DISEASES OF ORAL CAVITY AND GASTROINTESTINAL TRACT Disease

DISEASES OF ORAL CAVITY AND GASTROINTESTINAL TRACT Disease of: oral cavity Esophagus Stomach Small and large intestine

Diseases of Oral Cavity I Ulcerative and inflammatory lesions: a. Aphthous Ulcer b. Herpes virus infection c. Fungal infection II Leukoplakia III Cancers of the oral cavity and tongue.

Diseases of Oral Cavity Ulcerative and inflammatory lesions: q q q Aphthous Ulcer Very common, self limited. Small painful shallow ulcer. Appear single or multiple. Triggered by stress, fever, ingestion of certain food, activation of inflammatory bowel disease. Causes: unknown, ? autoimmune. May & may not be associated with systemic diseases e. g. Behcet’s and Reiter’s syndrome.

Diseases of Oral Cavity Ulcerative and inflammatory lesions. Herpes virus infection: Infection by HSV-1. Pathogen remain dormant in ganglia. Appear as vesicles containing clear fluid, cells with cytopathic effect. Tzanck test. Fungal infection: Oral candidiasis is common in patient with DM, anemia, newborn, antibiotic treatment, immune suppression and glucocorticoid therapy. Appear as adherent white plaque. May spread to esophagus.

Diseases of Oral Cavity I Ulcerative and inflammatory lesions: a. Aphthous Ulcer b. Herpes virus infection c. Fungal infection II Leukoplakia III Cancers of the oral cavity and tongue.

Diseases of Oral Cavity II. Leukoplakia: A whitish, well-define, mucosal patch caused by epidermal thickening or hyperkeratosis. Frequent among older men, alcoholic & smoker. Location: lower lip, buccal mucosa, hard and soft palate and floor of mouth. Appear as localized or multifocal smooth or roughed white mucosal thickening. Histologically vary from hyperkeratosis to dysplasia.

Diseases of Oral Cavity II. Leukoplakia. Causes: - unknown. - strong association with the use of tobacco, chronic friction, alcohol abuse and HPV infection. 3 to 6 % undergo transformation to squamous cell carcinoma (more common in lip and tongue lesions). Leukoplakia must be differentiated from: 1. 2. 3. hairy leukoplakia (EBV-related in patient with HIV infection) verrucous leukoplakia (hyperkeratosis, warty, insidiously spread and may harbor SCC) red erythroplakia (red, velvety or circumscribed area, expressing marked epithelial dysplasia with malignant transformation in more than 50% of cases).

Hairy Leukoplakia EBV-induced epithelial hyperplasia causes corregated white lesion HL mostly involves the lateral border of the tongue, but can involve other oral sites including the buccal mucosae. The clinical appearance is usually distinctive enough to make a diagnosis. Where doubt exists, an incisional biopsy should be undertaken.

Hairy Leukoplakia The presence of HL means that HIV infection must be excluded. HL can occur in the absence of HIV infection, for example in organ transplant patients who are immunosuppressed. No specific management is required. HL is not a premalignant condition. HL can resolve as a consequence of successful management of the underlying condition

Verrucous Leukoplakia A mucosal white patch with a warty surface that cannot be rubbed off

Red Erythroplakia q red, velvety or circumscribed area, expressing marked epithelial dysplasia with malignant transformation in more than 50% of cases).

Diseases of Oral Cavity I Ulcerative and inflammatory lesions: a. Aphthous Ulcer b. Herpes virus infection c. Fungal infection II Leukoplakia III Cancers of the oral cavity and tongue.

Diseases of Oral Cavity III. Cancers of the oral cavity and tongue Most common pattern is squamous cell carcinoma. Occur in old age (after 40) Readily accessible for early identification, but about half killed within 5 years. Clinically, asymptomatic, local pain

Diseases of Oral Cavity III. Cancers of the oral cavity and tongue Risk factor Erythroplasia Leukoplakia Infection by human papilloma virus type 16, 18, and 33 Tobacco (especially pipe smoking and smokeless tobacco) Alcohol

Cancers of the oral cavity The predominant sites are: 1. Vermilion border of the lateral margins of the lower lip. 2. Floor of the mouth. 3. Lateral borders of the mobile tongue. Gross Early lesions appears as pearly white to gray, circumscribed thickenings of the mucosa. Then they (advanced lesions) may grow in an: - exophytic fashion (palpable nodular and fungating lesions) or - endophytic, invasive pattern (cancerous ulcer).

Cancers of the oral cavity The squamous cell carcinomas are usually moderately to well-differentiated keratinizing tumors. In early stages, it may be possible to identify epithelial atypia, dysplasia, or carcinoma in situ in the margins. Spread to regional nodes at the time of diagnosis: – is rare with lip cancer – in about 50% of cases of tongue cancers – more than 60% of cases with cancer of the floor of the mouth.

Cancer of the oral cavity and tongue The overall 5 -year survival rates after treatment are about 40% for cancers without lymph node metastasis, compared with under 20% for those with lymph node metastasis. 5 year survival rate vary from 91% for lip cancer to about 30% for cancers of the base of the tongue, pharynx and floor of the mouth.

Diseases of the Oral Cavity Summary Aphthous ulcers are painful superficial ulcers of unknown etiology that are often triggered by stress. Herpes simplex virus infection causes a usually self-limited infection with vesicles (cold sores, fever blisters) that typically rupture and heal but may leave latent virus in nerve ganglia Candida infection is seen in immunosuppressed individuals and manifests as a plaque fungal dissemination is a potentially serious outcome. Leukoplakia is a mucosal plaque caused by epidermal thickening depending on the location 3% to 25% may progress to squamous cell carcinoma The majority of oral cancers are squamous cell carcinomas.

Salivary Gland Disease Sialadenitis: - inflammation of major salivary glands. - viral (mumps), autoimmune (sjogren’s syndrome: xerostomia, keratocojunctivitis sicca) or bacterial (secondary to ductal destruction by stone).

Sjögren’s syndrome

NECROTIZING SIALOMETAPLASIA

Tumors of salivary glands About 80% of tumors occur within the parotid glands and most of the others in the submandibular glands. M=F usually in the sixth and seventh decade of life. 70% to 80% of the Parotid glands tumors are benign, whereas in the submaxillary glands only half are benign.

Tumors of salivary glands Benign tumors Benign pleomorphic adenoma is the dominant tumor arising in the parotids. Papillary cystadenoma lymphomatosum (Warthin tumor) is less frequent. These two types account for 75% of Parotid tumors.

Tumors of salivary glands Malignant tumors Malignant mixed tumors: arising either de novo or in preexisting benign pleomorphic adenoma. Mucoepidermoid carcinoma (containing adenocarcinoma and squamous cell carcinoma features Whatever the type, they present clinically as a mass causing a swelling at the angle of the jaw.

Salivary glands tumor Pleomorphic adenoma (mixed tumor of salivary gland): - Benign, present as painless swelling. - Most common tumor of salivary gland. - Slow-growing, welldemarcated, encapsulated rarely exceeding 6. 0 cm. in diameter. - Encapsulated, but multiple projection of tumor cell (10% recurrence rate).

Salivary glands tumors Pleomorphic adenoma: Histologic features: - Epithelial component: ducts, acini, strands or sheets. - Connective tissue: myxoid stroma with islands of cartilage and bone. Cells are of myoepithelial origin. If present for many years, malignant transformation may occur (more common at submandibular glands – 40%).

Warthin Tumor (Papillary Cystadenoma lymphomatosum, Cystadenolymphoma) It is infrequent benign tumor occurs only in the region of the parotid gland is thought to represent heterotopic salivary tissue trapped within a regional lymph node during embryogenesis. Microscopically: benign tumor composed of epithelial cells and dense lymphoid tissue

Warthin’s tumor

Mucoepidermoid carcinoma • Squamous and glandular component • Most common malignancy of major and minor salivary glands

Salivary Gland Diseases Summary Sialedinitis: inflammation caused by infection (e. g. mumps, various bacteria) or autoimmune reaction (as in Sjögren syndrome). Pleomorphic adenoma (mixed salivary gland tumor): slow growing locally infiltrative tumor composed of heterogeneous epithelial elements and an often myxoid stroma. Warthin tumor: benign tumor composed of epithelial cells and dense lymphoid tissue

Diseases of the Esophagus

Diseases of the Esophagus Include bland esophagitis to cancer. Symptoms: dysphagia, heartburn, hematemesis

Hiatal hernia q Dilated portion of stomach protrude above the diaphragm. q Two patterns: § sliding (95%) § paraesophageal hiatal hernia. q May lead to reflux esophagitis, ulceration, bleeding, perforation or strangulation.

Diseases of the Esophagus Achalasia: - Incomplete relaxation of lower sphincter in response to swallowing with functional obstruction. - It could be primary or secondary achalasia (Chaga’s disease due to infection by Trypanosoma cruzi or due to tumor in this area ).

Achalasia: Complications - Progressive dilatation of the esophagus. - Dysphagia, carcinoma in 5%. Treatment Can actually cut the muscles in the location of the LES Can use a dilator to try to disrupt the muscle and force it open

Diseases of the Esophages Laceration (Mallory-Weiss Syndrome) - Encountered in chronic alcoholic after a bout of severe vomiting. - Tear may involve the mucosa or penetrate the wall.

Diseases of the Esophages Varices Increased blood pressure in the esophageal plexus produces dilated tortuous vessels. Occur in 2/3 of cirrhotic patients. Tortuous dilated vein in submucosa. Symptoms occur after rupture with 20% to 30% death rate. Rx: sclerotherapy

Diseases of the Esophagus Esophagitis Common condition worldwide: In China extremely high. In Iran 80%. In USA 10 -20%. Associated with reflux of gastric contents, gastric intubation, ingestion of corresive, radiation or chemotherapy.

Diseases of Esophagus Mechanism of Reflux Esophagitis ( GERD) 1. Decreased efficacy of esophageal antireflux mechanism 2. 3. 4. 5. caused by beta adrenergics, alcohol, smoking and caffeine. Inadequate esophageal clearance of refluxed material. Presence of sliding HH. Increased gastric volume and increased intra abdominal pressure e. g. pregnancy. Impaired reparative capacity of eosphageal mucosa by prolonged exposure to gastric juices.

Reflux Esophagitis Anatomic changes depends on the causative agent, duration and severity of exposure. Changes include hyperemia to ulceration. Histologic features: 1. Eosinophils and neutrophil infiltration. 2. Basal zone hyperplasia. 3. Lamina propria papillae elongation.

Reflux Esophagitis Clinical features: Affect adults (older than 40 ys) and rarely affect children Heartburn Sever chest pain Complications Bleeding Stricture Barrett esophagus Predispose to malignancy

Barrett Esophagus Replacements of the normal distal stratified squamous mucosa by abnormal metaplastic columnar epithelium containing goblet cells. A complication of long-standing gastroesophageal reflux (5% to 15%). Males to females ratio is 4: 1. More in whites 30 -100 fold increase in the risk to develop adenocarcinoma.

Barrett’s Esophagus Morphology: • Appear red, velvety mucosa between pale pink esophageal mucosa.

Barrett’s Esophagus Esophageal mucosa is replaced by metaplastic columnar epithelium. Dysplastic changes which are focal, variable from one site to next and necessitate repeated endoscopy.

Esophageal tumors Benign : - Mesenchymal tumor. - Mucosal polyp. - Inflammatory pseudotumor. - Squamous papilloma – rare. Malignant – In USA, 6% of cancer of GIT. Classification: 1. Squamous cell carcinoma (SCC) world wide, SCC – 90% of esophageal carcinoma but in the States, SCC and adenocarcinoma exhibit comparable incidence rates. 2. Adenocarcinoma. 3. Rare, e. g. Carcinoid, malignant melanoma, and undifferentiated carcinoma.

Benign Tumors

Tumor of Esophagus Malignant Tumors 6%, GI Ca, high mortality Squamous cell Ca 90% of esophagus cancers >50 yr. M>F (3: 1) B>W race Asia, Iran

Squamous cell carcinoma of the esophagus Most common primary malignant tumor of the esophagus, accounts for 2% of all fatal cancers in U. S. Geographic variations in rate suggest that environmental factors contributing to pathogenesis. In US, incidence for Caucasians = 6 cases/ 100, 000 annually; non. Caucasians 20. 5 cases/ 100, 000 annually. Most common in those of Japanese or Chinese origin. In Iran, the prevalence is well over 100 cases per 100, 000. Typically found late in its clinical course. Metastasis occurs early in the course, perhaps because of the lack of a serosal covering in the esophagus.

Squamous cell carcinoma of the esophagus Risk factors/associations: Chronic esophagitis. Dietary deficiency of vitamins: A, C, thiamine, pyridoxine deficiency of trace metals: zinc, molybdenum Nitrite/nitrosamine Fungal contamination of food stuffs. Heavy smoking and high alcohol consumption. Achalasia. Plummer-Vinson (Paterson-Kelly) syndrome (esophageal webs, atrophic glossitis, microcytic anemia, and other abnormalities associated with iron and vitamin deficiencies). Genetics (Tylosis, Celiac disease, ectoderma dysplasia).

Squamous cell carcinoma of the esophagus Clinical features Progressive dysphagia, usually not recognized until the lumen is 30 -50% occluded Pain (related to swallowing) Weight loss Anorexia Fatigue 5% five-year survival rate (overall)

Squamous cell carcinoma of the esophagus Spread: early local extension, lymphatic; mediastinal/paratracheal, gastric/celiac p 53 and p 16 mutation (not K-ras/APC) Morphologic patterns cervical, 50% middle, 30% lower, 20% upper third Early overt lesions appears as small, gray-white, plaquelike thickings or elevations of the mucosa. Polypoid exophytic (60%): obstruction Diffuse infiltrative neoplasms (15%): cause thickening, narrowing Necrotizing cancerous ulcerations (25%): extend deeply and erode the respiratory tree and the aorta. Invasive, Moderate/well differentiated, nests of squamous cells with keratin pearl formation

Squamous cell carcinoma of the esophagus

Squamous cell carcinoma of the esophagus Polypoid exophytic

Squamous cell carcinoma of the esophagus, ulcerated

Squamous cell carcinoma of esophagus

Squamous cell carcinoma of the esophagus

Adenocarcinoma of the Esophagus 10 -15% Half of all esophageal cancer reported in USA. Occur in patients over 40 years of age, more common in women & whites. Lower esophagus - ? Cardia. Arise from Barrett’s esophagus with dysplasia. Appear as flat patches, large nodular mass or ulcer. Mucin-producing glandular tumor with intestinal metaplasia. Prognosis is poor.

Esophageal tumors Clinical features: Dysphagia Wt. loss, fatigue, pain Advanced disease at time of diagnosis with spread to lymphatic and adjacent structures

Diseases of the Esophagus Summary Hiatal hernia: protrusion of segment of the stomach above the diaphragm; occasionally results in reflux and esophagitis. Lacerations (Mallory-Weiss syndrome): longitudinal tears at the esophago-gastric junction caused by severe retching and vomiting Varices: tortuous dilated veins at the distal esophagus and proximal stomach; caused by increased portal pressure (most often due to cirrhosis), may cause severe bleeding. Esophagitis: Inflammation of the esophageal mucosa most often caused by reflux of gastric contents Barrett esophagus: replacement of stratified squamous epithelium of distal esophagus by metaplastic columnar epithelium containing goblet cells associated with gastroesophageal reflux in ∼ 15% of cases; main harmful consequence is the development of dysplasia and 30 - to 100 -fold increased risk for adenocarcinoma. Esophageal carcinoma: Squamous cell carcinomas arise from dysplastic epithelium, associated with esophagitis, smoking; may be locally invasive. Adenocarcinomas arise usually in Barrett esophagus, now more frequent in the US