PATHOLOGY OF GASTROINTESTINAL SYSTEM PART I

PATHOLOGY OFGASTROINTESTINAL SYSTEM

PART I

Peerayut Sitthichaiyakul, M.D.

Content

• Pathology of Oral Cavity• Pathology of Salivary glands• Pathology of Esophgus• Pathology of Stomach

ORAL CAVITYORAL CAVITY

• Inflammatory and Reactive lesions

• Infections

• Oral Manifestations of Systemic Disease

• Tumor and precancerous lesion

Inflammatory/Reactive Lesions

• Fibrous proliferative lesions– Irritation Fibroma

– Pyogenic Granuloma

• Aphthous Ulcer (Canker Sores)– Mononulcear infiltration

Infections

• Herpes Simplex Virus Infections– Acute Herpetic Gingivostomatitis

– Recurrent Herpetic Stomatitis

– HSV‐1, HSV‐2

– Tzanck Test

– Intranuclear Inclusions

– Multinucleated giant cells

• Oral candidiasis (Trush)

Oral Manifestation of Systemic Diseases

• Scarlet fever – Rasberry tongue

– Strawberry tongue

• Measles– Koplik spot

• Infectious Mononucleosis– Pharyngitis and Tonsillitis

• HIV/AIDS– Oral infection

– Kaposi sarcoma

– Hairy Leukoplakia

• Dermatologic Conditions

• Hematologic Disorders– Pancytopenia

– Leukemia

• Melanotic Pigmentation– Addition disease

– Hemochromatosis

– Peutz‐Jegher syndrome

• Pregnancy– Pyogenic granuloma (pregnancy tumor)

• Hairy Leukoplakia– 80% HIV infection

– White, patches, hyperkeratotic thickenings

– Lateral border of tongue

– EBV infection

Tumor and Precancerous Lesion

• Leukoplakia and Erythroplakia– Leukoplakia: white patches or plaques  that cannot be scraped off and cannot be characterized clinically or pathologically as other diseases

– Erythroplakia: red, velvety, eroded area

– Speckled leukoerythroplakia

– Multifactorial, use of tobacco

• Squamous cell carcinoma– Most common head and neck cancer

– Most common site: oral cavity

– Multifactorial

– Chronic abuser of alcohol and tobacco

– Location: ventral surface of tongue, floor of mouth, lower lip, soft palate and gingiva

Patholgy of Salivary Glands

• Inflammation (Sialadenitis)

• Neoplasms

Inflammation

• Mucocele– Most common lesion of the salivary gland

– Lower lip

– Fluctuant swellings of lower lip

• Sialolithiasis and nonspecific sialadenitis– Bacterial infections: S. aureus, S. viridans

– Sialolithiasis

Neoplasm

• Benign tumors– Pleomorphic adenoma

– Warthin tumor 

• Malignant tumors– Mucoepidermoid carcinoma

– Adenocarcinoma, not otherwise specified

• Pleomorphic adenoma– Mixed tumor

– Major salivary gland

– Derived from ductal and myoepithelial cells

– Ronded, demarcated mass

– Malignant transformation• Carcinoma ex pleomorphic adenoma

• Warthin tumor (papillary cystadenomalymphomatosum)– Major salivary gland

– Round to oval, encapsulated mass

– Double layers of neoplastic epithelial cells

– Dense lymphoid stroma

• Mucoepidermoid carcinoma– Mixture of squamous cells, mucus‐secreting cells and intermediate cells

– Major salivary gland

• Adenoid cystic carcinoma– Minor salivary gland 

– Tubular, solid, cribiform patterns

– Small cells: dark, compact nuclei

Pathology of Esophagus

• Congenital anomalies

• Lesions Associated with Motor Dysfunction

• Esophageal varices

• Esophagitis

• Tumors

Congenital anomalies

• Ectopic tissue

• Atresia and fistula– Associated with congenital heart disease andother gastrointestinal tract malformations

• Webs, rings and stenosis

Lesions Associated with Motor Dysfunction

• Achalasia– Failure to relax

– Aperistalsis of the esophagus

– Partial or incomplete relaxation of the loweresophageal sphincter (LES) with swallowing

– Increased resting tone of the LES

– Proximal esophageal dilation, dysphagia, andregurgitation

– Risk of esophageal carcinoma is 2 to 7%.

– Manometry: Manometry shows aperistalsis,impaired relaxation of the LES, and increased LESresting tone.

– Morphologic features include:• Dilated esophagus above LES

• Thickened (muscular hypertrophy) or thinned(distention) muscular wall

• Diminished myenteric ganglia

• Secondary mucosal damage

• Hiatal hernia

– Sac‐like dilation of stomach with protrusion abovethe diaphragm

– Sliding (axial) hiatal hernia (90% of cases):Shortened esophagus, traction of upper stomachinto thorax

– Paraesophageal hiatal hernia (rolling hernia)(<10% of cases): Cardia of stomach dissectsalongside esophagus into thorax

• Diverticula

– Pharyngopharyngeal (Zenker) diverticulum: In theupper esophagus, the presumed result of motordysfunction

– Traction diverticulum: More distal location,attributed to fibrosing mediastinal processes orabnormal motility

– Epiphrenic diverticulum: Immediately aboveesophageal sphincter, unclear cause

• Laceration (Mallory‐Weiss syndrome)– Longitudinal tears in the esophagus at theesophagogastric junction, attributed to episodesof excessive vomiting

– Most frequently seen in alcoholics

– Massive hematemesis, inflammation, residualulcer, mediastinitis, or peritonitis

Esophageal Varices

• 90% of cirrhotic patients

• Prolonged and severe portal hypertension

• Formation of collateral bypass channels:through the coronary veins of the stomachinto esophageal subepithelial and submucosalveins (varices) and thence to the azygousveins and systemic circulation

• clinically silent until rupture

• Hematemesis—fatality rate is 40% for eachepisode of bleeding, with a 90% chance ofrecurrence within a year in survivors

Esophgitis

• Reflux esophagitis (Gastroesophageal Reflux Disease : GERD)– Reflux of gastric contents– Decreased efficacy of esophageal antirefluxmechanisms

– Presence of a sliding hiatal hernia– Delayed gastric emptying and increased gastricvolume

– Reduced reparative capability of the esophagealmucosa

– Symptoms include dysphagia, heartburn,regurgitation of sour brash, hematemesis, andmelena.

– Stricture or Barrett esophagus can develop asa result of reflux esophagitis.

• Barette esophgus– Replacement of the distal esophageal squamousepithelium by a metaplastic columnarepithelium

– Inflammation and ulceration of squamousmucosa; differentiate into more resistantgastric‐type or intestinal‐type epithelium

– Risk of adenocarcinoma is 30 times normal

• Infectious and chemical esophagitis– Ingestion of mucosal irritants

– Cytotoxic anticancer therapy

– Infection: HSV, CMV, Candida

– Uremia

Tumors

• Benign tumors– Polyp – Lipoma– Papilloma

• Malignant tumors– Squamous cell carcinoma– Adenocarcinoma

• Squamous cell carcinoma–Pathogenesis is multifactorial– Insidious onset–Dysphagia, obstruction, weight loss,hemorrhage,

– Sepsis secondary to ulceration, fistulaformation into respiratory tree withaspiration

• Adenocarcinoma–One half of esophageal cancers

–Majority of cases arise from the Barrette mucosa

Pathology of Stomach

• Congenital anomalies

• Gastritis

• Peptic Ulcer Disease

• Miscellaneous Conditions

• Tumors

Congenital Anomalies

• Pancreatic heterotopia• Diaphragmatic hernia

–Pulmonary hypoplasia

• Congenital hypertrophic pyloric stenosis–Hypertrophy and possibly hyperplasia ofcircular muscle of the muscularis propria ofthe pyloris

–Visible peritalsis, palpable mass

Gastritis

• Acute gastritis– Acute mucosal inflammatory process– Etiologiy includes:

• Chronic and heavy use of nonsteroidal anti‐inflammatorydrugs(NSAIDs), particularly aspirin

• Excessive alcohol consumption• Heavy smoking• Severe stress (bums, trauma, surgery)• Ischemia and shock• Ingestion of acid or alkali• Gastric irradiation• Mechanical trauma, Post‐distal gastrectomy

• Mechanisms of action include– Increased acid production with back‐diffusion– Decreased production of surface bicarbonate buffer– Reduced mucosal blood flow, disruption of mucus layer– Direct damage to mucosal epithelium

• Morphologic findings include– Moderate edema and hyperemia– Entry of neutrophils into the epithelial layer (activity)– Sloughing of the superficial epithelium (erosion)– Hemorrhage (acute hemorrhagic erosive gastritis)

• Chronic gastritis– The presence of chronic mucosal inflammatorychanges leading eventually to mucosal atrophyand epithelial metaplasia

– Etiologic associations are as follows:• Chronic infection, especially Helicobacter pylori

• Immunologic: Antibodies to parietal cells

• Toxic: alcohol and tobacco usage

• Postsurgical: postantrectomy reflux of bile

• Motor/mechanical: obstruction, atony

• Radiation

• Granulomatous conditions: Crohn disease

• Graft‐versus‐host disease, uremia, amyloidosi

– Microscopic findings are as follows:• Infiltrate of lymphocytes and plasma cells in laminapropria, involving either the superficial portion (fundus)or the entire mucosal thickness

• Activity (intraepithelial neutrophilic infiltrate)• Regenerative change• Variable atrophy• Metaplasia to intestinal‐type epithelium• Dysplasia• H. pylori

• Clinical Findings– Few symptoms: Nausea, vomiting, or upperabdominal discomfort

– Pernicious anemia occurs in autoimmunegastritis. Laboratory findings include gastrichypochlorhydria and serum hypergastrinemia.

Peptic Ulcer Disease

• Peptic ulcer– Breach in the mucosa of the alimentary tract thatextends through the muscularis mucosa into thesubmucosa or deeper

– Imbalance between the gastroduodenal mucosaldefense mechanisms and damaging forces

• Mucosal defense forces consist of– Surface mucus secretion

– Bicarbonate secretion into mucus

– Mucosal blood flow

– Apical epithelial cell transport systems

– Epithelial regeneration

– Role of prostaglandins

‐ H. pylori: Major factor in pathogenesis‐ H. pylori does not invade the tissue. It induces inflammation by increase production of cytokine

‐ Bacterial gene products cause epithelial cell injury and induction of inflammation 

‐ H. pylori secretes urease (breakdown urea to ammonium chloride), protease, orphospholipases.

‐ Enhance gastric secretion and impairs duodenal bicarbonate production 

– 98% found in duodenum and stomach, in a ratio of 4:1.

– Gross findings include a sharply punched‐outdefect with slightly overhanging mucosalborders and smooth, clean ulcer base.

–Malignant transformation is rare and relatedto underlying gastritis.

– Epigastric gnawing, burning, or aching painoccurs, which is worse at night and 1 to 3hours after meals.

– Nausea, vomiting, and weight loss occur.

– Complications include hemorrhage, anemia,perforation, and obstruction.

• Acute gastric ulceration–Acute gastric ulceration refers to focal,acutely developing gastric mucosal defectsappearing during severe stress (stressulcer).

–Curling ulcers: shock; extensive burns orsevere trauma

–Cushing ulcers: elevated intracranialpressure, as in trauma or surgery

Tumors

• Benign tumors– Polyps

– Adenoma

• Malignant tumors– Gastric carcinoma

– Lymphoma

– Carcinoids tumor

– Mesenchymal tumors

– Gross locations of carcinoma are:• Pylorus and antrum, 50 to 60%• Cardia, 25%• Body and fundus, 15 to 25%• Lesser curvature is involved in 40% and greater curvature in 12%.

– Factors associated with increased incidence of gastriccarcinoma

• Diet: use of preservatives (nitrosamines), lack of fresh fruit andvegetables

• Cigarette smoking increases risk 1.5‐ to 3.0‐fold• Infection by H. pylori leading to chronic gastritis• Autoimmune gastritis• Partial gastrectomy permitting gastroduodenal reflux

–Classification is according to the following:• Depth of invasion: greatest impact on clinical outcome

• Macroscopic growth pattern: exophytic, flat or depressed, or excavated. Uncommonly, diffuse invasion throughout the wall creates a rigid thickened stomach: linitis plastica.

• Histologic subtype:

– Intestinal type: Gland‐forming columnar epithelium; usually polypoid expansile growth pattern

– Diffuse type: poorly differentiated, single signet‐ring cells; mucin producing; infiltrative growth pattern

– Dissemination: Dissemination to ovaries generates Krukenberg tumors.

• Clinical Findings– Insidious diseases– Initially asymptomatic.– Findings include weight loss, abdominal pain, anorexia,vomiting, altered bowel habits, dysphagia, anemia, and hemorrhage.

• Prognosis depends only on depth of invasion– Resected early gastric cancer, 90 to 95% 5‐year survival– Advanced disease, less than 15% 5‐year survival

• Less common gastric cancers– Lymphoma

– Gastrointestinal stromal tumors