Helicobacter pylori Gastritis

Jeffrey D Goldsmith, MD Director 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 Gastric Physiology. 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 that will not be treated

Conclusions H. pylori remains a clinically significant pathogen and carcinogen  Pathologists continue to have a pivotal role in diagnosis 

Thank You!