Chapter 31. The Oral Cavity & Salivary Glands

The oral cavity is lined by a mucosa composed of nonkeratinizing stratified squamous epithelium, continuous with the skin at the lips and with the pharyngeal mucosa posteriorly. Specialized structures in the oral cavity include the following:

1.  The taste buds, which are specialized nerve endings with afferents in the ninth (posterior tongue) and seventh (anterior tongue) cranial nerves.

2.  The teeth, which are embedded in the maxilla and mandible. The part of the mucosa that is reflected onto the bone in relation to the teeth is called the gingiva (gum).

3.  Three major pairs of salivary glands, plus numerous minor salivary glands. The parotid glands are composed almost entirely of serous cells and are situated in front of and below the ear. They secrete saliva through a duct (Stensen's duct) that opens in the cheek adjacent to the molar teeth. The seromucous submandibular gland lies beneath the mandible and opens by a duct (Warthin's duct) into the floor of the mouth. The sublingual gland, also seromucous in type, is situated in the floor of the mouth and empties through 10–20 small ducts.

4.  Lymphoid tissue, which guards the pharyngeal opening (Waldeyer's ring). The tonsils, which are situated between the faucial pillars and adenoids in the nasopharynx, are the largest collections of lymphoid tissue.

The function of the oral cavity is to accept food and begin the process of digestion. Mastication, aided by the lubricant action of the saliva, converts the food into a bolus that is propelled back by the tongue muscles into the pharynx for swallowing. Saliva contains (a) amylase, which may initiate carbohydrate digestion; (b) lysozyme, which has bactericidal properties; and (c) secretory IgA. The salivary gland epithelium synthesizes “the secretor piece,” which complexes with IgA produced by plasma cells in the gland stroma.

Pain

The oral cavity is richly supplied with sensory nerve endings, and pain is a feature of almost all diseases that affect the mucosa. Pain in diseases of the teeth occurs only when pain-sensitive fibers in the root of a tooth are involved.

Changes of the Oral Mucosa

Alterations of the mucosa include ulceration, vesicular lesions (blisters), and changes in color. Oral ulcers occur in many diseases, including infections, allergy, trauma, and neoplasms. Vesicular lesions occur in infections (eg, herpesvirus infections) and immunologic diseases such as pemphigus vulgaris and erythema multiforme that primarily affect the skin. White plaques on the mucosa (leukoplakia) occur in hyperplastic and neoplastic conditions, and melanin pigmentation occurs in many systemic diseases (Table 31-1).

Masses

Mass lesions may be solid or cystic and may be found in any part of the oral cavity. Mass lesions arising in structures outside the oral cavity (eg, bone of the mandible and maxilla) may involve the oral cavity by extension.

Dental Caries

Etiology

Dental caries is a progressive decomposition of tooth substances caused by a wide variety of bacteria and fungi but most commonly Streptococcus mutans. The microorganisms proliferate in food residue on the teeth to form a hard adherent mass of calcified debris containing bacteria and desquamated epithelial cells (plaque, tartar; calculus when calcified). Enzymes and acids produced by the microorganisms cause proteolysis, decalcification, and decay of first the enamel covering of the tooth, then the dentin, and finally the tooth pulp. Cavities are detectable with probes when there is a break in continuity of the enamel.

Several factors influence the risk of dental caries:

1. Microorganisms are essential for formation of caries. Attempts to develop vaccines against common causative organisms have not proved successful. The use of antibiotics is not feasible because of the variety of microorganisms involved and the adverse effects of these drugs.

2. Regular brushing prevents accumulation of food residue and clearly reduces the incidence of caries.

3.   Sugar, particularly in a form that sticks to the teeth, promotes dental caries because bacteria utilize carbohydrates for metabolism. The stickiness of plaque is caused by dextran, which is a product of sucrose fermentation by Streptococcus mutans.

4. Once plaque has formed, it cannot be removed by simple brushing. Removal of plaque by regular use of dental floss or by scaling decreases the incidence of caries.

5. Fluoride has a dual protective effect: It makes the enamel more resistant to bacterial degradation and has a weak microbicidal action.

6. Saliva has a mechanical cleansing action and contains microbicidal substances (eg, lysozyme, IgA). Any cause of decreased salivary secretion, such as Sjögren's syndrome or radiation, increases the risk of dental caries. Patients who undergo radiation treatment to the oral cavity need careful dental care to prevent “radiation caries.”

Clinicopathologic Effects

(Figure 31-1)

Early Caries

Early dental caries does not cause symptoms but can be recognized by clinical dental examination. Because caries is slowly progressive, regular dental examination permits effective treatment at an early stage.

Pulp Infection

Deep caries that extends through the enamel and dentin layers into the tooth pulp permits the entry of microorganisms into the tooth pulp. Acute inflammation results, leading to the formation of a localized abscess or destruction of the entire pulp. Both are associated with severe pain (toothache) and swelling.

When there is a localized pulp abscess, simple drainage and antibiotic therapy may be sufficient treatment. Total destruction of the pulp requires clearance of the entire pulp cavity followed by replacement with an inert material and sealing (root canal therapy).

Periapical Infection

Extension of pulp infection to the apical periodontium results in an inflammatory lesion that progresses through several stages:

1. An apical abscess develops around the apex of the tooth and is intensely painful due to the high tissue tension that develops in the bone. The abscess enlarges and eventually drains through the gingiva (parulis, gumboil). Rarely, the infection spreads in the floor of the mouth and neck along fascial planes, associated with extensive tissue necrosis (Ludwig's angina).

2. Periapical granuloma is a more chronic inflammatory response around the apex of the tooth, characterized by bone resorption and infiltration by lymphocytes, plasma cells, and histiocytes. Symptoms may be minor—typically mild pain when biting down or increased sensitivity of the tooth to heat and cold. X-ray reveals a well-demarcated lucent area in the bone at the apex of the tooth.

Periapical granulomas tend to undergo epithelialization from the periapical region to form a cystic structure lined by squamous epithelium and containing the fluid debris of inflammation. This is called a radicular cyst.

Periodontal Disease

Periodontal disease is also a complication of plaque formation. As the incidence of dental caries decreases, periodontal disease has become the most common cause of tooth loss in adults in the United States. Accumulation of plaque (see above) in the crevice between the gingiva and the tooth causes inflammation (gingivitis), which may progress to periodontitis, involving not only the gingival crevice but also the periodontal membrane, alveolar bone, and the outer layer of the tooth itself. The end result is instability of the tooth, resorption of the gingiva and bone, purulent discharge from the gingival crevice (pyorrhea), and eventual tooth loss. Again, multiple bacteria are involved.

Gingival hyperplasia also occurs in pregnancy, in some patients receiving phenytoin therapy, and in response to local gingival hemorrhage (in scurvy, leukemia, or thrombocytopenia). Fibrous thickening of the gingiva may also occur in chronic gingivitis resulting from low-grade chronic bacterial infection.

Cysts of the Jaw

Cysts of the jaw are very common. Many of them—eg, radicular cysts, follicular cysts, and odontogenic keratocysts—occur in relation to the teeth. Others, such as fissural and inclusion cysts, are not related to the teeth but enter the differential diagnosis.

Radicular cyst is the most common and is the result of epithelialization of a periapical granuloma.

Follicular cysts arise from the epithelium of the tooth follicle. They may be associated with failure of eruption of the involved tooth. If the unerupted tooth is present in the cyst wall, the term “dentigerous cyst” may be applied.

Odontogenic keratocysts are lined by a keratinized squamous epithelium and occur at the root of the tooth. They may be multiple, in which case they are frequently associated with basal cell carcinomas of the skin.

Fissural or inclusion cysts are derived from epithelial inclusions along lines of fusion of the embryologic facial processes; they are classified according to their site, eg, median palatine cyst, globulomaxillary cyst. A similar cyst arising in nasopalatine duct remnants is called a nasopalatine cyst. All of these are fluid-filled cysts lined by squamous or respiratory epithelium.

Bone cysts are discussed in Chapter 67: Diseases of Bones.

Neoplasms of Tooth-Forming (Odontogenic) Tissues

The most common neoplasms in this region are those derived from bone (osteoma, osteosarcoma, etc) and soft tissues (neurofibroma, vascular neoplasms, etc). Ameloblastoma, although it is the most common odontogenic tumor, is rare, comprising 1% of cysts and tumors of the jaw. Other odontogenic neoplasms (cementomas, dentinomas, etc) are very rare.

Ameloblastoma occurs mainly in patients between 20 and 50 years of age, most often in the molar region of the mandible. It commonly is made up of both cystic and solid areas and arises from the epithelium of the dental lamina. It is a locally invasive neoplasm that does not metastasize, with a behavior and appearance similar to those of basal cell carcinoma of the skin. Because of its tendency to local invasion, it may recur after surgical removal.

(Table 31-1)

Inflammatory Lesions

Herpes Simplex Stomatitis

Herpes simplex type 1 is a common viral infection of the oral mucosa. The primary infection occurs in children or young adults as a widespread gingivostomatitis, characterized by multiple vesicles that rupture early to form ulcers. Systemic symptoms such as fever are present. Although locally severe, the disease is self-limited, and recovery is the rule.

Herpes simplex virus passes up the nerve trunks and infects the ganglia during the acute phase, where it remains dormant for long periods. Reactivation of the infection occurs repeatedly in some patients, with the virus passing down the nerve to the oral mucosa to form isolated vesicular lesions and ulcers (herpes labialis—fever blisters and cold sores). Reactivation is often precipitated by a concurrent fever or common cold or by exposure to sunlight. About 20% of the population is affected.

Candidiasis (Oral Thrush)

Candida albicans is a normal commensal of the mouth. Clinical infection of the oral mucosa usually represents an opportunistic infection in a patient with increased susceptibility. Persons at risk are those with immunosuppression, eg, acquired immune deficiency syndrome (AIDS) patients or those receiving cancer chemotherapy; newborn infants; patients with diabetes; and sick patients who receive long-term antibiotic therapy.

Candida produces inflammation and edema of the epithelium, forming white patches that leave raw ulcerated lesions when they are rubbed off. The budding yeasts and pseudohyphae of Candida can be identified in smears, cultures, or biopsy specimens from the lesion.

Aphthous Stomatitis

Aphthous stomatitis is a common disorder characterized by recurrent episodes of painful shallow ulcers (canker sores) on the oral mucosa. The pathologic picture is of nonspecific acute inflammation. The cause is unknown—psychosomatic and allergic mechanisms have been suggested; no infectious agent has been identified. The disease is usually self-limited. Rarely, it is associated with genital and conjunctival ulcers and neurologic abnormalities (Behçet's syndrome).

Rare Infections of the Oral Cavity

Actinomyces israelii and Actinomyces bovis cause chronic suppurative inflammation in the mouth and jaw. Patients present with an indurated jaw mass that has multiple sinuses opening to the skin surface, which drain pus. The pus typically contains visible small colonies of the organism (sulfur granules). Actinomyces species are gram-positive filamentous bacteria that are part of the normal mouth flora, and actinomycosis usually follows dental extraction. The organism is sensitive to penicillin.

A wide variety of spirochetes and fusiform bacilli inhabit the mouth. In debilitated or malnourished individuals, they may cause severe ulcerative gingivitis (Vincent's angina, or trench mouth).

Syphilis may involve the mouth in all three stages. In primary syphilis, the chancre may be on the lips or tongue; in secondary syphilis, superficial mucous patches and snail track ulcers may be present; in tertiary syphilis, chronic inflammation may produce tongue ulcers or large granulomas (gummas). Congenital syphilis also produces scarring at the angles of the mouth (rhagades). Abnormalities in the permanent teeth—Hutchinson's incisors and Moon's ulcers—are described in Chapter 54: Sexually Transmitted Infections.

Skin Diseases Manifesting in the Mouth

The following skin diseases are frequently manifested in the mouth, with or without concurrent skin lesions: (1) lichen planus, (2) pemphigus vulgaris, (3) bullous pemphigoid, and (4) erythema multiforme (Stevens-Johnson syndrome). The histologic features of these lesions are characteristic and permit diagnosis (Chapter 61: Diseases of the Skin).

Benign “Tumors” of the Oral Cavity

A large number of lesions present clinically as a mass in the oral cavity. Not all are neoplasms.

Mucocele (Mucus Escape Reaction)

Mucoceles represent a localized inflammatory reaction to the escape of mucus from a ruptured minor salivary gland or duct. They are usually small white cystic structures. More rarely, they become large and stretch the overlying mucosa. Large mucoceles of the floor of the mouth resulting from damage to the submandibular or sublingual salivary ducts are called ranulas.

Pyogenic Granuloma

Pyogenic granuloma is a common oral lesion that is the result of a reactive inflammatory proliferation of granulation tissue. It presents as a small, bright red nodule with ulceration of the overlying mucosa (Figure 31-2). Pyogenic granulomas occur commonly during pregnancy (pregnancy tumor). The cause is unknown. They resolve spontaneously.

Epulis

The term epulis signifies a local reactive inflammatory lesion of the gum that presents as a mass. It includes pyogenic granuloma as well as a distinct lesion composed of multinucleated giant cells (giant cell epulis). A form of congenital epulis is characterized by the proliferation of large cells with abundant granular cytoplasm (granular cell epulis).

Lingual Thyroid

Thyroid tissue at the root of the tongue is a rare condition that represents incomplete descent of thyroid tissue in the embryo. It usually coexists with a normal thyroid but in rare cases represents the individual's only thyroid tissue.

Benign Neoplasms of the Oral Cavity

Benign neoplasms in the oral cavity may arise from the squamous epithelium (squamous papilloma), from mesenchymal cells (fibroma, lipoma, neurofibroma), or from minor salivary glands (adenomas). One benign tumor that occurs commonly in the tongue is the granular cell tumor, probably a variant of a schwannoma in which the cells have abundant granular cytoplasm.

Squamous Carcinoma of the Oral Cavity

Incidence & Etiology

Squamous carcinoma accounts for over 95% of malignant neoplasms in the oral cavity and 5% of all cancers in the United States. Cancers arising in the lower lip (40%), the tongue (20%), and the floor of the mouth (15%) account for the majority. Involvement of the upper lip, palate, gingiva, and tonsillar area (5% each) is less common. The mucosa of the cheek is rarely the primary site for squamous carcinoma.

Oral cancer is much more common in men than in women. In the United States, oral cancer is most strongly related to tobacco chewing, particularly in baseball players. Cigarette and pipe smoking and alcohol are also associated.

Oral cancer is extremely common in Sri Lanka and parts of India, where chewing betel is common—betel is a green leaf that is mixed with areca nut, limestone, and tobacco to form a cud. The carcinogenic agent is believed to be in either the limestone or the tobacco. In parts of Italy where it is customary to smoke cigars with the lighted end inside the mouth, polycyclic hydrocarbons are believed to be the agents responsible for causing squamous carcinoma.

Clinical Features

Squamous cancer begins as a painless indurated plaque on the tongue or oral mucosa that commonly ulcerates to form a malignant ulcer. The lesion is usually readily visible, and diagnosis is made by biopsy. A significant number of patients with oral cancer present first with involved cervical lymph nodes. In very advanced local disease, there may be fixation of the tongue, interfering with speech and swallowing.

Pathology

The earliest lesion is squamous epithelial dysplasia, the most severe form of which is carcinoma in situ. At this stage there may or may not be visible whitish thickening (leukoplakia) of the epithelium (see below); however, most lesions are invasive to a variable depth at the time of diagnosis. The degree of differentiation varies; most tumors are well differentiated.

Oral cancer spreads primarily by lymphatics. Cervical lymph nodes are involved early. Bloodstream metastasis occurs late.

Leukoplakia is a term applied to visible flat, white lesions of the oral or genital mucous membranes. In most instances, it is due simply to hyperkeratosis (increased thickness of keratin layer) resulting from chronic irritation. In some instances, however, epithelial dysplasia is present, and the lesion is then considered precancerous. Persistent leukoplakia should therefore be biopsied.

Treatment & Prognosis

Treatment of oral squamous carcinoma is by radical surgery, radiotherapy, and chemotherapy. Squamous carcinoma of the oral cavity is sensitive to radiation therapy. The prognosis depends on the stage of the disease and is relatively good in the absence of cervical lymph node involvement.

Other Malignant Neoplasms of the Oral Cavity

Rare malignant neoplasms in the oral cavity include malignant lymphomas and carcinomas of minor salivary gland origin. Malignant melanoma is very rare.

Inflammatory Lesions of the Salivary Glands

Salivary Duct Calculi (Sialolithiasis)

Calculi occur mainly in the duct of the submandibular gland, possibly related to the thicker mucoid secretion of this gland. Obstruction of a salivary gland duct produces acute inflammation (acute sialadenitis) followed by chronic inflammation, glandular atrophy, and fibrosis (chronic sialadenitis).

Sjögren's Syndrome

Sjögren's syndrome is an autoimmune disease in which there is immune-mediated destruction of the lacrimal and salivary glands. It is manifested clinically as dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) due to failure of gland secretion. It is commonly associated with other autoimmune diseases, notably rheumatoid arthritis. Patients with Sjögren's syndrome have an increased incidence of malignant lymphomas in the salivary gland.

About 75% of patients have rheumatoid factor in the blood, and 70% have antinuclear antibodies. Specific autoantibodies directed against ribonucleopro-teins designated anti-Ro [Sjögren's Syndrome (SS)-A] and anti-La (SS-B) have been identified in the serum of 60% of patients with Sjögren's syndrome.

Histologically, the lacrimal and salivary glands show marked lymphocytic and plasma cell infiltration with destruction of the glandular epithelium and fibrosis.

The diagnosis can be made by clinical tests to demonstrate absence of secretion of tears and by lip biopsy, which shows the typical histologic changes in the mucus glands of the lip (Figure 31-3).

Infections of the Salivary Glands

The parotid gland is the most common site of involvement in mumps virus infection. The gland is painfully enlarged in the acute phase. Mumps is a self-limited illness.

Bacterial parotitis occurred commonly in the past in debilitated patients with dehydration and poor oral hygiene. It was characterized by painful enlargement of the gland, frequently complicated by abscess formation. Improvement in oral hygiene in patients at risk has made bacterial parotitis uncommon.

Neoplasms of the Salivary Glands

(Table 31-2)

Salivary gland neoplasms are common and varied. About 80% occur in the parotids, 15% in the submandibular gland, and 5% in minor salivary glands. All present as a mass causing enlargement of the affected gland. Computerized tomography is helpful in assessment of the location and extent of salivary gland neoplasms. Diagnosis requires cytologic (fine-needle aspiration) or histologic examination.

Benign Neoplasms

Pleomorphic Adenoma (Mixed Tumor)

Pleomorphic adenoma accounts for over 50% of salivary gland tumors. Although the lesion is benign and well circumscribed, encapsulation is incomplete, and simple enucleation is followed by a high rate of local recurrence due to regrowth of residual tumor. Wide excision is necessary for cure.

Pleomorphic adenoma is a firm, solid mass. Histologically, the tumor presents a greatly varied appearance. Uniform epithelial and myoepithelial cells are distributed in cords, nests, and strands within a matrix of mucoid material (Figure 31-4A), which frequently resembles cartilage (hence the mistaken notion that this was a mixed mesenchymal and epithelial tumor).

Warthin's Tumor (Adenolymphoma)

Most Warthin tumors occur in the parotid gland. They may rarely be multicentric and bilateral. The histologic appearance is distinctive (Figure 31-4B), with cystic spaces lined by a uniform double-layered epithelium that is frequently thrown into papillary folds. The neoplastic epithelial cells are large, with abundant pink cytoplasm, and are surrounded by a dense lymphocytic infiltrate.

Malignant Salivary Gland Neoplasms

Malignant neoplasms of the salivary glands are of several different pathologic types (Table 31-2).

Most of these neoplasms are slow growing. The exceptions are the rare undifferentiated carcinomas and the high-grade mucoepidermoid carcinomas. Low-grade mucoepidermoid carcinoma (Figure 31-4C) is a well-circumscribed neoplasm with variable solid and cystic areas that is cured in over 90% of cases by surgical removal. Adenoid cystic carcinoma (Figure 31-4D) is a highly infiltrative neoplasm with a tendency to invade along nerves. It is very rarely cured by surgery because of its invasiveness, and local recurrences and metastases often occur many (5–25) years after original treatment. Carcinomas arising in mixed tumors and acinic cell carcinoma have variable clinical courses.