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GASTROINTESTINAL GASTROINTESTINAL DISORDERSDISORDERSFe A. Bartolome, MD, FPASMAP
Department of Pathology
Our Lady of Fatima University
CLASSIFICATION CLASSIFICATION OF GI DISEASESOF GI DISEASES
Impaired Digestion & Impaired Digestion & AbsorptionAbsorption• Diseases of the stomach, intestine, biliary
tree & pancreas disrupt nutrient digestion and absorption
• Examples:1. Gastric hypersecretory syndromes (e.g.
Zollinger-Ellison syndrome) Damage intestinal mucosa Impair pancreatic enzyme activation
2. Lactase deficiency Most common intestinal
maldigestion syndrome3. Biliary obstruction from stricture or
neoplasm4. Chronic pancreatitis or pancreatic CA
Altered SecretionAltered Secretion
1. Gastric acid hypersecretion• Zollinger-Ellison syndrome, G cell
hyperplasia, duodenal ulcer disease
2. Decreased or absent gastric acid secretion• Atrophic gastritis or pernicious anemia
3. Fluid loss through impaired absorption or enhanced secretion• Inflammatory and infectious small-
intestinal and colonic diseases• Laxative abuse• Endocrine neoplasias with secretion of
vasoactive intestinal polypeptide (VIP)
Altered Gut TransitAltered Gut Transit
1. Mechanical obstruction
• Esophagus – acid-induced stricture or neoplasm
• Stomach – PUD or gastric cancer• Small intestines
Adhesions – most common Crohn’s disease, radiation-induced
strictures, malignancy• Colon
Colon cancer – most common Inflammatory strictures in patients
with inflammatory bowel disease
Altered Gut TransitAltered Gut Transit
2. Disordered gut motor function
• Achalasia – impaired esophageal body peristalsis
• Gastroparesis – symptomatic delay in gastric emptying of solid or liquid meals due to impaired gastric motility
• Injury to enteric nerves or intestinal smooth muscle intestinal pseudo- obstruction
• Impaired colonic propulsion constipation
Immune DysregulationImmune Dysregulation
• Celiac disease – mucosal inflammation due to ingestion of gluten-containing grains
• Eosinophilic esophagitis and gastroenteritis
• Ulcerative colitis & Crohn’s disease
• Bacterial, viral, and protozoal ileitis and colitis in selected patients
Impaired Gut Blood FlowImpaired Gut Blood Flow
• Gastroparesis may result from blockage of the celiac and superior mesenteric arteries
• Intestinal and colonic ischemia – more common; may be due to: Arterial thrombosis or embolus Venous thrombosis Hypoperfusion from dehydration,
sepsis, hemorrhage or reduced cardiac output
Neoplastic DegenerationNeoplastic Degeneration
• All GI regions are susceptible to malignant degeneration to varying degrees
• Most GI cancers are carcinomas, but lymphomas & tumors of other cell types are also observed
• Colorectal CA – most common in U.S.
• Gastric CA – worldwide & esp. in certain regions in Asia
• Esophageal CA – associated with chronic acid reflux & extensive alcohol and tobacco use
Disorders without Obvious Organic Disorders without Obvious Organic AbnormalitiesAbnormalities
• Irritable bowel syndrome, functional dyspepsia, non-cardiac chest pain, functional heartburn no abnormalities on biochemical or structural testing
• With altered gut motor function
• Exaggerated visceral sensory responses to noxious stimulation may cause discomfort
• Patients may exhibit significant emotional disturbances on psychometric testing
Symptoms of Gastrointestinal DiseaseSymptoms of Gastrointestinal Disease
Common Causes of Common GI Symptoms
Abdominal Pain
Appendicitis
Gallstone disease
Pancreatitis
Diverticulitis
Ulcer disease
Esophagitis
GI obstruction
Nausea & Vomiting
Medications
GI obstruction
Motor disorders
Functional bower d.o.Enteric infectionPregnancy
Endocrine disease
Diarrhea
Infection
Poorly absorbed sugarsInflam. Bowel dse.
Microscopic colitisFxnal bowel disorderCeliac dse.
Pancreatic insuff.
GI Bleeding
Ulcer disease
Esophagitis
Varices
Vascular lesionsNeoplasm
Diverticula
Hemorrhoids
Obstructive Jaundice
Bile duct stonesCholangio- carcinoma
Cholangitis
Sclerosing cholangitisAmpullary stenosisAmpullary CAPancreatitis
Symptoms of Gastrointestinal DiseaseSymptoms of Gastrointestinal Disease
Common Causes of Common GI Symptoms
Abdominal Pain
Inflammatory bowel dse.
Functional bowel d.o.
Vascular disease
Gynecologic causes
Renal stone
Nausea & Vomiting
Motion sickness
CNS disease
Diarrhea
Hyper- thyroidism
Ischemia
Endocrine tumor
GI Bleeding
Fissures
Inflammatory bowel dse.
Infectious colitis
Obstructive Jaundice
Pancreatic tumor
Abdominal PainAbdominal Pain
• GI disease and extraintestinal conditions involving the GUT, abdominal wall, thorax or spine
• Visceral pain midline in location and vague in character
• Parietal pain localized and precisely described
• Most common causes are IBS and functional dyspepsia
Abdominal PainAbdominal Pain
• Other causes:
Inflammatory Peptic ulcer, appendicitis, IBD,
diverticulitis, infectious enterocolitis Gallstone disease, pancreatitis
Non-inflammatory Mesenteric ischemia Neoplasia
Heartburn Heartburn
• Burning sub-sternal sensation
• Result from excess gastroesophageal reflux of acid
Nausea and VomitingNausea and Vomiting
• Mechanical obstruction of upper gut
• Others: gastroparesis & intestinal pseudo-obstruction; IBS and functional disorders of upper gut
Altered Bowel HabitsAltered Bowel Habits
• Constipation Infrequent defecation Straining with defecation Passage of hard stools Sense of incomplete fecal evacuation Causes:
1. Obstruction2. Motor disorders of colon3. Medications4. Endocrine diseases (hypothyroidism
and hyperparathyroidism)
Altered Bowel HabitsAltered Bowel Habits
• Diarrhea Frequent defecation Passage of loose or watery stools Fecal urgency Sense of incomplete evacuation Causes:
1. Inflammatory – (+) pus in stool IBS – constipation, diarrhea, or
alternating bowel pattern; (+) fecal mucus
2. Infectious3. Malabsorption – (+) steatorrhea4. Medications
GI BleedingGI Bleeding
• Upper GI bleed – (+) melena or hematemesis Most common causes are: ulcer disease,
gastroduodenitis, and esophagitis
• Lower GI bleed – passage of bright red or maroon stools Most common causes are: hemorrhoids,
anal fissures, diverticula, ischemic colitis, and arteriovenous malformations
• Chronic slow GI bleed (+) iron deficiency anemia
Other SymptomsOther Symptoms
• Dysphagia, odinophagia & unexplained chest pain esophageal disease
• Weight loss, anorexia, fatigue neoplastic, inflammatory, gut motility, pancreatic, small bowel mucosal, and psychiatric conditions
• Extraintestinal symptoms IBD – hepatobiliary dysfunction, skin &
eye lesions, arthritis Celiac disease – dermatitis
herpetiformis
ESOPHAGEAL DISORDERS
Signs and Symptoms of Esophageal Signs and Symptoms of Esophageal Disease Disease
1. Heartburn• Most commonly due to GERD
2. Dysphagia for solids alone• Symptom of an obstructive lesion• Examples: esophageal cancer,
esophageal web, stricture3. Dysphagia for solids and liquids
• Signify motility disordera) Oropharyngeal (upper esophageal)
Striated muscle dysmotility Dermatomyositis, myasthenia
gravis, strokeb) Lower esophageal
Smooth muscle dysmotility Systemic sclerosis, achalasia
Esophageal AtresiaEsophageal Atresia
• Incomplete development
• Thin, non-canalized cord replaces a segment of esophagus, causing mechanical obstruction
• Proximal and distal blind pouches connect to the pharynx and stomach, respectively
• Occurs most commonly at or near the tracheal bifurcation usually associated with fistula connecting the upper or lower esophageal pouches to a bronchus or the trachea
Esophageal Atresia: TypesEsophageal Atresia: Types
EA with distal TEF
EA with proximal TEF
Isolated EA
EA with double TEF
Isolated TEF
Esophageal AtresiaEsophageal Atresia
• Fistulae can lead to aspiration, suffocation, pneumonia, and severe fluid and electrolyte imbalances Abdominal distention in NB
air in stomach from fistula Regurgitation of food
• EA associated with congenital heart defects, GU malformations, and neurologic disease
Esophageal StenosisEsophageal Stenosis
• Incomplete form of atresia
• Esophageal lumen markedly reduced in caliber due to fibrous thickening of the wall partial or complete obstruction
• May involve any part of the GIT esophagus & SI most commonly affected
Esophageal StenosisEsophageal Stenosis
• Associated with atrophy of the muscularis propria & secondary epithelial damage
• Causes:1. Congenital – occasional2. Inflammation and scarring
Most common Due to GERD, irradiation or
caustic injury
• Progressive dysphagia
Congenital esophageal stenosis in a young man with long-standing dysphagia and occasional superimposed food impactions. Double-contrast esophagogram shows an area of mild narrowing in the mid-esophagus with distinctive ring-like indentations (“ringed esophagus”) (arrows) in the region of the stricture.
Nutcracker EsophagusNutcracker Esophagus
• High-amplitude esophageal contractions
• Outer longitudinal layer of smooth muscle contracts before the inner circular layer of smooth muscles lack of coordination
• Cause periodic short-lived esophageal obstruction
Diffuse esophageal spasmDiffuse esophageal spasm
• Cause increased esophageal wall stress
• Result in functional obstruction
• Can cause small diverticulae to form
Diffuse esophageal spasm produces intermittent contractions of the mid and
distal esophageal smooth muscle, associated with chest symptoms. Patient
experienced chest pain during examination
Esophageal diverticulaeEsophageal diverticulae
• Small mucosal outpouchings
True diverticulae – with true muscularis
Pseudodiverticulae – lack true muscularis
Zenker’s Diverticulum
• Pharyngoesophageal diverticulum
• Occurs in older women
• Posteriorly at site of Killian's dehiscence = superior boundary is thyropharyngeal muscle and inferior boundary is cricopharyngeal muscle
• Pulsion diverticulum
• False diverticulum = herniation of mucosa and submucosa through muscular layer
Esophageal diverticulae: TypesEsophageal diverticulae: Types
Traction Diverticulum
•Mid-esophageal diverticulum
•May be formed in response to pull from fibrous adhesions following lymph node infection (usually TB)
•Or, may form from increased intraluminal pressure and be pulsion diverticula
•True diverticulum = contains all 3 esophageal layers
Epiphrenic Diverticulum
•Location is usually in distal esophagus on lateral esophageal wall, right > left
•Often associated with hiatal hernia
•Pulsion diverticulum
•False diverticulum
Esophageal mucosal websEsophageal mucosal webs
• Uncommon ledge-like protrusions of mucosa
• Women > 40 y/o
• Often associated with: 1. Gastroesophageal reflux2. Chronic graft-versus-host disease3. Blistering skin diseases
• Most common in upper esophagus (at level of cricopharyngeus or C5-C6)
• Main symptom is dysphagia associated with incompletely chewed food
Barium esophagram demonstrates a thin membrane arising from the anterior wall of
the cervicalesophagus at the level of C5-C6
without circumferential involvement of the lumen
characteristicfor an esophageal web
An upper esophageal web (arrow) in a patient with
Plummer-Vinson syndrome.
Esophageal mucosal websEsophageal mucosal webs
• Patterson-Brown-Kelly or Plummer-Vinson Syndrome
Iron deficiency anemia Stomatitis Glossitis Dysphagia Spoon-shaped nails Esophageal webs
Atrophic glossitisEsophageal
web
Hypochromic, microcytic anemia
Koilonychia (spoon-shaped fingernails)
Cheilitis (rhagades,
angular stomatitis)
Esophageal ringsEsophageal rings
• Similar to webs but circumferential and thicker
• Include mucosa, submucosa, and in some cases, hypertrophic muscularis propria
• If present in distal esophagus, above the gastroesophageal junction; covered by squamous mucosa A rings
• If located at squamocolumnar junction (Z line) of lower esophagus & with gastric cardia-type mucosa on undersurface B rings (Schatzki rings)
Esophageal A-ring due to muscular contraction. It varies during examination and may not
persist.
The esophageal B-ring is located at the squamocolumnar junction, also termed the 'Z' line. The appearance does not change during
the examination.
AchalasiaAchalasia
• Triad:1. Incomplete LES relaxation2. Increased LES tone3. Aperistalsis of the esophagus
• Impaired smooth muscle relaxation increased tone of LES
• Primary – idiopathic; failure of distal esophageal inhibitory neurons
• Secondary – Chaga’s disease, diabetic autonomic neuropathy, malignancy, amyloidosis, polio, surgical ablation
LEFT: Dilated esophagus (arrows) appears as long, well-defined structure paralleling heart RIGHT: Dilated esophagus usually deviates to right, narrowing (arrow) at hiatus.
Esophageal Causes of Esophageal Causes of HematemesisHematemesis
Mallory-Weiss SyndromeMallory-Weiss Syndrome
• Longitudinal tears near the gastro-esophageal junction; superficial lacerations
• Usually associated with severe retching or vomiting due to acute alcohol intoxication
Boerhaave SyndromeBoerhaave Syndrome
• Distal esophageal rupture and mediastinitis
• Occurs rarely; catastrophic• Causes:
1. Endoscopy (~75% of cases)2. Retching3. Bulimia
• Complications:1. Pneumomediastinum
Air dissects into subcutaneous tissue
Produces a crunching sound (Hamman’s crunch) on P.E.
2. Pleural effusion contains food, acid, amylase
Chemical EsophagitisChemical Esophagitis
• Alcohol, corrosive acids or alkalis, excessively hot fluids, heavy smoking
• Generally causes only self-limited pain, particularly with swallowing
• Complications: hemorrhage, stricture, perforation
Corrosive esophagitis. This is a vinegar-induced esophageal burn. The patient had a fish bone in her throat. She ingested vinegar in an attempt to dissolve the fish bone but to no avail; this led to corrosive esophagitis.
Pill-induced EsophagitisPill-induced Esophagitis
• Occurs when medicinal pills lodge and dissolve in the esophagus rather than passing into the stomach
• Frequently occurs at the site of strictures that prevent passage of luminal contents
Infectious EsophagitisInfectious Esophagitis
• Frequently in debilitated or immuno- compromised individuals commonly HSV, CMV, or fungi (Candidiasis most common) HSV – punched-out ulcers CMV – shallower ulcerations +
char. nuclear and cytoplasmic inclusions
Candida – adherent, gray-white pseudomembranes
This is Candida esophagitis. Tan-yellow plaques are seen in the lower esophagus, along with mucosal hyperemia. The same lesions are also seen at the
upper right in the stomach.
Candidiasis (thrush) of the esophagus.
A ‘pseudomembrane’ is present (top) on the surface of the stratified squamous epithelium. It consists of desquamated epithelial cells and thin filament-like fungi. The fungi has penetrated the superficial layer of the squamous epithelium which is separated from relatively unaffected basal layer.
Here are two sharply demarcated "punched out" ulcerations of the mid esophagus in an
immunocompromised patient with herpes simplex infection.
A herpetic ulcer is seen microscopically to have a sharp margin. The ulcer base at the left shows loss of overlying squamous epithelium with only necrotic debris remaining. Biopsies of these lesions reveals intranuclear inclusions in squamous epithelial cells indicative of herpes simplex virus esophagitis. This patient was immune compromised from chemotherapy.
Cytomegalovirus Infection.Microscopic sections reveal typical intranuclear inclusions Viral particles confirmed by electron microscopy
Reflux EsophagitisReflux Esophagitis
• Reflux of gastric contents into the lower esophagus called gastroesophageal reflux disease (GERD)
• Due to conditions that increase abdominal pressure or decrease lower esophageal sphincter tone1. Alcohol and tobacco use2. Obesity3. CNS depressants4. Pregnancy5. Hiatal hernia6. Delayed gastric emptying7. Increased gastric volume
Reflux EsophagitisReflux Esophagitis
• Morphology:
Simple hyperemia may be the only alteration
Mild GERD histology unremarkable
Severe GERDo Eosinophils & neutrophils in
squamous mucosao Basal zone hyperplasia > 20% of
the total epithelial thicknesso Elongation of lamina propria
papillae
Reflux EsophagitisReflux Esophagitis
Gross appearance of a severe case of reflux esophagitis. Marked hyperemia with focal hemorrhage is present in the area of reflux.
Reflux EsophagitisReflux Esophagitis
Gastroesophageal Reflux with Ulceration.A common pattern of reflux are longitudinal ulcers
arising from the gastroesophageal junction
Reflux EsophagitisReflux Esophagitis
Intra-epithelial eosinophils
Reflux EsophagitisReflux Esophagitis
Degrees of Gastroesophageal Reflux.In response to acid reflux, the squamous epithelium
becomesthicker with basal cell hyperplasia and elongated rete
papillae.
Reflux EsophagitisReflux Esophagitis
• Clinical Features:
Most common in adults > 40
Most common clinical symptoms:1. Dysphagia2. Heartburn
Other symptoms may include: regurgitation of sour-tasting gastric content; attacks of severe chest pain (chronic)
Reflux EsophagitisReflux Esophagitis
• Clinical Features:
Complications:1. Esophageal ulceration2. Hematemesis3. Melena4. Stricture development5. Barrett esophagus
• Treatment: proton pump inhibitors or H2 histamine receptor antagonists symptomatic relief
Eosinophilic EsophagitisEosinophilic Esophagitis
• Majority of affected individuals are atopic with atopic dermatitis, allergic rhinitis, asthma, or modest peripheral eosinophilia
• Symptoms: adults food impaction and dysphagia Children feeding intolerance and
GERD-like symptoms
• Essentials for diagnosis:1. Large numbers of intraepithelial
eosinophils2. Failure of high-dose proton pump
inhibitor treatment3. Absence of acid reflux
Eosinophilic EsophagitisEosinophilic Esophagitis
A, Reflux esophagitis shows papillary lengthening, basal hyperplasia, and rare intraepithelial eosinophils (IEEs) (hematoxylin-eosin, original magnification ×20). B, Eosinophilic esophagitis shows prominent IEEs, aggregates of eosinophils, and superficial eosinophils (hematoxylin-eosin, original magnification ×20)
Hiatal HerniaHiatal Hernia
• Characterized by separation of the diaphragmatic crura and protrusion of the stomach into the thorax through the resulting gap part of stomach protrudes through the diaphragm and up to the chest
• Symptomatic in < 10% of adults associated with other causes of LES incompetence
• Symptoms include heartburn and regurgitation of gastric juices, similar to GERD
Hiatal HerniaHiatal Hernia
• Other potential contributing factors:
1. Permanent shortening of esophagus due to inflammation and scarring from reflux of gastric acid pulls stomach up
2. Abnormally loose attachment of esophagus to diaphragm allow esophagus and stomach to slip upward
Hiatal HerniaHiatal Hernia
Hiatal Hernia: TypesHiatal Hernia: Types
Sliding Hernia
• Most common type• Gastroesophageal junction + part
of stomach protrude into the chest
Para-esophageal Hernia
• Gastroesophageal junction stays where it belongs (attached at level of diaphragm) but part of stomach protrudes into the chest beside the esophagus
With sliding or axial hiatal hernia there is thinning and elongation of the phrenoesophageal membrane leading to herniation of the stomach into the posterior mediastinum. As such, there is no potential for incarceration or strangulation. With paraesophageal herniation, visceral elements herniate through a focal weakness in the phrenoesophageal membrane with the potential to lead to the usual array of complications associated with visceral herniation through a constricted aperture. (Source: Modified from Skinner.15 with permission from American Gastroenterological Association.)
Barrett EsophagusBarrett Esophagus
• Complication of chronic GERD
• Characterized by intestinal metaplasia within the squamous mucosa (+) goblet cells necessary for diagnosis
• Most common in white males, between 40 – 60 yrs old
• Increased risk of esophageal adenoCA pre-malignant condition
Patients with Barrett's esophagus have a 30- to 125-fold increased risk of the development of esophageal cancer in
comparison with the general population. The disease is most common in white males.
Barrett EsophagusBarrett Esophagus
• Gross: tongues or patches of red, velvety mucosa extending upward from gastro-esophageal junction alternating with residual smooth, pale squamous mucosa
• Classification:1. Long segment - > 3 cm of
esophagus involved2. Short segment - < 3 cm of
esophagus involved
Barrett EsophagusBarrett Esophagus
• Microscopic:
(+) goblet cells
Gland architecture: budding, irregular shapes, and cellular crowding
Classification if with dysplasia:1. Low grade2. High grade
Barrett EsophagusBarrett Esophagus
• Clinical Features: Identified only through
endoscopy and biopsy Usually prompted by GERD
symptoms
• Treatment options: surgical resection or esophagectomy
Esophageal VaricesEsophageal Varices
• Due to diseases that impede venous blood flow from GIT to the liver via portal vein before reaching IVC (first-pass effect) Alcoholic liver disease – 90% of
cirrhotic patients Schistosomiasis – second most
common cause worldwide
• Congested sub-epithelial and sub-mucosal venous plexus within the distal esophagus
Esophageal VaricesEsophageal Varices
• Tortuous dilated veins lying within the submucosa of the distal esophagus and proximal stomach
• Variceal rupture (+) hemorrhage into the lumen or esophageal wall overlying mucosa appears ulcerated and necrotic
Esophageal VaricesEsophageal Varices
Cirrhotic patient with portal hypertension, in whom upper endoscopy shows large esophageal varices with red spots on their surface - indicating a high risk of bleeding.
Esophageal VaricesEsophageal Varices
• Clinical Features:
Often asymptomatic Rupture massive hematemesis
o Contributory factors include:1. Inflammatory erosion of thinned
overlying mucosa2. Increased tension in progressively
dilated veins3. Increased vascular hydrostatic
pressure associated with vomiting
Esophageal VaricesEsophageal Varices
• Treatment: medical emergency Sclerotherapy – endoscopic injection
of thrombotic agents Endoscopic balloon tamponade Endoscopic rubber band ligation
• 50% die from first bleeding episode either as (1) direct consequence of hemorrhage, or (2) following hepatic coma triggered by hypovolemic shock
Esophageal Tumors: AdenocarcinomaEsophageal Tumors: Adenocarcinoma
• Typically arises in a background of Barrett esophagus and long-standing GERD Risk further increased by:
1. Tobacco use2. Obesity3. Prior radiation therapy
Risk reduced by diets rich in fresh fruits and vegetables, and some H. pylori serotypes
Esophageal Tumors: AdenocarcinomaEsophageal Tumors: Adenocarcinoma
• Epidemiology: Caucasians 7x more common in males 50% of esophageal cancers in the
U.S.
• Pathogenesis: Step-wise acquisition of genetic and
epigenetic changes Mutation or over-expression of p53 Amplification of c-ERB-B2 , cyclin D1 &
cyclin E genes Allelic loss of p16INK4α by hyper-
methylation Increased expression of TNF and
NFκβ
Esophageal Tumors: AdenocarcinomaEsophageal Tumors: Adenocarcinoma
• Morphology:
Distal 3rd of esophagus may invade gastric cardia
Initially flat or raised patches large masses
May infiltrate diffusely or ulcerate and invade deeply
Barrett esophagus usually present adjacent to the tumor
Most commonly produce mucin and form glands with intestinal-type morphology
Esophageal Tumors: AdenocarcinomaEsophageal Tumors: Adenocarcinoma
Endoscopic image of patient with esophageal adenocarcinoma seen at gastro-esophageal junction.
Esophageal Tumors: AdenocarcinomaEsophageal Tumors: Adenocarcinoma
H & E stain, Top - Low magnification,
Bottom - High magnification, Esophageal
Adenocarcinoma.
Esophageal Tumors: AdenocarcinomaEsophageal Tumors: Adenocarcinoma
• Clinical Features:
More commonly presents with: pain or difficulty in swallowing, progressive weight loss, hematemesis, chest pain, or vomiting
Tumor spread to submucosal lymphatic vessels by the time symptoms appear 5-year survival < 25%
5-year survival ~ 80% if limited to mucosa or submucosa
Esophageal Tumors: Squamous Cell CAEsophageal Tumors: Squamous Cell CA
• Epidemiology: U.S. – adults > 45 yrs old; 6x more
common in African-Americans 4x more common in males Risk factors:
1. Alcohol and tobacco use2. Poverty – more common in rural and
under-developed areas3. Caustic esophageal injury4. Achalasia5. Plummer-Vinson syndrome6. Frequent consumption of very hot
beverages7. Previous radiation therapy to
mediastinum
Esophageal Tumors: Squamous Cell CAEsophageal Tumors: Squamous Cell CA
• Pathogenesis:
Alcohol and tobacco synergize to increase risk
Nutritional deficiencies, polycyclic hydrocarbons, nitrosamines, fungus-contaminated foods, HPV infection in areas where alcohol and tobacco use is uncommon
Loss of tumor suppressor genes, including p53 and p16INK4α
Esophageal Tumors: Squamous Cell CAEsophageal Tumors: Squamous Cell CA
• Morphology:
50% occur in middle third Begins as in situ lesion called squamous
dysplasia early lesions small, gray white, plaque-like tumor masses (polypoid or exophytic) over months to years protrude into and obstruct lumen
Most are moderately to well-differentiated
LN metastases vary with tumor location: Upper 3rd cervical LN Middle 3rd mediastinal, paratracheal,
and tracheobronchial nodes Lower 3rd gastric & celiac nodes
Esophageal Tumors: Squamous Cell CAEsophageal Tumors: Squamous Cell CA
Ulcerating Squamous cell carcinoma of the lower end of the esophagus.
Malignant tumor of the esophageal squamous mucosa, most common in the middle and lower third of the esophagus, and strongly associated with tobacco and alcohol use.
Esophageal Tumors: Squamous Cell CAEsophageal Tumors: Squamous Cell CA
• Clinical Features:
Onset insidious
Dysphagia, odynophagia (pain on swallowing), and obstruction
Extreme weight loss & debilitation
Tumor ulceration (+) hemorrhage and sepsis
Overall 5-year survival = 9%
GASTRIC DISORDERS
Normal Normal
• pH of gastric lumen close to 1
• Normal defensive forces include:1. Mucin – secreted by gastric foveolar
cells a) Forms a thin layer of mucus
prevents large food particles from directly touching epithelium
b) Promotes formation of a layer of fluid over the epithelium protects mucosa & has neutral pH
2. Rich vascular supply delivers oxygen, bicarbonate, and nutrients while washing away acid that has back-diffused into the lamina propria
Signs & Symptoms of Stomach DiseaseSigns & Symptoms of Stomach Disease
1. Hematemesis• Vomiting of blood• Most commonly due to PUD• Other causes: esophageal varices,
hemorrhagic gastritis
2. Melena• Dark, tarry stool• Hemoglobin is converted into
hematin by gastric acid• Signifies bleed proximal to duodeno-
jejunal junction
Signs & Symptoms of Stomach DiseaseSigns & Symptoms of Stomach Disease
• Gastric analysis includes measurement of:1. Basal acid output (BAO)
Acid output of gastric juice collected via NGT over a 1-hour period on an empty stomach
Normal = < 5 mEq/hr
2. Maximal acid output (MAO) Acid output of gastric juice that is
collected over 1 hour after pentagastrin stimulation
Normal = 5 – 20 mEq/hr
3. BAO:MAO ratio - normally 0.20:1
Congenital Hypertrophic Pyloric StenosisCongenital Hypertrophic Pyloric Stenosis
• Also known as gastric outlet obstruction
• 3-4x more common in males; 1:300-900 live births
• Monozygotic twins with high rate of concordance (+) genetic basis
• Progressive hypertrophy of the circular muscles in the pyloric sphincter
• Associated with Turner syndrome and trisomy 18
Congenital Hypertrophic Pyloric StenosisCongenital Hypertrophic Pyloric Stenosis
Congenital Hypertrophic Pyloric StenosisCongenital Hypertrophic Pyloric Stenosis
• Presents in 2nd or 3rd week of life as new-onset regurgitation and persistent, projectile, non-bilious vomiting
• P.E.: hyperperistalsis + firm, ovoid abdominal mass
• May be acquired in adults due to antral gastritis or peptic ulcers near the pylorus, and CA of distal stomach and pancreas
GastroparesisGastroparesis
• Decreased stomach motility, usually due to autonomic neuropathy (e.g. DM)
• May also be due to previous vagotomy
• Manifestations include 1. Early satiety and bloating2. Vomiting of undigested food a
few hours after eating
Acute GastritisAcute Gastritis
• Transient mucosal inflammation brought about by disruption to protective mechanisms1. Elderly – reduced mucin synthesis2. NSAIDs – interfere with cytoprotection
provided by PGs or reduce secretion of bicarbonate
3. Uremic patients & those with H. pylori infection (+) inhibition of gastric bicarbonate transporters by ammonium ions
4. Ingestion of harsh chemicals (acids and alkalis), excessive alcohol consumption, NSAIDs, radiation therapy, and chemotherapy direct cellular injury
5. Decreased oxygen delivery
Acute GastritisAcute Gastritis
• Morphology:
Mild, acute gastritis:
Intact surface epithelium with scattered neutrophils among epithelial cells or within mucosal glands
Moderate edema and slight vascular congestion
Neutrophils above basement membrane in direct contact with epithelial cells active inflammation
Acute GastritisAcute Gastritis
• Morphology:
Severe acute gastritis: Development of
1. Erosions – loss of superficial epithelium (+) defect in the mucosa limited to lamina propria and accompanied by pronounced neutrophilic infiltrates + purulent exudate
2. Hemorrhage – dark punctae in a hyperemic mucosa
Hemorrhage + erosion acute erosive hemorrhagic gastritis
Acute GastritisAcute Gastritis
This is a more typical acute gastritis with a diffusely hyperemic gastric
mucosa.
Acute GastritisAcute Gastritis
At high power, gastric mucosa demonstrates infiltration by neutrophils. This is acute
gastritis.
Acute GastritisAcute Gastritis
Here are some larger areas of gastric hemorrhage that could best be termed "erosions" because the superficial
mucosa is eroded away.
Acute GastritisAcute Gastritis
Gross appearance of hemorrhagic gastritis as seen at autopsy. The entire gastric mucosa is involved by fresh hemorrhage.
Acute Gastric UlcerationAcute Gastric Ulceration
• Types:1. Stress ulcers
Most common in individuals with shock, sepsis, or severe trauma
2. Curling ulcers Proximal duodenum; severe
burns or trauma3. Cushing ulcers
Gastric, duodenal, and esophageal ulcers in patients with intracranial disease
High incidence of perforation
Acute Gastric UlcerationAcute Gastric Ulceration
• Pathogenesis:
NSAID-induced cyclooxygenase inhibition prevent PG synthesis
Intracranial injury direct stimulation of vagal nuclei gastric acid hypersecretion
Systemic acidosis decreased intracellular pH of mucosal cells
Stress-induced splanchnic vasoconstriction hypoxia and reduced blood flow
Acute Gastric UlcerationAcute Gastric Ulceration
• Morphology:
Acute stress ulcers• Rounded, < 1 cm in diameter• Found anywhere in the stomach• Gastric rugal folds normal• Margin and base of ulcers are
not indurated• Usually multiple• Microscopically: sharply
demarcated, with essentially normal adjacent mucosa
Acute Gastric UlcerationAcute Gastric Ulceration
Acute stress ulcers
Multiple acute ulcers of the stomach, occurring in a chronically debilitated patient. Microscopically, there was very little fibrous reaction in the ulcer bed.
Acute Gastric UlcerationAcute Gastric Ulceration
Curling's ulcer is an acute peptic ulcer of the duodenum resulting as a complication from severe
burns.
Acute Gastric UlcerationAcute Gastric Ulceration
• Clinical:
1. Bleeding 10 – 20% of patients Most common complication 25% of ulcer deaths May be the first indication of an
ulcer
2. Perforation Up to 5% of patients 2/3 of ulcer deaths Rarely the first indication of an
ulcer
Acute Gastric UlcerationAcute Gastric Ulceration
• Clinical:
3. Obstruction Mostly in chronic ulcers Secondary to edema or scarring Approx. 2% of patients Most often associated with pyloric
channel ulcers Incapacitating, crampy abdominal
pain Rarely cause total obstruction and
intractable vomiting
Acute Gastric UlcerationAcute Gastric Ulceration
• Treatment:
Prophylactic H2 histamine receptor antagonist or proton pump inhibitors
Blood transfusion for severe bleeding
Correction of underlying cause
Chronic GastritisChronic Gastritis
• Symptoms less severe but more persistent Nausea and abdominal discomfort Hematemes is uncommon
• Most common cause: Helicobacter pylori infection
• Other causes:1. Chronic irritants – psychologic stress,
caffeine, alcohol, tobacco use2. Autoimmune – most common cause of
atrophic gastritis; < 10% of cases3. Less common causes – radiation,
chronic bile reflux, mechanical injury, systemic disease (Crohn’s, amyloidosis, graft-versus-host disease)
Chronic Gastritis: Helicobacter pyloriChronic Gastritis: Helicobacter pylori
• H. pylori present in gastric biopsy specimens of almost all patients with duodenal ulcers, gastric ulcers or chronic gastritis
• Present in 90% of patients with chronic gastritis affecting the antrum
• Most common cause of duodenal ulcer
• 2nd most common cause of gastric ulcer
• Increased risk of gastric CA and gastric lymphoma
Chronic Gastritis: Helicobacter pyloriChronic Gastritis: Helicobacter pylori
• Most common cause of chronic gastritis
Most often presents as predominantly antral gastritis with high acid production
Some progress to involve the gastric body and fundus associated with multifocal mucosal atrophy, reduced acid secretion, intestinal metaplasia, and increased risk of gastric adenoCA
Chronic Gastritis: Helicobacter pyloriChronic Gastritis: Helicobacter pylori
• Four important virulence factors:
1. Flagella rapid motility easily penetrate mucus layer
2. Urease generates ammonia increase local gastric pH
3. Adhesins enhance bacterial adherence to surface foveolar cells
4. Toxins (cytotoxin-associated gene A or CagA) poorly-defined mechanisms
Chronic Gastritis: Helicobacter pyloriChronic Gastritis: Helicobacter pylori
• Morphology:
Organism typically found in the antrum
Antral mucosa usually erythematous with coarse or nodular appearance
Neutrophilic infiltrates within lamina propria accumulate in lumen of gastric pits create pit abscesses
Intra-epithelial neutrophils & subepithelial plasma cells characteristic
(+) lymphoid aggregates with germinal centers induced MALT may transform to lymphoma
H. pylori bacteria (red arrow) imbedded in stomach lining. Courtesy of wikimedia
commons.
Active chronic H. pylori gastritis. The gastric mucosa contains large numbers of lymphocytes and plasma cells while polymorphs infiltrate the foveolar epithelium. The surface epithelium shows marked degenerative changes. Hematoxylin and eosin; magnification, ×100.
Chronic H. pylori gastritis. This low-power view shows marked glandular atrophy, lymphoid follicles, and centrally a focus of intestinal metaplasia. H&E
×25.
Chronic Gastritis: Autoimmune GastritisChronic Gastritis: Autoimmune Gastritis
• < 10% of cases of chronic gastritis
• Typically spares the antrum & includes hypergastrinemia
• Characterized by:1. Antibodies to parietal cells & intrinsic
factor – detected in serum and gastric secretions
2. Reduced serum pepsinogen I concentration
3. Antral endocrine cell hyperplasia4. Vitamin B12 deficiency5. Defective gastric acid secretion
Autoimmune gastritisAutoimmune gastritis
• Pathogenesis:
Loss of parietal cells absent gastric acid production stimulation of gastrin release hypergastrinemia and hyperplasia of antral gastrin-producing G cells
Lack of intrinsic factor disables ileal vitamin B12 absorption B12 deficiency slow-onset megaloblastic anemia (pernicious anemia)
Autoimmune gastritisAutoimmune gastritis
Chronic Gastritis Complications: PUDChronic Gastritis Complications: PUD
• Most often associated with H. pylori-induced hyperchlorhydric chronic gastritis
• May occur in any portion of the GIT exposed to acidic gastric juices most common in the gastric antrum & first portion of duodenum
• Risk of development higher in males; females affected during or after menopause
• Gastric ulcers generally develop on a background of chronic gastritis
Chronic Gastritis Complications: PUDChronic Gastritis Complications: PUD
Gastric Ulcers
• Primary underlying causes: H. pylori infection (>70%) and NSAID use
• Other contributory factors:1. Zollinger-Ellison syndrome
Multiple peptic ulcerations in the stomach, duodenum, and even jejunum due to uncontrolled gastrin release by a tumor
2. Cigarette smoking Impair mucosal blood flow & healing
3. High-dose corticosteroids Suppress PG synthesis & impair
healing
Chronic Gastritis Complications: PUDChronic Gastritis Complications: PUD
Duodenal Ulcers
• More frequent in individuals with:1. Alcoholic cirrhosis2. COPD3. Chronic renal failure (+)
hypercalcemia stimulate gastrin release
4. Hyperparathyroidism – similar mechanism as CRF
• NEVER malignant!
Chronic Gastritis Complications: PUDChronic Gastritis Complications: PUD
• Morphology:
4x more common in proximal duodenum Duodenal ulcers usually within a few
centimeters of pyloric valve & involve anterior duodenal wall
Gastric ulcers predominantly located along the lesser curvature near the interface of the body and antrum
Solitary in > 80%
Lesions < 0.3 cm in diameter usually shallow; those > 0.6 cm usually deeper ulcers
Chronic Gastritis Complications: PUDChronic Gastritis Complications: PUD
• Morphology:
Classic ulcer: four layers in sequence noted in histologic sections
1. Necrotic debris2. Inflammation with predominance
of neutrophils3. Granulation tissue (repair tissue)4. Fibrosis
The inner lining of the stomach consists of a very thick mucosal layer consisting of tall rows of glandular cells running parallel to each other. The thick mucosa has a deep narrow gap extending to the bottom of the mucosa. This gap is the ulcer.
Normal stomach mucosa (40X2.8) Stomach mucosa with ulcer (40X2.0)
Chronic Gastritis Complications: PUDChronic Gastritis Complications: PUD
Feature Gastric Ulcers Duodenal Ulcers
% of ulcer cases 25% 75%
Epidemiology Male:female ratio 1:1Smoking does not cause PUD but delays healing
Male:female ratio 2:1Risk increased with MEN I, cirrhosis, COPD, renal failure, hyperparathyroidism
H. pylori ~ 80% of cases 90 – 95% of cases
Pathogenesis Defective mucosal barrier due to H. pyloriMucosal ischemia (reduced PGE), bile reflux, delayed gastric emptyingBAO & MAO normal to decreased
Defective mucosal barrier due to H. pyloriIncreased acid prod’n (inc. parietal cell mass)
BAO & MAO both increased
Chronic Gastritis Complications: PUDChronic Gastritis Complications: PUD
Feature Gastric Ulcers Duodenal Ulcers
Location Single ulcer in lesser curvature of antrum (same location for cancer)
Single ulcer on anterior portion of 1st part of duodenum ffed by single ulcer on posterior portion (danger for perforation into pancreas)
Complications Bleeding (most commonly in left gastric artery)Perforation
Bleeding (most commonly in gastro - duodenal artery)Perforation (air under the diaphragm, pain radiates to left shoulder)Gastric outlet obstruc- tion, pancreatitis
Clinical findings
Burning epigastric pain soon after eating
Burning epigastric pain 1 – 3 hours after eating
Chronic Gastritis Complications: Mucosal Chronic Gastritis Complications: Mucosal Atrophy and Intestinal MetaplasiaAtrophy and Intestinal Metaplasia
• Long-standing chronic gastritis loss of parietal cell mass intestinal metaplasia
• Presence of goblet cells
• Increased risk of gastric adenocarcinoma greatest in autoimmune gastritis
Due to overgrowth of bacteria produce carcinogenic nitrosamines
Chronic Gastritis Complications: DysplasiaChronic Gastritis Complications: Dysplasia
Chronic gastritis
Epithelium exposed to
Free radical damage
Proliferative stimuli
Genetic alterations
DYSPLASIA
CARCINOMA
Chronic Gastritis Complications: DysplasiaChronic Gastritis Complications: Dysplasia
• Morphologic hallmarks:
Variations in epithelial size, shape and orientation
Coarse chromatin texture Hyperchromasia Nuclear enlargement
Chronic Gastritis Complications: Gastritis Chronic Gastritis Complications: Gastritis CysticaCystica
• Exuberant reactive epithelial proliferation
• Associated with entrapment of epithelial-lined cysts
• May be found in:1. Submucosa gastritis cystica
polyposa2. Deeper layers of gastric wall
gastritis cystica profunda
• May mimic invasive adenocarcinoma
Hypertrophic GastropathiesHypertrophic Gastropathies
• Uncommon
• Giant cerebriform enlargement of the rugal folds due to epithelial hyperplasia without inflammation
• Associated with excessive growth factor release
Hypertrophic Gastropathies: Menetrier’s Hypertrophic Gastropathies: Menetrier’s DiseaseDisease
• Rare; due to excessive secretion of TGF-α
• Diffuse hyperplasia of foveolar epithelium of the body and fundus
• Protein-losing enteropathy hypo-proteinemia
• Increased risk of gastric adenoCA in adults
• Characteristic feature: hyperplasia of foveolar mucous cells
Hypertrophic Gastropathies: Menetrier’s Hypertrophic Gastropathies: Menetrier’s DiseaseDisease
Microscopic appearance of Menétrier's disease.
There is marked hyperplasia of the crypts accompanied by mild atrophy of the underlying secretory mucosa.
Hypertrophic Gastropathies: Hypertrophic Gastropathies: Zollinger-Ellison SyndromeZollinger-Ellison Syndrome
• Cause: gastrin-secreting tumors (gastrinomas) most commonly found in SI and pancreas 60% - 90% of gastrinomas malignant 25% of patients with MEN I
• Clinical: duodenal ulcers or chronic diarrhea
• Morphology: 5x increase in number of parietal cells
doubling of oxyntic mucosal thickness
Hyperplasia of mucous neck cells Mucin hyperproduction Proliferation of endocrine cells within
oxyntic mucosa
Hypertrophic Gastropathies: Hypertrophic Gastropathies: Zollinger-Ellison SyndromeZollinger-Ellison Syndrome
Gastric Polyps: Inflammatory & Hyperplastic Gastric Polyps: Inflammatory & Hyperplastic PolypsPolyps
• ~75% of all gastric polyps are inflammatory or hyperplasic polyps
• Most common in 50 – 60 yrs old individuals
• Develop in association with chronic gastritis
• Risk of dysplasia correlates with size
Gastric Polyps: Inflammatory & Hyperplastic Gastric Polyps: Inflammatory & Hyperplastic PolypsPolyps
Gross appearance of gastric polyps of hyperplastic type. Many of the lesions show central umbilication.
Low-power microscopic view of gastric polyps of hyperplastic type. The cystic dilatation of the glands is more evident on the left side.
Gastric Polyps: Fundic Gland PolypsGastric Polyps: Fundic Gland Polyps
• Occur sporadically in patients with familial adenomatous polyposis (FAP)
• Increased incidence in patients undergoing proton pump inhibitor therapy Reduced gastric acidity increased
gastrin secretion glandular hyperplasia
• 5x more common in women; ave. age 50 y/o
• Well-circumscribed lesions with a smooth surface
Gastric Polyps: Fundic Gland PolypsGastric Polyps: Fundic Gland Polyps
Endoscopic image of fundic gland polyposis taken on retroflexion of gastroscope. This patient was chronically taking proton pump inhibitors.
H&E stain of fundic gland polyp showing shortening of the gastric pits with cystic dilatation.
Gastric Tumors: Gastric AdenomaGastric Tumors: Gastric Adenoma
• 10% of all gastric polyps progressive increase in incidence with age
• 50 – 60 yrs old; males > females (3:1)
• Increased incidence in patients with FAP
• Almost always occur on a background of chronic gastritis with atrophy & intestinal metaplasia
• Risk of adenocarcinoma related to size of lesion (> 2 cm in diameter)
Gastric Tumors: Gastric AdenomaGastric Tumors: Gastric Adenoma
• Usually solitary; antrum
• Majority with intestinal type of epithelium
• All GI adenomas have epithelial dysplasia that can be classified as low grade or high grade.
Gastric Tumors: Gastric AdenomaGastric Tumors: Gastric Adenoma
Gross appearance of gastric adenomatous polyps. The larger lesion is a tangle of fingerlike projections.
Adenomatous polyp. (From Oota K, Sobin LH: Histological typing of gastric and oesophageal tumours, Geneva, World Health Organization, 1977)
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
• Most common malignancy of the stomach
• Risk factors:1. Intestinal metaplasia due to H.
pylori - most important2. Nitrosamines, smoked foods (Japan),
diets lacking fruits/vegetables3. Type A chronic atrophic gastritis4. Menetrier’s disease
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
• Pathogenesis:
1. Diffuse gastric cancer Germline mutations in CDH1
(encodes E-cadherin) BRCA2 mutations p53 mutations
2. Intestinal type gastric cancer Individuals with FAP Mutations in β catenin Microsatellite instability Mutations in p53, TGFβRII, BAX,
IGFRII & p16/INK4α
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
Morphology:
• Classified according to location in the stomach, gross & histologic morphology
• Most involve gastric antrum; lesser curvature > greater curvature
• If with intestinal morphology bulky and composed of glandular structures; exophytic or ulcerated
• If with diffuse morphology infiltrative pattern; composed of signet ring cells that do not form glands
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
Morphology:
• Diffuse type not associated with H. pylori
May infiltrate stomach wall desmoplastic reaction that stiffens the gastric wall called linitis plastica (leather bottle appearance)
Produce Krukernberg tumors of the ovaries
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
Gross appearance of gastric adenocarcinoma of polypoid type.
Gross appearance of gastric adenocarcinoma of
ulcerative type showing marked resemblance to
chronic peptic ulcer.
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
Typical gross appearance of diffuse carcinoma of linitis
plastica type. Practically the entire wall of the stomach is involved by tumor. Note the prominence of rugal folds.
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
Gastric adenocarcinoma of intestinal type.
Diffuse type of gastric adenocarcinoma. An Indian file pattern of infiltration of the muscularis externa can
be appreciated.
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
Clinical:
• Weight loss (most common), epigastric pain with vomiting
• Metastasis to left supraclavicular node (Virchow’s node)
• Paraneoplastic skin lesions1. Acanthosis nigricans2. Multiple outcroppings of seborrheic
keratoses• Metastasis to umbilicus (Sister Mary
Joseph sign)• Common metastatic sites: liver, lung,
ovaries
Gastric Tumors: Gastric AdenocarcinomaGastric Tumors: Gastric Adenocarcinoma
Gastric Tumors: LymphomaGastric Tumors: Lymphoma
• Most common extra-nodal site is GIT, particularly the stomach
• Nearly 5% of all gastric malignancies
• Often referred to as lymphomas of mucosa-associated lymphoid tissue (MALTomas)
• Usually arises at sites of chronic inflammation
• Most common cause: chronic H. pylori infection
Gastric Tumors: LymphomaGastric Tumors: Lymphoma
• Dense lymphocytic infiltrate in the lamina propria Infiltrate the gastric glands focally
create lymphoepithelial lesions diagnostic
• Express the B cell markers CD19 and CD20
• Most common presenting symptoms are dyspepsia and epigastric pain
Gastric Tumors: LymphomaGastric Tumors: Lymphoma
EXTRANODAL MARGINAL ZONE B-CELL (MALT)LYMPHOMA — This tumor, previously called MALT-typelymphoma or MALT lymphoma is now called extranodalmarginal zone B-cell lymphoma of mucosa-associated lymphoid tissue in the WHO classification system.
Gastric Tumors: LymphomaGastric Tumors: Lymphoma
MALT-type malignant lymphoma of stomach involving mucosa and submucosa.
Gastric Tumors: Carcinoid TumorGastric Tumors: Carcinoid Tumor
• Arise from diffuse components of endocrine system – majority found in the GIT; > 40% in the small intestines
• Associated with: endocrine cell hyperplasia, chronic atrophic gastritis, & Zollinger-Ellison syndrome
• Best considered as well-differentiated neuro-endocrine carcinomas
Gastric Tumors: Carcinoid TumorGastric Tumors: Carcinoid Tumor
• Gross: Intramural or submucosal masses Yellow or tan in color Very firm due to intense desmoplastic
reaction cause bowel kinking and obstruction
• Microscopic: islands, trabeculae, strands, glands, or sheets of uniform cells with scant, pink, granular cytoplasm and round to oval stippled nucleus
• Positive for endocrine granule markers (synaptophysin and chromogranin A)
Gastric Tumors: Carcinoid TumorGastric Tumors: Carcinoid Tumor
• Clinical:
Tumors that produce gastrin cause Zollinger-Ellison syndrome
Ileal tumors cause carcinoid syndrome Cutaneous flushing, sweating,
bronchospasm, colicky abdominal pain, diarrhea, and right-sided cardiac valvular fibrosis
Strongly associated with metastatic disease
Gastric Tumors: Carcinoid TumorGastric Tumors: Carcinoid Tumor
• Most important prognostic factor is location1. Foregut tumors
Found within the stomach, duodenum proximal to ligament of Treitz, and esophagus
Rarely metastasize & cured by resection
2. Midgut tumors Jejunum and ileum Multiple and aggressive
3. Hindgut tumors Appendix (at the tip) and colorectum Discovered incidentally Rarely > 2 cm in diameter except if
proximal colon
Gastric Tumors: Carcinoid TumorGastric Tumors: Carcinoid Tumor
Small carcinoid tumor of the stomach composed of enterochromaffin-like cells.