PRINTER FRIENDLY VERSION
17 June 2004, copyright (c) 2004 PathologyOutlines.com, LLC
Table of contents
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
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
Midline in floor of mouth
Present at birth but asymptomatic until inflamed
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
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
Hairy polyp
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
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
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
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
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
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
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
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 surround giant cells, vessels and collagen, and are themselves surrounded by chronic inflammatory cells
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
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
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
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
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
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
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
Amyloidosis of tongue a common finding in older individuals, isolated or part of systemic disease
Rarely causes diffuse macroglossia or localized tumor
Angiolymphoid hyperplasia with eosinophilia
In head and neck, usually in dermis or subcutaneous tissue
Case report in 82 year old man with tongue lesion, Hum Path 1991;22:837
Very rare
Case report of tongue tumor, Archives 1990;114:541
Case report of 73 year old woman with tongue mass, chronic rheumatoid arthritis and polyclonal hypergammaglobulinemia, Archives 1998;122:920
Micro: histiocytes filled with eosinophilic crystals; lymphocytes and plasma cells also present
Positive stains: crystals are immunoreactive with kappa and lambda light chain and gamma heavy chain
Ectomesenchymal chondromyxoid tumor
Myxoid tumor of anterior dorsal tongue, first described at AJSP 1995;19:519
Median age 32 years, range 9-78 years
Slow growing, painless nodules
Occasionally recurs after excision
Micro: lobular proliferation of ovoid and fusiform cells with multilobulated nuclei and focal mild atypia in chondromyxoid stroma; may entrap nerve or muscle fibers
Positive stains: GFAP, cytokeratin; variable smooth muscle actin and S100
Negative stains: desmin
Also called freckle; solitary melanotic macules, usually of lower lip
More common in women; associated with Peutz-Jeghers syndrome
Micro: hyperpigmentation of basal layer with elongation of rete ridges
DD: melanosis (pigmented patches in hard palate or gingiva), melanoacanthoma (melanocytes mixed with keratinocytes)
Also called fibroepithelial polyp, peripheral ossifying fibroma, fibrous hyperplasia
Fibroid mass in free gingiva
Due to chronic gingival inflammation, pyogenic granuloma or other causes
May calcify or ossify
X linked dominant trait
Associated with multiple oral papillomas of lips and other oral mucosal sites
Also associated with skin hypoplasia and associated ulcers, fatty herniation, bilateral syndactyly with “lobster claw” deformity, iris and choroid colobomas, strabismus
Also called Heck’s disease
Discrete, recurrent papillary lesions on oral mucosa in Native American and Eskimo children and elsewhere
Associated with HPV 1, 13, 32
Gross: well circumscribed, sessile, pale elevation of buccal mucosa
Micro: balloon cells in malpighian layers, localized areas of mucosal epithelial hyperplasia with marked acanthosis and parakeratosis
Ages 40-60 years
Micro: features similar to solitary fibrous tumor, plus irregularly shaped pseudovascular spaces lined by large mono- or multinucleated wreath like giant cells, plus cells with plump, fusiform or round nuclei, irregular folds and pale pseudoinclusions
Positive stains: CD34, bcl2, CD99
Negative stains: CD68 (giant cells)
Also called fibrous hyperplasia
Associated with diphenylhydantoin (Dilantin) ingestion; also cyclosporine A, nifedipine, other drugs
May require surgical excision
Usually tongue, but any site can be involved
Resembles congenital epulis of newborn females but different S100 staining
Micro: large cells with abundant granular cytoplasm and bland nuclei, florid pseudoepitheliomatous hyperplasia
Positive stains: S100, PAS
Commonly in gingiva and tongue
Benign, don’t recur
Micro: well formed, dilated vascular channels in superficial dermis with dissecting pseudoangiomatous pattern in deeper dermis; endothelium exhibits hobnailing and stromal papillae, but no multilayering or tufting; no/mild atypia; no mitotic figures
Positive stains: CD34, factor VIII related antigen, Ulex europaeus; variable CD31
DD: retiform hemangioendothelioma, well differentiated angiosarcoma, patch stage Kaposi’s sarcoma
References: AJSP 1999;23:97
Affects buccal mucosa along bite line or gingivodental margin
Micro: nodular mass of fibrous tissue covered by squamous mucosa
Usually sun exposed portion of lip, rarely is intraoral
Gross: cup-shaped with central keratin plug
Micro: pseudoepitheliomatous hyperplasia, may have blunt edge in base
Diffuse opalescent lesion of cheek mucosa that may extend to lips
Probably degenerative
Micro: intracellular edema or vacuolization of malpighian cells
Also called acquired progressive lymphangioma
Very rare, particularly in mouth/lip
Slow growing, solitary patch lesion
Usually not associated with other vascular anomalies or HIV infection
Treatment: complete excision
May recur locally
Case reports: diffuse, congenital tumor of tongue that grew for 5 years (Archives 2000;124:1349), 37 year old man with 1.5 cm mass in oral mucosa distal to third molar (reported with cases at other sites, AJSP 2000;24:1047)
Micro: anastomosing, often widely dilated vascular structures in superficial mucosa; at deeper levels, vascular spaces collapse and dissect collagen in angiosarcoma-like pattern; lining epithelium is flat, single layered, with stromal papillary projections resembling papillary endothelial hyperplasia and occasional intravascular red blood cells; smooth muscle often focally present around vascular spaces; endothelial cells may hobnail, may form morula resembling giant cells; no/rare mitotic figures; no/mild atypia
Positive stains: CD31, CD34, factor VIII related antigen, smooth muscle actin
DD: well differentiated angiosarcoma (elderly patients, red-blue plaques or nodules, more endothelial atypia, multilayering and micropapillary tufting, often epithelioid or spindle cell component, inflammatory response common), Kaposi’s sarcoma-patch stage (usually widespread multiple lesions in HIV+ patients or extensive lesion of lower extremities in elderly patients of Jewish or Mediterranean origin; usually lymphoplasmacytic infiltrate, with inflammatory cells aggregating around vessels, commonly extravasated red blood cells, often other forms of Kaposi’s sarcoma present)
Prominent benign lymphoid proliferations
Associated with cystic glandular structures
Common
Case report of papillary hyperplasia of palatine tonsils in 9 year old girl with pharyngeal obstruction simulating malignancy, AJSP 1983;7:579
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
Rare in oral cavity
Usually no granulation tissue or inflammatory cells
Case report: 4 year old girl with cleft palate and palatal lesion, Hum Path 1990;21:856
Also called mucocele
Either stromal reaction to extravasated mucin or retention mucocele
May be associated with granulomatous inflammation in Crohn’s disease, Hum Path 1987;18:405
Stromal reaction to extravasated mucin: due to injured salivary gland, usually lower lip of young person with granulation tissue surrounding mucin filled spaces; cyst may be superficial, appear as blue-domed sublingual cyst (ranula) or plunging ranula (extending into neck above hyoid bone)
Retention mucocele: older patients, floor of mouth or inside cheek; mucus-filled cyst linked by flat, cuboidal or cylindrical cells
Usually lips; compound or intradermal
For all sites, 10% are malignant; may be less in head and neck
Case reports: 79 year old woman with 1 cm tongue tumor, Archives 2000;124:877
Micro: submucosal growth of nests (“zellballen”) of uniform polygonal cells (chief cells) with abundant eosinophilic granular cytoplasm and large, regular, central nuclei; surrounded by cytoplasmic processes of elongated sustentacular cells in fibrovascular stroma; no mitotic figures, no anaplasia, no necrosis, no invasion
Positive stains: chromogranin, neuron specific enolase, S100 for sustentacular cells
Negative stains: cytokeratin, thyroglobulin, amyloid, calcitonin
EM: chief cells with large numbers of mitochondria, 100-200 nm neurosecretory granules
Men and women ages 40-60 years
Sites: soft tissue of posterior gingiva and ascending ramus, may occur in buccal mucosa
Arise from dental lamina remnants in gingiva (rests of Serres) or from surface epithelium with potential to differentiate along odontogenic lines
Same histology as intraosseous tumors (palisading basaloid cells with stellate reticulum), but benign behavior
Benign
Case reports of masses in lip or buccal mucosa, Mod Path 1998;11:60
Micro: reactive plasma cells in lobules separated by thick collagenous bands; variable lymphocytes and histiocytes
Negative stains: EBV
Rare plasma cell proliferative disorder of upper aerodigestive tract, AJSP 1994;18:1048
Mean 54 years, range 40-67 years
Treatment: no effective treatment
Gross: cobblestone or warty appearing mucosa, often at multiple sites
Micro: dense subepithelial plasmacytosis with overlying psoriasiform epithelial hyperplasia; plasma cells are mature but diffusely infiltrative
Stains: polyclonal immunoglobulins
DD: plasmacytoma (morphologically similar but monoclonal immunoglobulins)
Post-traumatic spindle cell nodule
May be confused with leiomyosarcoma
Pseudoepitheliomatous hyperplasia
Associated with granular cell tumor, fungal infection, Spitz nevus, necrotizing sialometaplasia, papillary hyperplasia, keratoacanthoma, Wegener’s granulomatosis, verrucous carcinoma, signet ring adenocarcinoma
Micro: hyperkeratotic, irregular and infiltrative-like tongues of mature squamous epithelium; no atypia
Also called lobular capillary hemangioma, pregnancy tumor
Most common tumor of gingiva
Affects gingiva (usually maxilla) of children, young adults, pregnant women; associated with gingivitis
A form of capillary hemangioma that regresses after pregnancy or undergoes fibrous maturation to resemble a fibroma; may be reactive
Treatment: excision
Gross: elevated, dark red lesion, variable ulceration
Micro: pedunculated lesion composed of granulation type tissue separated by bands of connective tissue; covering epithelium almost meets at base of lesion; has lobular arrangement of capillaries at base; lobules consist of discrete clusters of endothelial cells with indistinct to prominent lumina; superficial lesion may have secondary changes including stromal edema, capillary dilation, inflammation and granulation tissue reaction
DD: angiosarcoma
References: AJSP 1980;4:470
Uncommon; usually adults
Floor of mouth and tongue
Adult type: well circumscribed, often multiple; may recur locally, Archives 1983;107:638
Juvenile type: nodules of elongated, uniform spindle cells with distinct cytoplasmic cross striations; no immature mesenchymal cells, no rhabdomyomatous cells, Archives 1993;117:43
Rare, <50 cases reported; mean age 56 years
Slow growing, asymptomatic, submucosal tumor
Benign; no recurrence or metastases reported (similar behavior to other sites)
No associated systemic manifestations reported with oral cavity tumors
Sites: usually buccal mucosa, also tongue, lower lip; more likely on left side of mouth
Gross: 1-4 cm, well circumscribed, round/oval, smooth surface
Micro: well circumscribed tumor composed of hypercellular and hypocellular collagenous zones with haphazardly arranged, bland spindle and ovoid cells between thin and thick collagen fibers; prominent hemangiopericytoma-like vascular pattern, perivascular hyalinization; variable myxoid stromal change, focal fascicular or storiform patterns of spindle cells, smooth muscle-like cells with blunt ended nuclei, epithelioid cells, mitotic activity (up to 2 per 10 HPF), stromal multinucleated giant cells, mast cells; occasional encapsulation, nuclear pseudoinclusions; no atypical mitotic figures, no necrosis
Positive stains: CD34, bcl2, vimentin, Factor XIIIa (focal), CD99 (75%)
Negative stains: S100, cytokeratin, CD68, desmin, muscle specific actin
DD: hemangiopericytoma (may be CD34-, controversial whether it is a distinct entity), benign fibrous histiocytoma (CD34-, bcl2-), neurofibroma or schwannoma (S100+, CD34-), myofibroma/fibroma (smooth muscle actin+, muscle specific actin+, CD34- in myofibroma), spindle cell lipoma (usually prominent fat, lack of prominent vasculature)
References: AJSP 2001;25:900
Also called spindle and epithelial cell nevus
Case reports of 2 adults and one child with tongue lesions exhibiting pseudoepitheliomatous hyperplasia, AJSP 2002;26:774
Gross: raised lesion
Micro: cellular proliferation centered in subepithelial connective tissue with junctional component; tumor cells are spindled and mixed with polygonal epithelial cells, some multinucleated; cytoplasm of both cells is eosinophilic with no/sparse melanin granules; moderate nuclear atypia; no/scant mitotic figures; prominent pseudoepitheliomatous hyperplasia with frequent mitotic figures in elongated strands of squamous cells
Positive stains: melanocytes - S100; pseudoepitheliomatous squamous cells - keratin
Negative stains: melanocytes - HMB45, MelanA/Mart1, smooth muscle actin, desmin, CD68
DD: melanoma, squamous cell carcinoma
Common intraoral benign epithelial neoplasm
Mean age 38 years
50% associated with human papillomavirus (HPV 6 and 11); others may represent reactive epithelial hyperplasia
Sites: posterior hard palate, soft palate and uvula (34%), dorsum and lateral tongue borders (24%), gingiva (12%), lower lip (12%), buccal mucosa (6%)
Treatment: excision; 4% recur
Gross: white-pink cauliflower-like surface projections, 75% are less than 1 cm
Micro: delicate fibrovascular cores surrounded by benign squamous epithelium; hyperkeratosis in 82%, parakeratosis in 72%; variable hyperplasia of basilar, parabasilar, prickle cell or granular-cell layers, individual cell keratinization, abnormal mitotic figures; often no koilocytotic changes; no downward pushing growth into lamina propria
Dysplasia: significant cytologic atypia and maturation abnormalities
DD (solitary lesions): condyloma acuminatum, verrucae vulgaris, verrucous carcinoma
DD (multiple lesions): inflammatory papillary hyperplasia, juvenile papillomatosis, focal epithelial hyperplasia (Heck’s disease), focal dermal hypoplasia (Goltz-Gorlin syndrome), papillary-appearing lymphoid hyperplasia of tonsils
References: Hum Path 1988;19:1387
Associated with HPV
Micro: cup shaped margins, prominent hyperkeratinized spires
Rare lesion of oral mucosa
Raised granular or verrucous lesion, usually of gingiva or alveolar ridge
Probably reactive
Case report of multifocal lesion in upper aerodigestive tract of child with a systemic lipid disorder, AJSP 1989;13:309
Micro: foamy macrophages in lamina propria covered by acanthotic or verrucous epithelium
Positive stains: CD68
Premalignant or in-situ conditions
Similar age, sex distribution and sites as invasive oral carcinoma
Often adjacent to areas of invasive carcinoma
Single cell keratinization and severe keratinizing dysplasia suggest high likelihood of progression to or concurrent invasive carcinoma
Gross: often erythroplakia (red-velvety)
Micro: usually has marked nuclear abnormalities, abnormal maturation, disordered maturation with loss of orientation and dyskeratosis in lower epithelium; usually NOT full thickness abnormalities as in carcinoma in situ of cervix or other sites
DD: radiation atypia
Reference: AJSP 1989;13 Suppl 1:5
Dysplasia: abnormal epithelial growth with cytologic, architectural and maturational abnormalities
Mild dysplasia: may be reversible reactive changes and not be neoplastic
Lichenoid dysplasia: hyperkeratotic epithelium has prominent granular layer, irregular rete ridges, dense subepithelial band of lymphocytes resembling lichen planus; also disorderly keratinocytes with pleomorphism and hyperchromasia
Micro: loss of polarity of basal cells, two or more basaloid layers of cells, increased nuclear/cytoplasmic ratio, elongated rete processes, irregular stratification, increased mitotic figures or mitotic figures in superficial half of epithelium, cellular or nuclear pleomorphism, prominent nucleoli, single cell keratinization; may have verrucoid growth pattern
White patch or plaque, 5 mm or more, on oral mucous membranes that cannot be removed by scraping, not due to another disease entity such as lichen planus or candidiasis, and not reversed by removal of irritants
A non-specific clinical term; lesion must be considered precancerous until proven otherwise
Ages 40-70 years, 65% male, associated with tobacco use, alcohol, ill-fitting dentures, chronic exposure of persistent irritants, HPV-16 in tobacco lesions
Most common location is buccal gingival gutter; lesions in floor of mouth are often dysplastic
Erythroplakia (dysplastic leukoplakia): red, velvety, eroded area, level or depressed; usually associated with highly atypical epithelial changes with thin and atrophic epithelium and prominent vasculature
Speckled leukoplakia: leukoplakia and erythroplakia; often has Candida infection also
Overall 4% risk for carcinoma; highest if speckled or warty or occurs in floor of mouth or ventral surface of tongue
Biopsy if no response to tobacco or alcohol cessation
Gross: occurs anywhere in oral mucosa; solitary or multiple, variable appearance
Micro: varies histologically from acanthosis, hyperkeratosis, dysplasia or carcinoma in situ; carcinoma in situ is associated with lymphocytes and macrophages; erythroplakia is usually at least low grade dysplasia to superficial invasion, with intensive inflammation and vascular dilation that causes the red appearance
Slow growing, persistent, often multifocal
May represent precursor lesion to verrucous carcinoma, dysplasia or other carcinomas
29% of cases are associated with verrucous carcinoma
Micro: mature, hyperkeratotic proliferation, entirely exophytic with no downward proliferation of rete pegs
Squamous cell carcinoma
Squamous cell carcinoma of oral cavity-general
95% of oral cavity cancers are squamous cell carcinoma
Usually ages 50-70 years, 90% men
Represent 4% of malignant tumors in men and 2% in women; 30,000 new cases annually in US with 8,000 subsequent deaths
Recent trends show reduction overall in oral cancer deaths but increase in black men, black women and women overall
Causes: alcohol, tobacco (RR: tobacco 2-4x, alcohol 2-6x, tobacco and alcohol 15x), chewing tobacco, marijuana, betel nuts and pan (India); also syphilis, oral sepsis, iron deficiency, oral candidiasis, Fanconi’s anemia
HPV 6, 16 or 18 detected in 50% of Waldeyer’s tonsillar ring carcinomas versus 10% of other oral carcinomas
EBV detected in most tumor cells in all oral cancers, Hum Path 2002;33:608
Fruit and vegetable consumption significantly reduces risk
Sites: floor of mouth, tongue, hard palate, base of tongue (areas constantly bathed in saliva and with thin nonkeratinized squamous epithelium)
Hard palate and alveolar ridge: low metastatic risk, to buccinator, submandibular, jugular and occasionally retropharyngeal nodes
Other sites: submandibular and jugular nodes, rarely to posterior triangle / supraclavicular nodes; metastases may have melanocyte colonization (Hum Path 1983;14:373)
Bilateral cervical metastases more likely if primary is closer to midline
Site of nodal involvement is usually predictable (unless surgery or radiation was given), spreading to upper, then middle, then lower cervical nodes, although anterior oral cavity may spread directly to middle cervical nodes
Spreads locally, metastases to lung; also liver, bone, mediastinum
5 year disease free survival: in patients 40 years or less, survival rate is 76%
50% are fatal
Multiple primaries: present in 27% (probably due to field effect of local acting carcinogens); to be considered multiple must be intervening nonneoplastic mucosa or there must be proof that the second tumor has an in situ mucosal origin
Poor prognostic factors: low Karnofsky scale, either noncohesive, irregular, jagged small cords or infiltrative pattern of invasion or widespread single cells
Karnofsky scale: criteria of performance status
100 - normal, no complaints, no evidence of disease
90 - able to carry on normal activity, minor signs or symptoms of disease
80 - able to carry on normal activity with effort, some signs or symptoms of disease
70 - cares for self; unable to carry on normal activity or do active work
60 - requires occasional assistance but is able to care for most of own needs
50 - requires considerable assistance and frequent medical care
40 - disabled; requires special care and assistance
0 - patient dead
Treatment: surgery, radiation therapy
Gross: leukoplakia, then masses with necrosis, ulcers and rolled borders; induration is relatively specific for invasion
Micro: may have verrucoid growth pattern, but moderate/marked atypia at base, irregular and infiltrative stromal invasion
Positive stains: CK 8, CK19, usually CK 5/6, often p53 (Hum Path 1995;26:531)
Negative stains: CK20
Squamous cell carcinoma-buccal mucosa
2-10% of intraoral carcinomas
Associated with chewing tobacco or oral snuff dipping; men or women
Often verrucous subtypes
May involve adjacent muscles, skin or bone
May have late metastases to submandibular nodes
5 year survival: 40%-anterior buccal mucosa, 17% middle buccal mucosa, 10% posterior buccal mucosa
Prognostic factors: site (above), depth of invasion (best if < 3mm), tumor thickness (best if < 6 mm)
Squamous cell carcinoma-floor of mouth
12-17% of intraoral carcinomas
Most common site of intraoral carcinoma in blacks
Usually anterior caruncles of submaxillary gland and lingual frenulum
75% present with invasion of contiguous structures (sublingual gland, midline muscles, gingiva, mandible)
Metastases common to submandibular triangle and subdigastric nodes, rarely submental nodes
Note: clinical exam shows 56% false positives and 24% false negatives due to obstructive enlargement and nodal hyperplasia
5 year disease free survival: 20%
Poor prognostic factors: tumor thickness (metastatic rate: > 3.6 mm - 60%, 1.6-3.5 mm - 33%, < 1.5 mm - 2%)
Gross: raised leukoplakia or erythroplakia lesion
Squamous cell carcinoma - gingiva
6-12% of intraoral carcinomas
Occurs in mandibular bicuspid and molar areas at free gingival margin or at alveolar ridge in edentulous patients
Associated with loose teeth and invasion of alveolar bone
Spreads to periosteum, adjacent buccal mucosa, floor of mouth
Metastases to submandibular lymph nodes, often less well differentiated
Micro: usually well differentiated, often invades bone
DD: pyogenic granuloma, periodontitis, papilloma, epulis, melanoma
Most common oral cancer (42-45% of cases)
90% occur on lower lip, usually along vermillion border
Risk factors: chronic sunlight, pipe smoking, cigarette smoking, poor oral hygiene, fair complexion, organ transplant recipients
Low risk of metastatic extranodal spread; early to adjacent skin, orbicular muscle; late to buccal mucosa, mandible, mental nerve
Lower lip: metastases initially to ipsilateral submental and submandibular nodes, then jugular lymph nodes
Upper lip: metastases to preauricular and infraparotid lymph nodes
Midline lesions may metastasize to contralateral lymph nodes
5 year disease free survival: 90%
Poor prognostic factors: large size (metastatic rate: >4 cm - 73%, 2-4 cm - 50%, < 2 cm - 5%), nodal metastases
features in deep tumor - high tumor grade, tumor thickness > 6 mm, aggressive invasion pattern, perineural invasion
Squamous cell carcinoma-oropharynx
Palatine arch carcinomas are less aggressive than oropharynx proper tumors
Palatine arch (superior oropharynx): soft palate, uvula, anterior tonsillar pillars, retromolar trigone
Oropharynx proper: anterior - posterior 1/3 of tongue, vallecula, lingual epiglottis; lateral - palatine tonsils or tonsillar fossa, posterior tonsillar pillars, glossotonsillar sulcus; posterior - posterior and lateral oropharyngeal walls from soft palate to hyoid bone, including pharyngoepiglottic fold
Metastases to jugulodigastric, retropharyngeal and parapharyngeal nodes, often bilateral and contralateral
Micro: usually moderate to poorly differentiated
Squamous cell carcinoma-palate
5-6% of intraoral squamous cell carcinoma
Most common malignancy of palate
Usually soft palate, 60% male
Usually involves adjacent tissues at diagnosis (hard palate tumors involve underlying bone)
1/3 have metastases to internal jugular, submandibular and retropharyngeal nodes at diagnosis; rarely bilateral
Pathology report should describe involvement of underlying bone
Squamous cell carcinoma-tongue
16-22% of intraoral squamous cell carcinomas
Usually lateral aspect of middle third of tongue
More likely to metastasize than other intraoral carcinomas (70% have metastases at presentation)
Spread eventually to floor of mouth and root of tongue
5 year survival: 60% for anterior tongue vs. 40% for posterior tongue
Base of tongue tumors: 90% present at stage III/IV, often clinically silent, endophytic growth, poorly differentiated, bilateral metastases
Metastases: ipsilateral subdigastric, submandibular, midjugular nodes; may spread directly to lower jugular nodes
Poor prognostic factors: involvement of posterior third of tongue
Gross: erythroplakia or leukoplakia
Squamous cell carcinoma-tonsil
Common site of intraoral squamous cell carcinoma in US
High rate of nodal metastases, usually to ipsilateral digastric, middle and lower jugular, posterior cervical triangle lymph nodes
Nodal metastases may be cystic and have bland histology
Tumors in patients under 40 years old are associated with HPV 16 DNA by PCR, with higher Ki-67 and lower p53 staining score, AJSP 2003;27:1463
Poor prognostic factors: age < 40 years, large size, nodal metastases
Micro: often undifferentiated and solid; HPV positive tumors tend to have nonkeratinizing basal cell morphology
DD: branchial cyst, branchiogenic carcinoma, nasopharyngeal carcinoma
Squamous cell carcinoma - Waldeyer’s ring
Usually nonkeratinizing squamous cell carcinomas
Cervical lymph node metastases are often cystic and filled with necrotic tumor cells or clear fluid
Some of these tumors may arise from basaloid squamous cell carcinomas of large excretory ducts of submucosal minor salivary glands, Hum Path 2000;31:1096
Subtypes (all sites)
Basaloid squamous cell carcinoma
Uncommon, < 200 cases reported
Median 62 years old (range 27-88 years), 88% male, 92% smokers, 88% drinkers
Sites: base of tongue, tonsil, hypopharynx; also other sites outside upper aerodigestive tract
Aggressive with 68% having regional metastases at presentation, 77% stage III/IV, median survival 18 months
Metastases to lung
Treatment: radical surgery, radiation therapy or chemotherapy
Case reports: anterior floor of mouth tumor (