Gastrointestinal System: Oral Cavity

• The lecture is an introduction to the gastrointestinal (GIT) system
• The digestive system functions by processing food

Oral Cavity

• Oral inflammatory lesions include:
  • Aphthous ulcers
  • Herpes simplex virus infections
  • Oral candidiasis, also known as thrush

Aphthous Ulcers (Canker Sores)

• Canker sores, or aphthous ulcers, are a very common condition, affecting up to 40% of the population.
• Canker sores are more common in the first two decades of life.
• Canker sores are extremely painful and often recur.
• The etiology of aphthous ulcers is unknown, but may be related to viruses or hypersensitivity.
• Stress, fever, menstruation, pregnancy, and certain foods are triggers for the ulcers and may be familial.
• The ulcers may be associated with inflammatory bowel disease and Behcet syndrome.
• Aphthous ulcers are solitary or multiple and are typically shallow.
• The ulcers are covered by a thin exudate and rimmed by a narrow zone of erythema.
• Aphthous ulcers are typically less than 1 cm in size and may coalesce.
• Canker sores are self-limiting, typically resolving in a few weeks, but can recur.

Herpes Simplex Virus (HSV) Infections

• Most orofacial herpetic infections are caused by HSV-1, with the remainder caused by HSV-2
• HSV-1 generally causes herpetic infections in mouth
• HSV-2 is genital herpes
• Transmission happens from person to person
• Patients presents with vesicles (cold sores, fever blisters)
• The vesicles rupture and heal without scarring and often leave a latent virus in nerve ganglia.
• Primary herpes infection is self-limited.
• Reactivation occurs when someone is immunocompromised.
• Primary infections typically occur in children between the ages of 2 and 4 years and are often asymptomatic.
• However, 10% to 20% of primary infections manifests as acute herpetic gingivostomatitis.
  • Acute herpetic gingivostomatitis involves an abrupt onset of vesicles and ulcerations throughout the oral cavity.
• After the primary herpes infection, the virus persists in ganglia in a dormant state.
• In adulthood, the virus can be reactivated, resulting in a cold sore or recurrent herpetic stomatitis.
• Reactivation can be triggered by fever, sun or cold exposure, or upper respiratory tract infection (URTI).
• Most common locations herpes infect are lips, nasal orifices, buccal mucosa, gingiva, and hard palate.
• Herpes is self-limiting within a few weeks, but can recur.
• Herpes can persist in immunocompromised patients, who may require systemic antiviral therapy.
• The infected cells become ballooned and have large eosinophilic intranuclear inclusions
• The infected cells commonly fuse to form large multinucleated cells

Oral Candidiasis (Thrush)

• Candidiasis is the most common fungal infection of the oral cavity.
• Candida albicans is a normal component of the oral flora
• An altered oral microbiota can cause disease
• This may be from antibiotic use, or immunosuppression
• Invasive disease can occur in severe immunosuppressed individuals.
• The three major clinical forms of oral candidiasis include:
  • Pseudomembranous (most common, also known as thrush)
  • Erythematous
  • Hyperplastic
• Oral Candidiasis (Thrush) appears as:
  • Superficial
  • Curdlike
  • Gray to white inflammatory membrane composed of matted organisms
• This layer can readily be scraped off to reveal an underlying erythematous base
• Histologically, the oral candidiasis consists of densely matted pseudohyphae and budding spores.

Proliferative and Neoplastic Lesions of the Oral Cavity

• Proliferative and neoplastic lesions of the oral cavity include:
  • Fibrous proliferative lesions (fibromas and pyogenic granuloma)
  • Leukoplakia and erythroplakia
  • Squamous cell carcinoma

Fibromas

• Fibromas are submucosal nodular fibrous tissue masses that are formed when chronic irritation results in reactive connective tissue hyperplasia.
• Fibromas occur most often on the buccal mucosa along the bite line.
• Treatment: complete surgical excision and removal of the source of irritation.

Pyogenic Granuloma

• Pyogenic granuloma is an inflammatory lesion typically found on the gingiva of children, young adults, and pregnant women
• Complete surgical excision is definitive treatment.
• These lesions are highly vascular and typically ulcerated, giving them a red to purple color.
• In some cases, pyogenic granulomas can exhibit rapid growth, raising concerns of a malignant neoplasm.
• Histologically, there is proliferation of immature vessels similar to those seen in granulation tissue.

Leukoplakia

• Leukoplakia is a white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease.
• White patches due to obvious irritation or entities such as candidiasis are NOT considered leukoplakia.
• If leukoplakia is present, a biopsy is needed to check pathology
• 5% to 25% of leukoplakias are dysplastic and at risk for progression to squamous cell carcinoma.
• Thus, until proved otherwise, all leukoplakias must be considered precancerous.

Erythroplakia

• Erythroplakia is less common entity.
• It is a red, velvety, sometimes eroded lesion that is flat or slightly depressed relative to the surrounding mucosa.
• Erythroplakia is associated with a much greater risk for malignant transformation than leukoplakia (up to 50%).
• The usual age for Leukoplakia and erythroplakia presence is 40 - 70 years.
• Tobacco use (cigarettes, pipes, cigars, and chewing tobacco) is the most common risk factor for leukoplakia and erythroplakia.
• Erythroplakia results in squamous epithelial atypia (dysplasia).

Squamous Cell Carcinoma (SCC)

• 95% of oral cavity cancers are SCC.
• Squamous cells carcinoma most commonly found on:
  • Ventral surface of the tongue, floor of the mouth, lower lip, soft palate, and gingiva
• Squamous cells carcinoma, when diagnosed at advanced stage, have low survival rate
  • Less than 50% of the population survives after 50 years
• SCC of the oropharynx arises through two distinct pathogenic pathways:
  • Exposure to carcinogens, like exposure to chronic alcohol and tobacco
    • mutations frequently involve TP53 and genes that regulate cell proliferation, such as RAS
  • Infection with high-risk variants of human papillomavirus (HPV).
• HPV-related tumors tend to occur in the tonsillar crypts or the base of the tongue and harbor oncogenic high-risk subtypes, particularly HPV-16.
• HPV-related tumors have fewer mutations and often overexpress p16
• The prognosis for patients with HPV-positive tumors is better than for those with HPV-negative tumors.
• Microscopic view shows:
  • Marked atypical tumor cells with invasion and islands that show formation of keratin pearls
  • May be superimposed on a background of leukoplakia or erythroplakia

Diseases of Salivary Glands

• Three major salivary glands:
  • Parotid
  • Submandibular
  • Sublingual
• The diseases of salivary glands include:
  • Inflammation
  • Neoplasms ( Benign and Malignant)

Xerostomia

• Xerostomia is defined as a dry mouth resulting from decreased production of saliva.
• Causes:
  • Part of autoimmune disorder Sjögren syndrome, often accompanied by dry eyes
  • Complication of radiation therapy or medications
• Complications: include increased rates of dental caries and candidiasis, as well as difficulty in swallowing and speaking.

Sialadenitis (inflammation of the Salivary Glands)

• Sialadenitis may be induced by:
  • Trauma
  • Viral or bacterial infection
  • Autoimmune disease
• Viral sialadenitis is most commonly from mumps
  • Mumps predominantly involves the parotids and causes enlargement of salivary glands
  • Mumps produces interstitial inflammation marked by a mononuclear inflammatory infiltrate
  • Mumps in children is usually a self-limited benign condition
  • Mumps in adults can cause pancreatitis or orchitis

Mucocele

• Mucocele is themost common inflammatory lesion of the salivary glands
• Mucoceles result from blockage or rupture of a salivary gland duct.
• This results in consequent leakage of saliva into the surrounding connective tissue stroma.
• Mucoceles presents with fluctuant swelling of the lower lip that may change in size, particularly in association with meals
• Treatment: complete excision.

Salivary Gland Neoplasms

• 2% of all human tumors
• 65% to 80% arise within the parotid gland, 10% in the submandibular gland, and the remainder in the minor salivary glands, including the sublingual glands.
• Clinically, parotid gland neoplasms produce swelling in front of and below the ear.
• Benign tumors are slow-growing (months to years).
• Malignant, as opposed to benign tumors, come to attention promptly, probably because of their more rapid growth.

Pleomorphic Adenoma

• Pleomorphic Adenoma, also known as mixed tumor, are benign tumors
• Pleomorphic Adenomas consists of a mixture of ductal (epithelial) and myoepithelial cells (mesenchymal)
• 60% of tumors in the parotid are Pleomorphic Adenomas;
  • These are less common in the submandibular glands and others.
• Pleomorphic Adenomas have traits such as:
  • Slow-growing
  • Painless
  • Mobile discrete masses
• Pleomorphic Adenomas recur if incompletely excised
• Less than 2% of cases result in risk of malignant transformation
• Pleomorphic adenomas typically manifest as rounded, well-demarcated masses that rarely exceed 6cm in the greatest dimension.
• They consist of capsule, Chondromyxoid stroma, and Epithelial cells

Mucoepidermoid Carcinoma (MEC)

• Malignant neoplasm with variable biologic aggressiveness
• MEC is composed of variable mixtures of squamous cells, mucus-secreting cells, and intermediate cells
• Mucoepidermoid Carcinoma (MEC) is the most common form of primary malignant tumor of the salivary glands, accounting for 15% of all salivary gland tumors
• 60%-70% of those are on the parotids