PATHOLOGY OF THE GASTROINTESTINAL TRACT 1
PATHOLOGY OF ESOPHAGUS
Clinical signs of esophageal lesions:
-dysphagia- means difficulties in swallowing. Most diseases of esophagus
cause dysphagia
-retrosternal pain = heartburn-commonly occurs when acidic gastric juice
refluxes into the esophagus
-hematemesis= vomiting of blood
1) CONGENITAL ESOPHAGEAL DISORDERS:
-tracheoesophageal fistula- is the commonest congenital anomaly of
esophagus
abnormal communication between the trachea and esophagus
-clinical findings- cyanosis, respiratory distress- surgery needed
-esophageal atresia- very rare, narrowing or obstruction of a part of
esophagus
2) INFLAMMATORY LESIONS OF THE ESOPHAGUS:
-reflux esophagitis ( peptic esophagitis)
caused by reflux of acid gastric juice into the lower part of esophagus
-symptomatic esophagitis occurs when normal mechanisms of clearing the
esophagus are impaired (even in normal individuals without clinical signs of
esophagitis- some reflux occurs, but in normal persons- any fluid regurgitated into
the esophagus is rapidly returned to stomach by peristalsis)
causes of reflux esophagitis
-impairment of peristalsis- may cause symptoms of reflux esophagitis
-composition of regurgitated gastric juice- higher levels of acids and enzymes, as
well as the presence of bile and pancreatic enzymes
-relation to hiatal hernia- is not clear
hernia is defined as protrusion of part of stomach through the diaphragmatic
hiatus
pathology: superficial erosions of the mucosa of lower esophagus- peptic ulcus and
fibrous narrowing of esophagus
histology: hyperplasia of the basal cells of the squamous epithelium and presence
of neutrophils in the epithelium
clinically: low retrosternal sensation of burning pain called "heartburn"
-in chronic cases- the pain may be constant and is accompanied by dysphagia
-Barrett's esophagus
-intestinal metaplasia of the epithelium of lower part of esophagus,
presence of gastric mucosa of cardial type is normal within lowest 3 cm of
esophagus
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-primary adenocarcinoma of esophagus may arise in Barrett's esophagus or peptic
ulcer may appear
-infectious esophagitis
infections of esophagus are rare, except of in immunocompromised patients
(AIDS, patients receiving anti-cancer therapy), esophagitis is most commonly of
fungal origin-candida albicans
-esophageal candidosis
caused by Candida albicans, it is most common opportunistic infection
morphology: the yeasts infect superficial layers of the epithelium- the surface is
covered by white plaques - grossly visible, composed of cellular debris,
inflammatory cells and fungi
-viral esophagitis
common in AIDS- intranuclear inclusions and occurrence of herpetic giant cellscaused by herpes virus, other type is cause by cytomegalovirus- infects
submucosal endothelial cells- necrosis, hemorrhage, inflammation
3) FUNCTIONAL DISORDERS OF ESOPHAGUS
-Plummer-Vinson syndrome
consists of severe iron-deficiency anemia, koilonychia, atrophic glossitis and
dysphagia-results from the atrophy of pharyngeal mucosa, increased risk of
development of squamous cell carcinoma of tongue, esophagus and pharynx
-more common in women, -dysphagia is corrected if the iron-deficiency is treated
-achalasia of the cardia
-congenital, the cause is unknown
-”achalasia” means failure to relax- the cause of the disorders lies in the lack of
ganglia in the myenteric plexus- this results in failure of peristalsis- the cardiac
sphincter does not relax- the esophagus dilates massively and becomes elongated
-the patients present with dysphagia, retrosternal pain, vomiting, predisposition
to cancer
possible complications: reflux of the contents into the trachea- aspiration
pneumonia- lung abscess formation
treatment: myotomy and repeated dilatation of cardia
-esophageal diverticula
diverticulum- outpouching of the lumen outside the wall
-pulsion diverticulum- occurs when internal pressure forces an epithelial sac out
through weakened muscle layer
-traction diverticulum- are due to external infiltrative processes- accompanied
by fibrosis of periesophaeal tissue
-esophageal varices
occur in lower esophagus and in gastric fundus in patients with portal
hypertension- most common cause is liver cirrhosis
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morphology: dilated veins in submucosa may rupture- severe hemorrhage
(hematemesis, melena)
-Mallory-Weiss syndrome
-patients with prolonged vomiting (pregnancy, alcoholism)- longitudinal tears in
mucosa of the lower part of esophagus- hematemesis occurs
TUMORS OF ESOPHAGUS
1- Carcinoma
-accounts for over 95% of all malignant tumors of esophagus
-it is highly lethal-more common in old persons
etiologic factors: cigarette smoking and chronic alcoholism increase the risk of
carcinoma
premalignat conditions: include- Barrett's esophagus and Plummer-Vinson
syndrome
gross appearance of carcinoma: plaque-like thickening of the mucosa with
ulceration- stricture or narrowing of the lumen
microscopically: over 90% are squamous cell carcinoma
- adenocarcinoma is less common- it arises in mucosal glands or in Barrett
esophagus
spread of carcinoma through the esophageal wall- invasion of bronchial walltracheoesophageal fistula
-invasion of the aorta may cause massive fatal bleeding
lymphatic spread-is very rapid, through the lymphatic capillaries in the
submucosa- lymph node metastases
bloodstream spread- metastases to the liver and the lungs
clinically: most patients present with dysphagia abd pain, severe weight loss,
anemia-due to chronic bleeding
prognosis is poor
2- other tumors of esophagus- are rare, include leiomyoma-benign, derived
from smooth muscle
malignant- lymphoma, melanoma have been reported
PATHOLOGY OF THE STOMACH
Clinical manifestations of gastric diseases:
-pain and dyspepsia-pain is a feature of acute gastritis and peptic ulcer disease
-pain is often accompanied by nauses and vomiting
dyspepsia- includes pain, distension and eructation
-loss of apetiteloss of desire for food is called anorhexia
-it occurs in gastritis and gastric cancer
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-bleedingbleeding into gastric lumen is a common manifestation of gastric diseases with
mucosal erosions and ulcers
-when bleeding is rapid- the patient vomits bright red blood = hematemesis
-when bleeding is less rapid-blood is altered, it passes through the intestine,
produces black colour of the stools = melena
chronic slow GIT bleeding results in iron-deficiency anemia
-palpable mass in the epigastrium
NON - NEOPLASTIC DISORDERS OF THE STOMACH
1) Congenital pyloric stenosis
one of the most common congenital disorders of GIT, this disorder affects males
four to five times more often than females
-marked hypertrophy of pyloric sphincter results in obstruction of gastric
emptying
symptoms- 1-2 weeks after birth- projectile vomiting after feeding
treatment: surgical muscle splitting is curative
2) inflammatory lesions of stomach- gastritis
Gastritis is simply defined as inflammation of the gastric mucosa, inflammation
may be predominantly acute (neutrophilic leukocytes), or chronic (lymphocytes
and plasmacytes)
1- Acute gastritis
-is an acute mucosal inflammatory process of transient nature, may be
accompanied by hemorrhages- severe form of acute erosive gastritis may cause
acute GI bleeding
grossly: affected mucosa shows red colour, erosions, and hemorrhages
microscopically: hyperemia, edema, leukocytic infiltration of the lamina propria
etiologic factors: the pathogenesis is poorly understood, acute gastritis is
frequently associated with:
 Heavy use of nonsteroid anti-inflammatory drugs, such as aspirin, excessive
alcohol consumtion, heavy smoking, treatment with anti-cancer drugs, uremia,
systemic infections, such as salmonelosis, viral infections,severe stress,
ischemia and shock, gastric irradiation, etc.
 It must be emphasized that some patients have idiopathic acute gastritis
without any associated disorder
-decrease of resistence of gastric mucosa may be caused by the following
reasons:
-1- inhibition
of
prostaglandin
secretion- (smoking, aspirin,
anti-inflammatory drugs)
-2-interference with mucosal regeneration - (antimitotic drugs)
-3- ischemia- decreased mucosal blood supply plays a role in development
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of gastritis associated with shock
clinically: clinical course depends on the severity of anatomic changes-epigastric
pain, nausea, vomiting, anorrhexia occur in moderate degree of gastritis
-endoscopic and microscopic changes are minute
-in more severe types- massive hemorrhages, hematemesis, and potentially fatal
blood loss- in alcoholics
2- Chronic gastritis
chronic gastritis is defined as the presence of chronic mucosal inflammatory
changes leading possibly to mucosal atrophy and epithelial metaplasia, chronic
gastritis is notable for distinct causal subgroups with different location, histology
and clinical features.
Pathogenesis: the major etiologic associations of chronic gastritis are as follows
 Immunologic, associated with pernicious anemia,
 chronic infection, caused by Helicobacter pylori,
 toxic, as with heavy smoking and alcohol consumption
 postsurgical, especially following antrectomy and gastrectomy with reflux of
bilious duodenal secretions
 granulomatous conditions, such as in Crohn disease
 miscellaneous- GVHD, uremia, etc.
Basically, three major types of chronic gastritis can be distinguished:
Type A gastritis -associated with pernicious anemia
-involves mainly fundus and body
-is of autoimmune origin- antibodies to parietal cells- is characterized by
hypochlorhydria or achlorhydria (decreased acid secretion) resulting from
parietal cell destruction, up to 60% patients have decreased production of
intrinsic factor- leading to failure of vitamin B12 absorption and development of
pernicious anemia
on endoscopy: gastric mucosa is atrophic, appears markedly thinned
histologically gastric mucosa shows-chronic atrophy with decreased number or
absence of parietal cells,
lamina propria of mucosa reveals an intense lymphocytic infiltration, most are
CD4+ T lymphocytes, with admicture plasma cells and B lymphocytes
-as the infiltration persists, the oxynthic glands disappear and are replaced by
mucin producing glands
-erly stage disease is associated with proliferation of endocrine cells, some
patients may develop low grade gastric carcinoids
-complete intestinal metaplasia with Paneth and goblet cells is common, less
commonly glandular cell dysplasia occur-represents a precancerous lesion
Type B gastritis -much more common than type A
-involves mainly antral region of the stomach
-is of non-immune origin, is caused by infection of the mucosa of the stomach by
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H.pylori. This microorganism is a nonsporing, S-shaped gram negative rod
clinically: epigastric discomfort, pain, nausea
-patients with chronic g-itis caused by H. pylori usually improve when treated with
antimicrobial agents, and relapses are associated with reappearance of H.pylori in
the stomach
-very important is the relationship between chronic gastritis and peptic ulcer, the
patients are possibly in higher risk of development of gastric cancer
Eosinophilic gastritis -rare disease-believed to develop due to
allergic hypersensitivity, pathogenesis- unclear
microscopically: gastric mucosa is infiltrated by chronic inflammatory cells
including eosinophils-intestinal mucosa my be also affected, sometimes- small
vessel vasculitis and epithelioid granulomas
3) Peptic ulcer disease
-chronic, most often solitary ulcers in any portion of the alimentary tract
arising from exposure to acid-peptic juices- most cases occur in the duodenum
and stomach
epidemiology: most often in middle age, more common in men, duodenal ulcer is
more frequent in patients with alcoholic cirrhosis, chronic renal failure and
hyperparathyroidism
morphology: grossly- sharply punched out defect with overhanging mucosal
borders, smooth and clean ulcer base
microscopy: four layers can be identified -a thin superficial layer-necrotic debris,
zone of inflammation, which is underlaid by a layer of granulation tissue, beneath
which there is fibrous scar
-surrounding mucosa exhibits a chronic gastritis
Pathogenesis: peptic ulcers are produced by an imbalance between the
gastroduodenal mucosal defence mechanisms and damaging force of gastric juice
 mucosal defense mechanisms- include surface mucus secretion, bicarbonate
content in secretion, mucosal blood flow, apical epithelial cell transport
systems, epithelial regeneration, mucus defence is impaired by shock, ischemia,
delayed gastric emptying, and duodenal reflux
 damaging forces- include gastric acid and pepsin, H. pylori infection, aspirin,
cigarettes, alcohol, impaired regulation of acid secretion, stress-uncertain
Clinical features: typical symptoms are epigastric burning, aching pain that is
worse at night, or 1 to 3 hours after meals, nausea, vomiting, belching, etc.
complications include anaemia (because of occult bleeding), hemorrhage,
perforation, obstruction (oedema and/or scar in a pyloric channel), malignant
transformation
vascular gastropathy
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is characterized by abnormalities in gastric blood vessels without inflammation
-it may be dues to portal hypertension-called portal hypertensive
gastropathy
-important cause of gastric bleeding, changes confined to gastric body and
fundus-edema, red mucosal spots, marked vascular ectasias
-second lesion is gastric antral vascular ectasia (VAGE)- endoscopic
appearance of “watermelon stomach”-raised, red mucosal stripes of dilated and
tortuous blood vessels in antrum, often seen in elderly women with other
autoimmune
diseases,
histologically
multiple
intravascular
thrombi,
myofibroblastic proliferation in lamina propria
TUMORS OF THE STOMACH
 GASTRIC POLYPS AND BENIGN TUMORS
gastric polyps- are rare-there are two major types of epithelial polyps
the term polyp refers to any nodule or mass that projects above the level of the
surrounding mucosa, majority of gastric polyps are hyperplastic/inflammatory
(90%)
 -hyperplastic polyps -smooth-surfaced, sessile or pedunculated
-they represent non-neoplastic lesions- regenerative, inflammatory
-may be multiple
histologically: consist of epithelial tubules and cysts interspersed within an
inflammatory stroma
 -adenomatous polyps -benign neoplastic lesions
-usually single- lobulated surface
histologically: consist of closely packed tubular epithelial structures with varying
degree of cellular atypia and polymorphism- called dysplasia
-higher risk of malignant transformation
Multiple polyps are seen in polyposis syndromes, such as
 -familial adenomatous polyposis (FAP)
is an autosomal dominant polyposis exhibiting numerous adenomatous polyps in the
colon, stomach and elsewhere, with high risk of progression to adenocarcinoma
-treatment- prophylactic colectomy, adenomas elsewhere create continued
problems
 -Peutz-Jeghers syndrome
is an autosomal dominant inherited disorder composed of melanotic pigmentation
of mucosal and skin surfaces, hamartomatous polyps of the small intestine and
colon, and increased risk of carcinoma of breast, pancreas, lung, ovary and uterus
-hamartomatous polyp- is large pedunculated, with arborizing smooth muscle
surrounding normal abundant glands
 -Gardners syndrome
is an FAP variant exhibiting multiple osteomas (mandible, skull, long bones),
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epidermal cysts, fibromatosis (desmoid tumor), and numerous adenomatous polyps
in GI
 MESENCHYMAL TUMORS -uncommon, well-circumscribed benign tumors
within the wall of the stomach, covered by preserved mucosa, smooth surface
-neurofibroma
-lipoma
-leiomyoma
-epithelioid leiomyoma =leiomyoblastoma- is a variant of leiomyoma peculiar to
the stomach
-biologically benign, well circumscribed, may be large intramural mass
histologically: composed of large spindle or round pleomorphic cells with features
of smooth muscle cells
-inflammatory fibroid polyp=pseudotumor- rare, probably non-neoplastic lesion
-first description by prof. Vaněk as eosinophilic granuloma of the stomach
-histologically: it consists of highly vascularized myofibroblastic and fibroblastic
proliferation with polymorphic inflammatory infiltration dominated by eosinophilic
leukocytes
 MALIGNANT TUMORS
1. Gastric carcinoma
-accounts for over 90% of malignant tumors of the stomach
-geographic differences in the incidence- 10 times higher in Japan than in the
U.S.for example- environmental factors play role
-precancerous lesions for gastric carcinoma include:
-chronic atrophic gastritis with dysplasia- its association with PA
-adenomatous polyps with dysplasia
-chronic peptic ulcers
grossly:-early cancer- =gastric carcinoma restricted to the mucosa and
submucosa
-recognized in Japan- diagnosis by endoscopic examination and biopsy
-advanced gastric cancer- =gastric carcinoma that invades the gastric
wall-presents as- endoscopic gross morphology:
-fungating mass that protrudes into the lumen- polypoid
-as a malingant ulceration with raised edges
-as an ulcer resembling the peptic ulcer
- as a diffusely ifiltrating lesion that causes diffuse thickening of the
gastric wall
microscopically: all gastric carcinomas are adenocarcinomas of varying degree of
differentiation
-the most common -poorly differentiated so called diffuse carcinoma of
signet-ring cell type
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-well differentiated carcinoma resembling the tubular adenocarcinoma of the
intestine is less common= intestinal type of gastric cancer
spread: gastric carcinoma is locally aggressive- rapidly spreads through the whole
wall of the stomach
-lymphatic spread- rapid, lymph node metastases
-spread along the surfaces of the peritoneum
-bloodstream spread- to the liver and lungs
-Kruckenberg tumor = unilateral, and more often bilateral metastasis to
ovaries
clinically: early cancer- asymptomatic
advanced cancer-anorhexia, anemia, weight loss, hematemesis and melena
diagnosis: endoscopy and biopsy
prognosis: depends almost entirely on the depth of invasion of the tumor
early gastric cancer- 5-year survival rate of 85%
advanced cancer- " of only 30%
staging is very important, grading of little prognostic value
2. Malignant lymphoma
accounts for about 3 % of malignant tumors of the stomach
grossly: polypoid masses, ulcers or mucosal thickenings
diagnosis: only by endoscopic biopsy (histological examination of the specimen)
primary gastrointestinal ML= MALT lymphoma -arises in mucosa-associated
lymphoid tissue
-majority of lymphomas are of B-cell type, derived from follicular-center cells
gastric lymphoma- responds well to chemotherapy- better prognosis than that of
carcinoma
MALT-lymphomas have better prognosis than nodal lymphomas of the same typelower tendency to disseminate
3. Gastric leiomyosarcoma -accounts for about 2% of gastric malignancies
grossly: large masses that originates in the wall of the stomach -lower tendency to
metastasize than in carcinoma
microscopically: composed of malignant smooth muscle cells with high mitotic
activity, necroses and foci of hemorhages
clinically: bleeding, blood loss, anemia, palpable mass
tumor is often located deep in the wall- diagnosis by endoscopy usually impossiblevariant of this tumor- epithelioid leiomyosarcoma (mitotic activity, necroses,
aggressive growth )
4. Carcinoid -arises from neuroendocrine cells present within the mucosa
of the stomach- histological appearance and biological behaviour - similar to
identical tumours of the intestine
5. GIST (gastrointestinal tumor)
-is mesenchymal tumor of GIT (most common in intestine, but occurs from
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esophagus to rectum throughout the whole GIT) composed of spindle shaped cells
arranged in short fascicles with variable proliferative activity mitotic count,
necroses, locally aggressive growth pattern and about half of the cases recur and
cause metastases (liver)
-the most important factors for prognosis include size of the tumor, and
mitotic rate
grossly: large bulky intramural tumors or subserosal projections
on cross section: the tumor has a soft, fish-flesh appearance with or without
haemorrhages
genetics: the tumor arises from interstitial cells of Cajal, majority of the tumors
have mutations in genes encoding for the c-kit protein (immunohistochemically
positive staining for CD117/c-kit)
-c-kit protooncogene is located on chromosome 4q, and oncodes a
transmembrane tyrosine kinase receptor- this allows a treatment by selective
inhibitor of tyrosine kinase with activity against KIT (imatinib, gleevec)
therapy: surgical resection remains primary treatment
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