601 comp 12 working - Indiana University Bloomingtonmedsci.indiana.edu/c602web/602/c602web/docs/gastro/… ·  · 2012-10-31Lab test: CEA, stool for occult ... What is their function?

Gastrointestinal Pathology Dan Lodge-Rigal, MD Reading: Big Robbins, Chapter 17, plus Chapter 16 pp 758-762 Wheater: Alimentary chapter Online exercise: Mr. Jones’ Nausea, case 5 on the website and CD. Lab test: CEA, stool for occult blood, H. pylori antibodies, Celiac disease antibodies. Slides: 9, 19, 20, 21, 32, 59, 98, 104, 131, 138, 143, 144, 173, 183, 194, 199, 212, 216, 222 Reading: Robbins Basic Pathology 9th edition, Chapter 14 (pp. 551-602) OUTLINE Oral Cavity aphthous ulcers infections benign tumors leukoplakia and squamous epithelial abnormalities squamous cell carcinoma Salivary Gland inflammation and infection non neoplastic “tumors” neoplasms: benign neoplasms: malignant Esophagus congenital: esophageal atresia functional disorders: diverticula, webs and rings, achalasia, hiatal hernia gastroesophageal varices inflammation (esophagitis) gastroesophageal reflux disease (GERD) and Barrett esophagus eosinophilic esophagitis tumors: benign tumors: malignant Stomach congenital: pyloric stenosis gastritis: mechanisms acute and chronic gastritis

peptic ulcer disease gastric polyps gastric cancer other neoplasms of the stomach Large and Small Intestine congenital: Hirschprung disease diarrheal disease: classification celiac disease microscopic colitis infectious gastroenteritis: viral infectious enterocolitis: bacterial infectious enterocolitis: parasitic lab testing for diarrheal diseases inflammatory bowel disease diverticular disease ischemic bowel disease polyps: non-neoplastic polyps: adenomas colon cancer (adenocarcinoma) anal cancer Non-epithelial tumors of the GI tract carcinoid lymphoma Appendix

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Gastrointestinal Pathology Dan Lodge-Rigal, MD Oral Cavity Aphthous ulcers Infection: Herpes simplex Candida (thrush) Tumors: Benign: Fibroma Pyogenic granuloma Changes of the squamous epithelium: Hyperplasia (pseudoepitheliomatous hyperplasia) Leukoplakia and Erythroplakia (clinical diagnosis: white patch) Malignant: Cancer of the oral cavity (squamous cell carcinoma) Causative factors: 1) 2) 3) Natural history of squamous cell cancers of the oral cavity

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Salivary Glands Normal salivary gland structure and function Inflammation of the salivary glands: sialadenitis Infections: 1) 2) 3) Autoimmune Non-neoplastic "tumors": Mucocele and ranula Neoplasms: General concepts: Size of gland versus risk of malignancy Benign tumors Benign mixed tumor (pleomorphic adenoma) Warthin tumor (adenolymphoma) Malignant tumors Mucoepidermoid carcinoma Adenoid cystic carcinoma Lymphomas Metastatic tumors

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Esophagus Normal Esophagus: Layers: 1) 2) 3) 4) G-E Junction Z-line Lower esophageal sphincter Lower esophageal sphincter location: regulation of LES tone: Signs and symptoms of esophageal disease: 1) 2) 3) 4) Congenital disorders of the esophagus: Atresia and tracheo-esophageal fistula Functional (motor) disorders of the esophagus: Diverticula Stenosis Esophageal webs and Schatzki ring Achalasia primary versus secondary cancer risk

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Hiatal Hernia Esophageal hemorrhage Gastro-esophageal varices Pathogenesis: Natural history and treatment Inflammatory disorders of the esophagus (Esophagitis) Non-infectious 1) 2) 3) Infectious: 1) 2)

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Gastroesophageal reflux disease (GERD) Incidence: Causative factors for GERD: 1) 2) 3) 4) Effects of gastric acid on esophageal mucosa: 1) 2) Symptoms versus Pathologic changes Stricture Barrett Esophagus Definition: Significance of Barrett esophagus: Dysplasia Adenocarcinoma Natural history and management of Barrett esophagus: Eosinophilic esophagitis

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Tumors of the Esophagus Benign tumors (rare) Papilloma Leiomyoma Malignant tumors Carcinomas most common. Signs and symptoms of esophageal cancer: 1) 2) 3) 4) Adenocarcinoma Incidence: Risk factors: 1) 2) 3) Pathologic findings: Location and gross appearance: Histopathology:

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Squamous cell carcinoma Incidence: Risk factors: 1) 2) 3) Pathologic findings Location and gross appearance: Histopathology: Natural history and treatment of esophageal cancer Staging of esophageal cancers:

http://www.clevelandclinicmeded.com/medicalpubs/ diseasemanagement/hematology-

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Stomach Anatomy and histology of the stomach: Regions: 1) 2) 3) 4) Surface epithelium: Gastric glands, cell types 1) 2) Robbins 6th ed,

3) 4) Phases of digestion: 1) 2) 3) Factors controlling gastric acid secretion: 1) 2) 3) Factors maintaining gastric mucosal integrity: 1) 2) 3) 4) 5) Congenital disorder of the stomach: Pyloric stenosis Adults: acquired pyloric stenosis

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Gastritis (acute and chronic) Mechanisms of acute mucosal injury: Acute Gastritis Common causes of acute gastritis: 1) NSAIDS Mechanism: 2) 3) 4) 5) Pathology: Clinical course: Acute peptic ulceration: Stress ulcers Curling ulcers Cushing ulcers

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Chronic Gastritis Chronic Gastritis associated with Helicobacter Pylori Acquisition and incidence of H. pylori infection Pathogenesis of H. pylori infection Features of H. pylori 1) 2) 3) 4) Pathology of H.pylori associated gastritis Active chronic gastritis anatomic distribution of injury histopathology Peptic ulcer disease Intestinal metaplasia and dysplasia Complications of H. pylori infection: Neoplasms: 1) 2) Diagnosis of H. pylori infection: Antibody tests Antigen tests Biopsy Urea Breath tests (UBT)

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Treatment Chronic Gastritis associated with Autoimmune disease (pernicious anemia) Less common (10%) Pathogenesis: Antibodies: 1) 2) Pathologic features anatomic distribution of injury "atrophic gastritis" Intestinal metaplasia and dysplasia Peptic Ulcer Disease Incidence Major causes of PUD: 1) 2) Other: Pathogenesis of PUD: Relationship of Chronic gastritis to Peptic ulcer disease Other associated conditions: Pathologic features: Complications of peptic ulcers:

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Neoplasms of the Stomach Polyps: Hyperplastic polyps and Fundic gland polyps Adenomas Gastric Cancer Incidence and Epidemiology Hi incidence areas: Recent trends Pathogenesis: Associated factors: Genetics: Infections: H pylori Other: Pathology: Early vs Advanced Intestinal type: Diffuse type: Linitis plastica (leather bottle stomach) Natural history: Metastasis: Staging and Survival: https://gi.jhsps.org/Upload/200802291428_03949_000.jpg

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Other Neoplasms Carcinoid (neuroendocrine) Lymphoma Gastrointestinal stromal tumor (GIST)

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Diseases of Small and Large Intestine Normal gross and microanatomy Small intestine: Villi Cell types 1) 2) 3) 4) M A L T Large intestine: Crypts Congenital Disorder: "Congenital Megacolon" Hirschprung Disease Etiology: Clinical presentation and natural history Diarrheal Disease: Definition: Classification of diarrhea: Secretory Osmotic Malabsorptive Exudative

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Other: "motility disorders" Celiac Disease Definition and Epidemiology Clinical presentation Pathogenesis Pathologic findings: 1) 2) 3) Diagnosis of Celiac Disease Antibody tests: Molecular tests: Treatment

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Microscopic colitis: Collagenous colitis Lymphocytic colitis Infectious Enterocolitis Viral gastroenteritis Rotavirus Norovirus Bacterial Enterocolitis Clinical Scenarios: Acute watery diarrhea Dysentery Shigella, Campylobacter, non-typhoid salmonella, Shiga-toxin producing E coli Food Poisoning Staph aureus, Clostridium perfringens, Bacillus cerues Traveler's Diarrhea E coli Other: shigella, salmonella, campylobacter, aeromonas species, non-cholera vibrios Nosocomial diarrhea Clostridium difficile Specific Pathogens:

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Vibrio cholerae Campylobacter jejuni toxins and invasion extraintestinal complications Shigella species invasion and type III secretion system Shiga toxin Salmonella (non--typhoid strains) type III secretion system and invasion Salmonella typhi (typhoid fever) lymphatic and hematogenous dissemination E coli (4 types) 1) 2) 3) 4)

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Clostridium difficile and pseudomembranous colitis Pathogenesis and incidence: Diagnosis: Toxin tests PCR tests Treatment Epidemic strain: toxin hyperproducer (NAP-1 strain) Parasitic Disease Giardia lamblia Entamoeba histolytica

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Laboratory tests for Diarrheal Diseases: Tests for malabsorption: Hydrogen breath tests Fecal fat Fecal osmolarity Tests for inflammation Fecal leukocytes and lactoferrin C-reactive protein Tests for infectious agents Detection of toxins and antigens (rapid) (immunoassay) Detection of DNA (PCR) (rapid) Detection of the microorganisms: Stool culture Ova and Parasites Inflammatory Bowel Disease Ulcerative Colitis and Crohn Disease Epidemiology and Pathogenesis: Genetics: Mucosal immune responses: Epithelial defects: Microbiology: Pathologic features of Inflammatory Bowel Disease Common features: 1) 2) 3) 4)

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Crohn disease Incidence and epidemiology Anatomic distribution: Distinguishing features: 1) 2) 3) 4) Clinical course and complications: Ulcerative Colitis Incidence and epidemiology Anatomic distribution: Distinguishing features: 1) 2) 3) Clinical course and complications Extraintestinal manifestations of Inflammatory Bowel Disease 1) 2) 3) 4)

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Diverticular disease Epidemiology Pathogenesis Pathologic features Complications: 1) 2) 3) Ischemic bowel disease Normal vascular supply to intestine and areas at risk Pathogenesis (mechanisms) 1) 2) 3) 4) Other: Pathologic features: Robbins 6th ed.

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Tumors of the Small and Large Intestine Differences in neoplasms of small versus large intestine Polyps: Non-neoplastic polyps: Hyperplastic polyps Sessile serrated polyps Hamartomatous polyps: 1) 2) Adenomas Pathologic definition: Types of adenomas: gross appearance: 1) 2) microscopic appearance: 1) 2) 3) Adenomas as precursors to cancer epidemiological observations polyposis syndromes Familial Adenomatous Polyposis (FAP)

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and the APC gene Hereditary Non-polyposis Colon Cancer (HNPCC) Colon Cancer (Adenocarcinoma) Epidemiology Incidence: Death from colon cancer: Environmental factors: Molecular carcinogenesis: APC/Beta-catenin pathway Microsatellite instability (MSI) pathway Pathology of colon cancer Distribution of cancers Gross and endoscopic appearance:

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Microscopic features: Natural history: Local growth: Metastasis: Prognosis and Staging: http://www.coloncancersymptomssite.com/wpcontent/ uploads/2011/04/Colon-Cancer-Staging-And-Survival1.jpg

Treatment: Screening for colorectal cancer: Fecal occult blood tests: chemical (guaiac-based) immunochemical sigmoidoscopy and colonoscopy Anal Cancer: Epidemiology Pathologic features

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Natural history Non-epithelial neoplasms of the GI tract: Carcinoid (well differentiated endocrine carcinoma) Anatomic distribution and behavior Pathologic features Clinical features: carcinoid syndrome Lymphomas Anatomic distribution B cell lymphoma MALT-omas Other B cell lymphomas T cell lymphoma (rare) associations: Appendix Acute appendicitis Tumors of the appendix

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GASTROINTESTINAL PATHOLOGY

STUDY QUESTIONS Oral Cavity: 1) What is leukoplakia? What causes it? 2) What are some risk factors for cancer of the oral cavity? 3) What are 3 types of odontogenic cysts? Which one is likely to be clinically aggressive? Salivary Gland 1. What condition(s) predisposes to bacterial sialadenitis? 2. Correlate the clinical features of Sjogren syndrome with the pathologic features. 3. What salivary gland abnormalities are associated with HIV infection? What phase of HIV infection are they found in? 4. What is the most common tumor of salivary glands? 5. What are the most likely tumors to metastasize to salivary gland? 6. Tumors of minor salivary glands are more likely to be ?benign/malignant? Esophagus 1. What is Plummer-Vinson syndrome? 2. What are 2 types of hiatal hernia? Which is more common? Complications? 3. What are the 3 pathologic changes seen in reflux esophagitis? 4. Name 3 complications of reflux esophagitis. 5. What factors are associated with gastroesophageal reflux (GERD)? 6. What is Barrett’s esophagus? What is it’s clinical significance? 7. List 5 agents/conditions associated with esophagitis 8. What percentage of patients die with their first variceal bleed? 9. What are 6 factors associated with development of esophageal cancer? 10. What histologic type of esophageal cancer is most prevalent worldwide? 11. What factors contribute to the overall poor prognosis of patients with esophageal carcinoma? 12. To where does esophageal cancer spread? 13. What is achalasia? What causes it? What is a potential risk associated with achalasia? Stomach 1. What are the secretory product(s) of parietal cells?, chief cells?, G cells?, EC-like cells? 2. List 4 factors important in gastric mucosal protection. 3. Projectile vomiting in an infant with a palpable “mass” in the epigastrium is characteristic of

what disorder? 4. What is the mechanism underlying NSAID-related gastric mucosal injury? 5. What is the difference between a gastric EROSION and ULCER?

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6. Define chronic gastritis. 7. List 6 etiologies of chronic gastritis. 8. What are 4 virulence factors produced by Helicobacter pylori. What is their function? 9. List 4 associated gastric/duodenal disorders associated with H. pylori infection. 10. How does autoimmune gastritis differ from environmental (H-pylori associated) gastritis? 11. What metaplastic change is associated with chronic atrophic gastritis? 12. How does autimmune gastritis cause megaloblastic anemia? 13. Which type of chronic gastritis is associated with hyperplasia of G cells and achlorhydria? 14. What is the most common site of peptic ulceration? 15. Peptic gastric ulcers are most often located on the lesser/greater curvature. 16. Malignant gastric ulcers are most often located on the lesser/greater curvature. 17. What histologic zones can be seen in in a chronic peptic ulcer. 18. What are 3 potential complications of peptic ulcers/ 19. Name some conditions associated with acute (stress) gastric ulcerations. 20. Of what clinical significance are thickened gastric folds? 21. What is the mortality rate from gastric carcinoma in the US? Where are high incidence areas

for gastric cancer? 22. What histologic type of cancer is most commonly found in the stomach? 23. A “polyp” in the stomach is usually one of 3 possible histologic types. What are they? Which

one is most closely associated with carcinoma. 24. Compare intestinal versus diffuse types of gastric carcinoma with respect to incidence,

underlying gastritis, dysplasia, clinical behavior. 25. What are some etiologic factors associated with gastric carcinoma? 26. What is a Krukenberg tumor? 27. What is linitis plastica? 28. What is “early gastric cancer”? How do early and advanced gastric cancer differ as to

prognosis? Small and Large Intestine 1. What embryonic remnant gives rise to Meckel’s diverticulum? What significance can heterotopic mucosa have in a Meckel’s diverticulum? 2. What is the cause of Hirschprung disease? 3. Distinguish between secretory, osmotic, exudative, and malabsorptive diarrhea. What lab

tests might be useful in making this distinction? 4. What is dysentery? 5. What is the most common viral cause of diarrhea? 6. What are 3 mechanisms by which bacteria cause diarrheal illness? 7. What is pseudomembranous colitis? What are 2 causes of pseudomembranous colitis? 8. What is the organism responsible for Whipple’s disease? What is the treatment? 9. List 6 mechanisms for malabsorption. What are examples of each? 10. What is the significance of a positive anti-tissue transaminase antibody test? How does

genetic testing help in the diagnosis of celiac disease?

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11. What is the basic pathogenesis of celiac disease? 12. How do Crohn disease and Ulcerative Colitis differ as to: distribution of involved bowel,

extent of involvement of bowel wall, type of inflammation, complications, malignancy risk? 13. What segment of colon is most at risk for ischemic injury? What are 4 mechanisms of bowel ischemia? 14. What are 3 complications of diverticular disease? 15. What is intussesception? What segment is most commonly involved in young children? 16. What pathologic features characterized a colonic adenoma (adenomatous polyp) 17. What are Peutz-Jeghers polyps? 18. Describe the difference between a sessile and pedunculated polyp. 19. What features of a polyp are significant with regard to risk of carcinoma? 20. What is the significance of carcinoma arising in a polyp? What criteria must be met for

polypectomy to be assumed to be adequate therapy? 21. Describe the genetic abnormality in familial adenomatous polyposis coli (APC) and its

significance in colon carcinogenesis. What is other evidence for the “adenoma-carcinoma” sequence?

22. How do carcinomas of the right and left colon differ ? 23. What are sites of spread for colonic carcinoma? 24. What are the important components of the staging system for colon cancer? 25. What is the most common site of carcinoid tumors of the GI tract? 26. What is a MALT-oma? 27. How does carcinoma of the anal canal differ from colorectal cancer (adenocarcinoma)?