Oral cavity and oropharynx
Last revised 17 April 2008
Last major update June 2004
Copyright (c) 2004-2008, PathologyOutlines.com, Inc.
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Primary references, normal anatomy, normal histology
Congenital anomalies: dermoid/epidermoid cyst, duplication cyst, epithelial nests, epulis, Fordyce’s disease, hairy polyp, heterotopia, lingual thyroid, lingual tonsil, white sponge nevus
Infectious: general, aphthous ulcers, candidiasis, CMV, condyloma acuminatum, diphtheria, gingivitis, hairy leukoplakia, herpes simplex, histoplasmosis, HIV, infectious mononucleosis, measles, periodontitis, scarlet fever, syphilis, tuberculosis
Inflammatory (non-infectious): atypical histiocytic granuloma, Behcet’s disease, Crohn’s disease, fissured tongue, geographic tongue, glossitis, granulomatous inflammation, hyaline ring like structures, Melkersson-Rosenthal syndrome, necrotizing sialometaplasia, oral submucosal fibrosis, papillary hyperplasia, peripheral giant cell granuloma, sarcoidosis, tongue ulceration with eosinophilia, Wegener’s granulomatosis, xerostomia
Dermatologic conditions: erythema multiforme, lichen planus, melanotic pigmentation, pemphigus vulgaris, smokeless tobacco keratosis
Other benign tumors/conditions: amyloidosis, angiolymphoid hyperplasia, chondroma, crystal storing histiocytosis, ectomesenchymal chondromyxoid tumor, ephelis, fibroid epulis, focal dermal hyperplasia, focal epithelial hyperplasia, giant cell angiofibroma, gingival hyperplasia, granular cell tumor, hemangioma, irritation fibroma, keratoacanthoma, leukoedema, lymphangioendothelioma, lymphoid hyperplasia / polyp, mucinosis, mucous cyst, nevus, paraganglioma, peripheral ameloblastoma, plasma cell granuloma, plasmacytosis, post-traumatic spindle cell nodule, pseudoepitheliomatous hyperplasia, pyogenic granuloma, rhabdomyoma, solitary fibrous tumor, Spitz nevus, squamous papilloma, verruca vulgaris, verruciform xanthoma
Premalignant/in situ conditions: carcinoma in situ, dysplasia, leukoplakia, verrucous hyperplasia
Squamous cell carcinoma: general oral cavity, buccal mucosa, floor of mouth, gingiva, lip, oropharynx, palate, tongue, tonsil, Waldeyer’s ring; subtypes-basaloid, papillary, pseudoglandular, spindle cell, verrucous
Other carcinomas (non salivary gland): adenosquamous, basal cell, small cell
Minor salivary gland tumors/lesions: general, acinic cell carcinoma, adenoid cystic carcinoma, adenomatoid hyperplasia, basal cell adenoma, choristoma, clear cell carcinoma, cystadenocarcinoma, intraductal, inverted ductal papilloma, malignant mixed tumor, mucoepidermoid, myoepithelioma, Paget’s disease, pleomorphic adenoma, polymorphous low grade adenocarcinoma, sialadenoma papilliferum, signet ring adenocarcinoma
Other malignancies: angiosarcoma, follicular dendritic cell tumor, hemangioendothelioma, Kaposi’s sarcoma, liposarcoma, lymphoma, melanoma, metastases, plasmacytoma, post-transplant lymphoproliferative disorder, sarcoma-other
Miscellaneous: TNM staging, grossing, features to report
AJCC Cancer Staging Manual (6th Ed)
American Journal of Surgical Pathology (AJSP), March 1977 to June 2004
Archives of Pathology and Laboratory Medicine (Archives) January 1976 to June 2004
Human Pathology (Hum Path), March 1970 to May 2004
Modern Pathology (Mod Path), January 1988 to May 2004
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
Oral Pathology website - Dr. William Crawford (Univ Southern California)
Journal search terms: oral, mouth, tongue, gingiva, tonsil, oropharynx
Please refer to these primary references for more detailed discussions and photographs
Oral cavity extends from skin-vermilion junction of lips to junction of hard and soft palate above and to line of circumvallate papillae below
Dorsal tongue: villous, normally exposed surface
Ventral tongue: nonvillous undersurface
Anterior 2/3 of tongue (oral tongue): freely mobile portion of tongue that extends anteriorly from line of circumvallate papillae to undersurface of tongue at junction of floor of mouth; composed of four areas - the tip, the lateral borders, the dorsum and the undersurface (nonvillous ventral surface of tongue)
Base of tongue (posterior 1/3 of tongue): bound anteriorly by circumvallate papillae, laterally by glossotonsillar sulci, posteriorly by epiglottis
Buccal mucosa: all of the membrane lining the inner surface of cheeks and lips from line of contact of opposing lips to line of attachment of mucosa of alveolar ridge (upper and lower) and pterygomandibular raphe
Floor of mouth: semilunar space of myelohyoid and hyoglossus muscles, extending from inner surface of lower alveolar ridge to undersurface of tongue; posterior boundary is base of anterior pillar of tonsil; divided into two sides by frenulum of tongue, contains ostia of submaxillary and sublingual salivary glands
Gingiva: soft tissue in area of teeth and palate; extends from labial sulcus and buccal sulcus to a cuff of tissue around each tooth
Hard palate: semilunar surface between upper alveolar ridge and mucous membrane covering palatine process of maxillary palatine bones; extends from inner surface of superior alveolar ridge to posterior edge of palatine bone
Lip: begins at junction of vermilion border (mucocutaneous junction) with skin, includes only the vermilion surface or that portion of lip that comes into contact with opposing lip; upper and lower lip are joined at commissures of mouth; external surface is skin and mucous membrane; internally contains orbicularis oris muscle, blood vessels, nerves, areolar tissue, fat, small labial glands; inner surface of lip is connected to gum in midline by frenulum, a mucous membrane fold
Lower alveolar ridge: mucosa overlying alveolar process of mandible which extends from the line of attachment of mucosa in buccal gutter to line of free mucosa of floor of mouth; posteriorly, it extends to ascending ramus of mandible
Retromolar gingiva (retromolar trigone): mucosa overlying ascending ramus of mandible from level of posterior surface of last molar tooth to apex superiorly, adjacent to tuberosity of maxilla
Tonsillar area: anterior and posterior tonsillar pillars and tonsillar fossa
Upper alveolar ridge: mucosa overlying alveolar process of maxilla which extends from line of attachment of mucosa in upper gingival buccal gutter to junction of hard palate; posterior margin is upper end of pterygopalatine arch
Vermillion border: mucocutaneous junction of lip
Drawings: nose, mouth, pharynx and larynx; tongue surface, tongue and oral cavity, undersurface of tongue, coronal section of tongue
Stratified squamous epithelium with parakeratosis
No hair follicles or sweat glands present
Keratinization in areas most exposed to mastication (gingiva, hard palate, dorsum of tongue)
Lamina propria contains loose connective tissue, mucous glands and serous minor salivary type glands
Submucosa has collagenous, dense, fibrous tissue
Tonsillectomy specimens frequently contain skeletal muscle, Hum Path 2000;31:813
Micro images: lip, soft palate #1, #2, filiform papilla #1, #2, fungiform papilla #1, #2, circumvallate papilla #1, #2, #3, #4, #5, taste buds #1, #2
Midline in floor of mouth
Present at birth but asymptomatic until inflamed
Gross images: epidermoid cyst
Micro: lined by squamous epithelium, contains skin adnexae if dermoid cyst
Lined by indigenous mucosa of segment it is duplicating
Case reports: congenital duplication cyst of ventral surface of tongue with gastrointestinal and respiratory epithelium in newborn (Archives 1989;113:1301), enteric duplication cyst of floor of mouth and base of tongue in 7 year old (Archives 2000;124:614)
Treatment: excision; may recur if incompletely excised
Gross images: sublingual duplication cyst
Micro images: colonic and gastric mucosa in cyst wall
Not actually a congenital anomaly, but normal occurring neuroepithelial structure called organ of Chievitz, Chievitz’s paraparotid organ, or juxtaoral organ
Reported in 56% of adult autopsies without oral mucosal lesions
Occur within intraoral sensory nerve
May undergo nodular hyperplasia
Micro: squamous like epithelium, occasionally with lumen lined by cuboidal cells; associated with small nerves and resembling perineural invasion
References: AJSP 1979;3:147
Congenital granular cell tumors that occur exclusively in girls
Sites: anterior alveolar ridge of maxilla and mandible, usually overlying future canine and lateral incisor teeth
Don’t recur, even if incompletely excised
Micro: confluent to nodular submucosal growth of tumors composed of large polygonal cells with eosinophilic granular cytoplasm and small, central nuclei
References: AJSP 1981;5:37
Common; normal sebaceous glands within oral cavity
May be hyperplastic and nodular
Gross images: multiple small yellow papular lesions, various gross/micro images #1
Rare, arises from oropharynx or nasopharynx
Micro: polypoid lesion of epidermis, hair follicles, sebaceous glands, eccrine sweat glands; variable adipose tissue, smooth muscle, striated muscle and cartilage in core
Gastric or intestinal epithelium in tongue and floor of mouth that may become cystic, or glial and ependyma-lined clefts in palate and parapharyngeal space
Thyroid tissue at base of tongue due to failure of descent
In 10% of normals; 70% with grossly evident lingual thyroid lack a normal thyroid gland
Fairly common; raised red areas at lateral tongue base containing lymphoid tissue
Gross/micro images: various gross/micro images
Autosomal dominant disease
Large white plaques in oral mucosa with striking intracellular edema in malpighian layer
Infectious conditions
Oral cavity defenses against infection include competition by organisms of low virulence, secretory IgA (from submucosal lymphocytes and plasma cells), antibacterial effects of saliva, diluting effects of food and drink
Also called canker sores
Affect 40% in US; more common up to 20 years; painful, recurrent, familial
Treatment: symptomatic
Gross: single or multiple, shallow, hyperemic ulcerations covered by a thin exudate with hyperemic rim
Micro: initially mononuclear infiltrate, then neutrophilic infiltrate from secondary bacterial infection
Normal flora that overgrows due to diabetes, neutropenia, AIDS, immunosuppression, xerostomia, antibiotics
Gross: superficial curdy, gray-white inflammatory membrane
Micro: membrane composed of fungi in a fibrinopurulent exudate resting on an inflammatory base
Ulcerated lesion
Associated with HPV
Case report of HIV- woman who acquired HPV 6/11 in late teens and developed disseminated condylomas of oropharynx, nasopharynx, anogenital region, urethra and bladder, with no known immune defect, AJSP 1998;22:1291
Micro: acanthosis, koilocytotic atypia
Gross: dirty white, fibrinosuppurative, tough, inflammatory membrane over tonsils, posterior pharynx
Painless inflammation of gingiva around gingival sulci or cuff surrounding each tooth, due to bacterial plaque
Most commonly due to Streptococcus, Fusobacterium, Actinomyces, Veillonella, Treponema
May be due to scurvy, endocrine alterations (teenagers, pregnancy), disseminated tuberculosis, phenytoin or other drugs
Gross: erythematous and edematous gingiva adjacent to teeth
Micro: initially neutrophils, later T lymphocytes, finally B lymphocytes and plasma cells
Acute necrotizing gingivitis
Also called trench mouth, Vincent’s stomatitis, ulcerative stomatitis
Caused by fusospirochetal complex of microbes
Heals with scarring and blunting of interdental papillae; may recur
Predisposing factors: poor oral hygiene, smoking, emotional anguish, age 12-29 years in US and Northern Europe
Gross: highly inflamed mucosa with enlargement of interdental papillae and presence of gray pseudomembrane with hemorrhagic tissue below; occasional ulceration of papillae
Micro: necrosis of interdental gingival papillae, focal abscess
Associated with HIV infection (AIDS may appear within 2-3 years), but actually due to EBV infection
Gross: white, confluent patches of fluffy (hairy) mucosa along lateral tongue
Gross images: hairy leukoplakia #1
Micro: hyperkeratotic oral mucosa due to piling of keratotic squamous epithelium; Cowdry type A intranuclear inclusions; EBV present in clear cells of spinous layer; variable koilocytosis, superimposed Candida infection
EM: herpes type virions
Reference: AJSP 1989;13:114 (intranuclear inclusions)
Also called cold sore
Usually HSV1
Lasts 3-4 weeks, then virus tracks along regional nerves and becomes dormant in trigeminal or other local ganglia
Most infected adults have latent HSV-1 that is activated by upper respiratory infection, excessive exposure to cold, wind, sun, allergies
Acute herpetic gingivostomatitis: rare, children 2-4 years with diffuse involvement of oral and pharyngeal mucosa, tongue, gingiva; fiery red mucosa and swelling with clusters of vesicles
Recurrent herpetic stomatitis: groups of 1-3 mm vesicles on the lips, nasal orifices, buccal mucosa; milder than acute, lesions dry up in 4-6 days, heal in 7-10 days
Tzanck test: microscopic examination of vesicle fluid shows giant cells, inclusions
Gross: vesicles (mm size) to bullae (cm size) with clear serous fluid, painful shallow ulcers
Gross images: lip lesions, acute herpetic gingivostomatitis (various images)
Micro: intra- and intercellular edema (acantholysis), intranuclear inclusions, multinucleate polykaryons (giant cells)
Ulcers, nodular lesions, verrucous masses
Micro: noncaseating granulomas or nonspecific inflammatory infiltrate
Positive stains: GMS, PAS
DD: squamous cell carcinoma
Human immunodeficiency virus (HIV)
Associated with opportunistic infections, herpes simplex virus, Candida, fungi, Kaposi’s sarcoma, hairy leukoplakia
Lymphoid hyperplasia of Waldeyer’s ring is a frequent symptomatic complication of HIV infection, often with HIV+, EBV- multinucleated giant cells in crypt or surface epithelium, Hum Path 1999;30:1383, Mod Path 2000;13:1293
Micro: adenoids and tonsils - florid follicular hyperplasia, follicle lysis, attenuated mantle zone, multinucleated giant cells adjacent to surface or tonsillar crypt epithelium; may have marked lymphoid depletion with no germinal centers, plasmacytosis and stromal vascular proliferation
Micro images: multinucleated giant cells in Waldeyer’s ring
References: AJSP 1996;20:572
Acute pharyngitis and tonsillitis with gray-white exudate, lymphadenopathy in neck
Due to Epstein-Barr virus infection
Micro: tonsil - reactive lymphoid hyperplasia (polymorphous transformed lymphocytes) with extensive immunoblastic proliferation in sheets and nodules, marked atypia resembling Reed-Sternberg cells
Negative stains: CD15, CD30
References: AJSP 1987;11:122
Koplik spots: ulcerations on buccal mucosa around Stensen duct; spotty enanthema in oral cavity, may precede rash
Recurrent and continuous gingivitis that affects alveolar bone
Causes bone destruction and pockets around teeth > 3 mm in depth
Plaque within pockets serves as nidus for mineralization (dental calculus), causing progressive disease until gingival scarring and bony erosion lead to loss of teeth
Treatment: scaling and planing of root surfaces to remove focal irritants, surgery, brushing and flossing
Fiery red tongue with prominent papillae (raspberry tongue), white coated tongue through which hyperemic papillae project (strawberry tongue)
May produce painless indurated gummatous mass in tongue or palate
Associated with tongue cancer in older studies
Micro: granulomas with giant cells, plasma cells, vascular changes
Rare; painful ulcer of tongue or buccal mucosal lesion
Associated with advanced pulmonary disease
Micro: caseating granulomas
Inflammatory (noninfectious) lesions
Atypical histiocytic granuloma
Reactive nodule with marked histiocytic infiltration and variable mitotic activity
Affects skin, oral mucosa and eyes
Micro: leukocytoclastic vasculitis
Initial presentation may be in oral cavity and pharynx
6% have oral lesions at some time (lip, gingiva, vestibular sulci, buccal mucosa)
Micro: edema, ulcers, papillary hyperplastic mucosa, dilation of lymphatics, chronic inflammatory infiltrate, giant cells, rarely noncaseating granulomas
Also called furrowed tongue
Grooves get deeper and more prominent with age
50% also have geographic tongue
May have true fissure with ulceration
Treatment: brushing tongue
Gross images: fissured tongue, various images
Also called benign migratory glossitis, glossitis migrans
1-2% of population, usually adults
Associated with common cold, work/home stresses
Associated with tongue fissures
Gross: erythematous flat zone on tongue dorsum due to loss of filiform papillae
Gross images: geographic tongue #1, #2, various images #1,
Micro: acanthosis with neutrophils throughout epithelium and surface microabscesses, plus inflammatory infiltrate in lamina propria; resembles psoriasis
Inflammation or beefy red tongue associated with deficiency states
Due to atrophy of tongue papillae, thinning of mucosa and exposure of underlying vasculature
Median rhomboid glossitis: red patch in posterior dorsal tongue
Causes: pernicious anemia (Vitamin B12 deficiency), deficiency of riboflavin, niacin or pyridoxine; sprue, iron deficiency anemia; also associated with jagged teeth, ill fitting dentures, rarely syphilis, burns, ingestion of corrosive chemicals
Plummer-Vinson / Patterson-Kelly syndrome: iron deficiency anemia, glossitis, esophageal webs
Gross images: median rhomboid glossitis #1, #2, atrophic tongue #1
Associated with chronic recurrent tonsillitis
Usually no specific organism is recovered
Usually benign course
Also called pulse granuloma (pulse is edible seed of legumes), oral vegetable granuloma, giant cell hyaline angiopathy
Rarely associated with chronic periostitis, edentulous patients
May be a degenerative change in vessel walls from vasculitis or a reaction to legume cells at various stages of digestion
Treatment: excision or curettage
Micro: hyaline ring like structures, some containing granular necrotic material that surrounds giant cells, vessels and collagen, and is itself surrounded by chronic inflammatory cells
Micro images: pulse granuloma from rectum
Orofacial swelling, peripheral facial nerve paralysis and plicated tongue
Cheilitis granulomatosa: may be a variant
Micro: granulomatous inflammation of lip stroma
DD: sarcoidosis, Crohn’s disease
Reactive condition of minor or occasionally major salivary glands, probably due to ischemia or vasculitis
Gross: ulcerated lesion of hard palate
Gross/micro images: as part of case history #1
Micro: ulcerated surface mucosa; intraductal proliferation of metaplastic squamous epithelium containing trapped mucous cells in lobular (not infiltrative) pattern; pseudoepitheliomatous hyperplasia common; vascular proliferation with prominent inflammatory infiltrate and partial necrosis of salivary glands, associated with squamous metaplasia of adjacent ducts and acini
DD: squamous cell carcinoma, mucoepidermoid carcinoma, post-radiation changes
Mainly in residents of India and Pakistan
Reactive, but risk factor for squamous cell carcinoma
Micro: subepithelial fibrosis, chronic inflammation, hyalinization, loss of vascularity; overlying epithelium is atrophic or hyperplastic and hyperkeratotic
Papillary hyperplasia (inflammatory papillary hyperplasia)
Common, usually involves palate or lingual mandibular gingiva
Called palatal papillomatosis in palate
Associated with ill fitting dentures or partial dentures, wearing prostheses at night, poor oral hygiene
Not a premalignant condition
Treatment: complete excision, proper fitting dentures; removal of offending agent
Gross: multiple red polyp-like projections, often under ill-fitting dentures, usually in palate
Gross images: inflammatory papillary hyperplasia #1, #2 (various gross/micro images) Micro: exophytic mucosal epithelial hyperplasia, including pseudoepitheliomatous hyperplasia, submucosal fibrous hyperplasia; islands of hyperplastic squamous mucosa may appear in submucosa; may have chronic inflammation of accessory salivary glands; no dysplasia
Peripheral giant cell granuloma
Also called giant cell epulis
Reactive gingival mass resembling pyogenic granuloma, but pushes teeth aside and may erode alveolar bone or involve periodontal membrane
Usually women, mean age 30 years, although may involve children or elderly patients without teeth
Treatment: excision with curettage of base of lesion extending into adjacent periodontal membrane
Recurs if not completely excised or source of irritation not removed
Gross: inflammatory lesion up to 1.5 cm that protrudes from gingiva at site of chronic inflammation; covered by gingival mucosa or ulcerated
Gross images: various gross/micro images
Micro: nonencapsulated aggregates of foreign body giant cells and fibroangiomatous stroma with hemorrhage, hemosiderin, acute and chronic inflammatory cells; alveolar bone often expanded in edentulous patients leading to superficial bone loss with peripheral cuffing
DD: giant cell granuloma of maxilla/mandible, giant cell “brown tumors” of hyperparathyroidism
Central giant cell granuloma
Similar to peripheral giant cell granuloma, but multiloculated
Sites: oral mucosa, gingiva, tongue, hard palate and major salivary glands
Lower lip biopsy is relatively sensitive; 58% demonstrate noncaseating granulomas
Tongue ulceration with eosinophilia
Also called ulcerative eosinophilic granuloma, Riga-Fede disease, traumatic granuloma
Resembles carcinoma clinically
Presumed due to crush injury of tongue muscle
Micro: eosinophils and other inflammatory cells in submucosa, mucosa and salivary glands; dilated vessels often present
5% of cases present with oral cavity lesion
Gross: red-purple hyperplastic gingiva
Micro: epithelioid histiocytes, giant cells, eosinophils, pseudoepitheliomatous hyperplasia, rarely vasculitis
Dry mouth
Associated with Sjogren’s syndrome (dry eyes, inflammatory enlargement of salivary glands, xerostomia)
Gross: dry mucosa, atrophy of tongue papillae with fissures, ulcerations
DD: radiation therapy, anticholinergic drugs
Dermatologic conditions
Called Stevens-Johnson syndrome if it involves lips and oral mucosa
Maculopapular, vesiculobulbous eruption, due to infection, drugs, cancer, collagen vascular disorder
Subacute to chronic mucocutaneous disorder of unknown etiology
Involves skin, nails, mucosal surfaces (oral mucosa, pharynx, perineum)
Mucosal disease primarily affects women ages 40-60 years
Treatment: topical steroids or cyclosporine
Gross: reticulate, lacelike, white keratotic lesions; rarely bullous or ulcerated
Gross: buccal mucosa, various gross/micro images #1
Micro: keratosis, subepithelial T cell infiltrate
Associated with Addison’s disease, hemochromatosis, fibrous dysplasia of bone (Albright’s syndrome), Peutz-Jegher syndrome
Vesicles and bullae prone to rupture, leaving erosions covered with exudate
Autoimmune disease with antigen-antibody complexes at desmosomes
Treatment: steroids
Micro: intraepithelial blister with acantholysis and chronic inflammation
Micro images: various gross/micro images
Occurs in users of smokeless tobacco (snuff) or tobacco chewers
Severity related to length of exposure and tobacco brand
Reversible with cessation of use
Gross: filmy, gray-white opalescence at areas of contact with tobacco
Micro: parakeratosis or hyperorthokeratosis with parakeratin spires (“chevrons”), acanthosis, mild chronic inflammation, PAS+ marked hyalin deposition resembling amyloid
Micro images: hyperorthokeratosis, parakeratosis and acanthosis, diffuse hyalinization of lamina propria, PAS+ hyaline material, lower lip mucosa, buccal mucosa
DD: hyalinosis cutis et mucosae (deposition begins around vessels, eccrine glands and epithelial-stromal interface, then fills entire dermis of all oral mucosa, tongue, pharynx, larynx, vocal cords)
References: Archives 2004;128:e17
Benign tumors/conditions