Pathology of Stomach

Dr. Rupinder Kaur

Stomach-anatomy/histology

❖ Mucosa- 2 layers-
• Superficial Layer- contains tall columnar mucus secreting
cells
• Deep Layer: opens into the bottom of crypts consists of
3 types of cells
❖ Cell types: mucous cells, parietal cells, chief cells,
endocrine cells
❖ Cardia and antrum: mucinous glands
❖ Body and fundus: oxyntic glands
Stomach- histology
 Mucosal protection
► Mucus secretion: mucus is relatively impermeable to H+
► Bicarbonate secretion creates pH neutral microenvironment adjacent to cell surface
► Intercellular tight junctions prevent back-diffusion of H+
► Rich blood flow supplies HCO3 and nutrients & removes acid
► Muscularis mucosa limits injury
 Stomach: physiology
► General functions: digestion, motility, microbial defense
► Partially digests food boluses received from the esophagus
► Mechanical digestion: back and forth churning by inner oblique layer of muscularis
propria
► Chemical digestion: acidic milieu breaks down proteins and kills food derived microbes
❖ Parietal cells secrete hydrochloric acid (HCl), which maintains acidic pH of stomach and denatures
proteins
❖ Chief cells secrete pepsinogen, which breaks down proteins when activated to pepsin by the acidic
environment
► Smooth muscle contractions (peristalsis) are controlled by the interstitial cells of Cajal)
► Majority of nutrient absorption occurs in small bowel
 Stomach- Pathology

► Congenital anomalies: Diaphragmatic hernia & pyloric stenosis

► Inflammations
- Gastritis: Acute & Chronic, Autoimmune
- Ulcer: Peptic ulcer
► Tumors
- Polyps
- Adenocarcinoma
- Lymphoma
 Gastritis
► Inflammation of the gastric mucosa
► Overused term and underdiagnosed condition
► Classification:
▪ 1) Acute gastritis
▪ 2) Chronic gastritis: most cases; prevalence exceeds 50% in adults >50 yrs; usually
asymptomatic or cause few symptoms (upper abdominal discomfort, nausea and
vomiting)
►Helicobacter pylori associated gastritis: main cause
►Autoimmune (atrophic) gastritis
►Hypertrophic gastritis (gastropathy)
►Granulomatous gastritis; eosinophilic gastritis
 Acute gastritis: Etiology
► Acute mucosal inflammation, usually of transient nature

► Risk Factors:

▪ Heavy use of NSAIDs, especially aspirin (up to 25%)

▪ Excessive alcohol consumption
▪ Heavy smoking
▪ Severe stress, e.g. trauma, burns, surgery
▪ Ischemia and shock; suicidal attempts with acids/alkali
▪ Mechanical trauma (NG tube); post-gastrectomy
▪ Chemotherapeutic Rx; uremia; systemic infections
 Acute gastritis: pathogenesis
► Multifactorial due to loss of balance between:
▪ Gastric acidity: stimulation of acid secretion by H+ back-diffusion, decreased
bicarbonate buffer production
▪ Mucosal resistance: reduced mucosal blood flow, mucosal cell disruption or
direct epithelial damage
 Acute gastritis- risk factors & morphology
► Clinical features depend on severity: asymptomatic or variable epigastric
pain, nausea, vomiting, hemetemesis (particularly alcoholics), melena &
fatal blood loss
► Morphology
Mild Form:
❖ Edema & hyperemia of lamina propria
❖ ScaIered neutophils in LP
❖ Intact surface epithelium
Severe Forms:
❖ Acute hemmorhagic gastritis
❖ Erosion and hemorrhage
❖ Robust acute inflammatory infiltrate
 Chronic gastritis: definition

► Def:

Presence of chronic mucosal inflammatory changes leading eventually to

mucosal atrophy and epithelial metaplasia,
usually in the absence of erosions.
The epithelial changes may become dysplastic, and
constitute a background for development of carcinoma
 Chronic gastritis: Introduction

► Most commonly encountered lesion in biopsies

► Recurrent attacks of acute gastritis
► Etiology- same as acute gastritis
► Other causes: Reflux of duodenal contents, associated stomach or duodenal disease
(ulcer, carcinoma),immunological, atrophic gastritis and H,pylori infection
► Based upon type of mucosa affected divided into 3 types- Type A (autoimmune), Type B
(H.Pylori related) and Type AB (chronic atrophic gastritis)
 Chronic gastritis: classification
► Type A- involves fundus and body
❖ parietal cell and intrinsic factor antibodies
❖ Depletion of parietal cells and impaired secretion of IF
❖ Significant gastric atrophy, intestinal metaplasia
❖ Patients develop pernicious anemia
❖ Associated with other autoimmune disorders (hashimoto’s thyroiditis, addisons
disease etc)
► Type B- antral mucosa
❖ Hypersecretory gastritis
❖ Excessive secretions of acid due to H.pylori infection
► Type AB- invloves body, fundus and antrum
❖ Most common type
❖ Mucosal atrophy , intestinal or pyloric metaplasia
 PBQ-1
► A 50-year-old woman with long-standing rheumatoid arthritis complains of weakness
and fatigue. She states that her stools have recently become black after taking a new
nonsteroidal anti-inflammatory drug (NSAID). Gastroscopy shows numerous superficial,
bleeding mucosal defects.
H.Pylori
► Over 50% of the World’s population affected
► Discovered by Warren and Marshall in Australia in 1983
► More than half the world's population is infected
► H. pylori prevalence reflects the level of urbanization, sanitation, access to clean
water and varied socioeconomic status
► Gram-negative spiral bacillus
► Fastidious in terms of growth requirements
:strictly micro-aerophilic
:require C02 for growth on charcoal medium
► Has a tuft of sheathed unipolar flagella; especially
adapted to colonise mucous membranes

• The first bacterium classified as a carcinogen

• Implicated in gastric adenocarcinoma and MALT

lymphoma
• Organisms colonize the antrum first by binding to
gastric mucins in a pH dependent manner
• The organisms have affinity for gastric mucous cells
but do not attach to small intestinal or other gastric
epithelial cell types
 H.Pylori
► Hallmark of the species is production of urease enzyme
-urease breaks urea down to C02+NH3
-ammonia is a strong base
-process helps H. pylori survive strongly acidic stomach condition
► Highly adapted organism that lives only on gastric mucosa
► Gastric antrum is the most favoured site
► Present in the mucus that overlies the mucosa
► Intestinal metaplasia common
► Bismuth quadruple, levofloxacin triple or rifabutin triple therapies are used for
treatment
 Cag A:
Distrupts tight junctions,provokes
proinflammatory and mitogenic response

Vac A:
• Cytochrome c release and activation of proapoptotic factor leading to
apoptosis
• Gastric inflammation is a result of H. pylori infection mediated
upregulation of cytokines, reactive oxygen and nitrogen species,
produced by host gastric epithelial cells
H. Pylori: Pathogenesis
Diseases Associated with Helicobacter pylori Infection

Disease Association
Chronic gastritis Strong causal
association

Peptic ulcer disease Strong causal

association

Gastric carcinoma Strong causal

association

Gastric MALT Definitive etiologic

lymphoma* role
 H.Pylori: Diagnosis
► Invasive (endoscopic)techniques:
➢ Biopsy urease test: sensitivity and specificity, 90% and 95%
➢ Histology: sensitivity and specificity, 95% and 98%
➢ Bacterial culture and sensitivity test: high specificity, low sensitivity as H. pylori is difficult
to culture
► Noninvasive testing:
❖ Urea breath test: sensitivity and specificity, 88 - 95% and 95 - 100%
❖ Stool antigen test: sensitivity and specificity, 94% and 97%
❖ Serology: sensitivity and specificity, 85% and 79%
❖ Other tests: 13C urea assay: serodiagnostic test using a 13C urea assay
PCR: detect low bacterial loads and to identify specific mutations associated with
antimicrobial resistance
 H.Pylori: Diagnosis
► Identification of the bacteria: Invasive & Non- invasive techniques
❖ Histopathology using H&E stain. Giemsa, Warthin starry stain, IHC
 PBQ-2
► A 40-year-old woman presents with a 2-month history of burning epigastric pain that
usually occurs between meals.
► The pain can be relieved with antacids or food.
► The patient also reports a recent history of tarry stools. She denies taking aspirin or
NSAIDs.
► Laboratory studies show a microcytic, hypochromic anemia (serum hemoglobin = 8.5
g/dL).
► Gastroscopy reveals a bleeding mucosal defect in the antrum measuring 1.5 cm in
diameter.
► An endoscopic biopsy shows that the lesion lacks mucosal lining cells and is composed
of amorphous, cellular debris and numerous neutrophils.
 Stomach : Peptic Ulcer

► Breach in the mucosa of the alimentary tract, which extends through the
muscularis mucosa into the submucosa or deeper
► Location: Following location in decreasing order of frequency:
• Duodenum, first portion
• Stomach, usually antrum
• Within Barrett’ s mucosa
• In the margins of a gastroenterostomy (stomal ulcer)
• Duodenum, stomach or jejunum – in ZE syndrome
• Within or adjacent to a Meckel’s diverticulum that contains ectopic gastric
mucosa
 Peptic ulcers: Risk factors
► H. pylori infection
► Cigarette smoking
► Chronic obstructive pulmonary disease (COPD)
► Illicit drugs,e.g. cocaine,that reduce mucosal blood flow
► NSAIDs (potentiated by corticosteroids)
► Alcoholic cirrhosis (primarily duodenal PUD)
► Psychological stress (can increase gastric acid secretion)
► Endocrine cell hyperplasia (can stimulate parietal cell growth & gastric
acid secretion)
► Zollinger-Ellison Syndrome (PUD of stomach, duodenum, and jejunum)

► Viral infection (CMV,HSV)

 Peptic Ulcer disease
► Chronic most often solitary, lesions that occur in any portion of the gastrointestinal
tract exposed to the aggressive action of acid-peptic juices
► PUD is characterized by
❖ Degeneration and necrosis of GI mucosa exposed to acid-peptic secretions
❖ Can occur at any level of GIT
❖ Most common site –duodenum or stomach (4:1)
❖ Can be acute or chronic
► Pathogenesis: Two most important factors in peptic ulcer
- Exposure of mucosa to gastric acid and pepsin secretion
- H.Pylori infection (strong association)
 Peptic ulcer disease: GU & DU

► Two distinct diseases with different pathogenesis

► However similar morphology
❖ Solitary in >80%
❖ Round to oval, sharply punched out ; Mucosal margin may overhang the base
slightly
❖ Etiology: Psychological stress/ Physiological stress- shock, severe trauma,
septicemia, extensive burns(curlings ulcer), intracranial lesions, drugs ( aspirin,
steroids, NSAIDS), local irritants ( alcohol, smoking, coffee)
 Gastric peptic ulcer
► Gastric peptic ulcer – along lesser curvature – interface of body and antrum
► Pathogenesis
❖ Impaired gastric mucosal defenses against acid -pepsin secretion
❖ Hyperacidity- due to increased gastrin levels in response to ingested food in an atonic
stomach
❖ Some patients have low to normal gastrin levels- damage of mucosa due to other
factors like cigarette smoke, gastritis, bile reflux etc
❖ Depletion in quantity or quality of gastric mucus- H.Pylori
 Duodenal ulcers

► High acid pepsin secretion- main cause

❖ Hypersecretion of gastric acid into fasting stomach (night)
❖ Increase hurrying /rapid emptying of food- exposure of mucosa to aggressive
action of gastric acid
► H.Pylori
❖ breakdown of gastric mucosal defence by urease, catalase etc by the bacteria
❖ H.pylori infected epithelium releases proinflammatory cytokines (IL-1,IL-6, IL-8) &
TNF- incite intense inflammatory reaction
❖ CagA and Vac A released by the bacteria also induces release of cytokine
 Peptic ulcers: Morphology
► Gross – GU- lesser curvature of pyloric antrum; DU- 1st part of duodenum; can be seen
in cardia, margical ulcer, meckel’s diverticulum
► Solitary (80%), small(1-2.5cms) round to oval, punched out, flat margins, with mucosal
folds converging towards the ulcer; superficial or deep ulcers
► DU & GU can be coexistant (10-20%)
► Chronic DU- always benign; GU- can become malignant (1%)
► M/E: 4 histological zones
❖ Necrotic zone- floor of the ulcer, fibrinous exudates, necrotic debris & leukocytes
❖ Superficial exudative zone- coagulative necrosis of underlying tissues-eosinophilic
smudgy appearance, nuclear debris
❖ Granulation tissue zone- non specific inflammatory cells and proliferating blood vessels
❖ Zone of cicatrisation- dense fibrocollagenic scar over which granulation tissue rests,
thrombosed sclerotic arteries+
 1 2
3 4
 Peptic Ulcers: Complications & clinical features

► Obstruction: 2% ; associated with DU

► Hemorrhage/ bleeding ; 15-20%; may be the first indicator; common cause of death
► Perforation: 5%; accounts for 2/3rd of the ulcer deaths
► Malignant transformation
Clinical features
❖ Age: 5-6th decade
❖ People at risk: DU- stress
❖ Pain: Gnawing, burning, aching pain, epigastric
❖ Vomiting, hematemesis, Malena
❖ Appetite: GU-good appetite; afraid to eat, DU-good appetite
❖ Weight loss- common in GU
Duodenal versus gastric ulcers
 PBQ-3
► A 60-year-old man presents with an 8-week history of progressive weight loss, nausea,
and upper abdominal pain
► There is no response to antacids or H2-receptor antagonists.
► Laboratory studies show iron-deficiency anemia.
► Gastroscopy reveals a crater-like, ulcerated lesion
in the antrum, with raised, irregular, and indurated margins.
► The patient undergoes partial gastrectomy
Gastric Tumors
 GASTRIC TUMORS

► BENIGN:
▪ POLYPS (HYPERPLASTIC vs. ADENOMATOUS)
▪ LEIOMYOMAS (Same gross and micro as sm. muscle)
▪ LIPOMAS (Same gross and micro as adipose tissue)
► MALIGNANT
▪ (ADENO)Carcinoma : 90-95%
▪ LYMPHOMA ( 4%)
► POTENTIALLY MALIGNANT
▪ G.I.S.T. (Gastro-Intestinal “Stromal” Tumor): 2%
▪ CARCINOID (NEUROENDOCRINE):3%
 Gastric polyps
► Hyperplastic /inflammatory polyps
❖ Associated with chronic gastritis leading to injury
and reactive hyperplasia
❖ Non neoplastic, single/multiple; located in
antrum
❖ Sessile/pedunculated, soft
❖ C/o irregular hyperplastic glands; cystic changes±;
no cellular atypia
 Gastric polyps
► Fundic gland polyp
❖ In gastric body and fundus
❖ Sporadic & in individuals with Familial adenomatous polyposis (FAP)
❖ Increase use of Proton pump inhibitors
❖ Single / multiple
❖ Cystically dilated glands lined by parietal cells
❖ Dysplasia / cancer may in FAP associated cases
 Gastric adenoma

► 10% of all gastric polyps

► Always occur on a background of chronic gastritis with atrophy and intestinal
metaplasia.
► Risk of adenocarcinoma is related to the size of the lesion( ˃2 cm in diameter)
► Gross: solitary ˂2cms, antrum
► M/E: intestinal type of epithelium
Dysplasia+; low or high grade
Gastric carcinoma
 Gastric adenocarcinoma: etiopathogenesis
► 4-6th decade; M>F: 3:1
► High incidence in some countries – Japan, Chile, China
► Fifth most commonly diagnosed cancer type worldwide (2018)
► 3rd leading cause of cancer related death and was responsible for 8.2% of all
deaths from cancer
► Symptoms: Often nonspecific, frequently diagnosed at an advanced stage (>
70%)
► 35% of gastric cancer patients in the U.S. have metastasis at diagnosis (clinical
stage 4)
► Classification
 Gastric adenocarcinoma: etiology
► Environmental:
❖ H.Pylori infection- 3-6times higher risk
❖ EBV: 5-10% association
❖ Diet: more in areas where irritant food exert maximum effect ( lesser curvature,
antrum), smoked food, pickled raw vegetables,
❖ Tobacco smoke, alcohol
► Geographical factors: Japan, chile, Itlay
► Racial factors: blacks, American Indians, Chinese
► Host factors: Chronic gastritis (hypo/achlorhydria, intestinal metaplasia), adenomatous
polyps, stump ca following gastrectomy
► Genetic factors: blood group A; germ line mutation in E-cadherin gene (C/a in younger
age)
Gastric adenocarcinoma: Location, C/F and Complications

► Location:

► Clinical features:
❖ Persistent abdominal pain
❖ Distention, vomiting
❖ Loss of weight & appetite
❖ Anemia, malaise
► CX: hematemesis, malena, obstruction, perforation, jaundice
 Gastric carcinoma: Morphology
► Most common and worldwide histological classifications for gastric cancer are the
Lauren and the WHO classifications
► Lauren classification: Diffuse ( infiltrative) and intestinal (glandular) type
❖ Diffuse type:
✓ Lack of or poor cohesion between the neoplastic cells
✓ Composed of scattered, small clusters or rows of cells with little or no gland formation
✓ Neoplastic cells usually show an atypical morphology with irregular nuclear contours
and variable amounts of eosinophilic cytoplasm
✓ In some cases, there is a variable component of cells showing the so called signet ring
morphology
✓ Signet ring cells show ample cytoplasmic mucin, which appears optically clear on H&E
staining and an eccentrically placed nucleus
 Gastric carcinoma: Morphology
❖ Intestinal type:
✓ Composed of tubular or glandular structures similar to intestinal adenocarcinoma
✓ Neoplastic cells usually contain apical mucin vacuoles
✓ Unlike diffuse gastric cancer, intestinal tumors grow along broad cohesive fronts to
form an exophytic mass
► WHO classification: based on tubular formation
❖ Well differentiated
❖ Moderately differentiated and ( corresponds to lauren intestinal type)
❖ Poorly differentiated (corresponds to lauren diffuse type)
Gastric adenocarcinoma: morphology
 Gastric adenocarcinoma: morphology

► Early gastric carcinoma

❖ Limited to mucosa/submucosa
❖ Gross: 3 patterns- polypoid, superficial & ulcerated
❖ M/E- well differentiated adenocarcinoma
❖ Prognosis after complete resection- good
❖ 5 yr survival- 93-99%
 Gastric adenocarcinoma- morphology

► Advanced gastric carcinoma

❖ Invasion into muscularis propria and beyond
❖ Ulcerative: MC, flat infiltrating & ulcerative growth with irregular necrotic based &
raised edges; M/e- poorly differentiated adenocarcinoma
❖ Fungating/polypoid: fundus, well differentiated, papillary type
❖ Schirrhous: prominent rugae, thickened wall due to desmoplasia; leather like stomach;
pyloric antrum/entire stomach; M/e- signet ring cell type
❖ Colloid: fundus, mass with gelatinous appearance/e- abundant pool of mucin with small
no. of tumour cells
Gastric adenocarcinoma: Morphology(Gross)
Gastric adenocarcinoma: Morphology(microscopic
features)
Gastric adenocarcinoma: Morphology
 Gastric adenocarcinoma- spread

► Direct: MC, transcelomic infiltration, ovaries , oesophagus, lesser & greater omentum,
pancreas liver, CBD, spleen, TC
► Lymphatic: schirrous c/s, regional LN;s lesser & greater curvature; LN’s supraclavicular
❖ Virchow node – supraclavicular node metastasis
❖ Sister Mary Joseph nodule – periumbilical metastasis
❖ Krukenberg Tumor - visceral metastasis in one/both ovaries
► Hematogenous: liver, lung, brain, bones, kidneys and adrenals; poorly differentiated
 Benign versus malignant ulcers

► Age
► Duration
► Location
► Gross: size, shape , mucosal folds,
ulcer bed
► Barium studies
► Acidity
► Treatment
 PBQ-4
► A 57-year-old male presents to his family physician with occasional abdominal pain, dull
in nature over the past 6 months. There is history of loss of appetite, with early staiety
and significant weight loss (around 20 lbs) in the preceding six months
► Patient also complains of nausea and vomiting off and on
► PMH: Patient is hypertensive, controlled with an ACE inhibitor. He has an 80-pack-per-
year smoking history.
► Vital signs: Temperature of 99.2°F, pulse of 91 bpm, and blood pressure of 131/82 mm
Hg.
► A physical examination reveals vague left upper quadrant tenderness.
► Palpation of the left supraclavicular region reveals a nontender, nonmobile mass.
► A fecal occult blood test is positive.