esophagus .concentric ring partially occluding the esophagus .

DiverticulaDiverticula : outpouching of the esophageal wall : outpouching of the esophageal wall

ACQUIRED ANATOMIC/MOTOR DISORDERS OF THE ESOPHAGUSACQUIRED ANATOMIC/MOTOR DISORDERS OF THE ESOPHAGUS

HIATAL HERNIAHIATAL HERNIA Protrusion of a dilated sac-like segment of Protrusion of a dilated sac-like segment of

stomach above the diaphragmstomach above the diaphragm Separation of the diaphragmatic cruraSeparation of the diaphragmatic crura Incidence: 1-20% of adults; increase with ageIncidence: 1-20% of adults; increase with age Mostly asymptomaticMostly asymptomatic c/o heartburn & regurgitation of gastric juices in c/o heartburn & regurgitation of gastric juices in

9% due to LES incompetence; related to position; 9% due to LES incompetence; related to position; symptoms are accentuated by positions favoring symptoms are accentuated by positions favoring refluxreflux

Patients with severe reflux esophagitis usually Patients with severe reflux esophagitis usually have HH; however, HH & reflux are not the same have HH; however, HH & reflux are not the same conditioncondition

TYPES OFTYPES OF

HIATAL HERNIAHIATAL HERNIA 2 anatomic patterns:2 anatomic patterns:

– Sliding (axial): 95% of cases; bell-shaped dilation; due Sliding (axial): 95% of cases; bell-shaped dilation; due to congenital short esophagus, strictures, spasm or to congenital short esophagus, strictures, spasm or long-standing fibrous scarring of esophagus, resulting long-standing fibrous scarring of esophagus, resulting in traction on stomachin traction on stomach

– paraesophageal (non-axial or rolling): segement of paraesophageal (non-axial or rolling): segement of cardiac stomach dissects alongside esophagus cardiac stomach dissects alongside esophagus through a defect. May follow traumatic rupture of through a defect. May follow traumatic rupture of diaphragm; may strangulate and infarctdiaphragm; may strangulate and infarct


ACHALASIAACHALASIA Failure to relax, i.e., incomplete relaxation of LES in Failure to relax, i.e., incomplete relaxation of LES in

response to swallowing, producing functional response to swallowing, producing functional obstruction & dilation of more proximal esophagusobstruction & dilation of more proximal esophagus

c/o progressive dysphagia to liquids and solid food, c/o progressive dysphagia to liquids and solid food, nocturnal regurgitation & aspiration of undigested nocturnal regurgitation & aspiration of undigested food, aspiration pneumoniafood, aspiration pneumonia

Abnormal manometric studies: aperistalsis, partial Abnormal manometric studies: aperistalsis, partial relaxation of LES, & increased basal tone of LES relaxation of LES, & increased basal tone of LES

Pathology: deranged innervation of LES; absent Pathology: deranged innervation of LES; absent myenteric ganglia in the body of esophagus; normal, myenteric ganglia in the body of esophagus; normal, hypertrophic , or thining of muscles; associated hypertrophic , or thining of muscles; associated mucosal inflammation, ulcer or fibrosismucosal inflammation, ulcer or fibrosis

TYPES OFTYPES OF

ACHALASIAACHALASIA Two main types:Two main types:

– Primary (sporadic): Commoner. Unknown causePrimary (sporadic): Commoner. Unknown cause ? Autoimmune. ? Previous viral infection.? Autoimmune. ? Previous viral infection.– Secondary:Secondary:

» ChagaChaga’’s disease: s disease: Tryponosoma cruziTryponosoma cruzi infection causing infection causing destruction of myenteric plexus ganglion cells in the GIT & destruction of myenteric plexus ganglion cells in the GIT & ureter; megaduodenum, megacolon, megaureterureter; megaduodenum, megacolon, megaureter

» Diabetes (Diabetes (Autonomic neuropathyAutonomic neuropathy); vagus nerve injury ..); vagus nerve injury ..

Esophageal squamous cell carcinoma in 5% Esophageal squamous cell carcinoma in 5% usually in younger age than in patients without usually in younger age than in patients without this diseasethis disease


LACERATIONS LACERATIONS aka: Mallory-Weiss syndromeaka: Mallory-Weiss syndrome Longitudinal tears at the esophago-gastric Longitudinal tears at the esophago-gastric

junctionjunction Encountered in alcoholics, after bout of severe Encountered in alcoholics, after bout of severe

retching or vomitingretching or vomiting Pathogenesis: inadequate relaxation of LES Pathogenesis: inadequate relaxation of LES

muscle during vomitingmuscle during vomiting May occur in patients without hx of vomitingMay occur in patients without hx of vomiting HH is found in 75% of patients with MWSHH is found in 75% of patients with MWS Linear irregular lacerations, few mm-cm in lengthLinear irregular lacerations, few mm-cm in length Involve mucosa or deeply penetrate & perforate Involve mucosa or deeply penetrate & perforate

wallwall 5-10% of all cases of massive hemetemesis; 5-10% of all cases of massive hemetemesis;

however, the majority do not cause profuse however, the majority do not cause profuse bleedingbleeding

VASCULAR LESIONS OF THE ESOPHAGUSVASCULAR LESIONS OF THE ESOPHAGUS

VARICESVARICES Due to portal hypertension, which leads to formation of Due to portal hypertension, which leads to formation of

portal-systemic collateral bypass channelsportal-systemic collateral bypass channels Collateral veins will develop in the region of lower Collateral veins will develop in the region of lower

esophagus when portal flow is diverted through the esophagus when portal flow is diverted through the coronary veins of stomach into the plexus of esophageal coronary veins of stomach into the plexus of esophageal submucosal veins into azygous veinssubmucosal veins into azygous veins

Most common cause of portal hypertension is liver Most common cause of portal hypertension is liver cirrhosiscirrhosis

Rare causes: portal vein thrombosis, hepatic vein Rare causes: portal vein thrombosis, hepatic vein thrombosis (Budd-Chiari syndrome), pylephlebitis, tumor thrombosis (Budd-Chiari syndrome), pylephlebitis, tumor compression or invasion into major portal radicalscompression or invasion into major portal radicals

VASCULAR LESIONS OF THE ESOPHAGUSVASCULAR LESIONS OF THE ESOPHAGUS

ESOPHAGEAL VARICESESOPHAGEAL VARICES Tortuous dilated veins directly beneath mucosa Tortuous dilated veins directly beneath mucosa

or in periesophageal tissue. Overlying mucosa or in periesophageal tissue. Overlying mucosa may be normal or eroded & inflammed; +/- may be normal or eroded & inflammed; +/- thrombosisthrombosis

Asymptomatic until they rupture when massive Asymptomatic until they rupture when massive hemetemesis results; rupture may be hemetemesis results; rupture may be spontaneous or secondary to vomiting; spontaneous or secondary to vomiting; hemorrhage rarely subsides spontaneously; 40% hemorrhage rarely subsides spontaneously; 40% die after 1st episodedie after 1st episode

70% of survivors will rebleed within 1 year; 70% of survivors will rebleed within 1 year; mortality rate 40% mortality rate 40%

Develops in 2/3 of cirrhotic patients; accounts for Develops in 2/3 of cirrhotic patients; accounts for 50% of deaths in liver cirrhosis50% of deaths in liver cirrhosis

INFLAMMATIONS OF THE ESOPHAGUS INFLAMMATIONS OF THE ESOPHAGUS

ESOPHAGITISESOPHAGITIS Caused by multiple factors: Caused by multiple factors:

– 1. Reflux of gastric contents (reflux esophagitis)1. Reflux of gastric contents (reflux esophagitis)– 2. Ingestion of irritants (alcohol, corrosive acids, alkali, 2. Ingestion of irritants (alcohol, corrosive acids, alkali,

excessive hot fluids like tea, heavy smoking)excessive hot fluids like tea, heavy smoking)– 3. Bacteremia & viremia with direct infection of 3. Bacteremia & viremia with direct infection of

esophageal wall or contiguous structures (HSV, CMV)esophageal wall or contiguous structures (HSV, CMV)– 4. Fungal infections in immunocompromised patients 4. Fungal infections in immunocompromised patients

(Candidasis, mucormycosis, aspergillosis)(Candidasis, mucormycosis, aspergillosis)– 5. Systemic desquamative skin diseases (pemphigoid)5. Systemic desquamative skin diseases (pemphigoid)– 6. Graft-versus-host disease6. Graft-versus-host disease– 7. Radiation; cytotoxic therapy; uremia7. Radiation; cytotoxic therapy; uremia

INFLAMMATIONS OF THE ESOPHAGUSINFLAMMATIONS OF THE ESOPHAGUS

REFLUX ESOPHAGITISREFLUX ESOPHAGITISGastroesophageal Reflux Disease ( GORD )Gastroesophageal Reflux Disease ( GORD )

Reflux of gastric contents is commonest cause of Reflux of gastric contents is commonest cause of esophagitisesophagitis

Pathogenesis:Pathogenesis:– Frequent & protracted reflux due to incompetence of Frequent & protracted reflux due to incompetence of

LES & decreased efficacy of other antireflux LES & decreased efficacy of other antireflux mechanisms (diaphragm, cardio-esophageal angle, mechanisms (diaphragm, cardio-esophageal angle, pressure on intraabdominal esophagus)pressure on intraabdominal esophagus)

– Disordered esophageal motility: gastric contents Disordered esophageal motility: gastric contents remains longer in contact with mucosaremains longer in contact with mucosa

– Elevated acid peptic levels of regurgitated fluid and Elevated acid peptic levels of regurgitated fluid and duodenal bile acids & lysolecithinduodenal bile acids & lysolecithin

– Impaired reparative capacity of the esophageal mucosaImpaired reparative capacity of the esophageal mucosa

CLINICAL FEATURES OFCLINICAL FEATURES OF

REFLUX ESOPHAGITISREFLUX ESOPHAGITIS Predisposing factors:Predisposing factors:

– Fat, chocolate, alcohol, smoking Fat, chocolate, alcohol, smoking ……– Hiatal herniaHiatal hernia– PregnancyPregnancy– DrugsDrugs

Consequences of reflux:Consequences of reflux:– If occasional: no consequencesIf occasional: no consequences– It recurrent & persistent: inflammation, It recurrent & persistent: inflammation,

ulceration, bleeding, stricture, Barrettulceration, bleeding, stricture, Barrett’’s s esophagus, dysplasia ..esophagus, dysplasia ..

PATHOLOGY OFPATHOLOGY OF

ESOPHAGITISESOPHAGITIS Pathologic findings:Pathologic findings:

– Depend on the cause, duration & severityDepend on the cause, duration & severity– Hyperemia, edema, wall thickening, pseudo-Hyperemia, edema, wall thickening, pseudo-

membrane formation, necrosis & ulcerationmembrane formation, necrosis & ulceration– Fibrosis & stricture formation may followFibrosis & stricture formation may follow– Candidal esophagitis: gray-white inflammatory Candidal esophagitis: gray-white inflammatory

pseudomembranespseudomembranes– Viral esophagitis: intranuclear inclusionsViral esophagitis: intranuclear inclusions

– Reflux esophagitis: basal zone hyperplasia & Reflux esophagitis: basal zone hyperplasia & presence of intra-epithelial eosinophils &/or PMNspresence of intra-epithelial eosinophils &/or PMNs

PRE-MALIGNANT LESIONS OF THE ESOPHAGUS PRE-MALIGNANT LESIONS OF THE ESOPHAGUS

BARRETT’S ESOPHAGUSBARRETT’S ESOPHAGUS Condition in which a gastric or intestinal type of Condition in which a gastric or intestinal type of

mucosa (i.e., metaplasia) lines the distal esophagus mucosa (i.e., metaplasia) lines the distal esophagus above the LESabove the LES

Mostly acquired & in adults, but may be seen in Mostly acquired & in adults, but may be seen in children, and rarely congenital in originchildren, and rarely congenital in origin

Complication of long-standing reflux Complication of long-standing reflux

inflammation and ulceration of squamous mucosa inflammation and ulceration of squamous mucosa healing by re-epithelialization & ingrowth of healing by re-epithelialization & ingrowth of pluripotential stem cells which differentiate into pluripotential stem cells which differentiate into gastric or intestinal epitheliumgastric or intestinal epithelium

CLINICAL FEATURES OFCLINICAL FEATURES OF

BARRETT’S ESOPHAGUSBARRETT’S ESOPHAGUS Clinical symptoms:Clinical symptoms:

– Dysphagia, retrosternal pain, hemetemesis, melenaDysphagia, retrosternal pain, hemetemesis, melena

Secondary complications:Secondary complications:– BarrettBarrett’’s ulcerss ulcers– StricturesStrictures– Dysplasia Dysplasia – Adenocarcinoma: 8-10% of patients develop Ca Adenocarcinoma: 8-10% of patients develop Ca

(patients with Barrett(patients with Barrett’’s esophagus have 30-100X s esophagus have 30-100X higher risk than general population)higher risk than general population)

BarrettBarrett’’s esophagus is the only recognized s esophagus is the only recognized precursor of esophageal precursor of esophageal adenoadenocarcinomacarcinoma

ESOPHAGEALESOPHAGEAL

TUMORSTUMORS Benign tumors are rare: leiomyoma is the Benign tumors are rare: leiomyoma is the

most common, and is usually small, most common, and is usually small, asymptomatic and discovered incidentallyasymptomatic and discovered incidentally

Malignant tumors: Esophageal cancer is the Malignant tumors: Esophageal cancer is the 7th most common tumor in humans7th most common tumor in humans– More common in males (M:F=3:1)More common in males (M:F=3:1)– Great variation in geograhic distributionGreat variation in geograhic distribution– Commonest types: Squamous cell carcinoma Commonest types: Squamous cell carcinoma

and adenocarcinomaand adenocarcinoma

TUMORS OF THE ESOPHAGUSTUMORS OF THE ESOPHAGUS

SQUAMOUS CELL CARCINOMASQUAMOUS CELL CARCINOMA 80-85% of esophageal cancers80-85% of esophageal cancers

10% of all GIT cancers; higher contribution to mortality 10% of all GIT cancers; higher contribution to mortality (asymptomatic with late diagnosis)(asymptomatic with late diagnosis)

Patients: most patients are adults >50 yrs; M>FPatients: most patients are adults >50 yrs; M>F– Higher incidence in certain countries (Iran, China..)Higher incidence in certain countries (Iran, China..)– Higher incidence in blacks than whitesHigher incidence in blacks than whites

Etiology & pathogenesis: multifactorial with environmental Etiology & pathogenesis: multifactorial with environmental & dietary factors acting synergistically& dietary factors acting synergistically

RISK FACTORS FOR ESOPHAGEALRISK FACTORS FOR ESOPHAGEAL

SQUAMOUS CELL CARCINOMASQUAMOUS CELL CARCINOMA Associated factors:Associated factors:

– 1) Dietary:1) Dietary:» Fungal contamination of food (Aspergillus)Fungal contamination of food (Aspergillus)» High content of nitrites/nitrosaminesHigh content of nitrites/nitrosamines» Deficiency of vitamins (A, C, riboflavin, thiamin, ..)Deficiency of vitamins (A, C, riboflavin, thiamin, ..)» Deficiency of trace metals (zinc, molybdenum)Deficiency of trace metals (zinc, molybdenum)

– 2) Esophageal disease: achalasia, reflux 2) Esophageal disease: achalasia, reflux esophagitis , strictures, Plummer-Vinson syndromeesophagitis , strictures, Plummer-Vinson syndrome– 3) Lifestyle: Alcohol & tobacco abuse3) Lifestyle: Alcohol & tobacco abuse– 4) Racial or genetic predisposition: blacks; celiac 4) Racial or genetic predisposition: blacks; celiac disease, Tylosis, ...disease, Tylosis, ...- 5) ? HPV in squamous cell carcinoma5) ? HPV in squamous cell carcinoma- 6) p16/INK4 tumor supressor gene & EGF receptor 6) p16/INK4 tumor supressor gene & EGF receptor abnormalities. p53 mutations in 50% .abnormalities. p53 mutations in 50% .

PATHOLOGY & CLINICAL FEATURES OF ESOPHAGEALPATHOLOGY & CLINICAL FEATURES OF ESOPHAGEAL

SQUAMOUS CELL CARCINOMASQUAMOUS CELL CARCINOMA Pathology:Pathology:

– 50% in mid 1/3; 30% in lower 1/3; 20% in upper 1/350% in mid 1/3; 30% in lower 1/3; 20% in upper 1/3– Starts as in situ lesion; thickening of mucosaStarts as in situ lesion; thickening of mucosa– Polypoid fungating (60%); ulcer (25%); diffuse (15%)Polypoid fungating (60%); ulcer (25%); diffuse (15%)– Grade: Most are well to moderately differentiatedGrade: Most are well to moderately differentiated– Stage: I (<5 cm), II (>5 cm; resectable LN), III (>10 cm; Stage: I (<5 cm), II (>5 cm; resectable LN), III (>10 cm;

extension to adjacent tissue; inoperable); IV (perforation; extension to adjacent tissue; inoperable); IV (perforation; metastasis)metastasis)

Clinical feature: symptoms are gradual & late; include Clinical feature: symptoms are gradual & late; include dysphagia, extreme weight loss, aspiration, hemorrhage & dysphagia, extreme weight loss, aspiration, hemorrhage & sepsissepsis

Rx: surgery & radiotherapyRx: surgery & radiotherapy Px: 70% die within 1 yr; 5 yrs survival 5-10%Px: 70% die within 1 yr; 5 yrs survival 5-10%

TUMORS OF THE ESOPHAGUSTUMORS OF THE ESOPHAGUS

ADENOCARCINOMAADENOCARCINOMA 5-10% of esophageal cancers; rising incidence5-10% of esophageal cancers; rising incidence Middle or lower third; may extend to stomachMiddle or lower third; may extend to stomach Vast majority arise from BarrettVast majority arise from Barrett’’s esophaguss esophagus Most are adults >40 yrs; M:F=5:1; v. rare in blacksMost are adults >40 yrs; M:F=5:1; v. rare in blacks Mass or nodular elevation of mucosa; frequently Mass or nodular elevation of mucosa; frequently

multicentricmulticentric Histologic types: intestinal, diffuse (signet cell) or Histologic types: intestinal, diffuse (signet cell) or

adenosquamousadenosquamous Grade: most are moderately to poorly Grade: most are moderately to poorly

differentiateddifferentiated Stage: similar to squamous cell carcinomaStage: similar to squamous cell carcinoma c/o: progressive dysphagia; long standing c/o: progressive dysphagia; long standing

symptomssymptoms

Barrett’s &AdenocarcinomaBarrett’s &Adenocarcinoma

Progression of low grade dysplasia is very Progression of low grade dysplasia is very lowlow

Progression of high grade dysplasia is about Progression of high grade dysplasia is about 10% or more per year10% or more per year

Overall risk is 30-fold to more than 100-Overall risk is 30-fold to more than 100-fold above normalfold above normal

P53 mutations P53 mutations Alterations in HER-2 and B-catenin Alterations in HER-2 and B-catenin

DISEASES OF THEDISEASES OF THE STOMACHSTOMACH

Congenital anomaliesCongenital anomalies– Diaphragmatic hernia & pyloric stenosisDiaphragmatic hernia & pyloric stenosis

InflammationsInflammations– GastritisGastritis– Acute erosions & ulcerationsAcute erosions & ulcerations– Peptic ulcerPeptic ulcer

TumorsTumors– PolypsPolyps– AdenocarcinomaAdenocarcinoma– LymphomaLymphoma

CONGENITAL ANOMALIES OF THE STOMACHCONGENITAL ANOMALIES OF THE STOMACH

DIAPHRAGMATIC HERNIADIAPHRAGMATIC HERNIA Weakness or partial-to-total absence of a Weakness or partial-to-total absence of a

region of the diaphragm, permitting abdominal region of the diaphragm, permitting abdominal contents to herniate into the thoraxcontents to herniate into the thorax

Defect does not involve the hiatal orifice (vs. Defect does not involve the hiatal orifice (vs. HH)HH)

Hernia wall often be composed of peritoneum Hernia wall often be composed of peritoneum & pleura& pleura

Portion of stomach, small intestine or liver Portion of stomach, small intestine or liver may protrude into hernial pouchmay protrude into hernial pouch

Symptoms depend on size: Asymptomatic to Symptoms depend on size: Asymptomatic to acute respiratory distress in newbornacute respiratory distress in newborn

RareRare

CONGENITAL ANOMALIES OF THE STOMACHCONGENITAL ANOMALIES OF THE STOMACH

PYLORIC STENOSISPYLORIC STENOSIS Familial condition (multifactorial inheritance)Familial condition (multifactorial inheritance) Patients: 1:300-900 live births; M:F=3:1Patients: 1:300-900 live births; M:F=3:1 Pathology: Hypertrophy & hyperplasia of circular Pathology: Hypertrophy & hyperplasia of circular

muscle of muscularis propria of pylorus; muscle of muscularis propria of pylorus; narrowing of lumen leads to mucosal edema and narrowing of lumen leads to mucosal edema and inflammationinflammation

c/o: regurgitation & persistent projectile vomiting c/o: regurgitation & persistent projectile vomiting usually appear in 2nd-3rd week of life. usually appear in 2nd-3rd week of life.

o/e: visible peristalsis & firm ovoid palpable mass o/e: visible peristalsis & firm ovoid palpable mass in abdomenin abdomen

Rx: PyloromyotomyRx: Pyloromyotomy

INFLAMMATIONS OF THE STOMACHINFLAMMATIONS OF THE STOMACH

GASTRITISGASTRITIS Inflammation of the gastric mucosaInflammation of the gastric mucosa Overused term and underdiagnosed conditionOverused term and underdiagnosed condition Classification:Classification:

– 1) Acute gastritis1) Acute gastritis– 2) Chronic gastritis: most cases; prevalence exceeds 50% 2) Chronic gastritis: most cases; prevalence exceeds 50%

in adults >50 yrs; usually asymptomatic or cause few in adults >50 yrs; usually asymptomatic or cause few symptoms (upper abdominal discomfort, nausea and symptoms (upper abdominal discomfort, nausea and vomiting)vomiting)» Helicobacter pylori associated gastritis: main causeHelicobacter pylori associated gastritis: main cause» Autoimmune (atrophic) gastritisAutoimmune (atrophic) gastritis» Hypertrophic gastritis (gastropathy)Hypertrophic gastritis (gastropathy)» Granulomatous gastritis; eosinophilic gastritisGranulomatous gastritis; eosinophilic gastritis


ACUTE GASTRITISACUTE GASTRITIS Acute mucosal inflammation, usually of transient Acute mucosal inflammation, usually of transient

naturenature May be accompanied by hemorrhage & erosionsMay be accompanied by hemorrhage & erosions Pathology: spectrum of severity: acute simple Pathology: spectrum of severity: acute simple

gastritis, acute hemorrhagic gastritis, acute erosive gastritis, acute hemorrhagic gastritis, acute erosive gastritis, acute stress gastritis & perforated acute ulcergastritis, acute stress gastritis & perforated acute ulcer

Pathogenesis isPathogenesis is poorly understood: multifactorial due poorly understood: multifactorial due to loss of balance between: to loss of balance between: – gastric acidity: stimulation of acid secretion by Hgastric acidity: stimulation of acid secretion by H+ + back-back-

diffusion, decreased bicarbonate buffer productiondiffusion, decreased bicarbonate buffer production– mucosal resistance: reduced mucosal blood flow, mucosal mucosal resistance: reduced mucosal blood flow, mucosal

cell disruption or direct epithelial damagecell disruption or direct epithelial damage

RISK FACTORS & CLINICAL FEATURES OFRISK FACTORS & CLINICAL FEATURES OF ACUTE GASTRITISACUTE GASTRITIS

Frequently associated with:Frequently associated with:– Heavy use of NSAIDs, especially aspirin (up to 25%)Heavy use of NSAIDs, especially aspirin (up to 25%)– Excessive alcohol consumption Excessive alcohol consumption – Heavy smokingHeavy smoking– Severe stress, e.g. trauma, burns, surgerySevere stress, e.g. trauma, burns, surgery– Ischemia and shock; suicidal attempts with acids/alkaliIschemia and shock; suicidal attempts with acids/alkali– Mechanical trauma (NG tube); post-gastrectomyMechanical trauma (NG tube); post-gastrectomy– Chemotherapeutic Rx; uremia; systemic infectionsChemotherapeutic Rx; uremia; systemic infections

Clinical features depend on severity: asymptomatic Clinical features depend on severity: asymptomatic or variable epigastric pain, nausea, vomiting, or variable epigastric pain, nausea, vomiting, hemetemesis (particularly alcoholics), melena & fatal hemetemesis (particularly alcoholics), melena & fatal blood lossblood loss


CHRONIC CHRONIC HELICOBACTER PYLORIHELICOBACTER PYLORI GASTRITISGASTRITIS

Commonest form of gastritisCommonest form of gastritis H. pylori H. pylori is a widespread noninvasive curved is a widespread noninvasive curved

gram -ve rod, which is present in gastric gram -ve rod, which is present in gastric mucosal surface of 50% of adults >50 yrs oldmucosal surface of 50% of adults >50 yrs old

Infection may be acquired in childhood Infection may be acquired in childhood Most infected individuals have gastritis but Most infected individuals have gastritis but

are asymptomaticare asymptomatic Pathogenesis: Directly by bacterial enzymes Pathogenesis: Directly by bacterial enzymes

& toxins, and indirectly by recruitment of & toxins, and indirectly by recruitment of PMNs which release noxious chemicalsPMNs which release noxious chemicals

PATHOLOGY & CLINICAL FEATURES OFPATHOLOGY & CLINICAL FEATURES OF CHRONIC CHRONIC HELICOBACTER PYLORIHELICOBACTER PYLORI GASTRITIS GASTRITIS Appearance: Hyperemic edematous gastric Appearance: Hyperemic edematous gastric

mucosamucosa Pathology: Pathology:

– Lymphocytic & plasma cell infiltrate in lamina Lymphocytic & plasma cell infiltrate in lamina propria, accompanied by PMNs inflammation propria, accompanied by PMNs inflammation of neck region of mucosal pits (cryptitis and of neck region of mucosal pits (cryptitis and crypt abscess)crypt abscess)

– Proliferation of lymphoid tissueProliferation of lymphoid tissue Clinical features are variableClinical features are variable Rx: anti-acid drugs and antibioticsRx: anti-acid drugs and antibiotics Px: Relapses are associated with reappearance Px: Relapses are associated with reappearance

of of H. pyloriH. pylori; peptic ulcer disease; association ; peptic ulcer disease; association with gastric lymphomawith gastric lymphoma

Table 17-2. Diseases Associated with Helicobacter pylori Infection

Disease Association

Chronic gastritis Strong causal associationPeptic ulcer disease Strong causal associationGastric carcinoma Strong causal associationGastric MALT lymphoma*Definitive etiologic role

Clinical significance of Helicobacter Clinical significance of Helicobacter associated chronic gastritisassociated chronic gastritis

Most common cause of chronic gastritis and Most common cause of chronic gastritis and peptic ulcer disease.peptic ulcer disease.

Long term risk for gastric carcinoma (5 fold Long term risk for gastric carcinoma (5 fold risk). gastric atrophy, intestinal metaplasia, risk). gastric atrophy, intestinal metaplasia, and dysplasia role.and dysplasia role.

Long term risk for gastric MALT-Long term risk for gastric MALT-lymphoma.lymphoma.

?Future possible prophylactic vaccines?Future possible prophylactic vaccines

pathology of the gastrointestinal tract ismail matalka,mrcpath department of pathology jordan...

Documents