Gastric Pathology

Dr. RAFIF AL SAADY

Assistant Professor
MBChB, FICMS, EBP, DipRCPath
rafif@qu.edu.qa
Gastric Anatomy
Gastric Histology
Regulation of Gastric acid secretion
 Objectives

• Acute gastritis and gastropathy.

• Chronic gastritis: H.pylori gastritis and autoimmune.

• Peptic ulcer disease (PUD): risk factors, pathological features

and its associated complications.

• Common gastric neoplasms: benign and malignant.

 Acute Gastritis and Gastropathy
 Gastritis: is a mucosal inflammatory process.
 Due to imbalance between mucosal defense and acid environment.
 Acid damage lead to superficial inflammation, erosion (loss of superficial epith.) or
ulcers (loss of mucosal layer).

 If neutrophil are present →acute gastritis, if not →gastropathy.

 If untreated can lead to bleeding → acute erosive hemorrhagic gastritis and
perforation.

 Asymptomatic disease to mild epigastric pain, nausea, and vomiting or coffee-

ground hematemesis & melena in severe complicated disease.
Acute Gastritis & Gastropathy Risk Factors
 Drugs as NSAIDs.
 Heavy alcohol consumption.
 Chemotherapy and radiation.
 Bile reflux.
 Uremic patients (inhibition of gastric bicarbonate transporters by ammonium ions).
 Infections as H.pylori (urease secreting o.g.).
 Old age: ↓ mucin and bicarbonate secretion suggested as factors that explain the
increased susceptibility of older adults.to gastritis.

 Ingestion of harsh chemicals, acids, or bases, → severe gastric mucosal damage

due to direct injury (epithelial and stromal cells).
 Stress –Related Mucosal Disease
 Extensive burn → Curling ulcers (proximal duodenum).
 ↑ intracranial pressure & brain injury → Cushing ulcers ( stomach, duodenum
& esophagus).
 Major surgery, serious medical disease & severe physiological stress.
 Shock & sepsis → Stress ulcers ( local ischemia, caused by systemic
hypotension or ↓blood flow resulting from stress-induced splanchnic
vasoconstriction).
-Range from shallow erosions to deep penetrating, multiple ulcers (perforation
& bleeding), but end by complete reepithelization and healing.
Prophylactic PPI in ICU patients.
 Acute gastritis & Gastropathy Pathology
Gastropathy with Microscopy: acute
Acute gastritis: diffusely erosions superficial gastritis with
hyperemic gastric mucosa. mucosa is eroded away. neutrophils in mucosa
 Chronic Gastritis
 Chronic Inflammation of the stomach.
 Could be H. pylori gastritis or Chronic autoimmune gastritis.
 Other : NSAIDs, radiation, bile reflux (reflux gastropathy or chemical gastritis),
& systemic diseases (Crohn disease, amyloidosis, or graft-versus-host
disease)…

 Symptoms are less severe than acute gastritis but more persistent.
 Nausea & upper abdominal pain are typical, sometimes with vomiting, but
hematemesis is rare.
 H. Pylori Chronic Gastritis
 Most common cause of gastritis 90%.
 Antrum is the most affected part of the stomach.
 H. pylori secrete ureases & proteases with inflammation will weaken the
mucosal defense → ulceration (peptic ulcer disease).
 Patient usually present with epigastric abdominal pain and later with
peptic ulcer disease and complications.
 H. Pylori Chronic Gastritis Pathogenesis

 H. pylori infection most often presents as a predominantly antral

gastritis (N or ↑ acid production → duodenal ulcer).

 Or body & fundus gastritis→ multifocal atrophic gastritis with patchy

mucosal atrophy → reduced parietal cell mass & ↓ acid secretion →

intestinal metaplasia, ↑ risk of adenocarcinoma.

What determines H.pylori pathogenesis
 Virulence
• Flagella, allow it to be motile in viscous mucus.
• Urease, that generates ammonia from endogenous urea → ↑ local
gastric pH & enhances bacterial survival.
• Adhesion that enhance adherence to foveolar cells surface.
• Toxins, as cytotoxin-associated gene A (CagA), that is involved in
disease progression (more in patient with ↑cancer risk).
What determine H.pylori pathogenesis(continue)

 Host factors
• ↑ expression of the proinflammatory cytokines (TNF) &
interleukin-1β (IL-1β)
• ↓ expression of the anti-inflammatory cytokine interleukin-10
(IL-10) are associated with development of pangastritis & ↑
cancer risk.
• Also iron deficiency anemia may ↑ the risk.
 H. Pylori Diagnosis
 Noninvasive serologic test for antibodies to H. pylori (active & prior infection).
 Fecal bacterial antigene detection.
 Urea breath test: based on the generation of ammonia by the bacterial urease.
 Gastric biopsy specimens can be analyzed by the rapid urease test.
 Bacterial culture (not commonly done).
 Bacterial DNA detection by PCR.
 Biopsy with histological identification of bacteria.
No need to memorize

Copyrights apply
 H. Pylori pathological features

Intraepithelial and
lamina propria
neutrophils infiltration.
 H. Pylori pathological features (continue)

• Lymphoid aggregates with germinal

centers & subepithelial plasma cells
within lamina propria are
characteristic of H. pylori gastritis.
• Represent an induced form of
mucosa-associated lymphoid tissue,
or MALT, that has the potential to
transform into lymphoma
H. Pylori pathological features (continue)

S or Spiral-shaped H.
pylori highlighted by
Warthin-Starry silver
stain. Organisms are
abundant within surface
mucus.
 Chronic Autoimmune Gastritis
 Less than 10% of f chronic gastritis, but most common form of chronic gastritis in patients without H.
pylori infection

 Autoimmune destruction of gastric parietal cells, Type IV hypersensitivity reaction (mediated by CD4+
T lymphocytes) in body & fundus.

 Antibodies against parietal cells &/or intrinsic factor (IF).Dx.

 Defective acid secretion (Achlorhydria) → ↑ gastrin level, Antral G-cell hyperplasia, endocrine cell
hyperplasia (Tumor).

 Reduced serum pepsinogen I concentration results from chief cell destruction.

 Megaloblastic ( pernicious) anemia due to lack IF (Vitamin B12 deficiency).

 Atrophy of mucosa with intestinal metaplasia → Increase risk of gastric adenocarcinoma.

 Most common cause of diffuse atrophic gastritis

Chronic Autoimmune Gastritis Microscopy
 Chronic Gastritis Complication

 PUD.

 Mucosal atrophy & intestinal metaplasia → Dysplasia &

adenocarcinoma.

 Lymphoma (MALT).
 Peptic Ulcer Disease (PUD)
 Mucosal ulcer involving proximal duodenum (90% of
cases) or distal stomach (10%). Other parts of GIT
 Due to ↓ mucosal protection against gastric acid or ↑
gastric acid secretion or both.
PUD Risk Factors
 Duodenal Ulcer
 Due to H. pylori (˃ 95%) ,
 Rarely due to ZE syndrome.
 Present with epigastric pain that Decreases with meals
 May be complicated by rupture with bleeding or acute
pancreatitis, or pyloric channel & duodenal obstruction.
 Ulcers usually on anterior wall, few centimeter from pyloric
valve.

ZE syndrome = Zollinger Ellison syndrome (gastrin-producing tumour-gastrinoma)

 H.Pylori and DU
 H. pylori in antrum will cause Duodenal ulcer due to destruction
of somatostatin producing cells in antrum.
 This lead to increase gastrin effect leading to increase acid
secretion.
 H.pylori also release cytotoxins that inhibit duodenal bicarbonate
production. All lead to DU.
 Gastric Ulcer
 Due to H. pylori ( 75%),
 Other as NSAIDs and bile reflux.
 Present with epigastric pain that can be Greater with meals
 Located at lesser curvature of antrum.
 May be complicated by rupture with bleeding or ↑ risk of cancer.
 H.Pylori and GU
 H.pylori in body lead to gastric ulcer.
 It caused multifocal atrophic gastritis due to parietal cell
destruction
 Gastrin normal and HCL normal or low.
 Ulcer due to bacterial products (ammonia & cytotoxic) and
inflammatory response
 Peptic Ulcers Morphology

Gross Features:

• The lesions are usually round

to oval, sharply punched-out
defect.

• Less than 0.3 cm in diameter

tend to be shallow.
Peptic Ulcers Morphology
 PUD Complications

Acute
→hematemesis/melena
chronic→ anemia
Anterior duodenal ulcers can
perforate into the anterior
abdominal cavity, → leading to
pneumoperitoneum ( may see
free air under diaphragm) with
referred pain to the shoulder
via irritation of phrenic nerve.

Penetration into Pancreas

(rare)→ Post. DU → deep
pain &↑ pancreatic enzymes.
 Gastric Tumors
 Benign
Polyps: nodules or masses, project above the level of the surrounding mucosa.

Types: Inflammatory hyperplastic polyps, Fundic gland polyps, Adenomatous

polyps...

 Malignant
I. Primary : Adenocarcinoma.

Carcinoid.

GIST (Gastrointestinal stromal tumour).

Lymphoma.

II. Secondary : uncommon

 Gastric Polyps

FAP =Familial adenomatous polyposis; PPIs= proton pump inhibitors .

 Gastric Cancer risk factors
• Environmental factors: H. pylori infection (certain genotypes: vacAs1, vacAm1,
and cagA positive).

Epstein-Barr (EBV) infection.

Smoking and alcohol.

Diet ( high salt diet & nitrosamine as smoked fish in Japan).

Obesity, previous gastric surgery..….

• Host related factors: Familiar predisposition i.e. aggregate within families, possibly genetic
polymorphism (IL-1, TNF).

Hereditary gastric cancer: HDGC (germline mutations in the CDH1 gene

encoding E-cadherin), GAPPS, FIGC)

Association with other inherited cancer syndromes.

Others as Pernicious anemia (chronic atrophic gastritis.).

 Gastric Adenocarcinoma
 Most common type of gastric malignancy
 Sub classified pathologically into intestinal and diffuse (Lauren
classification).

 Patient present late with weight loss, abdominal pain, anemia and early
satiety & metastasis.

 Other presentation : acanthosis nigricans.

Leser-Trelat sign.
Intestinal Type Gastric Adenocarcinoma
• More common.
• Follows a step-wise progression from chronic gastritis → intestinal
metaplasia→ dysplasia→ carcinoma insitu→ invasive carcinoma.
• Longstanding chronic superficial gastritis caused by chronic H.
pylori infection, pernicious anemia, or possibly, a high-salt diet leads
eventually to chronic atrophic gastritis and intestinal metaplasia.
• Endoscopy (gross) : seen as large ulcer involve lesser curvature of antrum
(similar to gastric ulcer D. DX!!).
Benign versus Malignant Gastric Ulcer
Benign ulcer: small < 3cm, sharply Malignant ulcer: large, irregular with
demarcated (punched out) heaped up margins.
surrounded by radiating fold of
mucosa.
Gastric intestinal type adenocarcinoma microscopy

• tumors with an intestinal

morphology, composed of columnar,

gland-forming cells infiltrating

through desmoplastic stroma.

• More in antrum, in lesser curvature.

Diffuse Type Gastric Adenocarcinoma
 Not associated with H. pylori.
 Endoscopy (gross): seen as thickening in stomach wall (linitis plastica).
 Microscopy: diffuse infiltration of signet ring cells with desmoplastic
reaction.

 Worse outcome than the intestinal type.

 May be associated with CDH1 gene mutation.
 Diffuse Type Gastric Adenocarcinoma Gross
A mass difficult to appreciate, but
infiltrative tumors often evoke a
desmoplastic reaction → stiffens the
gastric wall & provide a valuable
diagnostic clue → diffuse rugal
flattening & a rigid, thickened wall may
impart a leather bottle appearance
termed linitis plastica.
Diffuse Type Gastric Adenocarcinoma Microscopy
• Signet-ring cells recognized by their large
cytoplasmic mucin vacuoles & peripherally
displaced, crescent-shaped nuclei. These
cells do not form glands

• They permeate the mucosa and stomach

wall individually or in small clusters
 Spread and Metastasis
 Spread to draining lymph node, may involve supraclavicular lymph node (Virchow
node) or axillary node (Irish node).

 Metastasis: commonly to the liver,

Periumbilical region (sister Mary Joseph nodule); intestinal type.

Ovaries (Krukenberg tumour); diffuse type.

Blumer’s Shelf (rectal shelf): palpable mass on digital rectal exam

suggesting metastasis to POD.
Gastric Carcinoma Distant Metastasis
 Primary Gastric Lymphoma
 Forms 5% of gastric malignancies.
 In the stomach, MALT lymphoma is induced, typically as a result of chronic
gastritis.
 H. pylori infection is the most common inducer in the stomach and, therefore, is
found in association with most cases of gastric MALToma.
 Grossly: mass +/- ulcer, thickened gastric wall, or polypoid lesions.
 Microscopy: monomorphous infiltrate of B-cell type lymphoid cells (CD19 &
CD20).
 Remarkably, H. pylori eradication results in durable remissions with low rates of
recurrence in most MALToma patients
MALT=mucosa-associated lymphoid tissue
Gastric Gastrointestinal stromal tumour (GIST)
 Most common mesenchymal tumor of the abdomen, More than half of these
tumors occur in the stomach.

 Arise from the interstitial cells of Cajal, or pacemaker cells, of muscularis propria.
 75% to 80% of all GISTs have oncogenic, gain-of-function mutations in the
receptor tyrosine kinase KIT.

 8% of GISTs have mutations in platelet-derived growth factor receptor α

(PDGFRA).

 The molecular phenotype is an important consideration in the treatment of

patients with unrespectable, recurrent, or metastatic GISTs. Those with mutations
in KIT or PDGFRA often respond to the tyrosine kinase inhibitor (imatinib).
 GIST Morphology
Gross: fleshy mass covered by intact Microscopy: composed of bundles,
mucosa & projecting inside stomach. or fascicles, of spindle-shaped
tumor cells.
 Gastric Carcinoid
 Carcinoid tumors arise from the diffuse components of the endocrine
system and are now properly referred to as well-differentiated
neuroendocrine tumors.

 Gastric carcinoid
. tumors may be associated with endocrine cell hyperplasia,
autoimmune chronic atrophic gastritis, MEN-I, and Zollinger-Ellison
syndrome.

 Gastric endocrine cell hyperplasia has been linked to proton pump inhibitor
therapy, but the risk of progression to a neuroendocrine neoplasm in this
circumstance is extremely low.
 Carcinoid Tumour Morphology
Microscopically: nest of tumor cells
Gross: submucosal tumor nodule
embedded in dense fibrous tissue, with bland
cytology. The chromatin texture, with fine and
coarse clumps “salt and pepper” pattern.
Summary
 References
 Robbins and Cortan Pathologic Basis of Disease.
 https://masaka.luxiarweddingphoto.com/pneumoperitoneum/
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 https://www.webmd.com/skin-problems-and-treatments/acanthosis-
 Fundamental of Pathology (pathoma) nigricans-overview

 First aid for step 1 USMLE  https://dermnetnz.org/topics/sign-of-leser-trelat/

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vector-image191300476 neoplasms-qplummer-diagram/

 https://www.researchgate.net/figure/Normal-gastric-mucosa-histology-a-H-  https://painepodcast.com/2020/03/
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Questions??