Gastrointestinal PathologyDan Lodge-Rigal, MDReading: 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 Cavityaphthous ulcersinfectionsbenign tumorsleukoplakia and squamous epithelial abnormalitiessquamous cell carcinoma

Salivary Glandinflammation and infectionnon neoplastic “tumors”neoplasms: benignneoplasms: malignant

Esophaguscongenital: esophageal atresiafunctional disorders: diverticula, webs and rings, achalasia, hiatal herniagastroesophageal varicesinflammation (esophagitis)gastroesophageal reflux disease (GERD) and Barrett esophaguseosinophilic esophagitistumors: benigntumors: malignant

Stomachcongenital: pyloric stenosis

gastritis: mechanismsacute and chronic gastritispeptic ulcer diseasegastric polypsgastric cancerother neoplasms of the stomach

Large and Small Intestinecongenital: Hirschprung diseasediarrheal disease: classificationceliac diseasemicroscopic colitisinfectious gastroenteritis: viralinfectious enterocolitis: bacterialinfectious enterocolitis: parasiticlab testing for diarrheal diseasesinflammatory bowel diseasediverticular diseaseischemic bowel diseasepolyps: non-neoplasticpolyps: adenomascolon cancer (adenocarcinoma)anal cancer

Non-epithelial tumors of the GI tract

carcinoidlymphoma

Appendix

Gastrointestinal PathologyDan 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

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

Esophagus

Normal Esophagus:Layers:1)2)3)4)

G-E Junction Z-line Lower esophageal sphincter

Lower esophageal sphincterlocation: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

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)

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 EsophagusDefinition:

Significance of Barrett esophagus:

Dysplasia

Adenocarcinoma

Natural history and management of Barrett esophagus:

Eosinophilic esophagitis

Tumors of the Esophagus

Benign tumors (rare)

PapillomaLeiomyoma

Malignant tumors

Carcinomas most common.

Signs and symptoms of esophageal cancer:1)

2)

3)

4)

AdenocarcinomaIncidence:

Risk factors:1)2)3)

Pathologic findings:Location and gross appearance:

Histopathology:

Squamous cell carcinomaIncidence:

Risk factors:1)2)3)

Pathologic findingsLocation and gross appearance:

Histopathology:

Natural history and treatment of esophageal cancer

Staging of esophageal cancers:

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Stomach

Anatomy and histology of the stomach:Regions:1)2)3)4)

Surface epithelium:

Gastric glands, cell types1)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

Gastritis (acute and chronic) Mechanisms of acute mucosal injury:

Acute GastritisCommon causes of acute gastritis:1) NSAIDS Mechanism:

2)3)4) 5)

Pathology:

Clinical course:

Acute peptic ulceration:Stress ulcers

Curling ulcers

Cushing ulcers

Chronic GastritisChronic Gastritis associated with Helicobacter Pylori

Acquisition and incidence of H. pylori infection

Pathogenesis of H. pylori infection

Features of H. pylori1)

2)

3)

4)

Pathology of H.pylori associated gastritisActive 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)

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 DiseaseIncidence

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:

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:

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Other Neoplasms

Carcinoid (neuroendocrine)

Lymphoma

Gastrointestinal stromal tumor (GIST)

Diseases of Small and Large Intestine

Normal gross and microanatomy

Small intestine:Villi

Cell types1)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

Other: "motility disorders"

Celiac DiseaseDefinition and Epidemiology

Clinical presentation

Pathogenesis

Pathologic findings:1)

2)

3)

Diagnosis of Celiac DiseaseAntibody tests:

Molecular tests:

Treatment

Microscopic colitis:

Collagenous colitis

Lymphocytic colitis

Infectious Enterocolitis

Viral gastroenteritis

Rotavirus

Norovirus

Bacterial Enterocolitis

Clinical Scenarios:Acute watery diarrhea

DysenteryShigella, Campylobacter, non-typhoid salmonella, Shiga-toxin producing E coli

Food PoisoningStaph aureus, Clostridium perfringens, Bacillus cerues

Traveler's DiarrheaE coli

Other: shigella, salmonella, campylobacter, aeromonas species, non-cholera vibrios

Nosocomial diarrheaClostridium difficile

Specific Pathogens:

Vibrio cholerae

Campylobacter jejunitoxins and invasion

extraintestinal complications

Shigella speciesinvasion 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)

Clostridium difficile and pseudomembranous colitisPathogenesis and incidence:

Diagnosis:Toxin tests

PCR tests

Treatment

Epidemic strain: toxin hyperproducer (NAP-1 strain)

Parasitic Disease

Giardia lamblia

Entamoeba histolytica

Laboratory tests for Diarrheal Diseases:

Tests for malabsorption:Hydrogen breath tests

Fecal fat

Fecal osmolarity

Tests for inflammationFecal leukocytes and lactoferrin

C-reactive protein

Tests for infectious agentsDetection 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 DiseaseCommon features:1)2)3)4)

Crohn diseaseIncidence and epidemiology

Anatomic distribution:

Distinguishing features:1)

2)

3)

4)

Clinical course and complications:

Ulcerative ColitisIncidence and epidemiology

Anatomic distribution:

Distinguishing features:1)

2)

3)

Clinical course and complications

Extraintestinal manifestations of Inflammatory Bowel Disease1)2)3)4)

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 6 th ed.

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) 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:

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

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 lymphomaMALT-omasOther B cell lymphomas

T cell lymphoma (rare)associations:

Appendix

Acute appendicitis

Tumors of the appendix

GASTROINTESTINAL PATHOLOGY

STUDY QUESTIONSOral 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 Gland1. 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 esophagitis8. 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?

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 Intestine1. 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?

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)?