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Oral cavity
Reviewers: Patricia DeVilliers, D.D.S., M.S., Nella Cristina Fernandez, M.D., Charu Thakral, M.D. (see Reviewers page)
Revised: 19 June 2013, UPDATE IN PROGRESS
Copyright: (c) 2004-2013, PathologyOutlines.com, Inc.
See also Salivary glands
Table of contents
General: primary references anatomy 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 osseous choristoma 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: staging-lip & oral cavity staging-oropharynx staging-mucosal melanoma grossing features to report
top
American Journal of Clinical Pathology
American Journal of Surgical Pathology
Archives of Pathology and Laboratory Medicine
Human Pathology
Modern Pathology
Please refer to these primary references for more detailed discussions and photographs
Benign tumors/conditions
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
Micro images: hemangioma of gingiva
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
Clinical images: buccal mucosa
Micro: nodular mass of fibrous tissue covered by squamous mucosa
Micro images: various images (click on thumbnails)
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)
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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
Definition: choristoma is a proliferation of tissues foreign to the site at which it is located Choristomas of mature bone (osseous choristomas) are rare in soft tissue of oral cavity
Epidemiology: all ages from 2 months (J Pediatr Surg 1987;22:365), usually women (Med Oral Patol Oral Cir Bucal 2008;13:e627, Ear Nose Threat J 1998;77:316)
Clinical: present as hard tumor-like masses, 85% in tongue, usually posterior third (Indian J Pathol Microbiol 2009;52:86, Kaohsiung J Med Sci 1998;14:727, Gerodontology 2009;26:78); less commonly in oral mucosa (Med Oral 2003;8:220), soft palate (Eur Arch Otorhinolaryngol 1990;247:264), submandibular region (J Craniomaxillofac Surg 2006;34:57)
Case reports: 17 year old woman (Case of Week #142)
Treatment: surgical excision is curative; local recurrence is rare (Oral Surg Oral Med Oral Pathol 1991;72:337)
Micro: irregular mature bone trabeculae and fibrous connective tissue; no osteoblastic activity; no atypia
Differential diagnosis:
● heterotopic ossification (myositis ossificans) - typically occurs within muscle, and has more osteoblastic activity
● ossifying fibroma - does affect the craniofacial skeleton, but has a proliferation of round, polyhedral or spindly cells, not seen in this case
● dystrophic calcification - often found in old thrombi, hemartomas or keratin-filled cysts, but it does not resemble bone.
For all sites, 10% are malignant; may be less in head and neck
Xray images: CT scan shows mass at base of tongue
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
Micro images: nests of chief cells
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
EM images: 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
Reactive (AJSP 1998;22:479),
Probably not HPV related (APMIS 2005;113:629, Archives 2005;129:e62, but see Am J Dermatopathol 2000;22:447)
Case reports: Case of the Week #82; multifocal lesion in upper aerodigestive tract of child with a systemic lipid disorder (AJSP 1989;13:309)
Treatment: excision; does not recur (J Formos Med Assoc 2007;106:141)
Gross: raised granular or verrucous
Micro: foamy macrophages within dermal papillae covered by acanthotic or verrucous epithelium without atypia
Micro images: palate lesions - image #1; #2; #3; #4
Positive stains: CD68, vimentin, Factor XIII
Negative stains: S100, keratin (or weak)
DD: squamous cell carcinoma, verrucous carcinoma (ulcerating or fungating lobules of mature squamous epithelium with minimal atypia, no prominent foamy macrophages), condyloma accuminatum (prominent koilocytosis in upper epidermis, no prominent foamy macrophages)
References: Oral Oncol 2003;39:325
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
Micro images: EGFR expression #1; #2
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 (Archives 1994;118:1229)
Micro: lobules, nests or cribriform patterns of small basaloid cells with peripheral palisading and a thick basement membrane; cells have minimal cytoplasm, are moderately pleomorphic with hyperchromatic nuclei, often abrupt transition to squamous epithelium; single cell necrosis and comedonecrosis are common; often contiguous with carcinoma in situ in surface epithelium; frequent mitotic activity, stroma often hyalinized or myxoid; variable pseudoglandular spaces resembling adenoid cystic carcinoma; rarely has spindle cell component (Archives 1995;119:181)
Positive stains: 34betaE12 (100%), EMA (83%), AE1/AE3 or CAM 5.2 (80%), neuron specific enolase (75%, weak), CEA (53%), S100 (39%)
Negative stains: chromogranin, synaptophysin, muscle specific actin, GFAP
DD: small cell carcinoma, adenoid cystic carcinoma, adenosquamous carcinoma, peripheral ameloblastoma
References: AJSP 1992;16:939, Hum Path 1998;29:609 (stains), Hum Path 1986;17:1158
Papillary squamous cell carcinoma
Rare; precursor lesion unknown
Micro: malignant exophytic squamous proliferation with fibrovascular growth pattern of papilloma, but marked cytologic atypia, irregular cords of invasion into stroma at base; cells may resemble dysplastic basal and parabasal-type cells or dysplastic squamous epithelium; variable keratosis
DD: squamous carcinoma in situ, squamous papilloma with dysplasia, verrucous carcinoma
Pseudoglandular squamous cell carcinoma
Also called adenoid carcinoma (not adenoid cystic)
Usually in lip, associated with actinic radiation
Morphology may be due to acantholysis
Also called sarcomatoid carcinoma or carcinosarcoma
Rare
Mean age 50+ years, men with history of tobacco use, alcohol abuse, poor oral hygiene, prior radiation therapy
Sites: vermillion border of lower lip, tongue, alveolar ridge, gingiva
Metastases: have variable histology
Highly aggressive, 61% mortality, mean survival 1-2 years
Poor prognostic factors: local recurrence, cervical nodal metastases
Treatment: surgery, often with radiation therapy
Case reports: 51 year old with polypoid tongue tumor, Archives 2001;125:433
Gross: 2/3 appear as polypoid mass on mucosal surface, 1/3 are sessile or ulcerated
Gross images: exophytic and polypoid tumor
Micro: biphasic squamous cell carcinoma and malignant spindle cell stroma; larger tumor cells may have hyaline globules; malignant features may occur only at base of polypoid mass; may be superficially invasive with no apparent connection to atypical spindle cells or a classic squamous cell carcinoma present deep within sarcomatoid component; has variable squamous and spindle cell differentiation with bone or cartilage; often resembles malignant fibrous histiocytoma
Micro images: squamous cell carcinoma within sarcomatous stroma
Positive stains: keratin (50%), variable actin and desmin
DD: sarcoma, reactive angiofibroblastic proliferations, radiation effect
Also called Ackerman’s tumor
Locally invasive, may recur (as nonverrucal types) but nonmetastasizing
5% of intraoral carcinomas
Men, ages 60+ years; associated with chewing tobacco, snuff dipping or heavy smoking
Not associated with alcohol abuse; HPV found in 28% but unclear if relevant
20% coexist with typical squamous cell carcinoma - these cases have risk of metastasis
Enlarged lymph nodes are reactive, due to trauma or infection
Sites: buccal mucosa, gingiva, tongue, palate, tonsillar pillar
Treatment: surgical excision, radiation therapy if poor surgical candidate (although 30% of radiated tumors become poorly differentiated and aggressive)
Gross: exophytic, warty or plaque-like; granular, red-white, hyperkeratotic; 1-10 cm; may invade adjacent soft tissue and bone
Micro: well differentiated hyperplastic squamous epithelium with orderly maturation (upwards and downwards), hyperplastic surface papillae with keratin also in invaginations; broad, blunt, downward-pushing rete pegs; minimal atypia; mitotic activity is present; lymphoplasmacytic infiltrate in lamina propria; per Ackerman “if it looks like carcinoma cytologically, is not verrucous carcinoma”
Contributed by Dr. Asmaa Gaber: #1; #2
DD: squamous papilloma, keratoacanthoma, hyperkeratosis, pseudoepitheliomatous hyperplasia, dysplasia, papillary squamous cell carcinoma
Other carcinomas (non salivary gland)
Rare, aggressive
Derived from minor (but not major) salivary glands and ducts
>90% men, mean 58 years old (range 32-99 years)
Sites: tongue, floor of mouth, nasal cavity, larynx
Metastases: 70-80% incidence even with primaries < 1 cm; variable histology
Treatment: surgical resection with neck dissection
5 year survival: 25%
Gross: 2 mm to 1 cm erythroplakic ulcer or indurated submucosal nodule
Micro: adenocarcinoma, squamous cell carcinoma and mixtures resembling mucoepidermoid carcinoma; may have multifocal carcinoma in situ involving salivary gland ducts, upward extension of intraductal carcinoma to involve mucosal epithelium; composed of glassy squamous cells; commonly perineural invasion and widespread invasion of submucosa
Positive stains: mucicarmine, PAS with diastase, Alcian blue (pH 2.5 and 1.0)
DD: mucoepidermoid carcinoma, squamous cell carcinoma, pseudoglandular squamous cell carcinoma
Develops on sun exposed skin, usually upper face and forehead, but also lip
Low potential for metastases (0.1%), but can kill by direct invasion if untreated
Frequently appears to disappear
High risk: fair skin, sun exposure, older adults, males
Treatment: excision
Gross: elevated area with ulceration, crusting
Micro: nests of cells with clefting from overlying surface epithelium; cells have pallisading nuclei, minimal pleomorphism
Aggressive; pure or with squamous cell carcinoma
Micro: small to medium sized ovoid cells with minimal cytoplasm and hyperchromatic nuclei; rarely squamous or ductal differentiation; does not arise from surface epithelium but may involve it secondarily
Positive stains: neuroendocrine markers
EM: variable dense core secretory granules
References: Mod Path 1990;3:631
Minor salivary gland tumors/lesions
Slowly progressive tumors - good prognosis for 10-15 years, but 80% die after 20 years
Micro: cribriform and pseudoglandular patterns of basaloid cells with hyalinized stroma, frequent perineural invasion, minimal nuclear pleomorphism, no squamous differentiation, no high grade dysplasia or squamous carcinoma in situ, no extensive necrosis
Positive stains: muscle specific actin
Nodular hyperplasia of minor salivary glands
Usually hard palate, also retromolar
Also called canalicular adenoma
Almost exclusively in minor salivary glands of upper lip
Micro: elongated and branching canaliculi separated by hyaline stroma
Gross/micro images: upper lip lesion
DD: adenoid cystic carcinoma
Gingival nodule of disorganized seromucinous salivary gland tissue mixed with sebaceous glands
Clear cell carcinoma-hyalinizing type
Usually adult women with painless mass in minor salivary glands
Low grade malignancies with occasional nodal metastases but no recurrence or death due to disease at short follow up, AJSP 1994;18:74
Micro: trabeculae, cords, islands or nests of monomorphic clear cells surrounded by hyalinized bands with foci of myxohyaline stroma; also cells with eosinophilic and granular cytoplasm; infiltrative borders; no/minimal atypia, no/rare mitotic figures
Positive stains: PAS+ diastase sensitive (glycogen), cytokeratin, EMA
Negative stains: mucin, S100, smooth muscle actin
EM: abundant glycogen, desmosomes, peripheral tonofilaments, prominent interdigitating microvilli without actin myofilaments or dense bodies
References: AJSP 1994;18:74
Mean 59 years, range 20-86 years
Often in major salivary glands, but also in lips, buccal mucosa, palate, tongue, retromolar area, floor of mouth
Usually indolent, but occasionally recurs locally or metastasizes
Gross: cystic masses, 0.4 to 6 cm
Micro: invasive, cystic growth pattern, 75% had conspicuous papillary component; composed of small cuboidal cells, large cuboidal cells, tall columnar cells or mixture; cyst rupture with hemorrhage and granulation tissue is common
References: AJSP 1996;20:1440
Rare (< 20 cases reported), in situ form of salivary duct carcinoma; a controversial entity
Mean 62 years, range 32-91 years
Usually affects major salivary glands
Excellent prognosis, no metastasis or mortality reported; may recur with incomplete excision
May represent preinvasive phase of some salivary duct carcinomas
Recommended to sample extensively and stain for myoepithelial cells (p63 and actin) to rule out invasion
Case report of 44 year old woman with mass in buccal mucosa arising from minor salivary glands, AJSP 2004;28:266
Micro: intraductal neoplasm in micropapillary, cribriform, solid, comedo or clinging patterns, with preservation of myoepithelial cells surrounding intraductal tumor, resembles breast DCIS; mild to severe atypia, variable mitotic figures, no invasion
Positive stains: epithelial cells - EMA, S100 (50%), myoepithelial cells - p63 (nuclear stain), muscle specific actin
Negative stains: ER, PR, p53
Resembles inverted papilloma of nasal cavity
Benign
Gross: small submucosal mass
Micro: complex invaginations of well differentiated squamous epithelium with microcysts, mucous cells and columnar cell lining
May arise from excretory ducts
Aggressive, 30-80% recur, 5 year survival of 20%
Usually not fatal if 2.5 cm or less
Micro: similar to adenosquamous carcinoma, but no anaplastic nuclear features, no squamous cell carcinoma in situ
Hard palate tumor
Benign behavior
Micro: solid pattern of hyaline or plasmacytoid cells with mild nuclear pleomorphism
DD: plasmacytoma, skeletal muscle tumors
Very rare
Case report of rapidly spreading erythroplakia of oral mucosa with widespread carcinoma in situ of minor salivary gland ducts and a small, invasive, poorly differentiated salivary gland carcinoma, AJSP 1988;12:890
Also called benign mixed tumor
50% of salivary gland tumors of palate
Polymorphous low grade adenocarcinoma
Usually palate; second most common tumor at this location after adenoid cystic carcinoma
Median age 54 years, range 22-71 years, 2/3 women
30% recur, nodal metastases in 15%, 10% have distant metastases or tumor related death, AJSP 2000;24:1319
Micro: nonencapsulated; uniform plump columnar cells with bland nuclei with diverse growth patterns (tubular, cribriform, papillary, solid, fascicular, microcystic, single file, pseudoadenoid cystic [without true lumens], strand-like, mixed); perineural invasion common around small nerves; infiltrative borders; up to 12 mitotic figures per 10 HPF; rare tumor necrosis
Positive stains: S100, EMA, keratin, muscle specific actin and CEA (may be focal)
DD: pleomorphic adenoma, basal cell adenoma, adenoid cystic carcinoma
References: AJSP 1988;12:461 (stains), AJSP 1984;8:367
Rare benign tumor of salivary gland origin
Usually hard palate or parotid gland of men over 40 years
Gross: well circumscribed, round/oval, papillary tumor of mucosal surface
Micro: biphasic, with well differentiated papillary hyperplastic squamous epithelium covering ductal component of cleftlike cystic spaces lined by cuboidal or columnar epithelium with occasional goblet cells; variable oncocytes and squamous metaplasia; resembles Warthin’s tumor of parotid gland, papillary syringocystadenoma
Micro images: papillary squamous surface epithelium, underlying ductal structures and stains
Positive stains: squamous epithelium - CK7, AE1-AE3, CEA, EMA; ductal structures - CK7, AE1-AE3, CAM 5.2, CEA, EMA, S100
Negative stains: CK20, GFAP, desmin, muscle specific actin
EM: oncocytic cell is predominant cell; contains numerous mitochondria, parallel filaments within cell cytoplasm attached by desmosomes, Archives 1986;110:523
References: Archives 2001;125:1595
Signet ring cell adenocarcinoma
Rare subtype of adenocarcinoma (2% of primary minor salivary gland malignancies)
Appear to be slow growing with favorable outcome, although data is limited
Micro: non-circumscribed tumor composed of bland, mucin containing signet ring cells that invade in narrow parallel strands, with scattered small nests or individually infiltrating cells; no solid, cribriform or papillary components; often perineural invasion; minimal ductal differentiation, no angiolymphatic invasion
Positive stains: CAM 5.2, smooth muscle actin, GFAP, p63
Negative stains: calponin
References: AJSP 2004;28:89
DD: mucoepidermoid carcinoma, polymorphous low grade adenocarcinoma, colloid (mucinous) carcinoma
Other malignancies
Very rare
Tongue and lip most common sites
Mean age 55 years
Gingival tumors are usually metastases and lead to death within 3 years
May have good outcome
Tumor grade is not a good prognostic factor
Gross images: tongue tumor
Micro: vasoformative tumors, usually solid and occasionally papillary or epithelioid; low grade to high grade
Micro images: tongue tumor with solid growth (A), vasoformative and epithelioid areas #1, #2, secondary tumor to gingiva, Factor VIII, CD31, CD34
Positive stains: Factor VIII related antigen, CD31, CD34 (less reliable)
References: Mod Path 2003;16:263
Follicular dendritic cell tumor
Rare tumor of oral cavity (<30 cases reported) of antigen presenting cells of B cell follicles of lymphoid organs
Often misdiagnosed
40% recur, 25% metastasize, most commonly to lung, liver, peritoneum, lymph nodes; mortality of 17%
Sites: tonsil, palate
Case reports: soft palate and tonsil (AJSP 1994;18:148), tonsil (AJSP 1996;20:944, Mod Path 2002;15:50)
Micro: sheets, whorls and storiform arrays of spindled and syncytial-appearing cells with eosinophilic cytoplasm, oval nuclei, fine chromatin, small nucleoli, occasional nuclear pseudoinclusions; also multinucleated forms; may have irregular pseudovascular spaces; cohesive growth; sharp interface with fibrous stroma; marked atypia, high mitotic rate with atypical mitotic figures; background lymphocytic infiltrate with focal prominent perivascular cuffing; variable necrosis
Micro images: well circumscribed tonsillar tumor, focal storiform growth pattern, syncytial growth pattern and multinucleated giant cells, multinucleated giant cells, perivascular cuffing with lymphocytes, nuclear pleomorphism, CD21 and CD35
Positive stains: CD21, CD35, muscle specific actin, fascin; S100 (56%)
Negative stains: CD45/LCA, cytokeratin, EBV LMP
EM: long, complex, occasionally interdigitating cell processes joined by desmosomes
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Case report of tumor with various histologic patterns, reported with similar tumors at other sites, in 70 year old man with tongue lesion that recurred and metastasized to submandibular lymph node and thigh, AJSP 2000;24:352
Associated with HIV
Oral lesion may be first sign of disease
Usually palate
Case reports: older man, HIV-, non-African, with recurrence three times (Archives 1992;116:543), 90 year old HIV- woman with tongue mass containing HHV8 (Archives 2003;127:e279)
Gross: small, well delineated macular lesions or larger infiltrative nodules
Micro: diffuse infiltration by irregularly dilated, jagged vascular channels dissecting collagen, growing around preexisting normal vessels; newly formed vascular channels may be dilated; endothelium is flat, nonmultilayered, no marked atypia, no prominent mitotic activity; frequent lymphoplasmacytic infiltrate with inflammatory cells aggregating around vessels
Micro images: tongue mass, H&E, CD31, HHV8 DNA in tumor
Positive stains: CD31, factor VIII related antigen, vimentin; variable smooth muscle actin
Negative stains: cytokeratin
DD: bacillary angiomatosis
Rare
Median age 51 years
Most commonly in buccal mucosa, tongue, soft tissue overlying mandible
Most common subtype is well differentiated liposarcoma
May recur locally, but no deaths due to disease in one study, Mod Path 2002;15:1020
Tumors 5 cm or larger are more likely to recur
Treatment: complete local excision, careful follow up
Gross: mean 4 cm (range 1-6 cm)
Micro: usually well differentiated, myxoid or dedifferentiated; lipoblasts more common than at other sites
Dedifferentiated liposarcoma
Both patients in one study had prolonged survival, Mod Path 2002;15:1020
Micro images: tumor of buccal mucosa
Myxoid liposarcoma
Case report of floor of mouth tumor with rhabdomyoblastic differentiation, Archives 1998;122:740
Micro images: tumor of buccal mucosa, tongue
Well differentiated liposarcoma
<20 cases reported
Case report of 76 year old white man with long standing, well differentiated liposarcoma of base of tongue and tonsillar fossa, Archives 1996;120:292
High recurrence rate, but long survival and minimal tendency for metastases
Gross: multinodular mass, 2.5 cm
Micro: ill-defined tumor with infiltrating borders, composed of mature adipose tissue with occasional lipoblasts; focal spindle cells and pleomorphic lipoblasts; no mitotic figures
Micro images: tumors of tongue, buccal mucosa
Positive stains: S100
Negative stains: muscle specific markers
Most commonly in Waldeyer’s ring in palatine and lingual tonsil
Usually diffuse large B cell lymphoma (68%), MALT (15%), peripheral T cell lymphoma (8%, higher % in Japan), follicular lymphoma (6%), mantle cell (3%)
2/3 are female
Usually EBV negative (Am J Surg Pathol 1994;18:938)
AIDS patients often have plasmablastic lymphomas or diffuse large B cell lymphoma with poor prognosis
Gross: soft, bulky mass covered by normal or ulcerated mucosa
References: Hum Path 2002;33:153
AIDS associated plasmablastic lymphoma
Associated with AIDS, transplants, chemotherapy
Predisposition for gingival mucosa and palatal mucosa with extension to adjacent bone and abdomen, retroperitoneum, soft tissue and marrow
Poor prognosis - mean survival is 6 months
Micro: monomorphic population of immunoblasts with no/minimal plasmacytic differentiation; starry sky appearance at low power due to tingible body macrophages; tumor cells are large with abundant, basophilic cytoplasm and occasional paranuclear hofs; eccentric, round/oval nuclei with one or more prominent nucleoli; mitotic figures and apoptosis are present; tumor cells infiltrate in large cohesive masses with a relatively well delineated advancing edge; no mature plasma cells
Positive stains: EBV, CD38, CD138, MUM1 (100%), intracytoplasmic IgG (50%), variable light chain restriction
Negative stains: HIV1 (but adjacent benign T cells were HIV1+), HHV8, CD20, CD45, CD79a (may be weak, focal)
DD: undifferentiated carcinoma, sarcoma, plasmacytoma
References: Hum Path 2002;33:392, AJSP 2004;28:736
Diffuse large B cell lymphoma-tonsil
Includes patients with focal follicular features that may represent follicular colonization of high grade tumor (Hum Pathol 2002;33:732)
In Japan/Korea, 50% are germinal center origin (bcl6+ in uniform pattern and CD10+) vs. MALT origin (Hum Pathol 2003;34:610)
Micro: involvement of pericryptal follicles in tonsils with adjacent dominant diffuse areas; tumor cells are large, monomorphic, evenly spaced with clear cytoplasm, blastoid nuclei; residual germinal centers are present
Positive stains: usually sporadic bcl6 (<50% of tumor cells)
Negative stains: CD10 (usually)
DD: follicular lymphoma with diffuse areas (strong bcl6+, CD10+)
Hodgkin’s lymphoma
Very rare in oral cavity
Case report in Waldeyer’s ring, Archives 1996;120:285
Indolent T cell lymphoblastic proliferation
Case report of 35 year old man with indolent T cell lymphoblastic proliferation of oropharynx and myasthenia gravis, with multiple recurrences without systemic dissemination over 11 year period, AJSP 2001;25:411
Micro: lymphoblasts and mature lymphocytes; also scattered mature and immature granulocytes
Positive stains: CD1, CD3, CD4, CD8, TdT
Negative stains: keratin
Molecular: no T cell receptor gene rearrangement by PCR
DD: T cell lymphoblastic lymphoma
Peripheral T cell lymphoma
May resemble marginal zone B cell lymphoma, Mod Path 2002;15:420
Hard palate, tongue, tonsil
Micro: partial effacement with residual follicles surrounded by neoplastic small cells; usually lymphoepithelial lesions
Micro images: expansion of marginal zone, CD3, abundant clear cytoplasm; lymphoepithelial lesion, keratin, CD3, CD20
Molecular: T cell receptor rearrangement
Primary effusion lymphoma
Case report of coexisting pleural cavity and solid tongue based lesions (both HHV8+) in 42 year old HIV+ man, Hum Path 2004;35:632
Rare; annual incidence of 1.2 cases per 10 million; more common in Japanese, black Africans, Native Americans, Hispanics
Median 61 years old, 78% men
Differs from cutaneous melanoma due to lack of association with sun damage, family history or atypical nevi, and difference in prognostic factors
Nodal and distant metastases are common
Extremely poor prognosis, with median survival 2-3 years; some lower grade tumors without vascular invasion had median survival of 8 years
Poor prognostic factors: vascular invasion, polymorphous tumor cell population, necrosis; no prognostic value - tumor thickness, ulceration, level of invasion
Case reports: 17 year old Asian-American girl with tender lesion of hard palate (Archives 2002;126:1110), 47 year old man with tumor after low dose radiation therapy for lichen planus (Archives 1985;109:290)
Gross: mucosa covering maxillary bone (62%), labial mucosa (13%), lower gingiva (8%); usually flat, erythematous or pigmented, less commonly presents as a mass
Micro: mean 3 mm thick; pigmented or frequently amelanotic; morphology includes epithelioid, fusiform and polymorphous cells; some tumor giant cells in almost all cases; 90% have associated melanoma in situ; usually mitotic figures; frequent ulceration, necrosis, vascular invasion, perineural invasion; may have desmoplastic features, particularly if lower lip
Micro images: in situ and invasive, H&E and stains
Positive stains: S100 (97%), tyrosinase/T311 (94%), MelanA/Mart1/A103 (85%), microphthalmia associated transcription factor (MITF, D5, 74%), HMB45 (71%); desmoplastic melanoma - S100, tyrosinase
Negative stains: keratin, CD34, muscle specific actin
DD (amelanotic melanomas): poorly differentiated carcinoma, large cell lymphoma
References: AJSP 2001;25:782, AJSP 2002;26:883
Often to gingiva or tongue
Primary is often lung; also renal cell carcinoma, breast, melanoma, prostate, endometrium, colon
Case reports: 54 year old woman with metastatic lobular breast carcinoma to minor salivary gland of floor of mouth (Archives 2000;124:157), 78 year old woman with metastatic endometrial carcinoma to tongue (Archives 1992;116:965)
Micro images: metastatic breast lobular carcinoma to floor of mouth, EMA, ER, PR
DD: reactive plasma cell lesions (mature plasma cells, other inflammatory cells, associated with fibrosis)
Post-transplant lymphoproliferative disorder
Infrequent complication of childhood transplantation
Biopsy of tonsils and adenoids may permit early diagnosis, Hum Path 1995;26:525
Low grade myofibroblastic sarcoma
Spindle cell sarcoma with myofibroblastic differentiation, often involving tongue
Often recur or metastasize
Micro: cellular lesions with diffuse infiltration, composed of spindled cells in fascicles with poorly defined, pale eosinophilic cytoplasm, fusiform nuclei, small nucleoli, in collagenous matrix with prominent hyalinization; mild nuclear atypia, occasional mitotic figures (1-6 per 10 HPF)
Positive stains: at least one myogenic marker (desmin, smooth muscle actin, muscle specific actin)
EM: myofibroblasts
DD: fibromatosis, myofibromatosis, solitary fibrous tumor, fibrosarcoma, leiomyosarcoma
References: AJSP 1998;22:1228
Malignant peripheral nerve sheath tumor
Case report of oral cavity tumor with melanotic cells, recurrence and submandibular and hepatic metastases, Archives 1983;107:298
Rhabdomyosarcoma
11 year old boy with tonsillar embryonal rhabdomyosarcoma, Case of the Week #276
Micro images: image 1, image 2, image 3, image 4, image 5, actin, desmin, myogenin, myoD1
Miscellaneous
TNM staging-Lip and oral cavity
Excludes nonepithelial tumors (lymphoma, soft tissue, bone, cartilage)
See separate sections for Lip and Oral Cavity, Oropharynx/Hypopharynx, Mucosal melanoma of pharynx
Pathologic staging is required for nodal (pN) assessment; for T assessment, pT supplements but does not replace clinical assessment
Primary tumor (T) – lip and oral cavity
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor 2 cm or less in greatest dimension
T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3: Tumor more than 4 cm in greatest dimension
T4a: Moderately advanced local disease
(lip): Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth or skin of face; i.e. chin or nose
(oral cavity): Tumor invades adjacent structures only (e.g. though cortical bone [mandible or maxilla], into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus and styloglossus], maxillary sinus, skin of face)
T4b: Very advanced local disease - tumor invades masticator space, pterygoid plates or skull base or encases internal carotid artery
Note: superficial erosion alone of bone/tooth socket by gingival primary is not sufficient to classify a tumor as T4
Regional lymph nodes (N) – lip and oral cavity
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3: Metastasis in a lymph node more than 6 cm in greatest dimension
Notes
● Mediastinal lymph nodes are considered distant metastases
● Midline nodes are considered ipsilateral
● A designation of U or L may be used to indicate metastasis above the lower border of the cricoid (U) or below the lower border of the cricoid (L)
● Selective neck dissection ordinarily includes 6+ lymph nodes; radical / modified radical neck dissection ordinarily includes 10+ lymph nodes
● Survival is significantly worse when metastases involve lymph nodes beyond the first echelon of lymphatic drainage, particularly lymph nodes in levels IV and V; thus, the region of nodal involvement should also be reported
Level I: submental, submandibular; contains the submental and submandibular triangles bounded by the anterior and posterior bellies of the digastric muscle, and by the hyoid bone inferiorly, and the body of the mandible superiorly
Level II: upper jugular; contains the upper jugular lymph nodes and extends from the level of the skull base superiorly to the hyoid bone inferiorly
Level III: mid-jugular; contains the middle jugular lymph nodes from the hyoid bone superiorly to the level of the lower border of the cricoid cartilage inferiorly
Level IV: lower jugular; contains the lower jugular lymph nodes from the level of the cricoid cartilage superiorly to the clavicle inferiorly
Level V: posterior triangle; contains the lymph nodes in the posterior triangle bounded by the anterior border of the trapezius muscle posteriorly, the posterior border of the sternocleidomastoid muscle anteriorly, and the clavicle inferiorly; for description purposes, Level V may be further subdivided into upper, middle and lower levels corresponding to the superior and inferior planes that define Levels II, III and IV
Level VI: prelaryngeal, pretracheal, paratracheal; contains the lymph nodes of the anterior central compartment from the hyoid bone superiorly to the suprasternal notch inferiorly; on each side, the lateral boundary is formed by the medial border of the carotid sheath
Level VII: upper mediastinal; contains the lymph nodes inferior to the suprasternal notch in the superior mediastinum
Distant metastasis (M) – lip and oral cavity
M0: No distant metastasis
M1: Distant metastasis
Anatomic stage / prognostic groups – lip and oral cavity
0 : Tis N0 M0
I : T1 N0 M0
II : T2 N0 M0
III : T3 N0-1 M0 or T1-3 N1 M0
IVA : T4a N0-1 M0 or T1-4a N2 M0
IVB : Any T N3 M0 or T4b Any N M0
IVC : Any T Any N M1
Click here for staging of hypopharynx (in Larynx chapter)
Oropharynx
Primary tumor (T) – oropharynx
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor 2 cm or less in greatest dimension
T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3: Tumor more than 4 cm in greatest dimension or extension to lingual surface of epiglottis
T4a: Moderately advanced local disease – tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate or mandible
T4b: Very advanced local disease - tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx or skull base or encases carotid artery
Note: mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of larynx
Regional lymph nodes (N) – oropharynx
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension
N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension
N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension
N3: Metastasis in a lymph node more than 6 cm in greatest dimension
Notes
● Mediastinal lymph nodes are considered distant metastases
● Midline nodes are considered ipsilateral
● Metastases at level VII are considered regional lymph node metastases
● A designation of U or L may be used to indicate metastasis above the lower border of the cricoid (U) or below the lower border of the cricoid (L)
● Selective neck dissection ordinarily includes 6+ lymph nodes; radical / modified radical neck dissection ordinarily includes 10+ lymph nodes
● Survival is significantly worse when metastases involve lymph nodes beyond the first echelon of lymphatic drainage, particularly lymph nodes in levels IV and V; thus, the region of nodal involvement should also be reported
Level I: submental, submandibular; contains the submental and submandibular triangles bounded by the anterior and posterior bellies of the digastric muscle, and by the hyoid bone inferiorly, and the body of the mandible superiorly
Level II: upper jugular; contains the upper jugular lymph nodes and extends from the level of the skull base superiorly to the hyoid bone inferiorly
Level III: mid-jugular; contains the middle jugular lymph nodes from the hyoid bone superiorly to the level of the lower border of the cricoid cartilage inferiorly
Level IV: lower jugular; contains the lower jugular lymph nodes from the level of the cricoid cartilage superiorly to the clavicle inferiorly
Level V: posterior triangle; contains the lymph nodes in the posterior triangle bounded by the anterior border of the trapezius muscle posteriorly, the posterior border of the sternocleidomastoid muscle anteriorly, and the clavicle inferiorly; for description purposes, Level V may be further subdivided into upper, middle and lower levels corresponding to the superior and inferior planes that define Levels II, III and IV
Level VI: prelaryngeal, pretracheal, paratracheal; contains the lymph nodes of the anterior central compartment from the hyoid bone superiorly to the suprasternal notch inferiorly; on each side, the lateral boundary is formed by the medial border of the carotid sheath
Level VII: upper mediastinal; contains the lymph nodes inferior to the suprasternal notch in the superior mediastinum
Distant metastasis (M) – oropharynx
M0: No distant metastasis
M1: Distant metastasis
Anatomic stage / prognostic groups – oropharynx
0 : Tis N0 M0
I : T1 N0 M0
II : T2 N0 M0
III : T3 N0 M0 or T1-3 N1 M0
IVA : T4a N0-1 M0 or T1-4a N2 M0
IVB : T4b Any N M0 or Any T N3 M0
IVC : Any T Any N M1
Primary tumor (T) – mucosal melanoma
T3: Mucosal disease
T4a: Moderately advanced local disease – tumor involving deep soft tissue, cartilage, bone or overlying skin
T4b: Very advanced local disease - tumor involving brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space or mediastinal structures
Regional lymph nodes (N) – mucosal melanoma
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastases
N1: Regional lymph node metastases present
Distant metastasis (M) – mucosal melanoma
M0: No distant metastasis
M1: Distant metastasis
Anatomic stage / prognostic groups – mucosal melanoma
III : T3 N0 M0
IVA : T4a N0 M0 or T3-4a N1 M0
IVB : T4b Any N M0
IVC : Any T Any N M1
At least one section per 1 cm of tumor for large tumors, including tumor center and periphery
Submit entire tumor if can do so in 5 sections or less
Resection margins
Save intervening levels on biopsies for special stains
Tumor histologic type and pattern
Tumor size and location
Tumor histologic grade
Depth of invasion (not used for TNM staging)
Pattern of invasion (noncohesive irregular cords, infiltrative single cells, well defined blunt pushing borders, thick rounded invasive cords)
Tumor extension to adjacent structures
Status of resection margins
Vascular invasion
Perineural invasion
Lymph nodes: for each level, number obtained, number involved by tumor, size of nodal metastases, presence of extracapsular spread
Dysplasia
References: Mod Path 2000;13:1038
Measurements
Endophytic tumors: measure perpendicularly from surface of invasive carcinoma to deepest area of involvement, using non-tangential sections with a clearly recognizable surface component
Exophytic tumors: measure tumor thickness from surface to deepest area
Ulcerated tumors: measure from ulcer base to deepest area, as well as from surface of most lateral extent of invasive carcinoma to deepest area
End of Oral Cavity chapter
