1. Non-neoplastic Stomach Vinay Prasad, MD Nationwide Children’s Hospital vinay.prasad@nationwidechildrens.org Narrated by Dr. Ben Swanson

2. Objectives  1. Describe the pathology and pathophysiology of the following gastric conditions: congenital anomalies and inflammation  2. Recognize the gross and histopathologic appearance of gastritis and peptic ulcer  3. Describe chronic active gastritis due to Helicobacter pylori infection  4. Describe the gross pathology of duodenal and gastric ulcer  5. Describe the pathophysiology of Zollinger-Ellison (ZE) syndrome  6. Describe the pathology of Ménétrier's disease

3. CONGENITAL ANOMALIES Diaphragmatic Hernias  Weakness or absence of portion of diaphragm (usually left side)  Permits herniation of abdominal contents into chest  May result in pulmonary hypoplasia  Treated surgically

4. Hiatal Hernia

5. CONGENITAL ANOMALIES PYLORIC STENOSIS  Projectile, nonbilious vomiting  2-3 week old  Familial, 4:1 M>F  Palpable mass “olive”  Narrowing of pyloric lumen due to hypertrophy of the muscularis propria  Surgical repair

6. ANATOMIC ABNORMALTIES OTHER CONDITIONS  Gastric Diverticulum  Cardia: can occur as an isolated lesion  Antrum: Often associated with a healing ulcer

7. ANATOMIC ABNORMALTIES OTHER CONDITIONS  Gastric Dilatation  Can be due to mechanical or functional obstruction of the pylorus  Bezoar-retained undigested material

8. ANATOMIC ABNORMALTIES OTHER CONDITIONS  Gastric Rupture  Associated with trauma, excessive drinking, cardiac resuscition and labor  Results in shock or death unless immediately treated surgically

9. INFLAMMATORY CONDITIONS  Acute Hemorrhagic Gastritis  Reactive (Chemical) Gastropathy  Helicobacter-associated Gastritis  Autoimmune Gastritis  Granulomatous Gastritis

10. ACUTE HEMORRHAGIC GASTRITIS  Pathogenesis: stress, ischemia, chemoradiation, cocaine, NSAIDs, alcohol  Frequent cause of upper GI bleeds  Gross: punctate hemorrhage, erosions, apthous ulcers  Micro: edema, acute inflammation, hemorrhage  Clinical course: asymptomatic to painful, nausea/vomiting  Resolution after correction of underlying etiology

11. ACUTE GASTRITIS

12. REACTIVE (CHEMICAL) GASTROPATHY  Pathogenesis: bile reflux, chemoradiation, NSAIDs  Gross: erythema, enlarged folds, polypoid change  Micro: foveolar hyperplasia, serrated pits, mucosal edema, dilated capillaries  Clinical course: nausea, bloating  Resolution after withdrawal of causative factor

13. HELICOBACTER-ASSOCIATED GASTRITIS General  S-shaped gram negative rod  Affects 50% of the World Population  >70% prevalence in developing world  ~40% of population >50 yo in western countries  Infection spread through person-person contact  Identified by Barry Marshall and Robin Warren (1982 Nobel Prize)

14. HELICOBACTER-ASSOCIATED GASTRITIS Histologic Findings  Active chronic gastritis  Antral predominant- increased acid, duodenal ulcer  Body predominant (pangastritis)- impaired acid secretion, gastric ulcer  Histologic features  Diffuse superficial mucosal chronic inflammation- plasma cells  Variable acute inflammation in glands- neutrophils  Lymphoid follicles  Bacteria are present in the epithelial mucus layer  Chronic infection leads to intestinal metaplasia and dysplasia  Multifocal atrophic gastritis- pseudopyloric and intestinal metaplasia, atrophy and fibrosis

15. HELICOBACTER-ASSOCIATED GASTRITIS HISTOLOGY Increased lymphocytes and plasma cells in the lamina propria

16. HELICOBACTER-ASSOCIATED GASTRITIS CHRONIC ACTIVE GASTRITIS Neutrophils within pits in addition to lymphocytes and plasma cells in lamina propria

17. HELICOBACTER ASSOICATED GASTRITIS ORGANISMS

18. HELICOBACTER-ASSOCIATED GASTRITIS COMPLICATIONS  Peptic ulcer disease-4X increased risk  Gastric Cancer- 3-6X increased risk  Gastric MALT lymphoma Infection-> increased lymphoid response -> lymphoma Remission of lymphoma active in 75% of patients following eradication of H. pylori

19. AUTOIMMUNE GASTRITIS  Pathogenesis: serum anti-parietal cells and anti-intrinsic factor (IF) antibodies  Gross: flattened rugal folds  Micro: dense lymphoplasmacytic infiltration, metaplastic changes  Vitamin B12 deficiency and pernicious anemia (some)  Increased incidence of mucosal dysplasia and neuroendocrine tumors

20. AUTOIMMUNE GASTRITIS HISTOLOGY

21. GRANULOMATOUS GASTRITIS  Infections- Tuberculosis, Histoplasma  Sarcoidosis  Crohn’s disease  Foreign Material  Impacted Food  Drugs

22. PROMINENT GASTRIC FOLDS  Zollinger-Ellison Syndrome  Menetrier Disease  Hypertrophic hypersecretory gastropathy  Other  Hyperplastic polyposis  Neoplastic  Inflammatory  Infiltrative (amyloid)

23. ZOLLINGER-ELLISON SYNDROME  Gastrinoma  Duodenum (50-70%)  Pancreas (20-40%)  Plasma gastrin >1000 pg/mL  Intragastric pH <2.0 (acidic)  Micro: Hypertrophic parietal cells  Treat: resect tumor, proton pump inhibitors, vagotomy/gastrectomy

24. Zollinger-Ellison Syndrome Histology

25. Ménétrier's Disease  5 th -6 th decade; M>F  Insidious onset  Giant gastric folds  Pit hyperplasia (elongated)  Cystic dilatation of the gastric glands  Decreased acid production  Protein loss  Treatment- gastrectomy

26. PEPTIC ULCER DISEASE  Chronic usually solitary mucosal defect  Can occur in any part of the GI tract exposed to peptic acid juices  Duodenum> stomach> esophagus> Meckel’s diverticulum  >75% associated with H. pylori  Others: infections, NSAIDs

27. PEPTIC ULCER DISEASE GROSS (ENDOSCOPIC) FINDINGS  Grayish exudate covering nodular erythematous mucosa  Round to oval shape and sharply demarcated  Duodenum-90% in the first portion  Stomach- anterior wall of antrum at the lesser curvature is most common

28. PEPTIC ULCER DISEASE MICROSCOPIC FINDINGS  Four histologic zones 1. Surface inflamed fibrinous debris 2. Acutely inflamed mucosa 3. Granulation tissue 4. Fibrous scar Fibrin Fibrosis Granulation tissue Inflammation

29. PEPTIC ULCER DISEASE CLINICAL COURSE  Presentation: Pain, anemia, hematemesis  Complications- perforation, severe bleeding, obstruction  Excellent outcome with treatment

30. Summary  A variety of inflammatory conditions can involve the stomach showing an array of histologic features  Helicobacter pylori infection causes chronic active gastritis with superficial mucosal chronic inflammation and variable acute inflammation  Zollinger-Ellison syndrome shows prominent rugal folds and hypertrophic parietal cells  Menetrier’s disease shows giant gastric folds with elongated pits and cystically dilated gastric glands  Peptic ulcers show four clear histologic zones and are caused by exposure to gastric juices

32. Thank you for completing this module Questions? Contact me at: vinay.prasad@nationwidechildrens.org

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