Oral cavity and oropharynx
Last revised 16 March 2010
Last major update June 2004
Copyright (c) 2004-2010, PathologyOutlines.com, Inc.
Bold and underlined topics are hypertext links and may open a new window
Primary references, normal anatomy, normal histology
Congenital anomalies: dermoid/epidermoid cyst, duplication
cyst, epithelial nests, epulis,
Fordyce’s disease, hairy polyp,
heterotopia, lingual
thyroid, lingual tonsil, white sponge nevus
Infectious: general, aphthous ulcers,
candidiasis, CMV, condyloma acuminatum, diphtheria,
gingivitis, hairy leukoplakia,
herpes simplex, histoplasmosis,
HIV, infectious mononucleosis, measles, periodontitis, scarlet fever, syphilis, tuberculosis
Inflammatory (non-infectious): atypical histiocytic granuloma, Behcet’s disease, Crohn’s disease, fissured tongue, geographic
tongue, glossitis, granulomatous inflammation, hyaline ring like structures, Melkersson-Rosenthal syndrome, necrotizing sialometaplasia, oral submucosal fibrosis, papillary hyperplasia, peripheral giant cell granuloma, sarcoidosis, tongue
ulceration with eosinophilia, Wegener’s granulomatosis,
xerostomia
Dermatologic conditions: erythema multiforme, lichen
planus, melanotic pigmentation, pemphigus vulgaris, smokeless
tobacco keratosis
Other benign tumors/conditions: amyloidosis, angiolymphoid
hyperplasia, chondroma, crystal storing histiocytosis, ectomesenchymal
chondromyxoid tumor, ephelis, fibroid epulis, focal
dermal hyperplasia, focal epithelial
hyperplasia, giant cell angiofibroma, gingival hyperplasia, granular
cell tumor, hemangioma, irritation fibroma, keratoacanthoma,
leukoedema, lymphangioendothelioma,
lymphoid hyperplasia / polyp, mucinosis, mucous cyst, nevus, 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
AJCC
Cancer Staging Manual (7th ed)
American Journal of Surgical
Pathology (AJSP), March 1977 to
June 2004
Archives of Pathology
and Laboratory Medicine (Archives) January 1976 to June 2004
Human
Pathology (Hum Path), March 1970 to May 2004
Modern Pathology
(Mod Path), January
1988 to May 2004
Rosai, J:
Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg,
S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins,
1999
Oral Pathology website -
Dr. William Crawford (Univ Southern California)
Journal search terms: oral,
mouth, tongue, gingiva, tonsil, oropharynx
Please
refer to these primary references for more detailed discussions and photographs
Oral cavity extends from skin-vermilion junction of
lips to junction of hard and soft palate above and to line of circumvallate
papillae below
Dorsal tongue: villous, normally exposed surface
Ventral tongue: nonvillous undersurface
Anterior 2/3 of tongue (oral tongue): freely mobile portion of tongue that extends
anteriorly from line of circumvallate papillae to undersurface of tongue at
junction of floor of mouth; composed of four areas - the tip, the lateral
borders, the dorsum and the undersurface (nonvillous ventral surface of tongue)
Base of tongue (posterior 1/3 of
tongue): bound anteriorly by
circumvallate papillae, laterally by glossotonsillar sulci, posteriorly by
epiglottis
Buccal mucosa: all of the membrane lining the inner surface of
cheeks and lips from line of contact of opposing lips to line of attachment of
mucosa of alveolar ridge (upper and lower) and pterygomandibular raphe
Floor of mouth: semilunar space of myelohyoid and hyoglossus
muscles, extending from inner surface of lower alveolar ridge to undersurface
of tongue; posterior boundary is base of anterior pillar of tonsil; divided
into two sides by frenulum of tongue, contains ostia of submaxillary and
sublingual salivary glands
Gingiva: soft tissue in area of teeth and palate; extends
from labial sulcus and buccal sulcus to a cuff of tissue around each tooth
Hard palate: semilunar surface between upper alveolar ridge and
mucous membrane covering palatine process of maxillary palatine bones; extends
from inner surface of superior alveolar ridge to posterior edge of palatine
bone
Lip: begins at junction of vermilion border (mucocutaneous junction) with
skin, includes only the vermilion surface or that portion of lip that comes
into contact with opposing lip; upper and lower lip are joined at commissures
of mouth; external surface is skin and mucous membrane; internally contains
orbicularis oris muscle, blood vessels, nerves, areolar tissue, fat, small
labial glands; inner surface of lip is connected to gum in midline by frenulum,
a mucous membrane fold
Lower alveolar ridge: mucosa overlying alveolar process of mandible which
extends from the line of attachment of mucosa in buccal gutter to line of free
mucosa of floor of mouth; posteriorly, it extends to ascending ramus of
mandible
Retromolar gingiva (retromolar
trigone): mucosa overlying ascending
ramus of mandible from level of posterior surface of last molar tooth to apex
superiorly, adjacent to tuberosity of maxilla
Tonsillar area: anterior and posterior tonsillar pillars and
tonsillar fossa
Upper alveolar ridge: mucosa overlying alveolar process of maxilla which
extends from line of attachment of mucosa in upper gingival buccal gutter to
junction of hard palate; posterior margin is upper end of pterygopalatine arch
Vermillion border: mucocutaneous junction of lip
Drawings: nose, mouth, pharynx and
larynx; tongue surface,
tongue and oral cavity,
undersurface of tongue,
coronal section of tongue
Stratified squamous epithelium with parakeratosis
No hair follicles or sweat glands present
Keratinization in areas most exposed to mastication
(gingiva, hard palate, dorsum of tongue)
Lamina propria contains loose connective tissue,
mucous glands and serous minor salivary type glands
Submucosa has collagenous, dense, fibrous tissue
Tonsillectomy specimens frequently contain skeletal
muscle, Hum
Path 2000;31:813
Micro images: filiform papilla; fungiform papillae; circumvallate papilla
Midline in floor of mouth
Present at birth but asymptomatic until inflamed
Micro: lined by squamous epithelium, contains skin adnexae
if dermoid cyst
Lined by indigenous mucosa of segment it is
duplicating
Case reports: congenital duplication cyst of ventral surface of
tongue with gastrointestinal and respiratory epithelium in newborn (Archives
1989;113:1301), enteric
duplication cyst of floor of mouth and base of tongue in 7 year old (Archives
2000;124:614)
Treatment: excision; may recur if incompletely excised
Gross images: sublingual
duplication cyst
Micro images: colonic
and gastric mucosa in cyst wall
Not actually a congenital anomaly, but normal
occurring neuroepithelial structure called organ of Chievitz, Chievitz’s
paraparotid organ, or juxtaoral organ
Reported in 56% of adult autopsies without oral
mucosal lesions
Occur within intraoral sensory nerve
May undergo nodular hyperplasia
Micro: squamous like epithelium, occasionally with lumen
lined by cuboidal cells; associated with small nerves and resembling perineural
invasion
References: AJSP
1979;3:147
Congenital granular cell tumors that occur
exclusively in girls
Sites: anterior alveolar ridge of maxilla and mandible,
usually overlying future canine and lateral incisor teeth
Don’t recur, even if incompletely excised
Micro: confluent to nodular submucosal growth of tumors
composed of large polygonal cells with eosinophilic granular cytoplasm and
small, central nuclei
References: AJSP
1981;5:37
Common; normal sebaceous glands within oral cavity
May be hyperplastic and nodular
Rare, arises from oropharynx or nasopharynx
Micro: polypoid lesion of epidermis, hair follicles,
sebaceous glands, eccrine sweat glands; variable adipose tissue, smooth muscle,
striated muscle and cartilage in core
Gastric or intestinal epithelium in tongue and floor
of mouth that may become cystic, or glial and ependyma-lined clefts in palate
and parapharyngeal space
Thyroid tissue at base of tongue due to failure of
descent
In 10% of normals; 70% with grossly evident lingual
thyroid lack a normal thyroid gland
Fairly common; raised red areas at lateral tongue
base containing lymphoid tissue
Autosomal dominant disease
Large white plaques in oral mucosa with striking
intracellular edema in malpighian layer
Infectious conditions
Oral
cavity defenses against infection include competition by organisms of low virulence,
secretory IgA (from submucosal lymphocytes and plasma cells), antibacterial
effects of saliva, diluting effects of food and drink
Also
called canker sores
Affect
40% in US; more common up to 20 years; painful, recurrent, familial
Treatment:
symptomatic
Gross:
single or multiple, shallow, hyperemic ulcerations covered by a thin exudate
with hyperemic rim
Micro:
initially mononuclear infiltrate, then neutrophilic infiltrate from secondary
bacterial infection
Normal
flora that overgrows due to diabetes, neutropenia, AIDS, immunosuppression,
xerostomia, antibiotics
Gross:
superficial curdy, gray-white inflammatory membrane
Micro:
membrane composed of fungi in a fibrinopurulent exudate resting on an
inflammatory base
Ulcerated
lesion
Associated
with HPV
Case
report of HIV- woman who acquired HPV 6/11 in late teens and developed
disseminated condylomas of oropharynx, nasopharynx, anogenital region, urethra
and bladder, with no known immune defect, AJSP
1998;22:1291
Micro:
acanthosis, koilocytotic atypia
Gross:
dirty white, fibrinosuppurative, tough, inflammatory membrane over tonsils,
posterior pharynx
Painless
inflammation of gingiva around gingival sulci or cuff surrounding each tooth,
due to bacterial plaque
Most
commonly due to Streptococcus, Fusobacterium, Actinomyces, Veillonella,
Treponema
May be
due to scurvy, endocrine alterations (teenagers, pregnancy), disseminated
tuberculosis, phenytoin or other drugs
Gross:
erythematous and edematous gingiva adjacent to teeth
Micro:
initially neutrophils, later T lymphocytes, finally B lymphocytes and plasma
cells
Acute necrotizing gingivitis
Also
called trench mouth, Vincent’s stomatitis, ulcerative stomatitis
Caused
by fusospirochetal complex of microbes
Heals
with scarring and blunting of interdental papillae; may recur
Predisposing factors: poor oral hygiene, smoking, emotional anguish, age
12-29 years in US and Northern Europe
Gross:
highly inflamed mucosa with enlargement of interdental papillae and presence of
gray pseudomembrane with hemorrhagic tissue below; occasional ulceration of
papillae
Micro: necrosis
of interdental gingival papillae, focal abscess
Associated
with HIV infection (AIDS may appear within 2-3 years), but actually due to EBV
infection
Gross:
white, confluent patches of fluffy (hairy) mucosa along lateral tongue
Gross images: hairy leukoplakia
#1
Micro:
hyperkeratotic oral mucosa due to piling of keratotic squamous epithelium;
Cowdry type A intranuclear inclusions; EBV present in clear cells of spinous
layer; variable koilocytosis, superimposed Candida infection
EM: herpes
type virions
Reference:
AJSP
1989;13:114 (intranuclear inclusions)
Also
called cold sore
Usually
HSV1
Lasts
3-4 weeks, then virus tracks along regional nerves and becomes dormant in
trigeminal or other local ganglia
Most
infected adults have latent HSV-1 that is activated by upper respiratory
infection, excessive exposure to cold, wind, sun, allergies
Acute herpetic gingivostomatitis: rare, children 2-4 years with diffuse involvement
of oral and pharyngeal mucosa, tongue, gingiva; fiery red mucosa and swelling
with clusters of vesicles
Recurrent herpetic stomatitis: groups of 1-3 mm vesicles on the lips, nasal
orifices, buccal mucosa; milder than acute, lesions dry up in 4-6 days, heal in
7-10 days
Tzanck test:
microscopic examination of vesicle fluid shows giant cells, inclusions
Gross: vesicles
(mm size) to bullae (cm size) with clear serous fluid, painful shallow ulcers
Micro:
intra- and intercellular edema (acantholysis), intranuclear inclusions,
multinucleate polykaryons (giant cells)
Ulcers,
nodular lesions, verrucous masses
Micro:
noncaseating granulomas or nonspecific inflammatory infiltrate
Positive stains: GMS, PAS
DD:
squamous cell carcinoma
Human immunodeficiency
virus (HIV)
Associated
with opportunistic infections, herpes simplex virus, Candida, fungi, Kaposi’s
sarcoma, hairy leukoplakia
Lymphoid
hyperplasia of Waldeyer’s ring is a frequent symptomatic complication of HIV
infection, often with HIV+, EBV- multinucleated giant cells in crypt or surface
epithelium, Hum
Path 1999;30:1383, Mod
Path 2000;13:1293
Micro: adenoids
and tonsils - florid follicular hyperplasia, follicle lysis, attenuated
mantle zone, multinucleated giant cells adjacent to surface or tonsillar crypt
epithelium; may have marked lymphoid depletion with no germinal centers,
plasmacytosis and stromal vascular proliferation
Micro images:
multinucleated
giant cells in Waldeyer’s ring
References:
AJSP
1996;20:572
Acute
pharyngitis and tonsillitis with gray-white exudate, lymphadenopathy in neck
Due to
Epstein-Barr virus infection
Micro: tonsil
- reactive lymphoid hyperplasia (polymorphous transformed lymphocytes) with
extensive immunoblastic proliferation in sheets and nodules, marked atypia
resembling Reed-Sternberg cells
Micro images: Lymphocytosis; showing reactive
lymphocytes #1; #2
Negative stains: CD15, CD30
References:
AJSP
1987;11:122
Koplik spots: ulcerations on buccal mucosa around Stensen duct; spotty enanthema in
oral cavity, may precede rash
Recurrent
and continuous gingivitis that affects alveolar bone
Causes
bone destruction and pockets around teeth > 3 mm in depth
Plaque
within pockets serves as nidus for mineralization (dental calculus), causing
progressive disease until gingival scarring and bony erosion lead to loss of
teeth
Treatment:
scaling and planing of root surfaces to remove focal irritants, surgery,
brushing and flossing
Fiery
red tongue with prominent papillae (raspberry tongue), white coated tongue
through which hyperemic papillae project (strawberry tongue)
May
produce painless indurated gummatous mass in tongue or palate
Associated
with tongue cancer in older studies
Micro:
granulomas with giant cells, plasma cells, vascular changes
Rare;
painful ulcer of tongue or buccal mucosal lesion
Associated
with advanced pulmonary disease
Micro:
caseating granulomas
Inflammatory (noninfectious) lesions
Atypical histiocytic granuloma
Reactive
nodule with marked histiocytic infiltration and variable mitotic activity
Affects
skin, oral mucosa and eyes
Micro:
leukocytoclastic vasculitis
Initial
presentation may be in oral cavity and pharynx
6%
have oral lesions at some time (lip, gingiva, vestibular sulci, buccal mucosa)
Micro:
edema, ulcers, papillary hyperplastic mucosa, dilation of lymphatics, chronic
inflammatory infiltrate, giant cells, rarely noncaseating granulomas
Also
called furrowed tongue
Grooves
get deeper and more prominent with age
50%
also have geographic tongue
May
have true fissure with ulceration
Treatment:
brushing tongue
Also
called benign migratory glossitis, glossitis migrans
1-2%
of population, usually adults
Associated
with common cold, work/home stresses
Associated
with tongue fissures
Gross:
erythematous flat zone on tongue dorsum due to loss of filiform papillae
Micro:
acanthosis with neutrophils throughout epithelium and surface microabscesses,
plus inflammatory infiltrate in lamina propria; resembles psoriasis
Inflammation
or beefy red tongue associated with deficiency states
Due to
atrophy of tongue papillae, thinning of mucosa and exposure of underlying vasculature
Median rhomboid glossitis: red patch in posterior dorsal tongue
Causes:
pernicious anemia (Vitamin B12 deficiency), deficiency of riboflavin, niacin or
pyridoxine; sprue, iron deficiency anemia; also associated with jagged teeth,
ill fitting dentures, rarely syphilis, burns, ingestion of corrosive chemicals
Plummer-Vinson / Patterson-Kelly syndrome: iron deficiency anemia, glossitis, esophageal webs
Associated
with chronic recurrent tonsillitis
Usually
no specific organism is recovered
Usually
benign course
Also
called pulse granuloma (pulse is edible seed of legumes), oral vegetable
granuloma, giant cell hyaline angiopathy
Rarely
associated with chronic periostitis, edentulous patients
May be
a degenerative change in vessel walls from vasculitis or a reaction to legume
cells at various stages of digestion
Treatment:
excision or curettage
Micro:
hyaline ring like structures, some containing granular necrotic material that
surrounds giant cells, vessels and collagen, and is itself surrounded by
chronic inflammatory cells
Micro images: pulse
granuloma from rectum
Orofacial
swelling, peripheral facial nerve paralysis and plicated tongue
Cheilitis granulomatosa: may be a variant
Micro:
granulomatous inflammation of lip stroma
DD:
sarcoidosis, Crohn’s disease
Reactive
condition of minor or occasionally major salivary glands, probably due to
ischemia or vasculitis
Gross:
ulcerated lesion of hard palate
Gross/micro images: as part of case history #1
Micro:
ulcerated surface mucosa; intraductal proliferation of metaplastic squamous
epithelium containing trapped mucous cells in lobular (not infiltrative)
pattern; pseudoepitheliomatous hyperplasia common; vascular proliferation with
prominent inflammatory infiltrate and partial necrosis of salivary glands,
associated with squamous metaplasia of adjacent ducts and acini
DD:
squamous cell carcinoma, mucoepidermoid carcinoma, post-radiation changes
Mainly
in residents of
Reactive,
but risk factor for squamous cell carcinoma
Micro:
subepithelial fibrosis, chronic inflammation, hyalinization, loss of vascularity;
overlying epithelium is atrophic or hyperplastic and hyperkeratotic
Papillary hyperplasia (inflammatory papillary hyperplasia)
Common,
usually involves palate or lingual mandibular gingiva
Called
palatal papillomatosis in palate
Associated
with ill fitting dentures or partial dentures, wearing prostheses at night,
poor oral hygiene
Not a
premalignant condition
Treatment:
complete excision, proper fitting dentures; removal of offending agent
Gross:
multiple red polyp-like projections, often under ill-fitting dentures, usually
in palate
Micro:
exophytic mucosal epithelial hyperplasia, including pseudoepitheliomatous
hyperplasia, submucosal fibrous hyperplasia; islands of hyperplastic squamous
mucosa may appear in submucosa; may have chronic inflammation of accessory
salivary glands; no dysplasia
Peripheral giant cell granuloma
Also
called giant cell epulis
Reactive
gingival mass resembling pyogenic granuloma, but pushes teeth aside and may
erode alveolar bone or involve periodontal membrane
Usually
women, mean age 30 years, although may involve children or elderly patients
without teeth
Treatment:
excision with curettage of base of lesion extending into adjacent periodontal
membrane
Recurs
if not completely excised or source of irritation not removed
Gross:
inflammatory lesion up to 1.5 cm that protrudes from gingiva at site of chronic
inflammation; covered by gingival mucosa or ulcerated
Micro:
nonencapsulated aggregates of foreign body giant cells and fibroangiomatous
stroma with hemorrhage, hemosiderin, acute and chronic inflammatory cells;
alveolar bone often expanded in edentulous patients leading to superficial bone
loss with peripheral cuffing
DD: giant
cell granuloma of maxilla/mandible, giant cell “brown tumors” of
hyperparathyroidism
Central giant cell granuloma
Similar
to peripheral giant cell granuloma, but multiloculated
Sites:
oral mucosa, gingiva, tongue, hard palate and major salivary glands
Lower
lip biopsy is relatively sensitive; 58% demonstrate noncaseating granulomas
Tongue ulceration with eosinophilia
Also
called ulcerative eosinophilic granuloma, Riga-Fede disease, traumatic
granuloma
Resembles
carcinoma clinically
Presumed
due to crush injury of tongue muscle
Micro:
eosinophils and other inflammatory cells in submucosa, mucosa and salivary
glands; dilated vessels often present
5% of
cases present with oral cavity lesion
Gross:
red-purple hyperplastic gingiva
Micro:
epithelioid histiocytes, giant cells, eosinophils, pseudoepitheliomatous
hyperplasia, rarely vasculitis
Dry
mouth
Associated
with Sjogren’s syndrome (dry eyes, inflammatory enlargement of salivary glands,
xerostomia)
Gross: dry
mucosa, atrophy of tongue papillae with fissures, ulcerations
DD:
radiation therapy, anticholinergic drugs
Dermatologic conditions
Called
Stevens-Johnson syndrome if it involves lips and oral mucosa
Maculopapular,
vesiculobulbous eruption, due to infection, drugs, cancer, collagen vascular
disorder
Subacute
to chronic mucocutaneous disorder of unknown etiology
Involves
skin, nails, mucosal surfaces (oral mucosa, pharynx, perineum)
Mucosal
disease primarily affects women ages 40-60 years
Treatment:
topical steroids or cyclosporine
Gross:
reticulate, lacelike, white keratotic lesions; rarely bullous or ulcerated
Micro:
keratosis, subepithelial T cell infiltrate
Associated
with Addison’s disease, hemochromatosis, fibrous dysplasia of bone (Albright’s
syndrome), Peutz-Jegher syndrome
Vesicles
and bullae prone to rupture, leaving erosions covered with exudate
Autoimmune
disease with antigen-antibody complexes at desmosomes
Treatment:
steroids
Micro:
intraepithelial blister with acantholysis and chronic inflammation
Occurs
in users of smokeless tobacco (snuff) or tobacco chewers
Severity
related to length of exposure and tobacco brand
Reversible
with cessation of use
Gross:
filmy, gray-white opalescence at areas of contact with tobacco
Micro:
parakeratosis or hyperorthokeratosis with parakeratin spires (“chevrons”),
acanthosis, mild chronic inflammation, PAS+ marked hyalin deposition resembling
amyloid
Micro images: hyperorthokeratosis,
parakeratosis and acanthosis, diffuse hyalinization of lamina propria, PAS+
hyaline material
DD:
hyalinosis cutis et mucosae (deposition begins around vessels, eccrine glands
and epithelial-stromal interface, then fills entire dermis of all oral mucosa,
tongue, pharynx, larynx, vocal cords)
References:
Archives
2004;128:e17
Benign tumors/conditions
Amyloidosis
of tongue a common finding in older individuals, isolated or part of systemic
disease
Rarely
causes diffuse macroglossia or localized tumor
Angiolymphoid hyperplasia with eosinophilia
In
head and neck, usually in dermis or subcutaneous tissue
Case
report in 82 year old man with tongue lesion, Hum
Path 1991;22:837
Very
rare
Case
report of tongue tumor, Archives
1990;114:541
Case
report of 73 year old woman with tongue mass, chronic rheumatoid arthritis and
polyclonal hypergammaglobulinemia, Archives
1998;122:920
Micro:
histiocytes filled with eosinophilic crystals; lymphocytes and plasma cells
also present
Positive stains: crystals are immunoreactive with kappa and lambda light chain and gamma
heavy chain
Ectomesenchymal
chondromyxoid tumor
Myxoid
tumor of anterior dorsal tongue, first described at AJSP
1995;19:519
Median
age 32 years, range 9-78 years
Slow
growing, painless nodules
Occasionally
recurs after excision
Micro:
lobular proliferation of ovoid and fusiform cells with multilobulated nuclei
and focal mild atypia in chondromyxoid stroma; may entrap nerve or muscle
fibers
Positive stains: GFAP, cytokeratin; variable smooth muscle actin and S100
Negative stains: desmin
Also
called freckle; solitary melanotic macules, usually of lower lip
More
common in women; associated with Peutz-Jeghers syndrome
Micro:
hyperpigmentation of basal layer with elongation of rete ridges
DD:
melanosis (pigmented patches in hard palate or gingiva), melanoacanthoma
(melanocytes mixed with keratinocytes)
Also
called fibroepithelial polyp, peripheral ossifying fibroma, fibrous hyperplasia
Fibroid
mass in free gingiva
Due to
chronic gingival inflammation, pyogenic granuloma or other causes
May
calcify or ossify
Images: Contributed
by Dr. Yuri Lemeshev: Subepithelial
nodular fibrous proliferation, perivascular inflammatory
infiltrate, focal
ulceration
X
linked dominant trait
Associated
with multiple oral papillomas of lips and other oral mucosal sites
Also
associated with skin hypoplasia and associated ulcers, fatty herniation,
bilateral syndactyly with “lobster claw” deformity, iris and choroid colobomas,
strabismus
Also
called Heck’s disease
Discrete,
recurrent papillary lesions on oral mucosa in Native American and Eskimo
children and elsewhere
Associated
with HPV 1, 13, 32
Gross:
well circumscribed, sessile, pale elevation of buccal mucosa
Micro:
balloon cells in malpighian layers, localized areas of mucosal epithelial
hyperplasia with marked acanthosis and parakeratosis
Ages
40-60 years
Micro:
features similar to solitary fibrous tumor, plus irregularly shaped
pseudovascular spaces lined by large mono- or multinucleated wreath like giant
cells, plus cells with plump, fusiform or round nuclei, irregular folds and
pale pseudoinclusions
Positive stains: CD34, bcl2, CD99
Negative stains: CD68 (giant cells)
Also
called fibrous hyperplasia
Associated
with diphenylhydantoin (Dilantin) ingestion; also cyclosporine A, nifedipine,
other drugs
May
require surgical excision
Usually
tongue, but any site can be involved
Resembles
congenital epulis of newborn females but different S100 staining
Micro:
large cells with abundant granular cytoplasm and bland nuclei, florid
pseudoepitheliomatous hyperplasia
Positive stains: S100, PAS
Commonly
in gingiva and tongue
Benign,
don’t recur
Micro:
well formed, dilated vascular channels in superficial dermis with dissecting
pseudoangiomatous pattern in deeper dermis; endothelium exhibits hobnailing and
stromal papillae, but no multilayering or tufting; no/mild atypia; no mitotic
figures
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)
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
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”
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
Tumors
usually in hard palate but also other locations
Deep
parotid tumors may present as intraoral masses
Tumors
are similar histologically to those of major salivary glands
Treatment:
surgical (initial surgery should be definitive to prevent recurrence),
radiation for high grade malignancies
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,
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:
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
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
Usually
EBV negative, AJSP
1994;18:938
2/3 are female
AIDS
patients often have plasmablastic lymphomas or diffuse large B cell lymphoma
with poor prognosis (see below)
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
May
have focal follicular features, particularly in tonsil, Hum
Path 2002;33:732
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
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
IVC
: Any T Any
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
IVC
: Any T Any
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
IVC
: Any T Any
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 and oropharynx chapter