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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

Primary references

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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

Giant cell angiofibroma

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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)

 

Gingival hyperplasia

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Also called fibrous hyperplasia

Associated with diphenylhydantoin (Dilantin) ingestion; also cyclosporine A, nifedipine, other drugs

May require surgical excision

 

Granular cell tumor

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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

 

Hemangioma

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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

 

Irritation fibroma

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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)

 

Keratoacanthoma

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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

 

Leukoedema

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Diffuse opalescent lesion of cheek mucosa that may extend to lips

Probably degenerative

Micro: intracellular edema or vacuolization of malpighian cells

 

Lymphangioendothelioma

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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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Lymphoid hyperplasia / polyp

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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

 

Mucinosis

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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

 

Mucous cyst

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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

 

Nevus

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Usually lips; compound or intradermal

 

Osseous choristoma

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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)

Xray images: #1; #2

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)

Gross images: #1; #2

Micro: irregular mature bone trabeculae and fibrous connective tissue; no osteoblastic activity; no atypia

Micro images: #1; #2; #3; #4

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.

 

Paraganglioma

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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

 

Peripheral ameloblastoma

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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

 

Plasma cell granuloma

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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

 

Plasmacytosis

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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

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May be confused with leiomyosarcoma

 

Pseudoepitheliomatous hyperplasia

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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

 

Pyogenic granuloma

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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

 

Rhabdomyoma

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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

 

Solitary fibrous tumor

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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

 

Spitz nevus

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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

 

Squamous papilloma

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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

 

Verruca vulgaris

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Associated with HPV

Micro: cup shaped margins, prominent hyperkeratinized spires

 

Verruciform xanthoma

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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

Carcinoma in situ

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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

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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

 

Leukoplakia

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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

 

Verrucous hyperplasia

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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

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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

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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

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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

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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

 

Squamous cell carcinoma-lip

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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

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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

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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

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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

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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

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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

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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

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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

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Also called adenoid carcinoma (not adenoid cystic)

Usually in lip, associated with actinic radiation

Morphology may be due to acantholysis

 

Spindle cell carcinoma

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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

 

Verrucous carcinoma

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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”

Micro images: #1; #2

Contributed by Dr. Asmaa Gaber: #1; #2

DD: squamous papilloma, keratoacanthoma, hyperkeratosis, pseudoepitheliomatous hyperplasia, dysplasia, papillary squamous cell carcinoma

 

 

Other carcinomas (non salivary gland)

Adenosquamous

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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

 

Basal cell carcinoma

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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

 

Small cell carcinoma

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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

Acinic cell carcinoma

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Adenoid cystic carcinoma

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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

 

Adenomatoid hyperplasia

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Nodular hyperplasia of minor salivary glands

Usually hard palate, also retromolar

 

Basal cell adenoma

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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

 

Choristoma

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Gingival nodule of disorganized seromucinous salivary gland tissue mixed with sebaceous glands

 

Clear cell carcinoma-hyalinizing type

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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

 

Cystadenocarcinoma

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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

 

Intraductal carcinoma

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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

 

Inverted ductal papilloma

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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

 

Malignant mixed tumor

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Mucoepidermoid carcinoma

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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

 

Myoepithelioma

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Hard palate tumor

Benign behavior

Micro: solid pattern of hyaline or plasmacytoid cells with mild nuclear pleomorphism

DD: plasmacytoma, skeletal muscle tumors

 

Paget’s disease of mucosa

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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

 

Pleomorphic adenoma

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Also called benign mixed tumor

50% of salivary gland tumors of palate

 

Polymorphous low grade adenocarcinoma

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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

 

Sialadenoma papilliferum

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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

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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

Angiosarcoma

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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

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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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Hemangioendothelioma

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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

 

Kaposi’s sarcoma

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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

 

Liposarcoma

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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

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Both patients in one study had prolonged survival, Mod Path 2002;15:1020

Micro images: tumor of buccal mucosa

 

Myxoid liposarcoma

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Case report of floor of mouth tumor with rhabdomyoblastic differentiation, Archives 1998;122:740

Micro images: tumor of buccal mucosa, tongue

 

Well differentiated liposarcoma

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<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

 

Lymphoma

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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

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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

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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

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Very rare in oral cavity

Case report in Waldeyer’s ring, Archives 1996;120:285

 

Indolent T cell lymphoblastic proliferation

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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

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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

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Case report of coexisting pleural cavity and solid tongue based lesions (both HHV8+) in 42 year old HIV+ man, Hum Path 2004;35:632

 

Melanoma

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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

 

Metastases to oral cavity

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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

 

Plasmacytoma

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DD: reactive plasma cell lesions (mature plasma cells, other inflammatory cells, associated with fibrosis)

 

Post-transplant lymphoproliferative disorder

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Infrequent complication of childhood transplantation

Biopsy of tonsils and adenoids may permit early diagnosis, Hum Path 1995;26:525

 

Sarcoma-other

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Low grade myofibroblastic sarcoma

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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

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Case report of oral cavity tumor with melanotic cells, recurrence and submandibular and hepatic metastases, Archives 1983;107:298

 

Rhabdomyosarcoma

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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

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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

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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

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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

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M0: No distant metastasis

M1: Distant metastasis

 

Anatomic stage / prognostic groups – lip and oral cavity

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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

 

TNM staging-Oropharynx

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Click here for staging of hypopharynx (in Larynx chapter)

 

Oropharynx

Primary tumor (T) – oropharynx

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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

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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

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M0: No distant metastasis

M1: Distant metastasis

 

Anatomic stage / prognostic groups – oropharynx

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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

 

TNM staging-Mucosal melanoma

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Primary tumor (T) – mucosal melanoma

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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

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NX: Regional lymph nodes cannot be assessed

N0: No regional lymph node metastases

N1: Regional lymph node metastases present

 

Distant metastasis (M) – mucosal melanoma

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M0: No distant metastasis

M1: Distant metastasis

 

Anatomic stage / prognostic groups – mucosal melanoma

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III : T3 N0 M0

IVA : T4a N0 M0 or T3-4a N1 M0

IVB : T4b Any N M0

IVC : Any T Any N M1

 

Grossing

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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

 

Features to report

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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