Helicobacter pylori Gastritis
Jeffrey D Goldsmith, MDDirector of Surgical Pathology Laboratory, Beth Israel Deaconess Medical Center
Consultant in Gastrointestinal Pathology, Children’s Hospital Boston
Assistant Professor, Harvard Medical School
Boston, MA
“Everyone thought they were oral contaminants”--- Harvey Goldman (~2002)
Outline
History Epidemiology Pathogenesis Sequelae Diagnosis
The Past
Epidemiology
Prevalence varies highly based on socioeconomic conditions◦ > 80% in developing countries◦ 20-50% in industrialized countries; decreasing
in the US
◦ Oral ingestion during childhood with lifelong persistence
Pathogenesis
Pathogenesis
The stomach is not a happy place for bacteria, but H. pylori loves it there◦ Urease and flagellae
Pathogenesis
The stomach is not a happy place for bacteria, but H. pylori loves it there
BabA
Lewis B
Pathogenesis
The stomach is not a happy place for bacteria, but H. pylori loves it there
Digestive Health Initiative, H. pylori on the gastric epithelial cell from the collection of Dr. David Peura and Dr. David Graham, 1994
Pathogenesis
The stomach is not a happy place for bacteria, but H. pylori loves it there◦ VacA
Pathogenesis The stomach is not a happy place for
bacteria, but H. pylori loves it there◦ CagA
Pathogenesis
Host Response◦ Th1 – Intracellular immunity◦ Th2 – Extracellular immunity
Pathogenesis
Gastric v duodenal ulcers
McColl KE, El-Omar E, Gillen D. Helicobacter pylori Gastritis and GastricPhysiology. Gastroenterology Clinics of North America, 2000; 29:693.
Gillen D, McColl KE. Clinical Gastroenterology and Hepatology 2005; 3:1180-1186.
Carcinogenesis: Type 1 Carcinogen
Adenocarcinoma: Two interrelated mechanisms◦ 1. Virulence factors: CagA Secretion of IL-8 (potent neutrophil activating
factor) Activation of ERK/MAP kinase cascade which leads
to increased c-fos, c-jun gene expression Disruption of e-cadherin / b-catenin complex which
leads to abnormal nuclear localization of B-catenin
◦ 2. Host factors
Carcinogenesis: Type 1 Carcinogen
Adenocarcioma: Two inter-related mechanisms◦ 1. Virulence factors◦ 2. Host factors Inflammation -> intestinal metaplasia -> dysplasia ->
adenocarcinoma Hypochlorhydria leads to colonization of the
stomach by nitrogen fixing bacteria -> carcinogenic N-nitroso compounds
Carcinogenesis: Type 1 Carcinogen
Lymphomagenesis: Different than carcinoma◦ Also associated with CagA positive strains Seems to be mostly due to unrestrained activation of b-cells
exacerbated by CagA induced gastric inflammation
Diagnosis Many non-invasive diagnostic tests exist
and have utility in a non-acute setting◦ Urease breath test: Sensitivity and specificity: 95%◦ Stool antigen test: Sensitivity: 90-100%; specificity: ~90%◦ Serology: Sensitivity and specificity: 90%
◦ Stool antigen test and breath test can be used to assess for eradication after therapy
Diagnosis
H&E = Histochemistry = IHC in the ‘classic’ histologic context◦ Things are different in the PPI era: Organisms can: Move Change location Change morphology
◦ IHC more useful now
Diagnosis
Diagnosis
Diagnosis
Diagnosis
Diagnosis – IHC indications
Chronic active gastritis without H. pylori on H&E
‘Chronic inactive gastritis’ without H. pylori on H&E*(* = significant inflammation)
◦ Germinal centers are an absolute indication
Any intraepithelial neutrophils without H. pylori on H&E
Inflamed cardia biopsy when no distal gastric biopsies procured
Lymphocytic gastritis, granulomatous gastritis, eosinophilic gastritis
Diagnosis – IHC Indications
Diagnosis – IHC Indications
Diagnosis – IHC indications
Clinician request based on abnormal endoscopy* (* = previously treated for H. pylori)
Visualizing H. pylori on H&E
Histologically normal biopsy
Chemical / reactive gastropathy* (*pure form)
Inflamed cardia biopsy when other biopsies are normal
Fundic gland polyp as a sole finding
Treatment
** Investigation for infection should NOT be performed in patients thatwill not be treated
Conclusions
H. pylori remains a clinically significant pathogen and carcinogen
Pathologists continue to have a pivotal role in diagnosis
Thank You!
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