Oral Cavity & Salivary Gland Pathology
Scrape it, biopsy it, or follow the nerve: sorting mouth lesions and parotid masses
Oral ulcers
Aphthous ulcers. Recurrent aphthous stomatitis (canker sores) produces small, shallow, round ulcers that are disproportionately painful, with a gray-white fibrinous base and a red halo. They arise on movable, nonkeratinized mucosa such as the buccal and labial mucosa and ventral tongue, and minor ulcers heal in 1 to 2 weeks without scarring. Occasional ulcers after minor trauma are common, but recurrent crops should prompt a search for Crohn disease, celiac disease, Behçet disease, HIV, or deficiency of vitamin B12, folate, or iron.
Behçet disease is an HLA-B51–associated vasculitis that combines recurrent oral aphthae with genital ulcers and uveitis. Lupus oral ulcers, by contrast, are classically painless.
Contrast with herpes. Recurrent intraoral HSV favors keratinized mucosa (attached gingiva, hard palate) and the lip vermilion and begins as clustered vesicles, whereas aphthae spare keratinized surfaces.
White and red lesions
| Lesion | Appearance | Scrapes off? | Cause | Malignant potential |
|---|---|---|---|---|
| Leukoplakia | White plaque; diagnosis of exclusion | No | Tobacco, alcohol | Yes; biopsy |
| Erythroplakia | Red, velvety, flat or depressed | No | Tobacco, alcohol | Highest; often high-grade dysplasia or carcinoma |
| Oral hairy leukoplakia | White, vertically ridged; lateral tongue | No | EBV in immunosuppression (HIV) | None |
| Thrush | Creamy, curd-like plaques | Yes, leaving a raw base | Candida albicans | None |
| Oral lichen planus | Lacy white striae (Wickham), often bilateral buccal | No | T cell–mediated; linked to hepatitis C | Small (erosive forms) |
Leukoplakia is a white plaque that cannot be scraped off and is not explained by any other diagnosis. Tobacco, smoked or chewed, and alcohol drive it, and histology ranges from simple hyperkeratosis to dysplasia. Because some lesions harbor dysplasia or carcinoma, every persistent leukoplakia is biopsied.
Erythroplakia is a red, velvety, flat or slightly depressed patch. It is far less common than leukoplakia but far more often shows high-grade dysplasia, carcinoma in situ, or invasive carcinoma; speckled (mixed red-and-white) lesions carry similar risk.
Oral hairy leukoplakia forms white, corrugated plaques with vertical ridges on the lateral tongue that do not scrape off. It reflects EBV replication in squamous epithelium in HIV or other immunosuppression and is not premalignant; in an otherwise healthy-appearing adult it should prompt HIV testing.
Thrush (pseudomembranous candidiasis) leaves a raw, bleeding base when scraped, and KOH shows budding yeast with pseudohyphae. Risks include infancy, dentures, inhaled corticosteroids, broad-spectrum antibiotics, diabetes, chemotherapy, and HIV. Topical nystatin or clotrimazole troches treat mild disease, oral fluconazole treats severe or esophageal disease, and rinsing after inhaled steroids helps prevent it.
Oral and oropharyngeal squamous cell carcinoma
Tobacco-related oral cancer. More than 90% of oral cancers are squamous cell carcinomas. Tobacco (smoked, chewed, or betel/areca nut) and alcohol act synergistically, and leukoplakia and erythroplakia are the visible precursors. Within the oral cavity, the floor of the mouth and the ventral and lateral tongue are favored; the lesion is typically an indurated, nonhealing ulcer or mass, and spread goes first to cervical lymph nodes. These tumors usually carry TP53 mutations. Because the whole mucosa is bathed in carcinogen (field cancerization), second primary tumors of the upper aerodigestive tract are common.
HPV-related oropharyngeal cancer. HPV-16–driven SCC arises in the tonsillar crypts and base of tongue, often in younger nonsmokers, and frequently presents as a cystic neck node. Viral E6 targets p53 for degradation and E7 inactivates Rb; the resulting p16 overexpression serves as the surrogate marker. Prognosis is better than for tobacco-related disease.
Location separates the two pathways: floor of mouth and lateral tongue suggest tobacco and alcohol; tonsils and base of tongue suggest HPV-16.
Salivary gland inflammation
Sialolithiasis. About 80–90% of salivary stones form in the submandibular gland and Wharton duct, because its saliva is alkaline, mucin-rich, and calcium-rich and must flow uphill through a long duct. The gland swells painfully at mealtimes and subsides afterward, and a stone may be palpable in the floor of the mouth. Dehydration, diuretics, and anticholinergics raise risk, and obstruction predisposes to infection. Hydration, sialogogues such as sour candy, massage, and warm compresses come first; persistent stones are removed.
Acute suppurative sialadenitis. Bacterial infection mostly strikes the parotid, usually S. aureus. Risks include dehydration, recent surgery, old age, poor oral hygiene, anticholinergic drugs, and duct obstruction. The gland is tender, red, and swollen, and pus can be milked from Stensen duct, which opens opposite the upper second molar (Wharton duct opens beside the lingual frenulum). Treatment is hydration, sialogogues, and antistaphylococcal antibiotics.
Mumps. This paramyxovirus causes painful, usually bilateral parotid swelling with a raised serum amylase and no pus. Complications include orchitis in postpubertal males (sterility is rare), aseptic meningitis, and pancreatitis; the live MMR vaccine prevents it. Chronic bilateral parotid enlargement with dry mouth and dry eyes suggests Sjögren syndrome instead, which raises the risk of marginal zone (MALT) lymphoma.
Salivary gland tumors
Where and how often. Roughly 65–80% of salivary neoplasms arise in the parotid, and most parotid tumors are benign. The smaller the gland, the likelier its tumor is malignant: submandibular tumors carry a larger malignant share, about half of minor salivary gland tumors are malignant, and most sublingual tumors are. The facial nerve runs through the parotid, so red flags for malignancy are pain, facial nerve (CN VII) palsy, rapid growth, fixation to skin or deep tissue, and cervical nodes.
| Tumor | Behavior | Clinical clues | Histology and genetics |
|---|---|---|---|
| Pleomorphic adenoma | Benign; most common salivary tumor | Painless, mobile mass near the jaw angle; recurs after enucleation | Epithelial and myoepithelial cells in chondromyxoid stroma; PLAG1 |
| Warthin tumor (papillary cystadenoma lymphomatosum) | Benign; second most common | Almost only parotid; smokers; bilateral or multifocal in ~10% | Cysts lined by double-layered oncocytes over lymphoid stroma with germinal centers |
| Mucoepidermoid carcinoma | Most common malignant | Usually parotid; behavior tracks grade | Mucous, squamous, and intermediate cells; CRTC1-MAML2, t(11;19) |
| Adenoid cystic carcinoma | Malignant; slow but relentless | Pain, facial nerve palsy; local recurrence; late lung metastases | Cribriform basaloid cells; perineural invasion; MYB-NFIB |
Pleomorphic adenoma is a painless, slow-growing, mobile mass near the angle of the jaw. It is biphasic, with epithelial and myoepithelial cells in a chondromyxoid stroma, and finger-like projections breach its incomplete capsule. Enucleation therefore leaves tumor behind and invites recurrence, so it is excised with a margin (superficial parotidectomy). Long-standing tumors can transform (carcinoma ex pleomorphic adenoma).
Mucoepidermoid carcinoma mixes mucus-secreting, epidermoid, and intermediate cells; low-grade tumors are indolent and high-grade tumors aggressive. Adenoid cystic carcinoma forms a cribriform ("Swiss cheese") pattern and tracks along nerves, so it causes pain and facial weakness, recurs locally, and metastasizes late, often to lung.
A parotid mass with pain or facial nerve weakness is malignant until proven otherwise; benign tumors such as pleomorphic adenoma rarely affect the facial nerve.
After parotid surgery, sweating and flushing over the cheek while eating (Frey syndrome) result from severed parasympathetic auriculotemporal fibers regrowing into sweat glands.