helicobacter pylori gastritis - uscap meeting (cm...helicobacter pylori gastritis jeffrey d...

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!