Download Gastrointestinal Hnd

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
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
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 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
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 Esophagus
Definition:
Significance of Barrett esophagus:
Dysplasia
Adenocarcinoma
Natural history and management of
Barrett esophagus:
Eosinophilic esophagitis
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:
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-
Stomach
Anatomy and histology of the stomach:
Regions:
1)
2)
3)
4)
Surface epithelium:
Gastric glands, cell types
1)
2)
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
Robbins 6th ed,
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
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)
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:
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
Other Neoplasms
Carcinoid (neuroendocrine)
Lymphoma
Gastrointestinal stromal tumor (GIST)
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
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
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:
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)
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
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)
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)
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.
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 lymphoma
MALT-omas
Other B cell lymphomas
T cell lymphoma (rare)
associations:
Appendix
Acute appendicitis
Tumors of the appendix
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?
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?
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)?