Oral Pathology I Review

Oral Pathology I
Final Review
Orofacial clefts
• See handout
What is this
Commisural lip pits
Etiology:
o Unknown - ?Failure of fusion of embryonal maxillary and mandibular processes
o Possibly autosomal dominant
Gender: M>F
Age:
o Adults (12-20%)
o Children (0.2-0.7%)
Site:
o Corners of mouth – unilateral, bilateral
Clinical features:
o Discovered on routine exam
o Asymptomatic, small invagination (blind pit) – 1-4mm in depth
o May express fluid (saliva) on squeezing
o May be associated with preauricular pits
Histology:
o Rarely biopsied
 Invagination lined by stratified squamous epithelium
 Minor salivary gland ducts and lobules
Treatment:
o No treatment necessary
o Excision if secondary infection
What is this?
Paramedian lip pits
AKA: Congenital lip pits
Etiology: Persistent lateral sulci on embryonic mandibular arch (sulci usually disappear by 6w)
Gender: Not specified
Age: Congenital
Site: Either side of midline lower lip vermillion – bilateral
Clinical features: Subtle depression, may be surrounded by prominent humps – 1.5mm in depth
o Bilateral, symmetric
o May express fluid (saliva)
o Can be component of syndrome:
 1. Van der Woude syndrome
Etiology: Mutation interferon regulatory factor 6
o Autosomal dominant – variable expressivity
o 1. Paramedian lip pits
o 2. CL and/or CP
 Occasionally, submucous palatal cleft
o ± Hypodontia
Histology: Rarely biopsied
o Invagination lined by stratified squamous epithelium
o Minor salivary gland ducts and lobules – chronic inflammation
Treatment: Excision for cosmetic improvement, further investigation to rule out syndromic involvement, genetic counseling if
indicated
 2. Popliteal pterygium syndrome
 3. Kabuki syndrome
What is this?
Double lip
Etiology:
o 1. Congenital: persistence of sulcus between pars glabrosa and pars villosa of lip
o 2. Acquired: trauma, oral habits (lip sucking) – more common
Age: Congential – birth, Acquired – adulthood
Site: Upper lip > lower lip
Clinical features: Excess fold of tissue upon smiling
o Ascher syndrome:
 1. Double lip
 2. Blepharochalasis (edema of upper eyelid  sagging of outer canthus)
 3. Non-toxic thyroid enlargement – 50% pt
 Cause unknown, ?autosomal dominant
Histology:
o Double lip: abundance of minor salivary glands, surrounding tissues normal
o Blepharochalasis: hyperplasia of lacrimal glands, prolapsed fat
• Treatment: no treatment, excision for cosmetic
What is this?
Fordyce granules
Etiology: variation of normal, ectopic sebaceous glands
Prevalence: >80% of population
Gender: No predilection
Age: Begin to appear at puberty, commonly noted in adulthood
Site: Buccal, labial mucosa; retromolar pad, ant. Tonsillar pillar, also seen
on genital mucosa
Clinical features: asymptomatic, yellow to yellow-white, macules or
papules, few to hundreds
Histology:
o Normal sebaceous glands just below surface epithelium
o Ductal communication with surface
o Sebaceous cells = polygonal cells with foamy cytoplasm, central nuclei
Treatment: No treatment necessary, can be diagnosed clinically, biopsy if
unusual clinical appearance, neoplastic transformation exceedingly rare,
reassure patient
What is this?
Leukoedema
Etiology: Likely a developmental variation of normal, may be more prominent in
smokers
Incidence: AA>Caucasian, mild presentation in Caucasians due to differences in
background pigmentation, 70-90% of AA adults
Age: Most often appears in adults
Site: Buccal mucosa; labial mucosa – bilateral
o Floor of mouth, palatopharyngeal mucosa, may see similar changes in genital, laryngeal
mucosa
Clinical features: Diffuse, gray-white, “milky” opalescent, folded; whitish streaks,
do not rub off
o Disappears when check stretched
Histology:
o Hyperparakeratosis (nuclei retained)
o Thickened epithelium
 Acanthosis (increased thickness of spinous layer due to intercellular edema between epithelial cells)
 Intracellular edema of superficial epithelial cells
Treatment: No treatment necessary, clinical recognition, reassure patient
What is this?
Microglossia
Microglossia, hypoglossia = small tongue
Aglossia = absence of tongue
Etiology: Developmental condition
Clinical features: May be isolated; mild cases difficult to
detect
o Most often component of oromandibular-limb hypogenesis
syndromes – limb anomalies
o May be associated with:
 Mandibular hypoplasia, missing mn incisors
 Cleft palate, intraoral bands
 Situs inversus (visceral organs reversed)
Treatment: Surgery and orthodontics if functional deficits
What is this?
Macroglossia
Macroglossia = enlargement of tongue  Increased risk for childhood tumors – Wilm’s tumor,
adrenal carcinoma, hepatoblastoma,
Etiology: Variety of causes – congenital, acquired rhabdomyosarcoma, neuroblastoma
o Most common causes are:  Nevus flammeus
 1. Vascular malformations
 2. Muscuslar hypertrophy
Histology: Depends on underlying conditions
o Down syndrome: normal structures
Gender: No predilection o Lymphangioma, hemangioma: proliferation of lympho-
Age: Commonly presents in childhood vascular vessels
Site: Tongue o Neurofibromatosis: histology of neurofibroma
Clinical features: Variable appearance o Beckwith-Wiedeman: muscular hyperplasia
o 1. Diffuse, smooth enlargement: Beckwith-Wiedeman o Amyloidosis: amyloid deposits
syndrome, hypothyroidism Treatment:
o 2. Multinodular enlargement: amyloidosis, o No treatment necessary in most cases
neurofibromatosis, MEN o Identify and treat underlying cause – address any
o 3. Pebbly, cluster of vesicle-like blebs – lymphangioma associated manifestations
o 4. Papillary, fissured surface – Down syndrome o Reduction glossectomy
o 5. Unilateral enlargement – hemifacial hyperplasia
o Functional problems – drooling, difficulty eating, speech
problems – lisping
o Open bite, mn prognathism
o Ulceration related to exposure
o Airway compromise in severe cases
o Beckwith-Wiedemann syndrome
 Omphalocele (intestinal protrusion through abdominal
wall)
 Visceromegaly (enlargement of organs)
 Gigantism
 Neonatal hypoglycemia
What is this?
Ankyloglossia
AKA: Tongue tie
Etiology: Developmental anomaly; Short, thick lingual frenum
Incidence: 1.7-4.4% neonates
Gender: M>F
Age: Wide age range; mostly children
Site: Lingual frenum
Clinical features: Variable severity, may cause clefting of tongue, may
cause periodontal problems, Other (controversial) implications: Anterior
open bite, speech defects, feeding difficulties in neonates, dyspnea
(anterior and superior displacement of epiglottis and larynx)
Treatment: No treatment necessary if no complications, may self-correct
over time.
o Surgical correction after age 4-5 yo
 1. Frenotomy – release of frenum
 2. Frenuloplasty – release of frenum + plastic repair
What is this?
Lingual thyroid
Etiology: Improper descent of thyroid bud  “ectopic” thyroid tissue between foramen cecum and epiglottis
Gender: F>M (hormonal influences)
Age: Onset of symptoms – puberty, adolescence, pregnancy, menopause
Site: Tongue, between foramen cecum, epiglottis, most common site ectopic thyroids (90%)
Embryology – thyroid gland development:
o Week 3 and 4: Epithelial proliferation in floor of pharyngeal gut, between tuberculum impar and copula of tongue (“thyroid
bud” = primitive thyroid gland)
o Week 7: Thyroid bud invaginates, descends into neck; anterior to hyoid bone, trachea, larynx; loops up behind, then below
thyroid cartilage; foramen cecum = site of invagination, junction anterior 2/3 tongue and posterior 1/3 tongue
Clinical features:
o Small, asymptomatic, nodule or mass, Reddish (vascular-appearing or normal color; large symptomatic lesions are rare
 Affects F>M, dysphagia, dyspnea, dysphonia
o Hypothyroidism – 33% pt
o Lingual thyroid only functioning thyroid tissue – 70%
Diagnosis: Thyroid scan (iodine isotopes, technicium – 99m)
o Imaging – CT, MRI
o Avoid biopsy if possible
 1. Risk hemorrhage
 2. May be only functioning thyroid tissue (70%)
Treatment:
o Asymptomatic – periodic follow-up
o Symptomatic – suppressive therapy, excision, radioactive iodine-131
Prognosis: Risk hypothyroidism with excision, radioactive I-131
o Malignant transformation (papillary thyroid carcinoma)
 Very rare (~1%), more common in males, prophylactic excision of lingual thyroids in males older than 30 (controversial)
What is this?
Fissured tongue
Etiology: May be hereditary, aging, environmental factors may contribute
Incidence: 2-5% of population, increases with age
Gender: M>F (slightly)
Age: Adults; can be seen in children
Site: Dorsal, lateral tongue
Clinical features: variable involvement, severity; diffuse fissuring – large central
fissure with branching fissures; Mostly asymptomatic – mild burning/soreness
o Often associated with geographic tongue**
o Component of Melkersson-Rosenthal syndrome
 1. Orofacial granulomatosis
 2. Facial paralysis
 3. Fissure tongue
Histology: some loss of keratin, epithelial hyperplasia, intraepithelial neutrophils,
deep grooves, mixed inflammation in connective tissues
• Treatment: No treatment necessary, clinical recognition, reassure patient, gentle
tongue brushing to
What is this?
Hairy tongue
AKA: Black hairy tongue, coated tongue
Etiology:
o Accumulation of keratin on filiform papillae
 1. Increase in keratin production
 2. Lack of normal keratin desquamation
o Secondary pigmentation from extrinsic factors, such as tobacco, foods, medications,
chromogenic bacteria
Incidence: 0.5% adults, higher in smokers; debilitated states, poor OH, history
radiation therapy to head and neck
Age: Adults
Site: Dorsum of tongue – midline, anterior to circumvallate papillae
Clinical features: Elongated filiform papillae; White, yellow, brown, black; Mostly
asymptomatic, gagging sensation, foul taste - **NOT hairy leukoplakia (EBV)
Histology: Elongated filiform papillae, hyperparakeratosis of filiform papillae,
surface bacterial debris
Treatment: No treatment necessary, encourage good OH, periodic scraping or
brushing, discontinue contributing factors (e.g. tobacco)
What is this?
Varicosities
AKA: Varices
Etiology: Abnormal dilation of veins
o age-related degeneration of CT tone supporting veins
o no association with hypertension, cardiopulmonary diseases
Age: Older adults
Site: Lateral-ventral tongue (sublingual varices), Lips, buccal mucosa
Clinical features: Usually asymptomatic, blue-purple, elevated, linear or papular, may be firm if
thrombosed (“buckshot” under mucosa), blanch with diascopy
o Clinical test – pressure applied to lesion with a transparent object
o Assess blanchability of vascular lesions
Histology:
o Dilated vein: wall – little smooth muscle, poorly developed elastic tissue
o Thrombus = rounded accumulation of platelets and erythrocytes (lines of Zahn) ± granulation tissue, may be
calcified (“phlebolith”)
Treatment:
o Sublingual varicosities: no treatment necessary, reassure patient
o Varicosities of lips, buccal mucosa: no treatment necessary upon clinical recognition; excision for definitive
diagnosis, esthetics
Coronoid hyperplasia
Excessive growth of coronoid
Etiology: Rare developmental anomaly, cause unknown – endocrine factors, heredity
Gender: M>F (5:1)
Age: Present in puberty
Site: Coronoid – bilateral>unilateral
Unilateral coronoid hyperplasia
o Clinical features:
 Limitation of mandibular movement – deviation of mandible towards affected side
 Typically painless, typically no malocclusion
o Radiographic features:
 Tip of coronoid – irregular, nodular enlargement - **May mimic true tumor (osteoma, osteochondroma)
Bilateral coronoid hyperplasia
o Clinical features: Limitation of mandibular movement – progressive worsening, peak late teenage yrs
o Radiographic features: Tip of coronoids – regular enlargement
o **CT scans, bone scintigraphy helpful in diagnosis
Treatment: Surgical removal (coronoidectomy, coronoidotomy) + post-operative physiotherapy
o Complications: Surgical fibrosis, coronoid regrowth
What is this?
Normal Proliferation
Condylar hyperplasia
Excessive growth of condyle
Etiology: Developmental anomaly, cause unknown – circulatory abnormalities?
endocrine factors?, trauma?
Age: Adolescents, young adults
Site: Condyle – usually unilateral
Clinical features: variable presentation, facial asymmetry, deviation of mandible
opposite to affected side, prognathism, compensatory maxillary growth, crossbite,
open bit; tilt of occlusal plane
Radiographic features: Enlargement of condylar head, elongation of condylar neck,
hyperplasia of ramus, CT scans, bone scintigraphy helpful in diagnosis
Histology: proliferation of condylar cartilage during active growth, normal-
appearing condyle on growth cessation
Treatment: Self-limiting, condylectomy if functional limitations or esthetic
concerns, prognathism – unilateral, bilateral mandibular osteotomies; distraction
osteogenesis, maxillary overgrowth – maxillary osteotomy; comprehensive
orthodontics
What is this?
Condylar hypoplasia
Underdevelopment of condyle
Condylar agenesis = complete lack of condyle or ramus
Etiology: Congenital or acquired
o Congenital – syndromes (mandibulofacial dysostosis, Goldenhar syndrome, hemifacial
microsomia)
o Acquired – trauma, infections, radiation therapy, arthritis (rheumatoid, degenerative)
Gender: not specified
Age: Not specified
Site: Condyles – unilateral or bilateral
Clinical features: Small mandible, class II malocclusion, distortion, depression of
face – affected side, devation of mandible towards affected side, if trauma-related
may be associated with TMJ ankylosis
Radiographic features: short condylar process, poorly-formed condylar head,
shallow sigmoid notch, prominent antigonial notch, CT scans may be helpful
Treatment: costochondral rib graft; osteotomies, distraction osteogenesis where
appropriate
What is this?
Bifid condyle
Double-headed condyle – usually medial and lateral
head
Etiology: rare developmental anomaly; cause unknown
- ?trauma, abnormal muscle attachment, teratogens,
persistent fibrous septum in condylar cartilage
Site: Condyle – unilateral>bilateral
Clinical features: usually asymptomatic, TMJ – “pop” or
“click”
Radiographic features: bilobed condyle – medial,
lateral heads
Treatment: No treatment if asymptomatic
What is this?
Exostosis
Etiology: Likely multifactorial; roles for bony hard ± overlying ulceration if
genetics and environmental factors secondary trauma
(local stresses, irritation); may develop Radiographic features: Well-defined
in area of gingival graft (graft radiopacity, may be superimposed
stimulates periosteum to lay down over roots of adjacent teeth
bone) Histology: benign, dense, lamellar
Gender: No predilection bone, ± hematopoietic bone marrow
Age: Adults Treatment: No treatment necessary
Site: upon clinical recognition,
o Buccal or facial aspects of mx/mn biopsy/removal for definitive diagnosis
alveolar ridge – usually bilateral if suspicious of other bony pathology,
o Palatal aspect of mx tuberosities = palatal
exostoses
removal if interferes with dentures,
o In areas of previous gingival grafts oral function or oral hygiene
o Under pontics of bridges = reactive
subpontine exostosis, subpontine
osseous proliferation/hyperplasia
Clinical features: Nodular growths,
What is this?
Torus
1. Torus palatinus – palate
2. Torus mandibularis – lingual mandible
Etiology: likely multifactorial – roles for genetics and environmental factors (e.g. masticatory stress)
Prevalence: Torus palatinus > torus mandibularis
Ethnic: More common in Asians and Inuits
Gender: Torus palatines F>M (2:1), Torus mandibularis – M slightly > F
Age: Early adult life
Clinical features:
o Torus palatinus
 Midline, hard palate, bony hard ± overlying ulceration if secondary trauma
 Clinical variants
1. Flat – broad base, slightly convex
2. Spindle – prominent midline ridge
3. Nodular – multiple protuberances with individual bases
4. Lobular – multiple protuberances on single base
o Torus mandibularis
 Lingual mandible – region of premolars, above mylohyoid ridge
 Typically bilateral, bony hard ± overlying ulceration
Radiographic features: radiopacity superimposed over roots of premolars
Histology: benign, dense, lamellar bone ± hematopoietic bone marrow
Treatment: No treatment necessary upon clinical recognition. Biopsy/removal for definitive
diagnosis, if suspicious of other bony pathology – removal if interferes with dentures or oral
function
What is this?
Eagle Syndrome
Etiology: Symptoms caused by impingement of nerves or blood vessels due to:
o 1. Elongation of styloid process
o 2. Calcification of stylohyoid ligament complex
 Styloid process = bony projection from inferior aspect of temporal bone
 Stylohyoid ligament = ligament connecting styloid process to lesser cornu of hyoid bone – flanked by internal, external
carotid arteries
o Classically associated with history of tonsillectomy – surgical fibrosis with mineralization stylohyoid complex
 impingement of CN V, VII, IX, X
 Carotid artery syndrome, stylohyoid syndrome
Symptoms of Eagle syndrome
Not associated with hx of tonsillectomy
Elongated, mineralized stylohyoid complex  impingement if internal and external carotid arteries, sympathetic nerve fibers
Age: Adults
Clinical features: vague facial pain – especially during swallowing, turning head, opening mouth;
dysphagia, dysphonia, otalgia, headache, dizziness, transient syncope, pain on palpation of tonsillar
fossa area
Radiographic features: Panorex, lateral-jaw radiographs – elongation of stylohyoid process,
calcification of stylohyoid ligament complex
Treatment: Mildly symptomatic – no treatment necessary, steroid injections; Severe symptoms –
surgical excision of styloid process or stylohyoid ligament
What is this?
Stafne defect
AKA: Stafne bone cyst, lingual mandibular salivary gland depression, static bone defect
Etiology: Developmental defect – Concavity of lingual mn, rarely completely intrabony
o Predominantly contains normal salivary gland tissue (submandibular gland)
o May be devoide of contents; contain other connective tissue elements
Incidence: 0.3% all panoramic
Gender: M>>F (80-90% males)
Age: Middle aged, older adults, “Develops” at later age
Site: Posterior mandible – unilateral>bilateral; rarely, anterior mandible (anterior lingual salivary
gland defect)
Clinical features: asymptomatic, may be palpable notch at inferior border of mn
Radiographic features: Round, radiolucent, well-defined; corticated, predominantly posterior
mandible, between molars and angle **Below inferior alveolar canal
Histology: normal salivary gland tissue; rarely, devoid tissue or CT elements
Diagnosis: based on clinical and radiographic findings, CT scan, MRI, sialography may help
Treatment: No treatment necessary upon clinical recognition; biopsy if doubt
Developmental cysts
Cyst = epithelial-lined cavity
o 1. Lumen
o 2. Epithelial lining
o 3. Cyst wall
o Fissural cyst = cyst deriving from epithelial
remnants trapped along embryonal lines of fusion
What is this?
Palatal cyst of the newborn
Etiology: Developmental “inclusion” cysts
o 1. Entrapment of surface epithelium during fusion of palatal shelves
o 2. Cystification of epithelial remnants of salivary glands
o Epstein’s pearls – median palatal raphe
o Bohn’s nodules – scattered over hard palate
o In contrast to gingival cysts of the newborn – odontogenic cysts, occur on alveolar ridge
Incidence: Common – 65-85% infants
Age: Infants
Site: Epstein’s pearls – median palatal raphe; Bohn’s nodules – scattered over
hard palate
Clinical features: White-yellow papules, small, 1-3mm
Histology: Rarely biopsied; epithelial lining: stratified squamous, thin and flat,
keratotic surface; Cyst wall: fibrous connective tissue (submucosa), keratin in
lumen
Treatment: No treatment necessary upon clinical recognition, most spontaneously
resolve, usually after several weeks
What is this?
Nasolabial cyst
AKA: Nasoalveolar cyst
Etiology: Two theories
o 1. “Fissural” theory: epithelial remnants along fusion line of maxillary, medial nasal, lateral
nasal processes
o 2. Misplaced epithelium from nasolacrimal duct (favored)
Gender: F>M (3:1)
Age: Adults – 4th-5th decades
Site: Upper lip, lateral to midline
Clinical features: swelling of upper lip, lateral to midline; elevation of ala of nose;
obliteration of maxillary mucolabial fold; pain if infected
Radiographic features: soft tissue cysts – usually, no radiographic changes; rarely,
pressure resorption of maxilla
Histology:
o Epithelial lining: pseudostratified columnar ± mucous cells
o Cyst wall: fibrous connective tissue, striated muscle ± inflammation
Treatment: Surgical excision – intraoral, transnasal approach, recurrences rare
What is this?
“Globulomaxillary” cyst
**Not a distinct entity, term should no longer be used
Etiology: Originally thought to be a fissural cyst – arising
from epithelium entrapped during fusion of globular
portion of medial nasal process and maxillary process; BUT,
no such fusion occurs embryologically – historically, term
given to radiolucency in lateral incisor/canine region –
“inverted pear” configuration.
All cysts previously termed “globulomaxillary” cysts have
been histologically diagnosed as:
o 1. Inflammatory odontogenic cysts (e.g. periapical cysts)
o 2. True developmental odontogenic cysts (e.g. odontogenic
keratocysts, lateral periodontal cysts)
What is this?
Nasopalatine duct cyst
AKA: Incisive canal cyst
Most common non-odontogenic cyst
Etiology: Developmental cyst; Likely, cystic degeneration of epithelial remnants of nasopalatine ducts
o Nasopalatine ducts
 Embryologic, epithelial structures that run from nasal cavity to oral cavity
 Housed within incisive canal (floor nasal cavity  palatal bone  incisive foramen)
 Degenerates in adults; leaves remnants
Prevalence: ~1% of population
Gender: M slightly > F
Age: 4th-6th decades
Site: Anterior palate, midline – at area of incisive papilla
Clinical features: asymptomatic, swelling; if infected, may be pain ± drainage; if entirely in soft tissue = “cyst of
incisive papilla” – soft and fluctuant; blush
Radiographic features:
o Size: ~1-2.5 cm if <6mm = normal incisive foramen
o Shape: Round to ovoid; Heart-shaped; inverted pear-shaped, unilocular
o Density: Radiolucent
o Borders: Well-defined, corticated
o Location: Between and apical to central incisors
Histology:
o Epithelium: stratified squamous, pseudostratified columnar, respiratory-type, simple columnar, simple cuboidal ± cilia, ± mucous
cells
o Wall: nerves, blood vessels, mucous glands, ± hyaline cartilage, ± mixed inflammation
Treatment: Surgical enucleation, recurrence rare
What is this?
Median palatal cyst
AKA: Median palatine cyst
Etiology: rare fissural cyst – derives from entrapped epithelium in fusion line between lateral
palatal shelves; May be mistaken for posteriorly displaced nasopalatine duct cyst
Age: Young adults
Site: Posterior hard palate (posterior to incisive papilla), midline
Clinical features: asymptomatic; rarely pain – firm or fluctuant swelling; ~2x2cm
o Size: ~2cm diameter
o Shape: Round, ovoid; unilocular
o Borders: Well-defined; corticated
o Location: Posterior hard palate, midline; symmetric
 NOT associated with non-vital tooth
 NO communication with incisive canal
Histology:
o Epithelium: stratified squamous ± pseudostratifed columnar areas
o Wall: fibrous connective tissue ± chronic inflammation
Treatment: Surgical enucleation, recurrences not noted
What is this?
Follicular cyst of the skin
Etiology:
o Epidermoid (infundibular) cyst of the skin: Most common; likely non-neoplastic proliferation
of infundibular epithelium – due to localized inflammation of hair follicle; AKA: “sebaceous”
cyst – not sebaceous in origin
o Epidermal inclusion cyst: traumatic implantation of epithelium
o Pilar (trichilemmal) cyst
Incidence:
o Epidermoid cysts of the skin – 80%
o Pilar cysts – 10-15%
Epidermoid cysts of the skin
o Gender: M>F
o Age: Young and older adults; if younger and multiple consider Gardner syndrome
o Site: acne-prone areas (head, neck, back); young adults – face; older adults – back
o Clinical features: fluctuant nodule; central pore – may express cheesy material; if non-
inflamed – white or yellow; if inflamed – red
o Histology:
 Epithelium: orthokeratinized stratified squamous epithelium, granular cell layer, keratin in lumen
 Wall: fibrous connective tissue (dermis) ± inflammation, foreign body giant cell reaction
o Treatment: conservative surgical excision, recurreneces rare
What is this?
Hair Cyst
follicle lumen
Cyst
Sebaceo lining
us glands Hair
follicle
Dermoid cyst
Etiology: Developmental cystic malformation, on spectrum of teratomas
o 1. Epidermoid cyst: cyst; no evidence of skin appendages, epidermoid cyst of the skin – different etiology
o 2. Dermoid cyst: cyst; evidence of skin appendages
o 3. Teratoid cyst (cystic teratoma): cyst; derivatives from all 3 germ layers
o 4. Complex (true) teratoma: neoplasm; derivatives from all 3 germ layers
Embryonic germ layers:
o 1. Ectoderm: epithelium, skin appendages (hair follicles, sebaceous glands, sweat glands), teeth
o 2. Mesoderm: connective tissue elements (muscle, nerve, blood vessels, fat, bone)
o 3. Endoderm: gastrointestinal lining, among others
Age: Children, young adults – congenital – 15% of cases
Site:
o Oral cavity – epidermoid cysts, dermoid cysts, complex teratomas very rare
o Dermoid cysts – most common floor of mouth, midline
Clinical features: Slow-growing; painless; swelling under tongue, midline; “doughy” on palpation; if above
geniohyoid muscle – sublingual swelling, may cause dysphagia, dysphonia, dyspnea; If below geniohyoid muscle
– submental swelling, “double-chin”
Radiographic findings: MRI, CT scans – cystic lesion
Histology:
o Epithelium: orthokeratinized stratified squamous; rarely, respiratory, granular cell layer
o Wall: fibrous connective tissue, skin appendages:
 1. Hair follicles
 2. Sebaceous glands
 3. Sweat glands
Treatment: surgical excision, recurrences uncommon, malignant transformation exceedingly rare
What is this?
Thyroglossal duct cyst
Etiology: developmental cyst, cystic degeneration of epithelial remnants of embryonic thyroglossal
duct - ?inflammation, secretions in duct, heredity
o Thyroglossal duct: recall thyroid development in session on “lingual thyroid”
 Thyroglossal duct = epithelial tract formed during descent of thyroid bud
 Tongue  anterior to hyoid bone  loops behind hyoid bone  lower neck
Age: First 2 decades (<20yo)
Site: Midline neck – may be deflected slightly lateral, anywhere from foramen cecum to
suprasternal notch
Clinical features: Painless, fluctuant, movable swelling; usually ~3cm in diameter; If attached to
hyoid or tongue, moves upon swallowing ± drainage, fistulous tract if infected
Histology:
o Epithelium: columnar or stratified squamous, or epithelial types
o Wall: fibrous CT, thyroid tissue – usually present
Treatment:
o Sistrunk procedure: removal of cyst, midline segment of hyoid bone, muscle along thyroglossal tract,
recurrence <10%
o Risk of malignant degeneration: ~1% cases, papillary thyroid carcinoma, prognosis still good
What is this?
Branchial cleft cyst
AKA: Cervical lymphoeptihelial cyst
Etiology: Developmental cyst, etiology controversial – many theories
o 1. Cystic degeneration of remnants of branchial clefts (favored) – 2nd branchial arch > 1st, 3rd,
4th
o 2. Cystic changes in parotid gland epithelium entrapped in cervical lymph nodes
Age: Young adults (20-40 yo)
Site: Upper lateral neck, anterior border of SCM, Left > Right
Clinical features: soft, fluctuant swelling, ~1-10cm in diameter ± tenderness, pain
if infected, ± sinust tract with drainage
Histology:
o Epithelium: stratified squamous ± keratinization (~90%), respiratory epithelium
o Wall: fibrous CT, lymphoid tissue
Treatment: surgical excision, malignant transformation exceedingly rare; true
malignant transformation questioned, criteria for malignant branchial cleft cyst
very strict, most “branchial cleft cysts” with malignant features – likely represents
cystic metastases from other primary H&N SCCs
What is this?
Oral lymphoepithelial cyst
Etiology: developmental cyst, invagination of surface epithelium into
lymphoid tissue (favored.
o Other theories: cystic degeneration of entrapped salivary or surface mucosa;
cystification of salivary excreteory ducts with secondary lymphoid response
Age: Any age; young adults
Site: Any site with lymphoid tissue – floor of mouth > ventral, posterior
lateral tongue, palatine tonsil, soft palate
Clinical features: asymptomatic; pain if traumatized, white or yellow,
smooth-surfaced, nodule or mass, soft or firm
Histology:
o Epithelium: parakeratinized stratified squamous, keratin lumen
o Wall: fibrous CT, lymphoid tissue
Treatment: surgical excision, if clinical recognition, biopsy may not be
required
What is this?
Hemihyperplasia
Unilateral overgrowth of one or more body parts due to increase in # of cells (“hyperplasia”)
AKA: Hemihypertrophy – term “hemihyperplasia” more appropriate
Etiology: etiology unknown - ?vascular, lymphatic abnormalities; CNS disturbances; endocrine
dysfunction, etc.; isolated/ associated with syndromes
Gender: F:M = 2:1
Age: Birth – asymmetry, increasingly evident with age, ceases upon overall growth cessation
Site: R>L; occasionally involves different areas on both sides
o 1. Complex – entire side of body
o 2. Simple – one limb
o 3. Face only – “hemifacial hyperplasia”
Clinical features: enlargement of affected structures, thickened skin - ± hyperpigmentation,
hypertrichosis (excess hair), telangiectasias (superficial blood vessels), nevus flammeus
o Mental deficiencies – 20%
o Abdominal tumors – 5.9% Wilm’s tumors, adrenal cortical carcinoma, hepatoblastoma
Orofacial manifestations: Unilateral macroglossia, enlargement of other oral soft tissues, hard
tissues – IAN and IAN canal, teeth; premature tooth development, eruption, malocclusion, open
bite
Histology: Hyperplasia of epithelium, epidermis, connective tissue elements
Treatment: Evaluation to rule out underlying syndromes, evaluation for abdominal tumors, surgical
reduction for esthetics – plastic surgery, orthognathic surgery, orthodontic therapy for malocclusion
What is this?
Progressive hemifacial atrophy
Progressive atrophic changes on one side of face
Etiology: degenerative condition, poorly understood - ? trophic malfunction of cervical sympathetic
nervous system, trauma, Borrelia infection (lyme disease), heredity, overlapping features with
scleroderma
Gender: F>M
Age: First 2 decades
Site: Face – unilateral
Clinical features: Follow dermatome of trigeminal nerve, atrophy, pigmentation of skin, sharp line
of demarcation between affected and unaffected skin (“en coup de sabre”)
o Eye – enophthalmos (recession of eye)
o Scalp – localized alopecia (loss of hair)
o May involve bone – esp, if onset in 1st decade
Orofacial manifestations: deviation of mouth and nose towards affected side, atrophy upper lip,
atrophy tongue, mandibular hypoplasia, delayed eruption of teeth, deficient roots, posterior open
bit
Other complications: trigeminal neuralgia, facial paresthesia, epilepsy
Histology: atrophy of epithelium, epidermis, ± chronic inflammation, ±fibrosis
Treatment: stabilizes with time, surgery to improve esthetics – plastic surgery, orthognathic surgery;
orthodontic therapy for malocclusion
What is this?
Crouzon syndrome
Craniosynostosis = syndromes caused by premature closure of sutures
Etiology: mutation in fibroblast growth factor receptor 2 (FGFR2) gene – autosomal dominant;
sporadic mutation; risk factors = increased paternal age
Gender: not specified
Age: apparent at birth
Site: skull and face, symmetric
Clinical features: Malformation of skull:
o 1. Brachycephaly – short head
o 2. Scaphocephaly – boat-shaped head
o 3. Trigonocephaly – triangle-shaped head
o 4. “Cloverleaf” skull (kleeblatt-schadel)
o Shallow orbits  ocular proptosis
o Visual impairment or loss (exposure of eyes, increased cranial pressure, compression optic nerves),
Headaches, Typically, no mental deficiencies
Orofacial manifestations: Maxillary hypoplasia; relative mn prognathism, crowding of teeth,
malocclusion, usually class III, rarely, CL and CP, lateral palatal swelling (“pseudocleft”)
Radiographic features: digital markings (“beaten-metal” pattern)
Treatment: Early craniectomy to open sutures; multidisciplinary approach:
o Medical, surgical: craniofacial surgery, including OS; neurosurgery
o Dental: orthodontic therapy
o Allied resources: social worker, speech therapist
What is this?
Apert syndrome
Etiology: craniosynostosis, mutation in FGFR2 gene – most sporadic, some autosomal dominant
o Risk factor: increased paternal age
Age: apparent at birth
Site: Skull and face, symmetric
Clinical features: malformation of skull – “acrobrachycephaly” – tower head, tall forehead; ocular
proptosis, hypertolerism; visual impairment or loss (exposure of eyes, increased cranial pressure,
compression optic nerves); middle ear infections, conductive hearling loss; beak-like nose
o Syndactyly = fusion of digits, hands and feet – always 2nd, 3rd, 4th digits; 1st and 5th may be affected
o Acne-like eruption of forearms, respiratory difficulties (reduced size of nasopharynx, narrowing of posterior
choanae), mental deficiencies
Radiographic features: Increased digital markings (“beaten metal”), fusion of phalanges – hand x-
ray
Orofacial manifestations: Midface hypoplasia; relative mn prognathism, “Trapezoid” – shaped
mouth, open mouth, mouthbreathing, V-shaped mx arch, teeth crowding, malocclusion – class III,
anterior open bite, posterior crossbite, cleft of soft palate, uvula -3/4 patients, lateral palatal
swelling (“pseudocleft”), gingival thickening – delayed eruption of teeth
Treatment: early craniectomy, Multidisciplinary approach
o Medical, surgical: craniofacial surgery, including OS; neurosurgery
o Dental: orthodontic therapy
o Allied resources: social worker, speech therapist
What is this?
Mandibulofacial dysostosis
AKA: Treacher Collins syndrome parotid gland hypoplasia
Etiology: Mutation of TCOF1 (treacle) gene Other complications: Respiratory difficulties
o Autosomal dominant; sporadic mutations, risk (nasopharyngeal, oropharyngeal,
factors: increased paternal age, variable hypopharyngeal hypoplasia)
expressivity, increased severity in subsequent Treatment: in severe cases, can consider
generations, defective development of
structures of 1st and 2nd branchial arches surgery, address any respiratory distress;
Gender: Not specified Multidisciplinary approach:
o Medical, surgical: plastic surgery (zygomas, ear),
Age: Apparent at birth craniofacial surgery
Site: Face, ears – symmetric o Dental: orthodontic therapy
Clinical features: Hypoplastic zygomas  o Allied resources: social worker, speech therapist
depressed cheeks, narrow face, downward-  Genetic counseling
slanting of lower eyelids, coloboma (notch of
outer lower eyelid), ear anomalies – deformed
pinnae, ear tags, conductive hearling loss,
tongue-shaped extension of sideburns
Orofacial manifestations: small mandible 
retrognathic profile, class II, hypoplasia of
condyle and coronoid processes, prominent
antigonial notching, cleft palate – 1/3 patients,
lateral facial cleft – 15% patients, may have
What is this?
Turner’s Hypoplasia
Caused by periapical inflammatory disease of overlying deciduous tooth
Most frequent in permanent premolars because of their relationship to overlying
deciduous molars
Factors that determine degree of damage to permanent tooth by overlying
infection include:
o Stage of tooth development
o Length of time infection remains untreated
o Virulence of infective organisms
o Host resistance to infection
Other causes include: traumatic injury to deciduous teeth
o Maxillary central incisors affected in most cases, maxillary lateral incisors less frequently
o Because of position of primary apices relative to the tooth bud –
 Facial surface of maxillary incisors = location frequently affected
Summary:
o Injury to deciduous tooth/teeth  defect occurs in permanent teeth
o Periapical infection deciduous posterior tooth  premolars affected
o Trauma to anterior deciduous teeth  facial surfaces of maxillary central incisors
What is this?
Dilaceration
Trauma causing displacement of already formed hard-
tooth substance in relation to soft tissue of remaining
developing tooth  bend in the tooth
Can affect crown or root of a tooth
Most frequently affected teeth:
o 1. Permanent maxillary incisors
o 2. Mandibular anteriors
Severity of angulation related to age of the patient and
direction and degree of force applied
Dilaceration of roots may produce delayed eruption or
difficulties during root canal therapy or extraction
What is this?
Congenital syphilitic hypoplasia
Hutchinson’s incisors
o Anterior teeth altered by syphilis
o Crowns shaped like straight-edged screwdrivers with
greatest circumference present in middle 1/3rd of the
crown and is constricted incisal edge
o Middle portion of incisal edge often demonstrates a
central hypoplastic notch
Mulberry molars
o Altered posterior teeth
o Demonstrate constricted occlusal tables with disorganized
surface anatomy resembling the bumpy surface of a
mulberry
Amelogenesis imperfecta
• See handout for information/PPT for pictures
What is this?
Dentinogenesis imperfecta
Hereditary developmental disturbance of dentin in the absence of any systemic disorder
Similar dental changes may be seen in conjunction with the systemic hereditary disorder of bone, osteogensis imperfecta
Third type of dentinogenesis imperfecta – Shields’ type III – not a separate disease – merely represents a variation of expression of Shields’ type II
o Witkop’s Brandywine isolate
Dentinogenesis imperfecta: defective dentin formation with opalescent teeth (deciduous and permanent) without systemic disease
Osteogenesis imperfect w/ opalescent teeth:
o Dentin defects associated w/ systemic bone disease
o Dentinogenesis imperfecta – a disorder distinct from osteogenesis imperfecta
Clinical features: Autosomal dominant, most cases in whites of English or French ancestry from communities close to the English Channel, occurs in ~
1:8000 whites
o Dental alterations in Dentinogenesis imperfecta and osteogenesis imperfecta w/ opalescent teeth have similar clinical, radiographic and histopathologic
changes
o All teeth in both dentitions affected
o Enamel hypoplasia – secondary defect
o Pulps usually obliterated by excess dentin production – some pulps may be normal or enlarged
 Shell teeth: normal enamel thickness, thin dentin, dramatically enlarged pulps, most common in deciduous teeth in presence of DI
o Affected from most to least severely: Deciduous teeth > Permanent incisors and first molars > Second and third molars
o Accelerated attrition
o Teeth have: Bulbous crowns, cervical constriction, thin roots, early obliteration of root canals and pulp chambers
Brandywine isolate: Slow but progressive root resorption occurs – current evidence strongly supports the Brandywine isolate representing nothing
more than variable expressivity of the gene for DI.
o 8% of kindred have enlarged pulp chambers, variable expressivity
Histopathologic features: altered dentin, dentin adjacent to enamel junction similar to normal dentin, atypical granular dentin matrix –
interglobular calcification, atypical odontoblasts, enamel is normal in most patients - ~33% of patients have hypoplastic or hypocalcified defects
Treatment and prognosis: root canals become threadlike and may develop micro-exposures  periapical inflammatory lesions, teeth are not good
candidates for full crowns because of cervical fracture, over the long term, most patients are candidates for full dentures or implants by 30 years of
age in spite of numerous interventions.
Dentinogenesis imperfecta cont.
What is this?
Dentin Dysplasia Type I
Clinical Features:
o Rootless teeth – loss of organization of root dentin often  shortened root length
o Autosomal dominant pattern of inheritance, 1:100,000
o Enamel and coronal dentin normally well-formed clinically
o Radicular dentin loses all organization – shortened dramatically
o Wide variation in root form – dentinal disorganization may occur during different stages of tooth development
o Variability: most pronounced in permanent teeth
o Shortened roots: extreme tooth mobility, premature exfoliation
o Radicular strength of dentin reduced – predisposes teeth to fracture during extractions
o Deciduous teeth: affected severely, little or no detectable pulp, roots are short/absent
o Permanent teeth: vary according to proportion of organized vs. disorganized dentin
o Early disorganization: pulp not detected, roots extremely short or absent
o Later disorganization: chevron shaped pulp chambers, shortened roots, no pulp canals
o Late disorganization: normal pulp chambers overlying roots with large pulp stone
o Teeth without root canals frequently develop periapical inflammatory lesions w/ obvious cause
Histopathologic features:
o Coronal enamel and dentin = normal
o Central portion of root = whorls of tubular dentin, atypical osteodentin
o W/ polarized light = “stream flowing around boulders”
Treatment and Prognosis:
o Preventive care, pulp vascular channels extend close to dentinoenamel junction
o Shallow occlusal restorations  pulpal necrosis
o Meticulous oral hygiene
Dentin dysplasia type I cont.
What is this?
Dentin dysplasia type II
Clinical features: Clinical features: no racial predilection, occurs in both dentitions, F>M,
o Exhibit numerous features of Dentinogenesis imperfecta focal area of dentition, with involvement of several contiguous teeth,
o Autosomal dominant inheritance, root length normal in both MX > MN (2.5:1), anterior teeth, involvement of deciduous dentition –
dentitions followed by similarly affected permanent teeth, surrounding bone
o Deciduous teeth closely resemble those of Dentinogenesis often exhibits a lower density, many affected teeth fail to erupt
imperfecta
o Erupted teeth – small yellow-brown, irregular crowns, rough surfaces
o Bulbous crowns, cervical constriction, thin roots, early obliteration of
o Caries associated with periapical inflammatory lesions common
the pulp
Radiographic features: thin enamel and dentin surrounding an
o Pulp chambers exhibit significant enlargement and apical extension
enlarged radiolucent pulp – pale wispy image of a tooth, lack of
o Altered pulpal anatomy described as thistle tube-shaped, flame- contrast b/w enamel and dentin, shorts roots w/ open apices, enlarged
shaped pulps frequently demonstrate one or more prominent pulp stones
o Pulp stones develop in enlarged pulp chambers Most common presenting signs and symptoms: delayed/failure of
Histopathologic features: eruption, early exfoliation, abscesses, malformed teeth, non-
o Deciduous teeth – same pattern described in Dentinogenesis inflammatory gingival enlargement
imperfecta Histopathologic features: follicular tissue surrounding crown may be
o Permanent dentition = normal enamel and coronal dentin enlarged and exhibits focal collections of basophilic enamel-like
o Adjacent to pulp = numerous areas of interglobular dentin calcifications called enameloid conglomerates
o Radicular dentin = atubular, amorphous, hypertrophic o Not specific for regional odontodysplasia
o Pulps stones develop in any portion of the chamber o Also seen in amelogenesis imperfecta
Treatment and prognosis: Treatment and Prognosis: retention of altered teeth whenever
o If PA inflammatory lesions develop – therapeutic choice is guided by possible, unerupted teeth should remain untouched, tooth
the root length
preparation contraindicated
• Regional Odontodysplasia (Ghost teeth)
Localized, nonhereditary developmental abnormality of teeth w/
extensive adverse effects on formation of enamel, dentin, and pulp
Most cases – idiopathic, often related to syndromes, growth
abnormalities, neural disorders, vascular malformations
Proposed causes: abnormal migration of neural crest cells, latent virus,
local circulatory deficiency, local trauma or infection, hyperpyrexia,
malnutrition, medication used during pregnancy, radiation therapy,
somatic mutation Most popular theory – altered vascular supply
What is this?
Regional odontodysplasia (Ghost
teeth)
Localized, nonhereditary developmental abnormality of teeth w/ extensive adverse effects on formation of
enamel, dentin, and pulp
Most cases – idiopathic, often related to syndromes, growth abnormalities, neural disorders, vascular
malformations
Proposed causes: abnormal migration of neural crest cells, latent virus, local circulatory deficiency, local trauma or
infection, hyperpyrexia, malnutrition, medication used during pregnancy, radiation therapy, somatic mutation
Most popular theory – altered vascular supply
Clinical features: no racial predilection, occurs in both dentitions, F>M, focal area of dentition, with involvement of
several contiguous teeth, MX > MN (2.5:1), anterior teeth, involvement of deciduous dentition – followed by
similarly affected permanent teeth, surrounding bone often exhibits a lower density, many affected teeth fail to
erupt
o Erupted teeth – small yellow-brown, irregular crowns, rough surfaces
o Caries associated with periapical inflammatory lesions common
Radiographic features: thin enamel and dentin surrounding an enlarged radiolucent pulp – pale wispy image of a
tooth, lack of contrast b/w enamel and dentin, shorts roots w/ open apices, enlarged pulps frequently
demonstrate one or more prominent pulp stones
Most common presenting signs and symptoms: delayed/failure of eruption, early exfoliation, abscesses,
malformed teeth, non-inflammatory gingival enlargement
Histopathologic features: follicular tissue surrounding crown may be enlarged and exhibits focal collections of
basophilic enamel-like calcifications called enameloid conglomerates
o Not specific for regional odontodysplasia
o Also seen in amelogenesis imperfecta
Treatment and Prognosis: retention of altered teeth whenever possible, unerupted teeth should remain
untouched, tooth preparation contraindicated
See handout for following information:
• Tooth Resorption **
• Tooth Discolorations
• Localized Disruptions in Eruption
• Developmental Alterations in the Number of
Teeth Developmental Alterations in the Size of
Teeth
• Developmental Alterations in the Shape of Teeth
• Periodontal Diseases
Pulpitis
Inflammation of the pulp may be worse in supine position, at night
 EPT response: Early – lower levels
Etiology: Inflammatory response of pulp to noxious stimuli Late – higher levels or no response ± mobility or sensitivity to percussion
 1. Eliminate invasive organisms May be asymptomatic
 2. Remove cellular debris 3. Chronic hyperplastic pulpitis (“pulp polyp”)
 3. Limit tissue damage
o Form of irreversible pulpitis
o During inflammation, inflammatory mediators cause vasodilation, increased blood flow,
o Etiology: Mechanical damage, bacterial damage  loss of dentinal roof, exposure of pulp;
and edema  localized increase in pulpal pressure Hyperplastic granulation tissue (= vascularized and inflamed connective tissue)
o Pulp chamber a confined space: increase in pulpal pressure  compression of o Gender: No predilection
vasculature  pulpal tissue necrosis o Age: Children, young adults
o Pulpal healing occurs in most cases.
o Site: Primary or permanent molars (large pulps)
o If insult is severe enough, healing mechanism overwhelmed  generalized pulpal necrosis o Clinical features: pink to red, nodular growth from pulp chamber, mostly asymptomatic
o 4 types of noxious stimuli:
 1. Mechanical damage: traumatic (accidents), iatrogenic (dental procedures), physiologic Histology:
(attrition, abrasion) o Most cases not examined histopathologically, histologic findings may not correlate with
 2. Thermal injury: heat conduction through metallic restorations, dental procedures, clinical severity
exothermic reactions from dental materials o Reversible pulpitis: hyperemia, edema, chronic inflammation, scattered acute
 3. Chemical irritation: erosion, acidic dental materials inflammatory cells
 4. Bacterial damage: direct damage from caries, indirect damage (vascular transport of
o Irreversible pulpitis: vessel congestion, necrosis with acute inflammatory cells,
bacteria)
surrounding and deeper pulpal CT – fibrosis, chronic inflammation
3 main types of pulpitis: o Chronic hyperplastic pulpitis: granulation tissue = well-vascularized and inflamed fibrous
o 1. Reversible pulpitis CT, stratified squamous epithelium ± ulceration, deeper pulp – fibrosis, chronic
o **Frank invasion by bacteria
inflammation
o 2. Irreversible pulpitis
o 3. Chronic hyperplastic pulpitis (“pulp polyp”)
Diagnosis:
o Dependent on:
1. Reversible pulpitis  1. Clinical presentation (onset of pain, duration of pain)
o Lower level of pulpal inflammation  2. Response to thermal stimuli
o Pulp can return to normal state after stimulus removed  3. Response to EPT
o Gender and age: No predilection  4. Response to percussion
o Site: Any tooth o Other conditions can have similar presentations – myofascial pain, trigeminal neuralgia,
o Clinical features: atypical facial neuralgia etc.
 Onset of pain: sudden Treatment:
 Duration of pain: short o Reversible pulpitis: removal of noxious stimulus/irritant, prognosis good, re-test for
 Stimulus: Cold, sweet or sour foods – Pain occurs with stimulus, subsides shortly after
vitality after symptoms alleviated
removal
 EPT response: responds to lower levels vs. cntrl o Irrversible pulpitis, chronic hyperplastic pulpitis: extraction of tooth OR endodontic
 No mobility, no sensitivity to percussion May progress to irreversible pulpitis therapy
2. Irreversible pulpitis
o Higher level of pulpal inflammation
o Pulp unable to return to normal state – irreversible damage
o Gender and age: No predilection
o Site: Any tooth
 Onset of pain: sudden, severe, sharp
 Duration of pain: long
 Stimulus: may be spontaneous, cold, heat, sweet or sour foods; Pain lingers after removal,
What is this?
Secondary and Tertiary Dentin
Dentin deposited throughout life  Significant traumatic injury  early obliteration of pulp
o Primary dentin – dentin deposited before completion of chamber and canal = calcific metamorphosis
crown Clinical features: reduced tooth sensitivity, reduced
o Secondary dentin – dentin deposited after completion of susceptibility to caries, dental trauma
crown o Impact on dental procedures:
o Tertiary dentin – dentin deposited in response to focal  Reduced susceptibility to mechanical trauma
injury  Reduced incidence of pulp exposures
Progressive reduction in size of pulp chamber and  Difficulty in endodontics (e.g. perforation)
o Calcific metamorphosis – yellow discoloration – usually
canals with age apparent ~1 year after trauma (early as 3 months)
• (Physiologic) Secondary Dentin Radiographic features:
o Etiology: Aging, occlusal forces, rare conditions (e.g. o Progressive decrease in size of pulp chamber and canals
progeria) o Calcific metamorphosis – early obliteration of pulp
o Gender: M slightly > F, association with calcification- chamber and canals
related diseases (arthritis, gout, kidney stones, HTN,
atherosclerosis)
Histology:
o Secondary dentin: regular dentin tubules, line of
o Age: Increases after age 35-40
demarcation b/w 1: and 2: dentin
o Site: Any tooth, generally proceeds from coronal to
o Tertiary dentin: depends on severity of stimulus;
apical, posterior teeth – primarily on pulpal floor > roof >
acellular dentin, irregular or disorganized dentinal
sidewalls
tubules
• Tertiary Dentin
o AKA: reactionary, reparative, irregular dentin
Treatment:
o Secondary dentin – no treatment
o Etiology: odontoblasts stimulated by focal injury e.g.
o Tertiary dentin – address etiology (caries)
attrition, abrasion, erosion, fracture, caries, etc.
 Mild damage – primary odontoblasts survive o Calcific metamorphosis: if PA pathology or non-vital:
 More severe damage – primary odontoblasts die Endo or extraction, PA surgery
Release of growth factors  formation of secondary  Bleaching, veneers or full coverage for esthetics
odontoblasts
What is this?
Pulpal calcifications
3 types of pulpal calcifications: o Site: Pulp chamber or canals
o 1. Denticles Clinical features (all 3 types):
o 2. Pulp stones o May cause difficulty in endodontics, otherwise, clinically
o 3. Diffuse linear calcifications insignificant
Increased incidence in: o Rarely, may interfere with root formation  early perio,
o 1. Teeth with long-standing chronic pulpitis tooth loss
o 2. Older teeth o Isolated; associated with several conditions – dentin
Denticles dysplasia (DD) II, pulpal dysplasia, tumoral calcinosis,
o Etiology: calcinosis universalis, Ehlers-Danlos syndrome
 Epithelial remnants in pulp induce odontoblastic Radiographic features:
differentiation of mesenchymal cells o Denticles, pulp stones: round/ovoid radiopacity in pulp
 Odontoblasts deposit dentin (round, ovoid) chamber or root canal
 Occurs during root development – denticles become o Diffuse linear calcifications: no radiographic changes
attached or embedded in dentin Histology:
o Site: Root canal, pulp chamber adjacent to furcation
o Denticles: aggregates of dentin attached or embedded
areas of multirooted teeth
o Pulp stones: mass of calcification, lamellar/concentric
Pulp stones pattern, free or attached
o Etiology: o Diffuse linear calc.: fine, linear calcification, along
 Calcification around nidus of pulp tissue – concentric, neurovasculature
round
 Occurs after root development – pulp stones free or Treatment: No treatment necessary upon radiographic
attached, rarely embedded recognition
o Site: Coronal portions of pulp chamber
Diffuse linear calcifications
o Etiology:
 Calcification that occurs parallel to neurovascular
elements – fine, fibrillar
 Occurs after root development
What is this?
Periapical abscess
Periapical abscess = accumulation of acute inflammatory cells at apex of non-vital tooth
Acute apical periodontitis = acute inflammation of periodontal ligament without abscess formation
o Non-vital tooth, trauma, high occlusal contacts, wedging by foreign object
o May or may not proceed to periapical abscess
Etiology: Inflammation of pulp (caries, iatrogenic, trauma)  abscess formation. May be:
o 1. Initial manifestation of periapical pathology or
o 2. Acute exacerbation of chronic PA pathology (phoenix abscess)
Age: No predilection
Site: Any tooth
Clinical features: may be symptomatic or asymptomatic; tenderness  intense pain later, no response to thermal tests, EPT, tooth sensitive to
percussion, extruded ± Systemic symptoms (headache, malaise, fever, chills)
o Spread through medullary spaces (osteomyelitis)
o Perforation, spread to soft tissues, skin (cellulitis)
o Drainage through oral mucosa, skin (sinus, fistulous tract)
 Swelling at opening of fistula (parulis, “gum boil”)
 Drainage often buccal, relief of symptoms on drainage, recurrence of symptoms on blockage
Radiographic features: Often no radiographic changes – insufficient time for significant bone destruction; thickening of apical pdl space, ± ill-defined
apical radiolucency
o Phoenix abscess – outline of initial chronic lesion ± new areas of bone loss
Histology: Most cases not examined histopathologically – sheets of neutrophils (PMNs), other inflammatory cells, histiocytes, necrosis, cellular
debris, bacterial debris,
o Fistulus tract, parulis – granulation tissue, PMNs
Treatment: incision and drainage – alleviate symptoms in ~48 hrs, treatment of offending tooth (exo or endo), analgesics (NSAIDs) for pain,
antibiotics if cellulitis, systemic symptoms, immunocompromised state (DM, AIDS, HIV, corticosteroid use, chemotherapy), surgical removal of
fistulous tract, parulis
o If not treated, most will progress to periapical granuloma and/or periapical cyst
o Severe, untreated cellulitis, serious complications:
 Cavernous sinus thrombosis, mediastinitis, necrotizing fasciitis, cerebral abscess
What is this?
Periapical granuloma
AKA: Chronic apical periodontitis radiographically identical**
Etiology: Histology: granulation tissue with chronic inflammatory cells
o Inflammation of pulp (caries, iatrogenic, trauma)  chronic (lymphocytes, plasma cels) ±histiocytes, ±cholesterol clefts, giant cells,
inflammation of pdl hemosiderin, ± RCT filling material, ± small collections of PMNs (focal
o Usually, defensive response to bacteria in root canal, spread of toxins abscess formation)
to apical area of tooth o **No epithelial lining**
o Rarely caused by fungi, viruses  No lining = PA granuloma
o May be:  Lining present = PA cyst
 1. Initial manifestation of PA pathology or Treatment:
 2. Consequence of untreated periapical abscess o Treat offending tooth, curettage of apical region of tooth
o Begins as acute apical periodontitis = acute inflammation of pdl o *Submission of all apical soft tissue to histology* - PA granulomas
 Acute inflammatory cells  activate osteoclasts  bone resorption
can mimic other pathologic processes (neoplastic, systemic), biopsy
o Progresses to chronic apical periodontitis (PA granuloma) = chronic
serves to rule out other pathology
inflammation of pdl
o Analgesics for pain, antibiotics if cellulitis, systemic symptoms; if not
 Inflammatory cells  activate fibroblasts and endothelial cells 
fibrous and granulation tissue treated, some will become PA cysts ± acute exacerbations
Gender and age: No predilection o Periodic follow-up at 1 and 2-years (at minimum) – assess lesional
changes, bone healing
Site: Any tooth o Many reasons for failure of therapy including pathology, may require
Clinical features: endo re-treatment or PA surgery, Re-biospy if lesion persistent,
o Early: Similar to irreversible pulpitis; dull, throbbing pain that lingers, enlarging, or non-healing to rule out other pathology
no response to thermal tests, EPT; may be sensitive to percussion
o Later: Most are asymptomatic, pain and sensitivity if acute
exacerbation, no response to thermal tests, EPT; typically, no mobility
or percussion sensitivity
o Size: <2cm; >2cm usually a periapical cyst
o Shape: Round, ovoid
o Borders: Well- or ill-defined
o Location: At apex of (periapical to) non-vital tooth; tooth may have
evidence of previous endo
o Effect on adjacent structures; loss apical Id ± root resorption
o **periapical granulomas, abscesses and cysts can appear
What is this?
Periapical scar
Etiology:
o Same as PA granuloma
o Healing defect - defect created by PA granuloma fills with scar tissue, may occur post-endo,
post extraction, post-PA procedures; most common loss of facial and lingual cortical plates
Gender and age: No predilection
Site: any tooth
Clinical features: Most are asymptomatic, tooth – no response to thermal tests,
EPT, no mobility or percussion sensitivity
Radiographic features: same as PA granuloma
o Borders: Well or ill-defined
o Locations: at apex of (periapical to) non-vital tooth, tooth with endo, no tooth
Histology: dense fibrous connective tissue (scar tissue) ± mild chronic
inflammatory infiltrate, ± RCT filling material **No epithelial lining**
Treatment: tooth usually already treated or extracted, biopsy for confirmation of
diagnosis, periodic follow-up as per PA granuloma
What is this?
Periapical cyst
AKA: Radicular cyst, apical periodontal cyst
Etiology: Inflammation of pulpal or periodontal origin – stimulation of epithelium at apex of non-vital tooth, may develop from periapical granuloma
Origin of epithelium: Rests of Malassez, crevicular epithelium, sinus lining, epithelial lining of fistulous tracts
Gender and age: no predilection
Site: Any tooth
3 clinical variants:
o 1. Periapical cyst – apex of non-vital tooth
o 2. Lateral radicular cyst – lateral aspect of non-vital tooth, necrosis of lateral canal, periodontitis
o 3. Residual periapical cysts – site of previously infected tooth that has been extracted
Clinical features: mostly asymptomatic, pain if acute exacerbation, mild swelling, if associated with tooth, tooth non-vital – no response to thermal
tests and EPT, unless multiple canals
o Shape: Round to ovoid; unilocular; generally >2cm
o Borders: Well or ill-defined, typically non-corticated
o Location: Periapical – apex; Lateral – lateral aspect; residual – no tooth
o Effect on adjacent structures: loss of lamina dura, may cause root resorption
o **Periapical granulomas, abscesses and cysts can appear radiographically identical**
Histology:
o Epithelial lining: stratified squamous, ± mucous cells, ±Ruston bodies
o Cyst wall: fibrous CT, chronic or acute inflammation
o Lumen: cellular debris, fluid
Treatment:
o Periapical cyst, lateral radicular cyst – same as periapical granuloma, enucleation of cyst *submit for histo exam*, re-biopsy if persistent, enlarging or non-
healing lesion
o Residual periapical cyst: excise and submit for histologic examination – rule out other pathologic processes
What is this?
Cellulitis
Etiology: Spread of acute inflammation, infection through fascial planes o Formation of septic blood clot in cavernous sinus due to infection
to soft tissues, skin – swelling – inability to drain  Cavernous sinus: dural sinus b/w meningeal and periosteal layers
Two forms of interest: o Contents of cavernous sinus:
 OTOM CAT = Oculomotor, Trochlear, Ophthalmic, Maxillary, Internal
o 1. Ludwig’s angina carotid artery, abducens
o 2. Cavernous sinus thrombosis o Venous drainage: from superior and inferior ophthalmic vein
Ludwig’s angina o Sources of infections:
o Cellulitis of sublingual, submental, submandibular spaces  1. Infection of maxillary premolar/molar teeth
o Sources of infections:  2. Infection of maxillary anterior teeth
 1. Acute infection of mn molars - ~70% of cases  3. External facial injuries
 2. Peritonsillar or parapharyngeal abscesses  Orodental infections ~10% CST cases
 3. Others – oral lacerations, factures of mandible, infections of o Clinical features: Periorbital enlargement and swelling, swelling of
submandibular gland lateral nose, medial eye, forehead, protrusion of eye, pain over eye
o Patients at risk: Immunocompromised (e.g. DM, organi and along involved nerves. Systemic symptoms – fever, chills,
transplantation, AIDS, aplastic anemia) headache
o Clinical features:  **CNS involvement – meningitis, tachycardia, tachypnea, stupor,
 1. Sublingual space – elevation, posterior enlargement, protrusion of delirium, brain abscess
tongue (woody tongue) o Treatment:
 2. Submental space – swelling of floor of mouth  1. Incision and drainage of infected area
 3. Submandibular space – enlargement and tenderness of neck  2. Antibiotic therapy
above hyoid (“bull neck”)  3. Eliminate source of infection
 Potential to spread to lateral pharyngeal space (laryngeal edema),  Systemic steroids and anticoagulants – recommended on individual
retropharyngeal space, mediastinum basis
 Massive swelling of neck, pain, restricted neck movement, o Prognosis: Mortality rates remain high (~30%)
dysphagia, dysphonia, drooling, sore throat; systemic symptoms –
fevers, chills, elevated ESR
 **Airway obstruction – woody tongue, neck swelling, laryngeal
edema
Signs: tachypnea, dyspnea, tachycardia, stridor, need to sit upright
o Treatment:
 1. Maintain/secure airway
 2. Incision and drainage of infected area
 3. Antibiotic therapy
 4. Eliminate source of infection
o Prognosis: Mortality has decreased with antibiotic use (<10%)
Cavernous sinus thrombosis
What is this?
Osteomyelitis
Acute or chronic inflammation that spreads through medullary spaces of bone – away from initial site of involvement
Etiology: Mostly bacterial infections (suppurative, bacterial, secondary osteomyelitis)
Sources of infection: odontogenic infection, traumatic fracture of jaws; ANUG, noma
Incidence: Relatively uncommon, increased since recognition of bisphosphonate-related osteonecrosis of the jaws (ONJ)
Predisposing factors: Chronic systemic disease, immunocompromised states (AIDS), conditions leading to hypovascularized bone
o Hx of radiation therapy, end stage cemento-osseous dysplasias, osteopetrosis, late Paget’s disease, hx of bisphosphonate use
Two conditions:
o 1. Acute suppurative osteomyelitis – acute inflammation in medullary spaces
o 2. Chronic suppurative osteomyelitis – sufficient time for host response, granulation tissue and fibrosis wall off infection  dead space, ~1 month after
initial acute infection, difficult to treat
Gender: M>>F (75%)
Age: no predilection
Site: Mn>Mx
Acute osteomyelitis
o Clinical features: fever, leukocytosis, lymphadenopathy, pain, swelling in affected area; purulent discharge
o Radiographic features: no changes, ill-defined radiolucency ± periosteal reaction (young pts)
Chronic osteomyelitis
o Clinical features: May or may not follow acute osteomyelitis, pain, swelling, fistula/sinus formation, tooth loss, pathologic fracture, exacerbations and
remissions common
o Radiographic features: Ill-defined, patchy radiolucency, “moth eaten”, ± periosteal reaction, can mimic jaw malignancies
o Sequestrum = fragment of necrotic bone separated from surrounding bone
o Involucrom = fragment of necrotic bone surrounded by vital bone
Histology:
o Acute osteomyelitis: necrotic bone: lacunae devoid of osteocytes, peripheral resorption; sheets of neutrophils within bone
o Chronic osteomyelitis: necrotic bone, granulation tissue, fibrosis, debris, foci of neutrophils
Treatment:
o Acute osteomyelitis: incision and drainage, culture and sensitivity, antibiotics
o Chronic osteomyelitis: challenging to manage because of dead space, surgical removal of necrotic bone, IV antibiotics, hyperbaric oxygen if standard
therapy fails
What is this?
Diffuse sclerosing osteomyelitis
Controversial, evolving group of conditions sclerosing osteomyelitis (DSO), Primary chronic osteomyelitis
Pain, inflammation, periosteal hyperplasia, sclerosis, lucency o 1. Microbiologic cultures
3 major conditions:  Positive: chronic supp. Osteomyelitis, DSO
 Negative: primary chronic osteomyelitis, others
o 1. Diffuse sclerosing osteomyelitis
o 2. Response to surgical debridement and antibiotic therapy
o 2. Primary chronic osteomyelitis
 Responds well: chronic supp. Osteomyelitis, DSO
o 3. Chronic tendoperiostitis  No response: primary chronic osteomyelitis, others
o 4. Primary chronic osteomyelitis with extragnathic manifestations) o 3. Radiographic and histologic appearance
Etiology:  Sclerosis: DSO, primary chronic osteomyelitis, others
o Diffuse sclerosing osteomyelitis  Inflammation, necrosis: chronic supp. Osteomyelitis
 Infection involving medullary spaces; granulation tissue, fibrosis  Treatment: Eliminate source chronic inflammation, sclerotic bone may
stimulates sclerosis of bone
persist after treatment –
 Source of infections: Odontogenic infection – PA infection,
periodontitis, pericoronitis o Hypovascular bone, prone to inflammation and necrosis
o Primary chronic osteomyelitis o Prevention of inflammation
 Often confused with chronic suppurative osteomyelitis – no definite
association with bacterial infection, no suppuration, no
sequestration
o Chronic tendoperiostitis
 Reactive hyperplasia of bone cause by overuse of masticatory
muscles, hx of parafunctional habits
o Primary chronic osteomyelitis with extragnathic manifestations
 1. Chronic recurrent multifocal osteomyelitis (CRMO)
 2. Synovitis-Acne-Pustulosis-Hyperostosis-Osteomyelitis (SAPHO)
syndrome
Age: Adults
Site: Mostly mandible
Clinical features: pain and swelling unusual
o Early – increase sclerosis around site of infection
o Late – diffuse radiopacities, multiple quadrants
Histology: sclerosis of bone, scant marrow, mild inflammation, ±
necrotic bone w/ granulation tissue
Differential diagnosis: Chronic suppurative osteomyelitis, diffuse
What is this?
Osteomyelitis with proliferative
periostitis
Formerlyknown as Garre’s osteomyelitis
Etiology: inflammation of bone  periosteal reaction  bone formation
within periosteal reaction
Source of infection: Odontogenic infection – PA infection, periodontitis,
fractures, etc
Age: Children and young adults (avg 13 y/o)
Site: Mandibular premolar, molar regions
Clinical features: swelling of inferior border of mandible > buccal, unifocal
> multifocal involvement
Radiographic features: radiopaque laminations parallel to cortical surface
(“onion-skinning”) – rarely, spicules perpendicular to cortical surface
Histology: parallel rows of reactive and cellular woven bone
Treatment: eliminate source of infection, consider biopsy
What is this?
Condensing osteitis
Etiology: inflammation of bone  focal sclerosis of bone
Source of infection: odontogenic infection
Gender: no predilection
Age: children and young adults, can persist into adulthood
Site: Mandibular premolar, molar regions
Clinical features: asymptomatic, no expansion
o Density: uniform radiopacity
o Borders: well-defined, localized
o Location: typically, apex of tooth – hx of pulpitis, pulpal necrosis, carious
tooth, tooth with large restorations, widened pdl space, periapical pathosis
o **can mimic other conditions such as idiopathic osteosclerosis, cemento-
osseous dysplasias
Treatment: eliminate source of infection  resolves, residual bone
scarring may occur
What is this?
Alveolar osteitis
AKA: Dry socket
Etiology: destruction/loss of blood clot from extraction site, lack of clot disrupts normal healing process (normal:
clot  granulation tissue fill  bone fill)
Pathophysiology:
o 1. Increased conversion of plasminogen to plasmin
o 2. Lysis of clot
o 3. Production of kinins (pain mediators)
Predisposing factors: “High-risk” patients
o 1. Local trauma
o 2. Estrogen
o 3. Presence of bacterial pyrogens (presurgical infections, pericoronitis, poor oral hygiene)
o 4. Inadequate irrigation during surgery
o 5. Tobacco use
o 6. History of alveolar osteitis
Incidence: all extractions 1-3%, impacted mn 3rd molars – 25-30%
Gender: No predilection (after accounting for OCP use)
Age: Highest 20-45 yo
Site: Mandibular molar regions
Clinical features: 3-4 days after extraction, loss of clot  bare, bony socket, severe pain – radiates to ipsilateral
ear, temporal region, eye; foul odor
Treatment: irrigation with warm saline water, inspect socket for debris, analgesics
Prevention: patients on OCP – schedule exo for days off estrogen, copious irrigation intraoperatively, chlorhexidine
rinse, intrasocket placement of antibiotics (controversial)
What is this?
Impetigo
Superficial bacterial infections of skin
Etiology: Streptococcus pyogenes (Group A strep), Staphylococcus aureus
Transmission: skin-to-skin contact – enters through breaks in the skin
Predisposing factors: immunocompromised states (HIV, AIDS, DM II), poor hygiene
Age: Young children; less often adults, infants and newborns (bullous impetigo)
Site: extremities (legs), trunk, scalp, face
2 major patterns:
o 1. Non-bullous impetigo
o 2. Bullous impetigo
Clinical features:
o Non-bullous impetigo: red macules or papules  fragile vesicles  thick amber crusts (“cornflakes glued to
surface”), pruritis, linear lesions, systemic symptoms rare
o Bullous impetigo: Mostly caused by S. aureus, superficial vesicles  flaccid bullae  thin, honey-colored
crusts (“lacquer”), weakness, fever, diarrhea
Diagnosis: clinical presentation, culture for S. pyogenes and/or S. auereus
Treatment: remove crusts + topical mupirocin. If bullous, systemic symptoms – oral antibiotic x 1
wk, culture if no response in 7 d, spread of lesions if untreated, serious complications rare
What is this?
Erysipelas
AKA: “Saint Anthony’s fire” (historical)
Superficial bacterial skin infection
Etiology: β-hemolytic streptococci, predominantly group A, rarely other bacterial
organisms. Affects dermis, spreads through lymphatic channels  filled with
fibrin, PMNs, bacteria
Gender: F slightly > M
Age: young, elderly
Predisposing factors: debilitated, diabetic, immunosuppressed pt, alcoholism,
obesity, areas of chronic lymphedema, surgical scars
Site: lower extremities, face – cheeks, eyelids, bridge of nose
Clinical features: bright red, well-demarcated, sharply-raised border, swollen –
indurated, painful; warm to touch, “Orange peel” texture to skin, eyelids – swollen
shut, high fever, lymphadenopathy, ± leukocytosis, nausea, vomiting
Diagnosis: clinical presentation, cultures often not useful
Treatment: Antibiotics, resolution in ~48 hours, recurrences noted
What is this?
Streptococcal tonsillitis and pharyngitis
Etiology: Mostly group A, β-hemolytic streptococci
Transmission: person-to-person via respiratory droplets; nasal oral secretions; late
winter, early spring summer
Inoculation period: short, 2-5 d
Age: mostly children
Site: tonsils, oropharynx
Clinical features: severity varies, mild-intense, sudden onset sore throat, fever,
dysphagia, enlargement of tonsils, redness of tonsils and oropharynx ± yellow
exudates, cervical LAD, palatal petechiae, other systemic symptoms, absence of
conjunctivitis, rhinorrhea, cough, discrete ulcerative lesions – rules out viral
origin
Diagnosis: throat culture, rapid antigen detection test when appropriate
o Distinguishing streptococcal tonsillitis from viral tonsillitis can be challenging
Treatment: self-limiting, administer treatment within 9 d of pharyngitis,
antibiotics, prevent development of acute rheumatic fever, other serious
complications, pt non-contagious within 24 hours of therapy
What is this?
Scarlet fever
Etiology: Group A, β-hemolytic streptococci – produces erythogenic toxin, attacks blood vessels 
skin rash, preceded by streptococcal tonsillitis and pharyngitis, susceptible patients lack antitoxin
antibodies
Incubation period: 1-7 d
Age: Children, 3-12 yo
Site: Oral mucosa, skin
Clinical features:
o 1. Fever: starts on day 2, returns to normal temp, on day 6, peak at 103:F
o 2. Enanthem (rash on inside surface of body)
 Site: tonsils, pharynx, soft palate, tongue, erythema, edema ± yellow exudates, palatal petechiae
 Early – white strawberry tongue, white coating + hyperplastic fungiform papillae
 Later – red strawberry tongue, white coating lost, erythematous dorsal surface
o 3: Exanthem (rash on outside surface of body)
 Site: skin of trunk, extremities “Sunburn with goose pimples” = erythema with pale, punctuate areas, pronounced skin
folds, face – generally spared, clears in 1 week, period of desquamation – lasts 3-8 weeks
Diagnosis: throat culture, rapid antigen detection test
Treatment: prevent development of acute rheumatic fever, antibiotics, NSAIDS, resolution in ~48
hrs
What is this?
Tonsillar concretions and
tonsillolithiasis
Etiology: tonsil – numerous invaginations (tonsillar crypts)
o Tonsillar concretion: accumulation of keratin, foreign material, bacteria
o Tonsillolith: calcification of tonsillar concretion, promoted by recurrent tonsillar infections
Age: wide range – mean 40 yo
Site: tonsils, can be bilateral, single or multiple
Clinical features:
o Tonsillar concretion: enlarged crypt; soft, yellow debris; surrounding mucosa not painful or
inflamed
o Tonsillolith: Hard, yellow mass, variable size, asymptomatic, pain, abscess formation,
ulceration, halitosis, dysphagia, small risk of pulmonary aspiration
Radiographic examination:
o Panorex: collection of round radiopacities superimposed over mid-ramus
o CT scan – collections of radiodensities in tonsil
Treatment: enucleation, tonsillectomy if associated with tonsillitis, redevelopment
common
What is this?
Diphtheria
Etiology: Corynebacterium diphtheria, produces lethal exotoxin  tissue necrosis
Transmission: contact with an infected person
Innoculation period: 1-5 d
Incidence: rare since vaccine, recent outbreak in Russia in 90’s, occurs in epidemics
Age: Childhood (epidemic), any age
Risk factors: Immunosuppressed, unimmunized populations, non-compliance with booster
injections, travel to disease endemic region
Site: predominantly mucosal surfaces, can occur on skin
Clinical features: low-grade fever, headache, malaise, anorexia, sore throat – gradual and mild
o Tonsils – patchy, yellow-white thin film  adherent gray thick covering  green/black membrane (necrotic)
o May spread to involve soft palate, larynx, trachea, rarely involves buccal mucosa, lips, cervical LAD, neck
enlargement (“bull neck”)
o Airway obstruction due to membrane dislodgement, toxin related paralysis of oculomotor, facial,
pharyngeal, diaphragmatic, intercostals muscles, systemic complications rare.
Diagnosis: culture from under membrane
Treatment: initiate at time of dx, antitoxin + antibiotics, cure defined by three negative cultures,
prevention by vaccination, booster every 10 yrs
Prognosis: mortality rates ~5% but unpredictable
What is this?
Syphilis
Tongue  lobulated; atrophy, loss of papillae
AKA: Lues
o Congenital syphilis
Etiology: Treponema pallidum  Manifests 2-3 weeks after birth
Transmission: sexual contact, maternal transmission  Growth retardation, fever, jaundice, anemia, hepatosplenomegaly, rhinitis, skin eruptions
Incidence: increasing – MSM, illegal drug-sex trade  Characteristics faces (saddle nose, high-arched palate, frontal bossing, gummas)
 Hutchinson’s triad (pt not exhibit all 3)
Gender: traditionally M>F; now ~1:1 1. Hutchinson’s teeth: screwdriver-shaped incisors, “mulberry” molars
Ethnic predilection: AA men 2. Ocular interstitial keratitis – opacified corneal surface; 5-25 yo
3. Eight nerve deafness
Age: peak 15-40 yo, congenital cases Histology:
Stages of syphilis: o 1⁰ and 2⁰ syphilis – epithelial hyperplasia, non-specific ulceration, perivascular plasma
o 1. Primary syphilis: 3-90 days cells
o 2. Secondary syphilis: 4-10 weeks, latent syphilis 1-30 yrs o 3⁰ syphilis – pseudoepitheliomatous hyperplasia (PEH), granulomatous inflammation
o 3. Tertiary syphilis – follows latent phase (giant cells, epitheloid histiocytes)
Syphilis and pregnancy: transmission can occur in all 3 stages, incl. latent o **Warthin-starry stain/Steiner stain: corkscrew-shaped spirochetes, may not be positive
o Pregnancy during highly infectious period (first 2 stages) – miscarriage, stillbirth, in latent, 3: stages
congenital malformations Diagnosis:
o Longer mother infected, less chance fetal infection o Immunofluorescent antibody assay on cytology smear of active lesion, tissue biopsy
o Fetal infection = congenital syphilis o Stains on smear, biopsy
 Development of stigmata begins at 4 mo gestation
o Serologic tests
 Incidence decreasing due to:
1. Decrease syphilis among women  Screening or diagnostic
2. Prenatal testing, early tx.  Screening tests – non-specific, low sensitivity, positive 1st , 2nd stages
Clinical features:  Diagnostic tests – specific, highly sensitive, positive at primary stage, throughout life
o Primary syphilis: Chancre: site of inoculation, 3-90 d after exposure Treatment:
 Site: genital mucosa, rarely oral mucosa, lips, tongue, palate, gingiva, tonsils o Penicillin: dosing dependent on stage, neurologic involvement, immune status of pt
 Genital – popular lesion with central ulceration  Jarisch-Herxheimer reaction = secondary release of bacterial endotoxin with ab therapy
 Oral – painless, clean-based ulceration; can be vascular proliferation 8 hrs after treatment, fever, malaise, resolves rapidly
 Heals in 3-8 weeks; Regional LAD o Response variable – failure in ~5% of cases
o Secondary syphilis: systemic symptoms o Serologic follow-up periodically recommended
 Painless LAD, sore throat, malaise, headache, musculoskeletal pain o Re-test pregnant females
 Multiple lesions, variety of presentations
 Heal spontaneously in 3-12 wks
 Relapses may occur
 1. Maculopapular rash of skin: widespread, may heal with hyper-/hypopigmentation
 2. Mucous patches (~30% of pts): tongue, lips, bu mucosa, palate, sensitive white patch that
sloughs
 3. Condyloma lata: genital, anal, rarely oral, papillary lesions
 4. Lues maligna: widespread form of 2: syphilis, atypical necrotic ulcerations of face, scalp,
oral mucosa, systemic manifestations – fever, pain, arthralgia, may be seen in AIDS patients
o Tertiary syphilis: inovlement of multiple systems
 1. Vascular system: early arteritis – aneurysms of ascending aorta, left ventricular
hypertrophy, aortic regurgitation, CHF
 2. CNS: tabes dorsalis, psychosis, dementia, death
 3. Ocular: iritis, choroidretinitis
 4. Granulomatous inflammation throughout body: skin, mucosa, soft tissues, bones,
internal organs
 Gumma: indurated, nodular or ulcerated lesions, may cause tissue destruction
Palate  palatal perforation
What is this?
Ep. histiocytes
Giant cell
Lymphocytes
Tuberculosis
o Rare, children/adolescents, gingiva, regional
Etiology: Mycobacterium tuberculosis LAD
Incidence: recent resurgence – HIV, decline health 2. TB osteomyelitis
o TB infection of bone, ill-defined radiolucency
care infrastructure, drug resistance
Histology: granulomatous inflammation
Transmission: Airborne droplets from infected pt o Rounded aggregates of
Ethnic: Hispanics > AA > Asians  1. Giant cells
Infection vs. active disease:  2. Epitheloid histiocytes
o Primary tuberculosis (infection)  3. Lymphocytes
 Previously unexposed individual  + central caseous necrosis – tubercle = individual
 Site: lungs granuloma
 Clinical features: usually asymptomatic; fever, pleural o **Acid-fast bacilli stain (AFB stain), Ziehl-Nielsen stain:
effusion may occur, chronic inflammatory reaction  mycobacterial organisms, organisms scarc **negative
fibrocalcified nodule(s) in lung; 5-10% progress to stain does not rule out TB
active disease Diagnosis: Tuberculin skin test (PPD, Matoux test)
o Secondary tuberculosis (“active disease”) o Positive = prior exposure to organism
 Reactivation of organism in previously infected o Does not distinguish b/w infection vs. active disease
individual
o False negatives: AIDS, sarcoidosis, Hodgkin’s lymphoma,
 Predisposing factors: immunocompromised (esp. AIDS),
DM, old age intradermal placement
 Site: lungs, especially apices; extrapulmonary – o Culture, stains of sputum, tissue biopsy – confirm active
lymphatic system, skeletal system, oral disease
 Clinical features: fever, malaise, anorexia, night sweats, Treatment:
productive cough, hemoptysis, lupus vulgaris, cervical o Multiagent therapy
lymph nodes > larynx > middle ear o May start before culture results are finalized, relapses,
Oral: tongue, palate, lip – chronic, painless ulcer, infected
sputum chemoprophylaxis
 Miliary tuberculosis = diffuse dissemination (via
vascular spread)
 Other rare forms of 2: TB:
1. Primary oral TB w/out pulmonary involvement
What is this?
Leprosy
AKA: Hansen disease  Site: skin; nasal, oral mucosa
Skin: ill-defined, hypopigmented papules, nodules, anesthesia, loss
Etiology: Mycobacterium leprae, low infectivity, exposure rarely of sweating, hair
results in clinical dz Nasal: epistaxis, stuffiness, anosmia, bridge on nose collapse
Oral: 19-60% of pt, hard and soft palat> la mx gingiva > tongue lips
Incidence: decreased dramatically over last 15 yrs > bum x gingiva > bu mucosa; yellow-red, firm papules  ulcerate,
Transmission: not entirely understood, initial site of infection may be necrose, scarring, loss of tissue
nasal, oropharyngeal mucosa. Historically, believed that organisms  Destruction of underlying bone
Facies leprosa
attracted to cooler sites in body – now disputed o 1. Atrophy nasal spin
Two clinical presentations: o 2. Atrophy of anterior maxilla
o 1. Paucibacillary leprosy (tuberculoid variant) – patients with high o 3. Endonasal inflammatory changes
 Neurologic involvement – CN V (mostly V2), VII – facial paralysis
immune reaction
 1. Scarce organisms on biopsy Histology:
 2. Positive skin test to lepromin o Paucibacillary – granulomatous inflammation, scarce organisms
 3. Localized disease o Multibacillary – absence of granulomatous inflammation
• o **Acid fast bacilli stain (AFB stain)
o 2. Mutlibacillary leprosy (lepromatous variant) patients with reduced What other conditions can present with granulomatous inflammation?
cell-mediated immune response o Tertiary syphilis, tuberculosis, paucibacillary leprosy
 1. Numerous organisms on biopsy Diagnosis: stains (AFB) on smear or tissue biopsy, molecular studies
 2. Negative lepromin skin test
Treatment: Mutiagent therapy
Stages of active disease: invasion  proliferation  ulceration  o Paucibacillary – 6 month regimen (rifampin, dapsone)
resolution with fibrosis o Multibacillary – 24 month regimen (rifampin, dapsone, clofazimine)
Incubation period: prolonged
o Paucibacillary: 2-5 years
o Multibacillary: 8-12 years
Clinical features: Classification as paucibacillary and multibacillary
mostly clinical, based on:
o 1. Number of lesions
o 2. Number of body areas affected
o Paucibacillary leprosy:
 # lesions: small
 Site: skin; rarely oral, well circumscribed, hypopigmented nodules,
loss of sensation, sweating affected sites
o Multibacillary leprosy:
 # lesions: numerous
What is this?
Noma
AKA: Cancrum oris, gangrenous stomatitis, necrotizing stomatitis
Etiology:
o Normal oral flora  pathogenic during periods of compromised immune status
o Fusobacterium necrophorum, Prevotella intermedia
o Noma neonatorum (neonates) – Pseudomonas species
Predisposing factors: poverty, malnutrition, poor OH, poor sanitation, proximity to livestock, illness, malignancy,
immunocompromised (AIDS)
o Often preceded by debilitating illness - Measles, herpes simplex, varicella, scarlet fevere, others
o Often begins as necrotizing ulcerative gingivitis (NUG)
Incidence: rare in developed countries, sub-saharan Africa
Age: Children (1-10 yo), adults with history of debilitating illness
Clinical features:
o Often begins as NUG
o Spreads to adj. oral tissues, areas of trauma  painful necrosis of oral mucosa
o Spreads to skin  blue-black discoloration  yellow necrotic zones
o Mostly well-defined, unilateral
o Foul odor, pain
o Fever, malaise, leukocytosis, anemia, regional LAD, can affect underlying bone (osteomyelitis)
Diagnosis: clinical presentation
Treatment: antibiotics, debridement of necrotic tissue, reconstruction, correction of underlying cause
Mortality: <10% in US – pneumonia, diarrhea, septicemia, Noma neonatorum – mostly fatal; septicemia
What is this?
Actinomycosis
Etiology: Actinomyces israelii, A viscosus, others, gram + anaerobic bacteria, normal oral flora, may be combined with staph. Strep
Age: no predilection
Site: cervicofacial (~55%), abdominal, pelvic (~25%), pulmonary
Clinical features: Rapidly progressive or slow, chronic infection
o Sulfur granules – yellow flecks = aggregates of organisms
Cervicofacial actinomycosis
o Oral – site of prior trauma, direct extension to submandibular, submental, cheek areas, angle of mn., lymph nodes, indurated, “woody” fibrosis, abscess
formation, sinus/fistulous tract
o Tonsils – infectious symptoms, tonsillar hyperplasia
o Salivary glands: submandibular, parotid glands, intraductal colonization  abscess formation
o Bone – actinomycotic osteomyelitis
 Site prior trauma, perio, non-vital teeth, exo sites, PA pathosis
 Radiographic: ill-defined radiolucency ± peripheral radiopacity
Localized actinomycosis
o Site: periapical, pericoronal inflammatory lesions
o May be difficult to resolve with conventional endo, rarely evolves to cervicofacial actinomycosis
Histology:
o Actinomycotic colonies (sulfur granules): basophilic central core, radiating club-shaped filaments at periphery, eosinophilic periphery can be highlighted
with GMS stains
Diagnosis: culture – positive in only 50% of cases, identification of actinomycotic colonies in tissue biopsy
Treatment: High dose antibiotics, I&D if abscess
o Cervicofacial: 5-6 w course to 12 most (deeper)
o Tonsils: tonsillectomy
o Bone: debridement + 3 mos Ab
o Localized: local excision; AB if fail
What is this?
Cat-scratch disease
Etiology: Bartonella henselae; rarely other species of Bartonella o 1. Acute sinusitis: may progress to chronic sinusitis
Transmission: o 2. Chronic sinusitis: recurrent acute sinusitis OR sinusitis > 3 months
 Possible development of antrolith = calcification around nidus of mucous, pus, tooth roots,
o cat-to-human: enters through break in skin after contact with cat
foreign bodies, dental materials
o Person-to-person: not reported
Clinical features:
Gender: No predilection o Acute sinusitis: fever, headache, malaise, facial pain, photophobia, obstructive nasal
Age: Children, young adults (<21 yo) **Most common cause of chronic regional LAD in symptoms, nasal and/or pharyngeal discharge
children o Chronic sinusitis: vague symptoms, headache, malaise, facial pressure, pain
Site: site of trauma, cervical lymph nodes  Maxillary sinusitis: cheek pain/pressure, toothache, headache, symptoms worse when
Clinical features: upright, improves when supine
o 1. Papule or pustule at site of trauma (3-14 d) Radiographic features: cloudy, radiodense change in sinus, thickening antral lining,
o 2. Lymphadenopathy (3 weeks) – submandibular LAD if scratch on face antrolith – well-defined, radiopaque mass
o Fever, malaise, rare complications – encephalopathy, spelnomegaly, etc Diagnosis: Nasal endoscopy and CT scans, plain radiographs
o Oculoglandular syndrome of Parinaud o Symptoms can mimic odontogenic infection – rule out/rule in odontogenic infection
 B. Henselae infection due to contact with eye o Suspect sinusitis if pain associated with several teeth, tenderness over mx sinus, nasal
1. Preauricular LAD
2. Conjunctival involvement
congestion, nasal discharge, foul odor
o Bacillary angiomatosis: also associated with B. henselae, AIDS patients, red-purple skin Treatment:
lesions, vascular proliferation ~ Kaposi’s sarcoma o Acute: mild  no antibiotics, More severe  antibiotics
Histology: lymph node – hyperplasia, stellate, suppurative necrosis, histiocytes, PMNs o Chronic sinusitis: functional endoscopic surgery, Caldwell-Luc operation
o **Warthin-Starry stain, Brown-Hopps stain – bacilli o If no response to conventional sinusitis therapy and evidence of calcification in sinus,
Diagnosis: Stains on tissue, indirect fluorescent antibody assay, molecular studies consider dx of non-invasive aspergillosis
Treatment: self-limitin – resolves in 4 months, local heat, analgesics, aspiration/drainage
of nodes, antibiotics if severe/prolonged
• Sinusitis
Normal anatomy of sinuses: 4 major paranasal sinuses
o 1. Frontal sinus
o 2. Maxillary sinus
o 3. Sphenoid sinus – 1-3 drain through middle meatus (MM)
o 4. Ethmoid sinuses
o All drain to nose through ostia = ostiomeatal complex
o Lined by pseudostratified columnar epithelium with cilia, contain bacteria
 Move sinus secretion to ostia
o Proper function dependent on:
 1. Patency of ostial openings
 2. Proper function of ciliary apparatus
 3. Quality of nasal secretions
o **Disruption leads to sinusitis
Etiology: Interruption of normal drainage due to disruption of ostiomeatal complex
o Less commonly, local infection  localized sinus inflammation
Predisposing factors: recent upper respiratory viral infection, allergic rhinitis, cystic
fibrosis, immunodeficiencies
Two types:
What is this?
Sinusitis
Normal anatomy of sinuses: 4 major paranasal sinuses
o 1. Frontal sinus
o 2. Maxillary sinus
o 3. Sphenoid sinus – 1-3 drain through middle meatus (MM)
o 4. Ethmoid sinuses
o All drain to nose through ostia = ostiomeatal complex
o Lined by pseudostratified columnar epithelium with cilia, contain bacteria
 Move sinus secretion to ostia
o Proper function dependent on:
 1. Patency of ostial openings
 2. Proper function of ciliary apparatus
 3. Quality of nasal secretions
o **Disruption leads to sinusitis
Etiology: Interruption of normal drainage due to disruption of ostiomeatal complex
o Less commonly, local infection  localized sinus inflammation
Predisposing factors: recent upper respiratory viral infection, allergic rhinitis, cystic fibrosis, immunodeficiencies
Two types:
o 1. Acute sinusitis: may progress to chronic sinusitis
o 2. Chronic sinusitis: recurrent acute sinusitis OR sinusitis > 3 months
 Possible development of antrolith = calcification around nidus of mucous, pus, tooth roots, foreign bodies, dental materials
Clinical features:
o Acute sinusitis: fever, headache, malaise, facial pain, photophobia, obstructive nasal symptoms, nasal and/or pharyngeal discharge
o Chronic sinusitis: vague symptoms, headache, malaise, facial pressure, pain
 Maxillary sinusitis: cheek pain/pressure, toothache, headache, symptoms worse when upright, improves when supine
Radiographic features: cloudy, radiodense change in sinus, thickening antral lining, antrolith – well-defined, radiopaque mass
Diagnosis: Nasal endoscopy and CT scans, plain radiographs
o Symptoms can mimic odontogenic infection – rule out/rule in odontogenic infection
o Suspect sinusitis if pain associated with several teeth, tenderness over mx sinus, nasal congestion, nasal discharge, foul odor
Treatment:
o Acute: mild  no antibiotics, More severe  antibiotics
o Chronic sinusitis: functional endoscopic surgery, Caldwell-Luc operation
o If no response to conventional sinusitis therapy and evidence of calcification in sinus, consider dx of non-invasive aspergillosis
For viral infections – see Woo’s PPTs
What is this?
Candidiasis
o Candidiasis with 2: hyperkeratosis
Historically known as moniliasis  4. Mucocutaneous candidiasis
Etiology: Immunologic disorder – immunologic defect
o Candida (mostly C. albicans) Sporadic or inherited (aut. Recessive)
Site: mucous membranes, skin nails
o Fungal organism Thick, white patches – may or may not wipe off
o Dimorphism = mold form; yeast form (pathogenic) Can have endocrine abnormalities (endocrine candidiasis syndrome), iron deficiency anemia
– risk of oral and esophageal carcinoma
o Can be part of normal oral flora, with no evidence of infection (~30-50% population)
o Infection depends on: Histology:
 1. Immune status of host: ↓immune status, ↑risk of infection o Candidal hyphae in superficial parakeratin layer – elongated structures
 2. Oral environment: ↑xerostomia, ↑risk of infection o Neutrophils in epithelium
 3. Strain of C. albicans o Epithelial acanthosis
o Candidiasis – most common oral fungal infection o Elongation of rete ridges
Age: Elderly, immunocompromised o Chronic inflammation in connective tissues
4 main clinical presentations in oral cavity: o **Periodic acid Schiff (PAS) stain – hyphae (magenta)
o May be single, in combination o Gomori-Grocott methenamine (GMS) stain – hyphae (black)
 1. Pseudomembranous candidiasis (“thrush”) o KOH prep
Risk factors: exposure to broad-spectrum Ab, impaired immune system
Site: bu mucosa, palate, dorsal tongue
Diagnosis:
Adherent white plaques (“cottage cheese”, milk curds), Can be wiped off (tongue blade, o Clinical features +
gauze), Underlying mucosa mostly erythematous, mild burning; unpleasant taste  1. Fungal culture – Sabourad’s agar, 2 days to 1 week for results
 2. Erythematous candidiasis  2. Cytology smear
Most common form of candidiasis, mucosal erythema; “bald” appearance of tissue, no  3. Tissue biopsy – in chronic hyperplastic candidiasis, will also rule out other conditions
white plaques, may be symptomatic; mild burning
A. Acute atrophic candidiasis
(epithelial dysplasia, SCC, lichen planus)
o Risk factors: exposure to antibiotics, xerostomia (med-related, RT, Treatment:
Sjogrens)
o Site: dorsal tongue, other mucosal sites
o Pseudomembranous candidiasis – topical or systemic antifungals
o Burning, “scalded” sensation o Chronic hyperplastic candidiasis – topical or systemic antifungals, if no resolution –
B. Central papillary atrophy (median rhomboid glossitis) biopsy to rule out epithelial pathology
o Site: mid-dorsal tongue
o Developmental defect, although mostly adults – failure of tuberculum impar o Erythematous candidiasis
to be covered by the lateral processes of tongue  Acute atrophic candidiasis, central papillary atrophy – topical or systemic antifungals
o Well-defined, bald area; loss filiform papillae – symmetrical; smooth or  Angular cheilitis – topical antifungal + steroid preparation ± ab
lobulated, complete or partial resolution with antifungal meds Rx: Lotrisone cream (clotrimazole + betamethasone) – apply to corners of mouth 2 x/day, 10
C. Angular cheilitis (perleche) days
o Risk factors: reduced vertical dimension Rx. Mycolog II cream (nystatin + triamcinolone) – apply to corners of mouth 2-3 x/day, 10 days
o Site: corners of mouth  Denture stomatitis – topical or systemic antifungals, denture hygiene instructions (take
o Erythema, fissuring, scaling of corners of lips
o Co-infection with Candida and Staphylococcus auerus
dentures out before bed, wash/soak dentures at night)
o If involves perioral skin = cheilocandidiais – habits (lip licking, thumb o Antifungals
sucking)  Polyenes
D. Chronic multifocal candidiasis Nystatin – suspension/lozenge; direct contact; sucrose
o Erythematous candidiasis, multiple sites Amphotericin B – IV, suspension
o Site: dorsal tongue (central papillary atrophy), hard and soft palate, angles  Imidazoles
of mouth (angular cheilitis) Clotrimazole – lozenge (troche), cream; direct contact
E. Denture stomatitis Ketoconazole – oral; acidic env.; liver toxicity; drug int.
o Risk factors: chronic denture-wearing, poor OHI
o Site: hard palate, alveolar ridges, corresponds to area of denture  Triazoles
placement Fluconazole – PO; drug interactions; drug resistance
o Well-defined erythema ± petecial hemorrhage, asymptomatic, mild burning o **Interactions with Dilantin, warfarin, and sulfonylureas, rifampin,
o Candidal colonization of denture base, rule out allergey, inadequate curing cisapride**
Itraconazole – PO, suspension; drug interactions
 3. Chronic hyperplastic candidiasis (candidal leukoplakia)
Site: anterior bu mucosa, thick, white patch, cannot be wiped off
Controversial entitiy
o Leukoplakia with 2: candidiasis
What is this?
Histoplasmosis
Etiology:  Risk factors: elderly, debilitated, immunosuppressed (esp. AIDS)
o Histoplasma capsulatum  Symptoms of acute histoplasmosis
 Dimorphic fungus  If affect adrenal gland, symptoms of Addison’s dz
 Humid environments, soil with bird or bat excrement (fertile river o Oral
valleys of Ohio, Mississippi Rivers)  Site: tongue, palate, bu mucosa, variably painful, white or
 Infection depends on # spores inhaled, host immune status, strain H. erythematous plaques with irregular surface
capsulatum  Solitary ulcer with firm, rolled margins
 **May mimic malignancy
Transmission: Inhalation of airborne spores
Risk factors: Immunosuppressed; pulmonary compromise Histology:
o Histoplasma organisms within histiocytes – round (~1-2 um)
(emphysema) o Granulomatous inflammation
Geographic: Central and South America, Europe, Asia > US o Pseudoepitheliomatous hyperplasia (PEH)
Gender: Not specified o **PAS, GMS stains – round spores
Age: elderly (disseminated form) Diagnosis: tissue biopsy, culture, serologies – antibodies against H.
Site: lungs, spread to extrapulmonary sites capsulatum, ag
Clinical features: Healthy pt, low number of spores – asymptomatic; Treatment:
mild, flu-like symptoms (1-2 wks), development of antibodies, o Acute histoplasmosis – supportive care
immunity (2-3 wks) o Chronic histoplasmosis – Antifungals, death in 20%
o 3 patterns of clinical disease: • Disseminated histo – antifungals, death in 80-90% untreated, 7-23%
 1. Acute, 2. Chronic, 3. Disseminated treated
o Acute histoplasmosis
 Site: lungs
 Symptoms ~ flu: fever, headache, myalgia, non-productive cough,
anorexia
 Self-limiting: resolves in ~2 weeks
 Radiographs: chest x-ray – calcification of hilar lymph nodes
o Chronic histoplasmosis
 Site: lungs
 Risk factors: elder.y males, h/o emphysema; immunosuppressed
 Symptoms ~ TB: cough, weight-loss, fever, dyspnea, chest pain,
hemoptysis
 Radiographs: chest x-ray – upper-lobe infiltrates and cavitation
o Disseminated histoplasmosis
 Progressive spread of infection to extrapulmonary sites
 Site: lungs; spleen, adrenals, liver, LN, kidneys, skin, oral mucosa
What is this?
Blastomycosis
Etiology: o Oral
o Blastomyces dermatitidis  Via hematogenous spread, local inoculation
 Dimporphic fungus, rich, moist soil – geographically  Variable pain
overlaps with H. capsulatum – eastern half of US,  White or erythematous plaques with verrucous surface
Wisconsin, Minnesota, Canadian provinces surrounding  Solitary ulcer with rolled borders
Great Lakes  **may mimic malignancy
 10x less common than histoplasmosis Histology:
Transmission: inhalation of airborne spores o Blastomyces organisms
Risk factors: same as histoplasmosis  Round (~8-20 um)
 Doubly refractile wall, broad attachment between
Gender: M>>F (9:1) parent and daughter cell
Age: Adults o Granulomatous inflammation
Site: Lungs – spread to extrapulmonary sites o PEH
(skin>bones> prostate, meninges, oropharyngeal  **PAS, GMS stains
mucosa, abdominal organs) Diagnosis:
o Biopsy or cytology smear
Clinical features: usually asymptomatic or mild o Culture (sputum, biopsy material) – Sabourad’s agar; 3-4
symptoms weeks for results
o Acute blastomycosis o KOH preparation – rapid
 Symptoms ~ pneumonia: high fever, chest pain, o DNA probe – 5-7 days
malaise, night sweats, productive cough
 Rarely, adult respiratory distress syndrome (ARDS)
Treatment:
o Chronic blastomycosis o No treatment required in most patients
 Symptoms ~ TB o IV amphotericin B (immunosuppressed; no improvement
 Radiographs: chest x-ray – no changes or infiltrates clinically; ill for >2-3 weeks)
(diffuse or solitary) o Chronic blasto, extrapulmonary inv. – itraconazole
o Skin o Disseminated blasto – death 4-22%
 Via hematogenous spread
 Erythematous nodules  verrucous, ulcerated masses
What is this?
Paracoccidioidmycosis
Etiology: Paracoccidioides brasiliensis
o Dimporphic fungus, endemic in South America (Brazil, Colombia, Venezuela, Uruguay, Argentina), Central America, immigrants,
visitors
Transmission: inhalation spores; role armadillo
Risk factors: occupation in agriculture in endemic regions
Gender: M>>F (15:1) – protective effect of estrogen (inhibits transformation to yeast form)
Age: Middle-aged
Site: Lung – spread to extrapulmonary sites (LN, skin, adrenal glands) hematogenous, lymphatic spread
Clinical features: symptoms of pulmonary infection (self-limiting) Addison’s disease symptoms of adrenal
involvement
o Oral
 Site: alveolar mucosa, gingiva, palate, lips, tongue, oropharynx, bu mucosa
 “Mulberry-like” ulderations
Histology: P. brasiliensis organisms
o Round (~30um)
o Narrow attachment between parent and daughter cells (“mickey mouse” ears, ship’s steering wheel)
o Granulomatous inflammation
o PEH
o **PAS, GMS stains
Diagnosis: Biospy, culture – long time for results
Treatment:
o Mild-to-moderate cases – sulfonamides
o Non-life-threatening – itraconazole
o Severe – IV amphotericin B
What is this?
Coccidioidmycosis
AKA San Joaquin valley fever, valley fever
Etiology: Coccidioides immitis
o Dimorphic fungus, Southwestern US and Mexico; immigrants and visitors
Transmission: Inhalation of airborne spores
Age: Not specified
Site: Lungs – spread to extrapulmonary sites (skin, LN, bones and joints, meninges) – hematogenous
Clinical features: Mostly asymptomatic, flu-like and pulmonary symptoms – 40%
o Erythema nodosum – hypersensitivity response; multiple, painful inflammatory nodules on legs, valley fever = erythema
nodosum due to coccidioidomycosis
o Chronic progressive coccidioidomycosis – rare; TB-like symptoms
o Disseminated coccidioidomycosis – spread to extrapulmonary sites
 Risk factors: systemic corticosteroids, chemotherapy pt, HIV, pregnant; infants, elderly
o Skin
 Site: any skin site; central face, nasolabial fold
 Papules, abscesses, verrucous plaques, ulcerated nodules
Histology: C. immitis organisms (endospores) in spherules – round (20-60 um)
o Granulomatous inflammation, neutrophilic infiltrate
o **PAS, GMS stains
Diagnosis: Biopsy, cytology (sputum), culture, DNA probes( in situ hybridization), serologic tests
Treatment: No treatment necessary if mildly symptomatic
o IV amophotericin B – immunosuppressed, severe pulmonary infection, disseminated, pregnant, life-threatening
o Fluconazole, itraconazole – others
What is this?
Cryptococcosis
Etiology: Cryptococcus neoformans
o Infection typically seen in immunocompromised pt; yeast in both soil and host
Transmission: inhalation of airborne spores (lives in pigeon excrement)
Risk factors: Immunocompromised, esp. AIDS – incidence in US ↓ since HAART
Age: Not specified
Site: Lungs; spread to extrapulmonary sites (meninges, skin, bone, prostate)
Clinical features: Asymptomatic or mild, flu-like symptoms
o Disseminated cryptococcosis
 CNS – cryptococcal meningitis (headache, fever, vomiting, neck stiffness)
 Skin – erythematous papules or pustules, discharge contains organisms
 Oral – rare; crater-like, non-healing ulcers
Histology:
o C. neoformans organism – round to ovoid with clear halo (4-6 um)
o Granulomatous inflammation
o **PAS, GMS stains Mucicarmine stain (capsule) – “+”
Diagnosis: Biopsy, culture, serologic studies for antigen
Treatment:
o Mild pulmonary cryptococcosis – fluconazole, itraconazole
o Cryptococcal meningitis – amphotericin B, flucytosine; followed by fluconazole or itraconazole
What is this?
Zygomycosis
AKA: Mucormycosis, phycomycosis
Etiology: Class Zygomycetes, including Absidia, Mucor, Rhizomucor, Rhizopus
Risk factors:
o Insulin-dependent diabetes – uncontrolled and ketoacidotic
o Immunocompromised
o Patients taking deferoxamine (iron-chelating agent) – treatment thalassemia
o Rare in healthy individuals
Age: Not specified
Site: Rhinocerebral zygomycosis – cranial sites (nose, eyes, sinuses, brain)
Clinical features:
o Rhinocerebral zygomycosis – nasal obstruction, bloody nasal discharge, facial pain, facial swelling, visual disturbances,
proptosis, cranial nerve palsies, blindness, lethargy, seizures, death.
 Maxillary sinus involvement – swelling of mx alveolus, palate; ulceration  black necrosis; extensive tissue destruction if untreated
 Rad: opacification, destruction of sinus walls
Histology: Large, non-septate hyphae
o 6-30 um, branch 90⁰ angles, invade vessels
o Necrosis, neutrophilic infiltrate
o **PAS, GMS stains
Diagnosis: Biopsy, smear and/or culture – usually treated immediately
Treatment: Radical surgical debridement of necrotic tissue + amphotericin B
o Prognosis poor, death ~60% (despite therapy)
What is this?
Aspergillosis
Etiology: Aspergillus species; mostly A. fumigates, A. flavus o Thin, spetate hyphae – 3-4 um, branch acute angles, invade vessels
o Non-invasive – immunocompetent host o Necrosis, granulomatous inflammation
 1. Allergic reaction (e.g. allergic fungal sinusitis) o Allergic fungal sinusitis – mucin, eosinophils, few hyphae
 2. Aspergilloma o Aspergilloma – tangled mass of hyphae
o Invasive – immunocompromised; rarely, immunocompetent o **PAS, GMS stains
 1. Disseminated aspergillosis Diagnosis: Biopsy, culture (more definitive) – usually treated
Transmission: inhalation of airborne spores immediately
Risk factors: immunocompromised (AIDS, transplant pt, uncontrolled Treatment: Depends on host factors, clinical form of aspergillosis
DM) o Non-invasive in immunocompetent host
o Hospital-acquired (“nosocomial”)  Surgical debridement, allergic fungal sinusitis – debridement +
Gender: Not specified steroids
Age: Not specified o Invasive, localized in immunocompetent
 conservative debridement + antifungal (voriconazole, itraconazole)
Site: Lungs – spread to extrapulmonary sites – paranasal, oral cavity
o Invasive, disseminated in immunocompromised
Clinical features:  Aggressive debridement + antifungal
o Immunocompetent host  Prognosis poor – death ~60%
 1. Allergy
Site: Sinus (“allergic fungal sinusitis”), bronchopulmonary tract
May induce asthma attack
 2. Aspergilloma = fungal ball
Site: mx sinus, lung
Result of long-standing, low-grade infection
If calcified  can appear ~ to antrolith
o Immunocompromised host
 Disseminated aspergillosis
Site: lung, extrapulmonary (CNS, eye, skin, liver, GI tract, bone,
thyroid gland)
Risk factors: pt with leukemia, pt on high dose corticosteroids
Pulmonary symptoms
Extrapulmonary manifestations
o Immunocompetent, immunocompromised host
 Oral aspergillosis
Site: exo socket, endo; mx posterior regions
May predispose mx sinus to Aspergillus infection  localized
pain, nasal discharge
Painful gingival ulcerations  gray-violet swelling  yellow-black
necrosis
Histology:
What is this?
Toxoplasmosis
Etiology: Toxoplasma gondii – protozoal organism
Incidence: relatively common – 16-23% US adults have asymptomatic infection
Transmission: Cat – host
o Fecal-oral – T. gondii infects feline intestinal tract  discharge oocytes in feces  ingested by humans, other animals; contact with oocytes
Risk groups:
o 1. Immunocompromised (AIDS, transplant, cancer pt)
o 2. Developing fetus
Clinical features:
o Immunocompetent pt: asymptomatic, mild symptoms ~ infectious mononucleosis (low-grade fever, fatigue), lymphadenopathy
o Immunocompromised pts: necrotizing encephalitis, pneumonia, myositis, myocarditis, CNS involvement – headache, lethargy, disorientation, hemiparesis
o Congenital toxoplasmosis : transmission from infected mother  fetus; blindness, mental retardation, delayed psychomotor development, most severe if
transmitted in 1st trimester
Histology:
o Lymph node – reactive germinal centers, eosinophilic macrophages
Diagnosis:
o Serologic studies – antibodies to T. gondii, highest 10-14 days after infection
o Biopsy of lymph node + identification of T. gondii with immunohistochemistry
**Immunocompromised patients
o Serologic studies may be negative
o Dx based on clinical presentation, response to empiric therapy
Treatment:
o Immunocompetent pt – no treatment necessary
o Immunocompromised pt
 Sulfdiazine and pyrimethamine (clindamycin if allergic)
 Prophylactic trimethoprim and sulfamethoxazole if CD4+ T-lymphocyte count <100 cells/uL
o Pregnant females
 Prevention is key
 Avoid handling or eating raw meat, wash hands thoroughly after handling raw meat; cook meat until well-done
 Avoid contact with any materials potentially infected with cat feces, avoid changing kitty litter
 Sulfdiazine and pyrimethamine + folate if exposure during pregnancy
What is this?
Transient lingual papillitis
• AKA: Lie bumps, tongue torches
• Etiology: unknown, variety of factors – local irritation, stress, GI disease, hormonal fluctuation,
upper respiratory tract infection, viral infection, topical hypersensitivity, etc
• Gender: F>M
• Age: Not specified
• Site: Dorsal tongue – fungiform papillae
• Clinical features: 3 patterns –
– 1. Localized
• Site: anterior dorsal tongue, one to several papillae; red, elevated papules  yellow ulceration, usually painful, mild to
moderate, resolve spontaneously in hours-days
– 2. Generalized
• Site: Tip, lateral tongue; large percentage of fungiform papillae, enlarged, erythematous papules  ulceration, painful;
fever, cervical LAD, spontaneously resolves in ~7d, spread among family members - ?viral
– 3. Diffuse (papulokeratotic variant)
• Histology: Localized, generalized
– Benign stratified squamous epithelium, ± surface ulceration, ± intraepithelial neutrophils, mixed
inflammation, increased vascularity
• Treatment: No treatment required, topical steroids – can reduce duration, topical anesthetics – can
reduce pain, identify triggering event if possible
What is this?
Recurrent apthous stomatitis
AKA: Canker sores  Yellow-white fibrinopurulent membrane with red halo – clusters of up to 100 lesions, 1-3
mm; painful – clinically ~HSV (“herpetiform”)
Very common  Resolve in 7-10 days; more frequent recurrences
Incidence: 5-66% population (mean: 20%) o Subclassification for treatment purposes:
Etiology: long debated, no single triggering event, factor – likely “different things in  1. Simple aphthosis: few lesions, heal in 1-2 weeks, recurrences infrequent
different people”, mucosal destruction due to T-lymphocyte-mediated immunologic  2. Complex aphthosis: multiple lesions >3, constant onset of new lesions, severe pain, large
size, longer healing, recurrences frequent
reactions Histology:
o ↓ CD4/CD8 ratio, ↑ T cell-receptor γδ+ cells, ↑ tumor necrosis factor-α (TNF-α)
o Fibrinopurulent membrane and neutrophils = ulcer
o Familial tendency – 90% child will have RAU if both parents affected, association with o Epithelial acanthosis
histocompatibility antigen
o Under ulcer, granulation tissue (inflamed and well-vascularized CT)
o Roles for allergy, genetics, nutritional deficiencies, hematologic abnormalities, hormones, o Adjacent to ulcer, band of lymphocytes and histiocytes
immunologic factors, infectious agents, tobacco cessation, trauma, stress
o 3 basic mechanisms of development
Diagnosis: clinical presentation AND evaluation to exclude underlying systemic disorders
 1. Primary immunodysregulation: cyclic neutropenia, AIDS Treatment: evaluate for underlying systemic disorder, attempt to identify triggering
 2. Decrease of mucosal barrier: non-keratinized mucosa, trauma, nutritional deficiencies, events/factors, conditions, antigen testing helpful in some cases
smoking cessation o Minor AU (simple) – no treatment necessary, OTC anesthetics, bioadhesive products,
 3. Increase in antigenic exposure: long list of potential antigens, sodium laurel sulfate in
topical steroids
toothpaste, various systemic medications, bacteria, viruses, foods
o Major AU, herpetiform AU (complex) - steroid injections, more potent topical steroids,
Association with systemic disorders: systemic corticosteroids
o 1. Behcet’s syndrome  Alternative to corticosteroids – efficacy not always established by clinical trials; some with
o 2. Inflammatory bowel disease: Crohn’s disease, ulcerative colitis significant side effects
o 3. Celiac disease • Topical Steroids
o 4. Cyclic neutropenia o Mild potency: dexamethasone elixir
o 5. Reiter’s syndrome o Moderate potency: fluocinonide
o 6. Immunocompromised states: AIDS, HIV o High potency: Clobetasol propionate
Gender: no predilection  **Overuse of topical steroids may predispose to oral candidiasis
Age: Children, young adults; recurs • Systemic steroids
Site: Mostly non-keratinized (NK) mucosa – buccal and labial mucosa, ventral tongue, o Medrol dosepak
floor of mouth, soft palate, very rarely occurs on keratinized mucosa – major and  ** can cause growth suppression in infants and children**
 Expensive
herpetiform variants
Clinical features: 3 clinical variants –
o 1. Minor aphthous ulceration
 Site: NK mucosa (bu and la mucosa>ventral tongue>MB fold> FOM>soft palate; rarely, K
mucosa (extension of lesion from adjacent NK mucosa)
 Erythematous macule  round, yellow-white fibrinopurulent membrane with red halo
1-5 lesions, 3-10 mm; painful
Resolve 7-14 days
o 2. Major aphthous ulcerations (Sutton’s disease)
 Site: NK>K mucosa (la mucosa > soft palate > tonsillar fauces)
 Yellow-white fibrinopurulent membrane with red halo – deeper than minor AU, 1-10
lesions, 1-3 cm, painful
 Resolve in 2-6 weeks with scarring
o 3. Herpetiform aphthous ulceration
 Site: NK > K mucosa
 Gender: F slightly > M
What is this?
Bechet’s syndrome
Etiology: Not entirely clear  Arthritis – knees, wrists, elbows, ankles
o Immunogenic basis – strong association with certain HLA types – HLA-  CNS involvement – paralysis, severe dementia
 Cardiovascular, GI, hematologic, pulmonary, muscular, renal
B51 – high frequency in Turkey, Japan, Eastern Mediterranean
countries Diagnosis:
o Associated with trigger events/factors – environmental antigens, o Behcet’s International Study Group criteria
 1. Recurrent oral ulcerations AND
bacteria, viruses, pesticides, heavy metals
 2. At least two of the following:
Geographic: Middle east, Japan Recurrent genital ulcers, eye lesions, skin lesions,” +”pathergy test
Gender: Not specified Histology:
Age: Young adults o ~AU
Site: Multisystem disorder w/ classic triad: 1. Oral, 2. Genital, 3. Ocular o Leukocytoclastic vasculitis = blood vessels exhibiting
Clinical features:  1. Heavy PMN infiltrate
 2. Fibrinoid necrosis
o Oral:
 3. Nuclear dust
 Incidence: 99% of pt with Behcets, first manifestation in 25-75% of
cases Treatment:
 ~ to AU with additional features: o Oral and genital lesions
1. >6 lesions  Topical, intralesional steroids; topical tacrolimus (Protopic)
2. Soft palate and oropharyngeal involvement  If severe – oral colchicine or dapsone
3. Ragged borders, wider zone of erythema  If recractory – thalidomide, methotrexate, systemic corticosteroids,
4. All 3 forms of AU can be seen: minor>major>herpetiform infliximab
o Genital: o Ocular, systemic disease – if severe – immunosuppressive and
 Incidence: 75% pt
immunomodulatory agents
 Site: vulva, vagina, glans penis, scrotum, perianal
 Ulcerations – deep, heal with scarring Prognosis:
o Ocular: o Variable course – multiple relapses and remittance
 Incidence: 70-80% pt o Most morbidity and mortality in early years of dx – early diagnosis and
 Gender: M>F; more severe in males treatment critical
 Posterior uveitis, conjunctivitis, corneal ulceration, papilledema, o Mortality – generally low; high if CNS disease, vascular involvement
arteritis  Causes of death: pulmonary hemorrhage, CNS hemorrhage, bowel
 May develop 2: ocular complications (cataracts, glaucoma, et.c) perforation
o Skin:
 Variety of appearances
 Positive “pathergy” test = hypersensitivity reaction
Pustule or tuberculin-like reaction in 1-2 days after insertion of
sterile needle
Positive in 40-88% pts
o Other findings
What is this?
Sarcoidosis
Multisystem granulomatous disorder characterized by non-caseating May be first manifestation of disease
granulomatous inflammation Histology:

Etiology: unknown cause; Inappropriate response to degradation of o Non-caseating granulomatous inflammation
 Tight, round aggregates, epithelioid histiocytes, lymphocytes, giant
antigen cells, ± calcifications, inclusions
o Antigen unknown, prolonged exposure to antigen, heavy antigenic o Granulomatous inflammation seen in many processes
exposure, immunodysregulation, defective regulation of initial  **Special stains (PAS, GMS) negative for fungus
immune response.  **Special stains (AFB) negative for mycobacteria
o Association with certain HLA types  **No foreign body material
Ethnic: AA Diagnosis:
Gender: F slightly > M o Clinical and radiographic presentation
Age: Two peaks: 25-35, 45-65 yo o Elevated serum angiotensin-converting enzyme (ACE) levels
 Other lab abnormalities: eosinophilia, leucopenia,
Site: Lungs, lymph nodes, skin, eyes, salivary glands; other organ thrombocytopenia, elevation serum alkaline phosphatase, ESR,
systems – endocrine, GI tract, heart, kidney, liver CNS, spleen, bone serum and urine Ca levels
Clinical features: o Biopsy – minor salivary gland; posterior parotid gland, to rule out
o Lungs: typically acute onset – days to weeks, symptoms variable, other pathologic processes
dyspnea, dry cough, chest pain, fever, malaise, fatigue, arthralgia, o Kveim test – skin test for sarcoidosis; used rarely
weight loss, ~20% asymptomatic Treatment:
o Lymph nodes (90% pt) mediastinal, paratracheal lymph nodes. o Resolves spontaneously in 60% pt – close observation during first 3-12
 Chest x-ray: bilateral hilar LAD months of dx
o Skin (25% pt): o Corticosteroids – indications: progressive disease, cardiac or
 Site: nose, ears, lips, face, limbs, back, buttocks neurologic involvement, hypercalcemia, serious skin and/or ocular
 Chronic, violaceous, indurated plaques
lesions
 Erythema nodosum – lower legs
o If refractory to corticosteroids – methotrexate, azathioprine,
o Eyes (25% pt)
 Anterior uveitis chlorambucil, cyclophosphamide
 Lacrimal gland inv.  keratoconjunctivitis sicca o Other medications” TNF-α antagonists, antimalarials
o Salivary gland – enlargement; xerostomia Prognosis:
 Eye and salivary gland symptoms similar to Sjogren syndrome o Mortality rate of 4-10%
o Oral (uncommon) • Pulmonary, cardiac, CNS complications
 Site: bu mucosa>gingiva, lips, FOM, tongue, palate, mandible, maxilla
 Oral mucosa – variable appearance
Normal, brown-red, violaceous or white
Submucosal mass, isolated papule, granular lesion, ulceration
Intraosseous – ill-defined radiolucency
What is this?
Orofacial granulomatosis
Variety of clinical presentations that show granulomatous o Cheilitis granulomatosa (of Meischer)
inflammation on biopsy  1. Orofacial granulomatosis involving lips only
Etiology: Histology:
o Cause unknown – “idiopathic” orofacial granulomatosis o Non-caseating granulomatous inflammation
 Epithelioid histiocytes, lymphocytes, ± giant cells, not as tight as
o Likely an abnormal immune reaction in response to a variety of
sarcoidosis
triggers (?dietary)  ± edema of CT, fibrosis
o Diagnosis of exclusion – must rule out other conditions before making o Granulomatous inflammation seen in many processes
dx of orofacial granulomaosis  **Special stains (PAS, GMS) negative for fungus
o Many conditions have clinical and histologic presentations similar to  **Special stains (AFB) negative for mycobacteria
orofacial granulomatosis  **No foreign body material
 Systemic: Chronic granulomatous disease, Crohn’s disease, Diagnosis:
Sarcoidosis, Tuberculosis, leprosy, syphilis o Histologic confirmation of granulomatous inflammation AND
 Local: chronic oral infection, foreign material, allergy (cosmetics,
exclusion of other granulomatous processes
food, OH products, restorative metals)
 Negative special stains (PAS, GMS, AFB)
o **Must rule out above before making dx of orofacial granulomatosis  No foreign body material
Gender: Not specified  Rule out other systemic and local causes
Age: Adults Treatment:
Site: Lips >> other intraoral sites (tongue, gingiva, buccal mucosa), o If systemic cause found, treat as indicated; if local cause found,
Other facial sites eliminate
Clinical features: o If no underlying cause found:
o Highly variable  Course variable – spontaneous regression, persistence
 Intralesional steroid, clofazimine (anti-leprosy agent with
o Lips – tender, persistent swelling ± vesicular areas
antigranulomatous properties
o Oral mucosa – edema, ulcers, papules  Surgical excision in some cases
o Tongue – edema, fissures, paresthesia, erosions
• Recurrences common
o Gingiva – swelling, erythema, erosions
o Bu mucosa – cobblestone appearance, hyperplastic folds, linear
ulcerations
o Palate – papules, hyperplastic tissue
o ± Swelling of other facial sites; cervical LAD
o Melkersson-Rosenthal syndrome
 1. Orofacial granulomatosis
 2. Facial paralysis
 3. Fissured tongue
 ± facial swelling
What is this?
Wegener’s granulomatosis
Etiology: unknown cause o Other orofacial features – facial paralysis, TMJ arthralgia, jaw
o ? abnormal immune reaction to non-specific infection claudication
o ? aberrant hypersensitivity response to antigen Histology:
Gender: No predilection o Leukocytoclastic vasculitis = blood vessels exhibiting
Age: Wider ange (avg. 40 yo)  1. Heavy PMN infiltrate
 2. Fibrinoid necrosis
Forms and sites of involvement:  3. Nuclear dust
o 1. Superficial – skin, mucosa o Histiocytes, lymphocytes, eosinophils, giant cells in CT, prominent
o 2. Limited – upper and lower respiratory tract vascularity
o 3. Generalized – upper and lower respiratory tract , skin, eventually o Gingiva – PEH, RBCs
kidney Diagnosis: clinical presentation AND microscopic findings
o Eyes, ears, oral mucosa (gingiva), salivary glands (rare)
o Pulmonary involvement: chest x-ray
Clinical features: o Renal involvement: serum creatinine, BUN
o Classic Wegener’s granulomatosis o Serologic studies – serum antibodies against cytoplasmic component
 1. Lung – necrotizing “granulomatous” lesions of upper and lower
of neutrophils (antineutrophil antibodies [ANCA]
respiratory tract
 2 patterns:
 2. Kidney – necrotizing glomerulonephritis 1. Perinuclear (p-ANCA)
 3. Vascular system – systemic vasculitis of small arteries and veins 2. Cytoplasmic (c-ANCA) – more specific for Wegener’s
 Variable severity and involvement of systems  Molecular studies (ELISA against proteinase-3 [Pr-3]) – positive c-
o Upper respiratory tract – purulent nasal discharge, chronic sinus pain, ANCA + ELISA: 73% sensitivity, 99% specificity
nasal ulceration, congestion, epistaxis, fever, otitis media, sore throat, Treatment: First line – oral prednisone nad cyclophosphamide –
destruction of nasal septum  saddle-nose deformity serious side effects, relapses frequently; Second line – trimethoprim-
o Lower respiratory tract – may be asymptomatic, dry cough, ssulfamethoxazole – localized cases, failure of first line therapy,
hemoptysis, dyspnea, chest pain
o Kidney – late in disease, glomerulonephritis – proteinuria, red blood
methotrexate as a substitute for cyclophosphamide
o Early diagnosis and treatment critical – 75% remission rate, cure if
cell casts
localized involvement and early tx.
o Oral mucosa
 Gingiva: “strawberry gingivitis” Prognosis: relapse rate of 30%, maintenance therapy, monitor with c-
Site: buccal>lingual; attached ANCA levels
Florid, granular hyperplasia, hemorrhagic, friable (red, bumpy), o Untreated, disseminated Wegener’s
destruction of bone, tooth mobility, usually before renal
involvement
 Mean survival: 5 months
 Palate: midline destruction, palatal perforation  Mortality rate: 80% at 1 yr, 90% at 2 yrs
 Other oral mucosal sites: non-specific ulceration, nodules, usually  Prognosis better for superficial > limited > generalized form
after renal involvement
o Salivary glands - Enlargement – early in disease course
What is this?
Allergic mucosal reactions to systemic
drug administration
AKA: Stomatitis medicamentosa o Pemphigus-like eruptions - ~to oral lesions of pemphigus vulgaris
Allergic mucosal reaction to systemic drugs, may be seen in addition o Site: Any mucosal surface (posterior bu mucosa, lateral tongue)
to other adverse drug reactions: xerostomia, dysgeusia, gingival Histology:
hyperplasia, others o Anaphylactic stomatitis: chronic inflammation of CT (lymphocytes,
Many patterns of allergic mucosal reaction eosinophils, PMNs)
o Fixed drug eruption: Chronic inflammation of CT (lymphocytes,
o 1. Erythema multiforme
eosinophils, PMNs), epithelial acanthosis; inflammatory cells in
o 2. Anaphylactic stomatitis
epithelium
o 3. Intraoral fixed drug eruption
o Lichenoid-like eruptions - ~histologic findings as namesake disorders
o 4. Lichenoid drug eruptions
– lichenoid: antibody (IgG) against basal cells of epithelium (basal cell
o 5. Lupus-erythematosus-like eruptions
cytoplasmic antibody) – “string of pearls” pattern
o 6. Pemphigus-like drug eruptions
o 7. Non-specific vesiculoerosive or aphthous-like lesions Diagnosis:
Etiology: Many medications implicated o Resolution of lesions after drug elimination
o Identification of offending drug may be challenging, patients on
o Rate adverse reactions increases with # medications used
 6% with 2 meds; 50% with 5; 100% with 8 multiple medications, temporal relationship between drug intake and
o List of medications associated with each reaction on lesion onset may be delayed
 Antibiotics, sulfa drugs, NSAIDS, beta-blockers, ACE-inhibitors, gout, Treatment: Elimination of medication, topical corticosteroids, if
many others systemic symptoms (anaphylactic stomatitis): epinephrine,
o Anaphylactic stomatitis – allergen binding to IgE-mast cell corticosteroids, antihistamines
complexes, mast cell degranulation
o Intraoral fixed drug eruption – allergen-induced inflammatory
reaction that recurs in same site after drug administration
Age: Any age; likely older due to # of meds
Site: depends on reaction pattern
Clinical features: Extremely variable
o Anaphylactic stomatitis: erythema; aphthous-like ulcerations ±
urticarial skin lesions; systemic symptoms of anaphylaxis (respiratory
distress, vomiting)
o Fixed drug eruption: erythema, edema, vesiculoerosive lesions,
frequently labial mucosa, recurs in same site
o Lichenoid-like eruptions - ~to oral lesions of lichen planus
o Lupus-like eruptions - ~to oral lesions of lupus erythematosus
What is this?
Allergic contact stomatitis
AKA: Stomatitis venenata Clinical features: Acute or chronic
Allergic mucosal reaction to direct contact with an o 1. Acute – burning; itching, stinging, tingling, erythema ±
agent edema; erosions
o 2. Chronic – erythema or white, hyperkeratotic area,
Etiology: Direct contact with a variety of agents periodic erosions, desquamation (sloughing), lips –
o Food, food additives, chewing gum, candies, dentifrices,
drying, scaling, fissuring, cracking of vermillion border
mouthwashes, gloves, rubber dams, dental materials –
restorative materials, denture materials, impression Diagnosis:
materials, denture adhesive o Acute: reaction shortly after contact with allergen
o Chronic: more challenging to diagnose
Incidence: Quite rare in oral cavity  Elimination of other causes, clinical presentation,
o Brief contact period, dilution and digestion of antigens by positive history of allergic reactions, patch testing –
saliva, quick removal of antigens due to high vascularity may helpful in dx.
of oral tissues, lower density of Langerhans cells and T- Treatment:
lymphocytes  lower recognition of antigens o Acute: mild cases – elimination of agent; more severe
Oral sensitization may not occur after initial skin cases – antihistamine ± topical anesthetic
sensitization BUT • Chronic: elimination of agent, topical corticosteroids
Skin sensitization usually occurs after initial oral
sensitization
May occur with other extraoral manifestations
o Exfoliative cheilitis, perioral dermatitis
Gender: F>M
Age: not specified
Site: Mucosa directly in contact with allergen
o Localized involvement – localized agent
o Generalized involvement – diffuse agent (food, OH
agents)
What is this?
Perioral dermatitis
Inflammatory skin disease of perioral area
Etiology:
o Poorly understood
o Inflammatory response to several agents – toothpastes, bubble gum, moisturizers, cosmetics,
initiates as an allergy, irritation, reaction to bacteria
o Corticosteroid therapy worsens condition
Gender: F>>M (90% in adult F)
Age: Wide age range
Site: Perioral skin, skin immediately adjacent lips mostly spared
Clinical features: erythema with papules and pustules, may be pruritic, skin
adjacent to lips usually spared
Histology: Variable, chronic inflammation (lymphocytes, histiocytes),
granulomatous inflammation surrounding hair follicles
Treatment: discontinue topical steroids (if being used), oral
tetracycline/erythromycin may help, topical metronidazole or erythromycin may
help, typically resolves in months
What is this?
Contact stomatitis from cinnamon
AKA: Cinnamon stomatitis
Inflammatory mucosal reaction to cinnamon oil
Etiology: Contact with cinnamon oils – most commonly agents with prolonged mucosal contact (e.g. candy,
chewing gum, toothpaste)
Age: Not specified
Site: Any mucosal site directly in contact with agent
o Toothpaste – more generalized
o Candy, gum – more localized
Clinical features: Depends on agent – burning, pain
o Gingival – enlargement, erythema, sloughing = “plasma cell gingivitis” – usually related to cinnamon-containing toothpaste
o Bu mucosa, tongue – erythema ± erosions (toothpaste), white plaque with ragged surface on erythematous base ± ulcerations
(candy, gum) – similar to other white-red lesions
o Skin (perioral) – erythema, papules, pustules, flaking
Histology: hyperkeratosis, epithelial acanthosis, neutrophilic infiltration of epithelium, heavy chronic
inflammation (lymphocytes, plasma cells, eosinophils), inflammation around blood vessels = perivascular
inflammation
Diagnosis: clinical presentation AND positive history of cinnamon exposure, histology may help support dx
o Patch testing of skin – may be helpful in dx
Treatment: resolution in ~1 week after discontinuation of cinnamon product , will reappear if cinnamon re-
introduced
What is this?
Lichenoid contact stomatitis from
dental restorative materials
Etiology: Hypersensitivity or toxic reaction to Histology: ~Lichen planus
metals in dental restorative materials o 1. Hyperkeratosis ± epithelial atrophy, ulceration
o Chronic > acute o 2. Degeneration of epithelial basal layer
o Amalgam >> gold, nickel o 3. Band-like infiltrate of chronic inflammatory
 1. Variable corrosion rates (lower in gold, nickel) – cells in superficial CT – lymphocytes, plasma
corrosion of metal  release metallic ion  cells, perivascular inflammation
mucosal reaction
 2. Local irritation from old restoration (Koebner
Diagnosis: Clinical presentation
phenomenon) o Need to distinguish from lichen planus, favor
 Dental resin – rare; excess free monomer lichenoid contact stomatitis if:
Gender: Not specified  1. Lesions do not migrate
 2. Affected mucosa in direct contact with dental
Age: Not specified restorative material
Site: Oral mucosa in direct contact with dental  3. Positive patch test to dental metals in some
patients (gold, nickel, mercury)
restorative materials  4. Improvement and/or resolution on smoothing,
o Posterior buccal mucosa, ventral-lat. Tongue recontouring restoration; removal of restoration
o Marginal gingiva (PFM crowns) o Biopsy – to rule out other pathology
Clinical features: Treatment:
o Asymptomatic, similar to lichen planus o Improved oral hygiene, local measures
 White or erythematous lesions ± striations (smoothing, polishing, recontouring
 May show erosions
questionable restorations)
o Lesions do not migrate, lesions confined to
o If no improvement, replacement of amalgam
mucosa in contact with resto
with other restorative material
o Resolve after removal of restoration
What is this?
Angioedema
AKA: Angioneurotic edema, Quincke’s disease Age: Hereditary (C1-INH): onset in childhood, adolescence
Etiology: Variety of mechanisms Site: skin – extremities, face, lips, neck, genitals
o 1. Mast cell degranulation o Mucous membranes – larynx, pharynx, uvula, tongue FOM
  histamine release, triggers of mast cell degranulation Clinical features:
A. IgE-mediated hypersensitivity reaction to drugs (ASA, NSAIDs),
foods, plants, dust
o All forms: rapid onset, unpredictable episodes and remissions,
B. contact allergic reactions to food, cosmetics, topical abdominal pain, skin swelling – itching, erythema, mucosal swelling –
medications itching, erythema, laryngeal involvement – hoarseness, dysphonia,
C. Physical stimuli (heat, cold, exercise, stress) dyspnea  respiratory distress, swelling resolves in 24-72 hrs
o 2. ACE inhibitor-related o Ace inhibitor form: typically witin hourse of initial use of drug, can be
 Severe form angioedema, not IgE-mediated, excess bradykinin
precipitated by minor trauma, including dental procedures
(degraded by ACE), decreased with newer generation (angiotensin II
receptor blockers, ARBs) o Hereditary, acquired (C1-INH) form: can be precipitated by minor
o 3. Abnormal C1 esterase inhibitor (C1-INH) activity – hereditary, trauma, including dental procedures
acquired Diagnosis: clinical presentation AND identification of stimulus (drugs,
 Complement pathway activation, abnormal C1-INH activity environmental stimulus, etc.)
Normal: C1-INH inhibits conversion of C1 to C1 esterase, without o Evaluate C1-INH activity if cause (stimulus) cannot be identified
C1 esterase, C4 and C2 remain uncleaved  Hereditary, types I & II: ↓ levels functional C1-INH, normal levels C1
Abnormal: Abnormally low C1-INH activity  Increased
conversion of C1 to C1 esterase, excess C1 esterase  cleavage of
 Acquired: ↓ levels functional C-INH, ↓ levels C1
C4, C2  angioedema Treatment: Eliminate stimulus, close observation for loss of airway,
A. Hereditary *intubation, tracheostomy if airway obstruction*, avoid vigorous
o Type I (85%) – autosomal dominant, ↓levels C1-INH
o Type II (15%) – autosomal dominant; dysfunctional physical activity, trauma, medical warning cards
C1-INH o Angioedema related to mast cell degranulation – antihistamines, IM
B. Acquired epi, IV corticosteroids and antihistamines
o Lymphoproliferative – antibodies against tumor cells,
activate C1  consumption of C1-INH, ↓ levels C1- o Ace inhibitor form: discontinue and avoid ACE inhibitors, including
INH Angiotensin II receptor blockers (ARBs), some response to C1-INH
o Autoimmune – autoab. Attach C1-receptor of C1-INH concentration
 ↓ levels of functional of C1-INH, consumption Cl
o Hereditary, acquired (lymphoproliferative) forms: C1-INH
o 4. High levels of antigen-antibody complexes
concentrate, esterase-inhibiting drugs – acute attacks, prophylaxis
 Abnormal antigen-antibody complexes – lupus erythematosus;
bacterial or viral infections with androgens (stimulates hepatic synthesis of C1-INH) – before
o 5. Grossly elevated peripheral blood eosinophil levels dental, surgical procedures; if ≥ 3 episodes/yr
Incidence: ACE inhibitor form: 0.1-0.2% of pts who use ACE inhibitors o Acquired (autoimmune) form – corticosteroids
Ethnic: ACE inhibitor form: AA
What is this?
Squamous papilloma
Etiology: A benign proliferation of stratified squamous epithelium,  Hoarseness, rapidly proliferating papillomas in juvenile-onset time,
may obstruct airway
resulting in a papillary or verruciform mass
o Presumably induced by HPV – comprises a large family of dsDNA Histopathology
viruses of the papovavirus subgroup A o Proliferation of keratinized stratified squamous epithelium arraywed
o 81% of normal adults have buccal epithelium cells that contain at least in finger-like projections
on type of HPV o CT cores may show inflammatory changes
o Virus becomes totally integrated w/ the DNA of host cell o Keratin layer is thickened, epithelium typically shows a normal
o 24 types are associated w/ lesions of H&N maturation pattern, occasional papillomas demonstrate basilar
o HPV can be identified by: hyperplasia and mitotic activity, can be mistaken for mild epithelial
 In situ hybridization, immunohistochemical analysis, PCR techniques dysplasia
 It is not visible w/ routine histopathologic staining o Koilocytes: virus altered epithelial cells w/ small dark nuclei,
o Viral subtypes 6 and 11 identified in up to 50% of oral papillomas sometimes seen high in the prickle cell layer
 <5% in normal mucosal cells Treatment and prognosis:
o Viruses in this lesion appear to have an extremely low virulence and o Conservative surgical excision, including the base of the lesion –
infectivity rate adequate treatment
o Latency or incubation period of 3-12 months (?) o Recurrence is unlikely
o Squamous papilloma occurs in 1/250 adults o Frequently, lesions have been left untreated for years w/ no
o Makes up ~3% of all oral lesions submitted for biopsy malignant transformation, continuous enlargement, dissemination
Clinical features to other parts of oral cavity
o Gender: M=W o Juvenile-onset laryngeal papillomatosis: continuously proliferative,
o Can arise at any age – diagnosed most often in persons 30-50 years of death by asphyxiation, surgical debulking
age o Adult-onset lesions: less aggressive, single, conservative surgical
o Sites of predilection = tongue, lips, soft palate, any oral surface can be removal
affected o In rare instances, SCC will develop in long-standing laryngeal
o Most common soft tissue mass arising from the soft palate papillomatosis, smoker, history of irradiation to larynx
o Painless, soft, pedunculated, exophytic, numerous finger-like
projections, “cauliflower”, white, red or normal in color, solitary,
enlarges rapidly to about 5.0 cm, afterwards not change
o Sometimes difficult to distinguish from verruca vulgaris, condyloma
acuminatum, verruciform xanthoma, focal epithelial hyperplasia
o Laryngeal papillomatosis – rare, potentially devastating disease of
larynx
 Juvenile onset
 Adult onset
What is this?
Verruca vulgaris
Etiology: Benign, virus-induced focal hyperplasia of o Chronic inflammatory cells often infiltrated supporting CT
stratified squamous epithelium o Elongated rete ridges tend to converge toward the
o HPV 2, 4, 5 an 40 – found in virtually all examples center of lesion, producing a “cupping” effect
o Contagious – can spread to other parts of a person’s skin o Prominent granular cell layer exhibits coarse, clumped
or mucous membranes by way of auto-inoculation keratohyaline granules
o Infrequently develops on oral mucosa but is extremely o Abundant koilocytes – often in superficial spinous layer
 Koilocytes – HPV altered epithelial cells with
common on the skin
perinuclear spaces and small, dark nuclei (pyknosis)
Clinical features: Treatment and prognosis:
o Frequently seen in children, occasionally middle age
o Skin verrucae: liquid nitrogen cryotherapy, conservative
o Skin of hands is usually site of infection
surgical excision or curettage, topical application of
o Oral mucosa involved – vermillion border, labial mucosa,
keratinolytic agents (salicylic acid, lactic acid)
anterior tongue
o Oral lesions: usually surgically excised, may be destroyed
o Painless papule or nodule w/ papillary projections or a
by laser, cryotherapy, electrosurgery
rough pebbly surface
o All destructive or surgical treatments should extend to
o Pedunculated or sessile
include the base of the lesion
o Cutaneous lesions – pink, yellow, white
o Recurrence – seen in small proportion of treated cases
o Oral lesions – almost always white
o W/out treatment:
o Enlarges rapidly to maximum size <5mm, size remains  Verrucae do not transform into malignancy
constant for months-years  2/3 will disappear spontaneously w/ in 2 years –
o Multiple/clustered lesions are common especially in children
o Cutaneous horn or keratin horn – on occasion, extreme
accumulation of compact keratin, may result in a hard
surface projection several millimeters in height
o Proliferation of hyperkeratotic stratified squamous
epithelium – arranged into fingerlike or pointed
projections
What is this?
Condyloma acuminatum (venereal
wart)
Etiology: A virus-induced proliferation of stratified squamous epithelium of the genitalia, perianal region, mouth, and larynx
o HPV types: 2, 6, 11, 53, and 54 are usually detected in the lesion
o High-risk types 16 and 18 – found w/ frequency, especially in anogenital lesions
o Considered STD, lesions develop at a site of sexual contact or trauma, represents 20% of all STDs diagnosed in STD clinics, may be an indicator of sexual
abuse when diagnosed in young children.
o Incubation is 1-3 months from time of sexual contact, auto-inoculation to other mucosal sites is possible.
Clinical features:
o Usually diagnosed in teenagers and young adults
o People of all ages are susceptible
o Oral lesions – most frequently occur on the labial mucosa, soft palate, and lingual frenum
o The typical condyloma appears as a sessile, pink, well-demarcated, nontender exophytic mass w/ short, blunted surface projections.
o Condyloma tends to be large than the papilloma – characteristically clustered w/ other condylomata – average lesional size is 1.0-1.5 cm – oral lesions as
large as 3 cm have been reported.
o Appears as a benign proliferation of acanthotic stratified squamous epithelium w/ mildly keratotic papillary surface projections
o Thin connective tissue cores support more blunted and broader papillary epithelial projections than those of squamous papilloma and verruca vulgaris –
imparts an appearance of keratin-filled crypts between prominences.
o Covering epithelium is mature and differentiated
o Prickle cells often demonstrate pyknotic nuclei surrounded by clear zones (koilocytes) – a microscopic feature of HPV infection
o Ultrastructural examination reveals virions w/ in the cytoplasm or nuclei of koilocytes
Treatment and prognosis:
o The oral condyloma is usually treated by:
 Conservative surgical excision
 Laser ablation also has been used – this treatment has raised some question as to the airborne spread of HPV through the aerosolized micro-droplets created by the
vaporization of lesional tissue.
o Regardless of the method used, a condyloma should be removed because it is
 Contagious and can spread to other oral surfaces and to other persons through direct (usually sexual) contact.
o In the anogenital area – condylomata infected w/ HPV-16 or HPV-18 are associated w/ an increased risk of malignant transformation to squamous cell
carcinoma – this has not been demonstrated in oral lesions.
What is this?
Focal epithelial hyperplasia (Heck’s
disease, multifocal papilloma virus
epithelial hyperplasia)
Etiology: appearance.
o Virus-induced, localized proliferation of squamous Histopathologic features:
epithelium, first described in native Americans and Inuits o The hallmark of focal epithelial hyperplasia is an abrupt
(Eskimos): and sometimes considerable acanthosis of the oral
 Currently – known to exist in many populations and epithelium.
ethnic groups o Some superficial keratinocytes show a koiocytic change
o Apparently produced by the HPV type 13 and possibly 32 similar to that seen in other HPV infections
o In some populations – as many as 39% of children are o Others occasionally demonstrate an altered nucleus that
affected resembles a mitotic figure (mitosoid cell)
o Multiple papillary lesions similar to focal epithelial Treatment and prognosis: spontaneous regression of
hyperplasia arise w/ increased frequency in AIDS
patients.
focal epithelial hyperplasia has been reported after
Clinical features: months/years, conservative surgical excision of lesions
o Usually a childhood condition, occasionally affects young may be performed for diagnostic or aesthetic
and middle-aged adults purposes, risk of recurrence after this therapy is
o There is no gender bias, sites of greatest involvement minimal, no malignant transformation.
include: •
 Labial, buccal, and lingual mucosa
 Gingival and tonsillar lesions also have been reported
o Typically appears as multiple soft, nontender, flattened or
rounded papules – usually clustered, the color of normal
mucosa – may be scattered, pale, or rarely white
o Occasionally lesions show a slight papillary surface
change
o Individual lesions are small (0.3 to 1.0 cm), discrete, and
well demarcated – frequently cluster so closely together
that entire area takes on a cobblestone or fissured
What is this?
Sinonasal papillomas
Three types:  Pressure erosion of the underlying bone is usually present
 Primary sinus lesions may be distinguished only as a soft tissue radiodensity or mucosal
o Benign
thickening on radiographs
o Localized proliferations of the respiratory mucosa of this region o Histopathologic features:
o Mucosa gives rise to 3 histomorphologically distinct papillomas:  Squamous epithelial proliferation into submucosal stroma
 1. Fungiform  Basement membrane remains intact
 2. Inverted  Goblet (mucous) cells and mucin-filled microcysts are frequently noted
 3. Cylindrical cell  Keratin production nuncommon
o In addition, a keratinizing squamous papilloma, similar to the oral squamous papilloma,  Immunohistochemical expression of CD44, a cell adhesion molecule, is increased in this
may rarely occur in the nasal vestibule papilloma, may help distinguish it from invasive papillary SCC which lacks such feature.
o Collectively, sinonasal papillomas represent 10-25% of all tumors of the nasal and o Treatment and prognosis:
paranasal region  Has a significant growth potential – if neglected may extend into the nasopharynx, middle
o Half of the sinonasal papillomas arise from mucosa of the lateral nasal wall – remainder ear, orbit, or cranial base
 In some studies, recurrence after conservative surgical excision has occurred in nearly 75%
predominantly involves the maxillary and ethmoid sinuses and the nasal septum
of all cases.
o Multiple lesions may be present  Recommended treatment: a lateral rhinotomy and en bloc excision of the involved lateral
o May represent neoplasma may be reactive hyperplasia secondary to environmental nasal wall.
stimulants  Mucosa of adjacent paranasal sinus also removed, consider radiotherapy
Fungiform:  W/ surgery, recurrence is <14% of cases
LONG-term follow-up is ESSENTIAL
o Similar to oral squamous papilloma, aggressive biologic behavior, varied epithelial types,  Continued tobacco smoking is associated with increased risk of multiple recurrences
represent 18-50% of all sinonasal papillomas in various investigations Cylindrical Cell
o Almost all examples are positive for HPV type 6 or 11
o Accounts for <7% of sinonasal papillomas
o Clinical and radiographic features: o Considered by some authorities to be a variant of the inverted papilloma because of:
 Almost exclusively on the nasal septum, twice as common in men than women, 20-50 years
 Similarity in clinical and histopathologic features, similarly low frequency of HPV
old
 Exhibits unilateral nasal obstruction or epistaxis, appears as a pink/tan, broad nodule w/ o Clinical features:
papillary or warty surface projections.  20-50 years of age
 M>>F
o Histopathologic features:
 Maxillary antrum > lateral nasal cavity wall > ethmoid sinus
 Microscopic appearance similar to oral squamous papilloma
 Presenting symptoms – unilateral nasal obstruction, beefy-red or brown mass w/ a
 Respiratory epithelium or “transitional” epithelium may be seen in some lesions
multinodular surface
 Mucus (goblet) cells and intraepithelial microcysts containing mucus often are present
 Mitoses are infrequent, and dysplasia is rare o Histopathologic features:
 Endophytic and exophytic growth
o Treatment and prognosis:
 Fibrovascular CT core
 Complete surgical excision is treatment of choice for fungiform papilloma
 Lesional epithelial cell is similar to an oncocyte
 Recurrence is common, developing in 1/3 of all cases – incomplete excision
 Cilia may be seen on surface
 Most authorities consider this lesion to have minimal or no potential for malignant
transformation o Treatment and prognosis:
 Treated in same manner as inverted papilloma
Inverted:  Potential for recurrence and malignant transformation seems to be lower than that of
o The most common (50-76%) sinonasal papilloma inverted papilloma
o The variant w/ the greatest potential for local destruction and malignant transformation
o HPV types 6, 11 and 16 have been identified in <7% of cases
o Clinical and radiographic features:
 Seldom occurs in patients <20 y/o – median age is 55 years
 2:1 male to female ratio
 Arises predominantly from the lateral nasal cavity wall or a paranasal sinus, usually the
antrum
 Results in unilateral nasal obstruction, may cause pain, epistaxis, purulent discharge, local
deformity
What is this?
Molluscum contagiosum
Etiology: plug, curd-like substance expressed
o A virus-induced epithelial hyperplasia produced by the Histopathologic features:
molluscum contagiosum virus: o Appears as a localized lobular proliferation of surface
 DNA poxvirus group stratified squamous epithelium, central portion of each
o At least 6% of the population (more in older age groups) lobule is filled with bloated keratinocytes that contain
has antibodies to this virus – few ever develop lesions  Molluscum bodies – large, intranuclear, basophilic viral
o Incubation period of 14-50 days  infection produces inclusions.
Begin as small eosinophilic structures in cells just above
multiple papules of the skin or rarely mucous basal layer
membranes As they approach surface, increase so much in size they
 Remain small for months or years and then become larger than original size of invaded cells
Central crater is formed at the surface as stratum
spontaneously involute
corneum cells disintegrate to release their molluscum
o During active phase, viruse is sloughed from a central bodies
core in each papule Treatment and prognosis:
o Routes of transmission include sexual contact, non- o In most cases, spontaneous remission occurs w/in 6-9
sexual contacts months
o Lesions have predilection for warm portion of skin, sites o Curettage and cryotherapy are effective treatment for
of recent injury papules removed electively
Clinical features: o Podophyllotoxin and tretinoin therapies are popular but
o Usually seen in children and young adults less effective
o Papules – almost always are multiple, occur o Topical imiquimod, an immune-response modifier,
predominantly on skin of the neck, face (particularly recently has been shown to be effective in reducing or
eyelids), trunk, and genitalia eliminating the lesions
o Infrequently, oral involvement occurs – usually on the o There is no apparent potential to transform into
lips, buccal mucosa, palate carcinoma, lesions tend to not recur after treatment.
o Nonhemorrhagic papules
 2-4mm diameter, pink, smooth-surfaced, sessile,
nontender
 Many show small central indentation or keratin-like
What is this?
Verruciform xanthoma
Etiology: thickened layer of parakeratin.
o A hyperplastic condition of the epithelium of the mouth, skin, and o On routine hematoxylin and eosin staining:
genitalia  The keratin layer often exhibits a distinctive orange coloration
o Has a characteristic accumulation of lipid-laden histiocytes beneath o Clefts or crypts between epithelial projections are filled w/
the epithelium parakeratin
o First reported in 1971 – it remains largely an oral disease, cause o Rete ridges are elongated to a uniform depth
unknown o Most important diagnostic feature:
o A papillary lesions – HPV doses NOT appear to play a role in  Xanthoma cells: accumulation of numerous large macrophages w/
foamy cytoplasm
pathogenesis
 Typically are confined to the CT papillae
o Probably represents an unusual reaction, immune response to  These foam cells contain lipid and periodic acid-Schiff (PAS) –
localized epithelial trauma or damage positive, diastase-resistant granules
 This hypothesis is supported by cases that have developed in
associated w/ disturbed epithelium
o Treated w/ conservative excision
o The lesion is histopathologically similar to other dermal xanthomas
o Recurrence after removal of lesion is rare
o Not associated w/ diabetes, hyperlipidemia, any other metabolic
o No malignant transformation has been reported
disorder
o Two cases have been reported in which a verruciform xanthoma
Clinical features: occurred in associate w/ carcinoma in situ or SCC – does not imply it is
o Typically seen in whites
a potentially malignant lesions
o 40-70 years of age
o Female predilection, 1:2 Male to female ratio
o ~half of intraoral lesions occur on gingiva an alveolar mucosa
o Any oral site may be involved
o Appears as well-demarcated, soft, painless, sessile, slightly elevated
mass w/ a white, yellow-white, red color and a papillary or roughened
(verruciform) surface, painless.
o Rarely, flat-topped nodules are seen w/ out surface projections
o Most lesions - <2 cm in greatest diameter
o No oral lesions > 4 cm has been reported
o Multiple lesions occasionally have been described
o May appear similar to squamous papilloma, condyloma
acuminatum, or early carcinoma
o Demonstrates papillary, acanthotic surface epithelium covered by a
What is this?
Seborrheic keratosis
Etiology: o Several histopathologic patterns may be seen in seborrheic keratosis:
o An extremely common skin lesion of older people  Acanthotic form: most common, little papillomatosis, marked
o Represents an acquired, benign proliferation of epidermal basal cells acanthosis, minimal surface keratinization
 Hyperkeratotic form: prominent papillomatosis, prominent
o The cause is unknown – there is a positive correlation w/ chronic sun
hyperkeratosis, minimal acanthosis
exposure, sometimes w/ a hereditary (autosomal dominant) tendency  Adenoid form: anastomosing trabeculae of lesional cells, little
o Seborrheic keratosis does not occur in the mouth hyperkeratosis or papillomatosis
Clinical features:  Dermatosis papulosa nigra: predominantly adenoid and acanthotic
o Begin to develop on the skin of the face, trunk, and extremities during types
the 4th decade of life Treatment and prognosis:
o Become more prevalent w/ each passing decade o Except for aesthetic purposes, a seborrheic keratosis seldom is
o Lesions are usually multiple removed
o Begin as small tan-brown macules that are indistinguishable clinically o Cryotherapy w/ liquid nitrogen or simple curettage – TOC for lesions
from actinic lentigines that are removed
o Gradually enlarge and elevate o No malignant potential
o Individual lesions are sharply demarcated plaques o Other more significant skin lesions may develop in areas contiguous to
o Have surfaces that are finely fissured, pitted, or verrucous it
o May be smooth, tend to appear “stuck onto” the skin o Leser-Trelat sign: The sudden appearance of numerous seborrheic
o Are usually <2cm in diameter keratoses w/ pruritis has been associated with internal malignancy, a
o Dermatosis papulosa nigra: rare event
 A form of seborrheic keratosis
 Occurs in ~30% of blacks, frequently has an autosomal dominant
inheritance pattern
 Typically appears as multiple, small (1-2 mm), dark-brown to black
papules scattered about the zygomatic and periorbital region
o Consists of an exophytic proliferation of basilar epithelial cells that
exhibit varying degrees of surface keratinization, acanthosis,
papillomatosis
o Entire epithelial hyperplasia extends upward – above normal
epidermal surface
o Horn cysts or pseudo-horn cysts:
 Lesion usually exhibits deep, keratinifilled invaginations that appear
cystic on cross-section
 Melanin pigmentation often is seen w/ in the basal layer
What is this?
Sebaceous hyperplasia
Charcterized by a localized proliferation of sebaceous glands of the skin
No known cause, common on facial skin, major significance is its clinical similarity to more serious
facial tumors such as basal cell carcinoma
Clinical features:
o Cutaneous sebaceous hyperplasia – usually affects adults older than 40 years of age
o Occurs most commonly on the skin of the face – especially the cheeks and forehead
o Characterized by one orm ore soft, nontender papules w/ white, yellow, or normal coloration
o Lesions are usually umbilicated w/ a small central depression
 Represents the area where the ducts of the involved sebaceous lobules terminate
o Most lesions are smaller than 5mm in diameter, take considerable to reach even this small size
o Compression of lesions usually causes sebum to be expressed in central depressed area
 Helps to clinically distinguish from basal cell carcinoma
o A collection of enlarged but otherwise normal sebaceous gland lobules
o Grouped around one or more centrally located sebaceous ducts
o No treatment is necessary for sebaceous hyperplasia except for
 Esthetic reasons, unless basal cell carcinoma cannot be eliminated from the clinical differential diagnosis of cutaneous
lesions
o Excisional biopsy is curative
What is this?
Ephelis
AKA: Freckle
Etiology: Focal increase in melanin production and deposition, genetic
predisposition (aut. Dominant)
Risk factors: fair complexion; blue, green eyes; blonde, red hair; h/o childhood
sunburns
Age: appear in first decade
Site: sun-exposed skin – face, arms, back
Clinical features: light-brown, uniform color, round to oval, macular, <3mm in
diameter, well-defined borders, darkens with sun exposure, vary in number
Histology: stratified squamous epithelium, increased melanin deposition in
epithelial basal cell region
o Melanin in CT macrophages = melanin incontinence
o No increase in melanocyte #
Treatment: No treatment necessary, prevention = sunblock, sunscreen
What is this?
Actinic lentigo
• AKA: Solar lentigo, age spot, liver spot
• Etiology: Chronic UV damage to skin
• Risk factors: same phenotype as ephelis, previous h/o ephelides
• Gender: no predilection
• Age: >70 yo; rarely <40 yo
• Site: Sun-exposed skin – dorsa of hands, face, arms
• Clinical features: brown to tan, well-demarcated, irregular borders,
macular, most <5mm, adjacent lesions may coalesce, no changes in
intensity with sun exposure
• Histology: stratified squamous epithelium, elongated rete ridges,
increased melanin deposition and melanocytes in epithelial basal cell
region
• Treatment: No treatment necessary, laser therapy, topical agents for
cosmesis, prevention with sunblock, sunscreen, new lesions can continue
to arise, malignant transformation not noted
What is this?
Lentigo simplex
Benign proliferation of melanocytes
Etiology: melanocytic hyperplasia of unknown cause
Age: Children, any age
Site: any skin site – trunk, extremities, no predilection for sun-exposed skin
Clinical features: uniform tan to dark brown – darker than ephelis, well-
demarcated borders, macular, usually solitary – if multiple, consider syndrome,
reaches maximum size in months, does not increase thereafter, no change in
intensity with sun exposure
Histology: stratified squamous epithelium, increased melanin deposition in
epithelial basal cell region, increased # of melanocytes in epithelial basal cell
region = melanocytic hyperplasia, melanin incontinence
Treatment: may fade with time; most lesions persistent, no treatment necessary,
surgical removal, laser therapy for cosmesis, dx malignant transformation NOT
noted.
•
What is this?
Melasma
AKA: mask of pregnancy
Acquired hyperpigmentation of sun-exposed skin
Etiology: exact cause unknown, associated with pregnancy, exogenous estrogen
and progesterone
Risk factors: darker complexions
Gender: F, extremely rare in M
Age: Adult
Site: Sun-exposed skin of face and neck – midface, forehead, upper lip, chin
Clinical features: light to dark-brown, macular, bilateral, symmetric, develops
slowly with sun exposure, may darken with time
Histology: Increased melanin deposition in epithelial basal cell region, melanin
incontinence
Treatment: avoid sun exposure during pregnancy; prevent with sunblock
o First line: prescription fading creams – triple-combination topical therapy
o Second line: glycolic acid peels, laser, may resolve after birth or d/c OCP, hormones
 Malignant transformation not noted
What is this?
Oral melantoic macule
Etiology: exact cause unclear, labial cases may be associated with sun exposure
o Focal increase in melanin deposition, possible increase in number of melanocytes
Age: Avg. 43 yo
Site:
o 1. Labial melanotic macule – lip vermillion (33%)
o 2. Oral melanotic macule – any other oral site – bu mucosa, gingiva, palate
Clinical features: Tan to dark brown, macular, round or ovoid, mostly solitary; may
be multiple, typically <7mm in diameter, no significant enlargement after diagnosis
Histology: increased melanin deposition in epithelial basal cell region, possible
increased melanocyte #, melanin incontinence
Treatment: If classic clinical presentation, can elect to observe surgical excision for
cosmesis, definitive diagnosis, malignant transformation not noted
o Biopsy/excise if recent onset, large size, irregular pigmentation, recent enlargement
o Rule of thumb for pigmented oral lesions – biopsy or excise if any doubt!
o If multiple, consider other conditions presenting with multifocal oral pigmentation –
physiologic/systemic, syndromic, medication-related
What is this?
epithelial
acanthosis
Oral melanoacanthoma
AKA: Melanocanthosis
Benign acquired pigmentation of oral mucosa
Etiology: reactive lesion (?trauma)
Gender: F>M
Ethnic: AA
Age: 3rd-4th decades
Site: Bu mucosa – lips, palate, gingiva, alveolar mucosa
Clinical features: dark brown to black, macular or slightly raised (plaque), solitary
or multiple, rapid increase in size (cm within few weeks)
Histology:
o 1. Epithelial acanthosis (“acanthoma”)
o 2. Dendritic melanocytes within epithelium (“melano”)
 Increased melanocyte # in epithelial basal cell region
 Mild inflammation in CT
Treatment: Incisional biopsy to r/o other melanocytic pathology – rapid growth
rate can be worrisome. No further treatment after diagnosis, spontaneous
resolution has been noted, malignant transformation not noted
What is this?
Acquired melanocytic nevi
AKA: Mole  1. Junctional – nevus cells in the epithelium only
(rete pegs)
Localized proliferation of nevus cells  2. Compound - nevus cells found in both
Etiology: Nevus cells – neural crest origin epithelium and connective tissue
Gender: F slightly > M  3. Intramucosal (intradermal if on skin) – nevus
cells in connective tissue only – deeper nevus cells
Ethnic: Caucasians > AA, Asians elongated, lack melanin
Age: Skin – appear in childhood; most present  Classification is dependent on histologic location
of nevus cells
by age 35
Site: Skin – mostly above waist, H&N, Oral – Treatment:
o Skin: no treatment; tend to involute (regress)
mostly palate, gingiva over time, excision for cosmesis, dx, chronic
Clinical features: Brown to black; early lesions irritation, malignant transformation rare (1:1
flat (macule), older lesions may lose million; melanoma)
pigmentation, become raised (papule, nodule) o Oral: Biopsy/excise if recent onset, large size,
– 1/5 intraoral nevi non-pigmented, typically irregular pigmentation, recent enlargement
<6mm
o Skin – may develop papillomatous surface ,hair,
may involute with time
Histology:
o Nevus cells: round to ovoid cells, uniform
nuclei, variable melanin in cytoplasm, present in
rounded nests (theques)
o Histologic types:
What is this?
Congenital melanocytic nevus
Localized proliferation of nevus cells
Etiology: Congenital
Prevalence: ~1% of newborns
Age: present at birth
Site: ~15% head and neck, intraoral rare
Clinical features:
o Can be small (<20cm) or large (>20 cm)
o Early: Tan, macular
o Older: brown to black, plaque-like or nodular
o Skin: roughened surface, excess hair (hypertrichosis), can become large (“bathing trunk
nevus”)
Histology: nevus cells in junctional, compound, intradermal distribution
o Nevus cells deeper in CT
 Surrounding adnexal structures (hair follicles, sebaceous and sweat glands)
 Surrounding neural and vascular structures
Treatment: conservative excision for cosmesis, diagnosis, malignant transformation
rate – 3-15% melanoma, careful long-term follow-up
What is this?
Blue nevus
Benign proliferation of dermal melanocytes
Types:
o 1. Common blue nevus – 2nd most common intraoral nevus
o 2. Cellular blue nevus
Gender: F>M (2:1)
Age: Common – children, young adults, cellular – 2nd – 4th decades
Site: Common – skin, mucosa (palate); cellular – skin (buttocks)
Clinical features: blue to blue-black (“Tyndall effect”)
o Common: Macular or popular, typically <1cm
o Cellular: Papular or nodular; rarely be macular, may be >2 cm
Histology:
o Common: pigmented spindled cells (dermal melanocytes) deep in CT – parallel to surface
o Cellular: highly cellular, pigmented spindled and plump cells (dermal melanocytes) deep in CT
Treatment: Conservative surgical excision, malignant transformation reported but
rare, oral lesions – biopsy/excise if any doubt
What is this?
Leukoplakia
Definition: “A white, plaque-like lesion which cannot be wiped o Lip vermilion, lateral-ventral tongue, floor of mouth, soft  Leukoplakia in high-risk site (lip vermilion, floor of mouth,
palate ventral/lateral tongue, soft palate):
off AND cannot be clinically diagnosed as any other disease   complete removal
 ~90% leukoplakias with dysplasia
entitiy”  High-risk sites for dysplasia and SCC  **preserve specimen for histologic exam
o Clinical term , not associated with specific histologic Clinical features: gray to white plaques, well-defined borders, o **Careful long-term follow-up**
diagnosis o Early-soft, thin, translucent o Cessation of contributing factors
Diagnosis of exclusion: Must exclude clinically distinct entities, o Recurrences – 83% granular, verruciform types
o Older –firm; thickened, opaque  fissured, granular,
including: nodular, verrucous surface Risk of dysplasia:
o 1) Frictional hyperkeratosis, morsicatio Clinical variants: thin, thick, granular/nodular, verruciform o Think leukoplakia: seldom (80% hyperkeratosis)
o 2) Leukoedema o Thick leukoplakia: 1-7%
Special variants: o Granular, verruciform leukoplakia 4-15%
o 3) Linea alba
o Proliferative verrucous leukoplakia (PVL) o Erythroleukoplakia: 18-47%
o 4) Nicotine stomatitis  Multifocal leukoplakias, thin to verruciform
o 5) smokeless tobacco keratosis  Sites: any oral mucosal site, especially gingiva Transformation to SCC rates:
o 6) Lichen planus  Female predilection, little assoc. with smoking o Moderate dysplasia: 4-11%
o 7) Many other clinically distinct white plaques  Typically, develops dysplastic changes, SCC o Severe dysplasia: 20-35%
5-25% of leukoplakias are diagnosed as epithelial dysplasia  Rarely regresses o Usually 2-4 years after onset of leukoplakia
o Erythroleukoplakia, speckled leukoplakia o Risk increased if persistent lesion, female patient, non-
(pre-cancer) after microscopic examination  Leukoplakia admixed with erythroplakia (red patches)
4% diagnosed as squamous cell carcinoma (SCC) (cancer) after smoker, FOM or ventral tongue location
 Typically, dysplastic changes
microscopic examination – depends in part on clinical Histology: hyperkeratosis, epithelial hyperplasia, and/or Future directions:
o 1. Biomarkers for malignant transformation
presentation; as high as 47% acanthosis  Loss of heterozygosity (LOH) of chromosome arms 3p and
Therefore, true leukoplakias are considered to potentially o 2 types of hyperkeratosis 9p; LOH of other istes
premalignant lesions  1. Hyperparakeratosis – nuclei in keratin layer  Microsatellite instability
 2. Hyperorthokeratosis – no nuclei in keratin layer,  Increased telomerase activity
Proposed etiologies: granular cell layer  Altered expression of molecular markers
o 1. Tobacco: >80% leukoplakias occur in smokers, higher o May show: o 2. Chemoprevention
incidence of leukoplakias in smokers vs. non-smokers  1. Dysplasia – pre-malignant  Isotretinoin; others
 Heavier smokers have greater #, size leukoplakias  2. Carcinoma in situ (CIS) – pre-malignant
 Large proportion of leukoplakias in smokers disappear  3. Squamous cell carcinoma – malignant
after 1st year of smoking cessation Histologic features of epithelial dysplasia:
 **alcohol alone has not been associated with leukoplakia
o Cellular features:
but has synergistic effects with tobacco.
 1. Enlarged nuclei and cells
o 2. Sanguinaria (sanguinaria-associated leukoplakia)  2. Large nad prominent nucleoli
 “Viadent” products  3. Increased nuclear-to-cytoplasmic (N:C) ratio
 Site: maxillary vestibule, maxillary alveolar mucosa  4. Hyperchromatic (dark-staining) nuclei
 Histology: may show epithelial dysplasia  5. Pleomorphic (abnormal, bizarre) nuclei and cells
 May persist even after discontinuation of sanguinaria  6. Dykeratosis (premature keratinization)
o 3. Ultraviolet radiation  7. Increased mitotic activity
 Site: lower lip vermilion  8. Abnormal mitotic figures
 Risk factors: immunocompromise, especially transplant pt. o Architectural features:
o 4. Microorganisms  1. Bulbous, tear-dropped rete ridges
 Bacterial: treponema pallidum, 3⁰ syphilis, site: dorsal  2. Loss of polarity (disorganized maturation towards the
tongue surface)
 Viral: HPV types 16 and 18, probable carcinogenic  3. Keratin pearls
potential in oral squamous cells, in vitro evidence HPV-16  4. Loss of epithelial cohesiveness
induces malignant change in oral squamous cells o Mild dysplasia: dysplasia involving the lower 1/3 of the
 Fungal: candidal leukoplakia, hyperplastic candidiasis
epithelium
o 5. Trauma:
o Moderate dysplasia: dysplasia involving the lower 2/3 of the
 Heat: nicotine stomatitis – response to heat of smoking,
reversible after habit cessation epithelium
 Mechanical: frictional hyperkeratosis, response to low- o Severe dysplasia: dysplasia extending to the upper 1/3 of the
grade trauma, reversible after elimination of trauma epithelium
 **No malignant potential, not true leukoplakias o Carcinoma in situ (CIS): dysplasia involving the entire
Incidence: 1.4-4.3% worldwide, most common oral thickness of the epithelium
premalignancy Treatment: Guided by histologic diagnosis, location:
Gender: M>>F o 1) If hyperkeratosis or mild dysplasia:
Age: >40 yo, avg. 60 yo  Clinical follow-up every 6 months Or
 Complete removal
Site: lip vermilion, bu mucosa, gingiva o 2) If moderate dysplasia or worse:
What is this?
Erythroplakia
Definition: “A red patch/plaque that cannot be Histology: lack of keratinization, often epithelial
clinically diagnosed as any other condition” atrophy
o Erythroleukoplakia, speckled leukoplakia = o Majority (>90%) will show:
leukoplakia admixed with erythroplakia  1. Dysplasia, usually severe
 2. Carcinoma in situ
Most erythroplakias (~90%) are diagnosed as  3. Squamous cell carcinoma
epithelial dysplasia, carcinoma-in-situ, or Treatment: Biopsy should be performed for
squamous cell carcinoma on microscopic exam histologic diagnosis. If irritation or trauma
Therefore, true erythroplakias are considered suspected, remove source and biopsy 2 weeks
to be premalignant lesions later. Treatment guided by histologic diagnosis
Etiology: Same as oral squamous cell and location.
carcinoma o 1. If hyperkeratosis or mild dysplasia:
Incidence: 0.0-0.83%, less frequent than  Clinical follow-up every 6 months OR
leukoplakia  Complete removal
o 2. If moderate dysplasia or worse:
Gender: M>>F  Leukoplakia in high-risk site (lip vermilion, floor of
Age: 65-74 yo mouth, ventral/lateral tongue, soft palate):
Site: Mostly ventral-lateral tongue, floor of   complete removal
 **preserve specimen for histologic exam
mouth, soft palate (high-risk sites) o **Careful long-term follow-up**
Clinical features: Red, plaque, patch, soft, o Cessation of contributing factors
velvety, ± adjacent leukoplakia o Recurrence, multifocality common
(erythroleukoplakia), may be multifocal
What is this?
Smokeless tobacco keratosis
AKA: Snuff pouch, spit tobacco, keratosis epithelial acanthosis, epithelial cells with intracellular
Etiology: Habit of chewing or holding smokeless edema, amorphous material in connective tissue, ±
tobacco in oral cavity – allows absorption of nicotine dysplasia, CIS, SCC (rare)
and other carcinogens through oral mucosa Treatment: Depends on histologic diagnosis – same
o 2 types: tx, recommendations as leukoplakia, erythroplakia
 1. Chewing tobacco o Risk of developing:
 2. Snuff (moist, dry)  1. Squamous cell carcinoma
Prevalence: 4.5% in US adults Relative risk (RR) of 2-26
Higher for dry snuff > moist snuff, chewing tobacco
o 20-27% US adolescents (SE, Midwestern states), moist Recent Swedish studies – no increase in risk with snuff
snuff use on the rise alone (controversial)
If combined with betel quid, risk 10x greater
Gender: M>F, F predominate in some populations,  2. Verrucous carcinoma
southern US o **98% of mild smokeless tobacco keratoses will resolve
Age: Habit begins ~8-14 yo on cessation of habit**
Site: sites where smokeless tobacco habitually placed o Encourage habit cessation
– typically, maxillary or mandibular vestibule o Periodic follow-up
Clinical features: gray-white, thin (translucent) plaque, o Biopsy if:
 1. Lesion persists >6w after habit cessation
ill-defined borders, fissured, rippled,
o Older, advanced lesions – leathery or nodular
• 2. Worrisome clinical characteristics
o Seen in: ~ 15% chewing tobacco users, ~60% snuff users
o Dependent on: habit duration, brand tobacco, hrs and
amount daily tobacco use
o Takes ~1-5 yrs to develop
o *Gingival recession, bone loss, dental caries, staining,
abrasion, halitosis*
Histology: Hyperkeratosis, parakeratin chevrons,
What is this?
Oral submucous fibrosis
Etiology: Chronic placement of betel quid chewer’s mucosa), fibrous bands on palpation,
(paan), freeze-dried betel quid substitute in staining of teeth
mouth Histology: dense, hypovascular fibrous CT, mild
o Betel quid – areca nut, tobacco, slaked lime, chronic inflammation
betel leaf, imparts feeling of euphoria o Early – subepithelial vesicles
 Areca nut  mucosal rigidity o Older – hyperkeratosis, epithelial atrophy
 Tobacco  pre-malignant epithelial changes,
carcinogenesis
o May show:
 1. Epithelial dysplasia (10-15%)
Geographic prevalence: Indian subcontinent,  2. Squamous cell carcinoma (6%)
Southeast Asia, Taiwan, Southern China, Papua Treatment: No regression seen with habit
New Guinea cessation, intralesional injections (steroids,
Risk factors: concurrent nutritional deficiency interferon), surgery to improve trismus,
Gender: F more susceptible encourage habit cessation, careful long-term
Age: First noted in young adults follow-up.
Site: Oral mucosa – bu mucosa, retromolar o Risk of malignant transformation:
area, soft palate, tongue  17-year transformation rate of 8%
 Pt with OSF 10x more likely to develop carcinoma
Clinical features: pain, burning with spicy
foods, trismus, mucosal pallor, stiffness,
leukoplakia ± vesicles, petechiae, melanosis,
tongue – depapillation, xerostomia, brown-red
discoloration; surface desquamation (betel
What is this?
Nicotine stomatitis
Etiology: response to heat from cigar or pipe-smoking, reverse smoking, long-term
use of hot beverages
Gender: M>F
Age: >45 yo
Site: Hard palate
Clinical: diffuse, gray-white changes, elevated papules with red centers ± staining
of teeth
o *look for concurrent leukoplakias/erythroplakias*
Histology: hyperkeratosis, epithelial acanthosis, chronic inflammation of CT,
around hyperplastic salivary ducts, ± dysplasia (rare) except in reverse smokers
Treatment:
o Mild cases reversible after 1-2 weeks of smoking cessation
o Biopsy if lesion persists after 6w of cessation
o Encourage habit cessation
o Periodic follow-up
o *Look for concurrent leukoplakias/erythroplakias – manage, treat accordingly
o *Risk for squamous cell carcinoma of palate in reverse smokers
What is this?
Solar elastosis
Actinic keratosis
AKA: Solar keratosis
Premalignant lesion of the epidermis (skin)
Etiology: cumulative UV exposure
o UV light mutations p53 tumor suppressor gene  mutations in telomerase gene
o Delayed apoptosis, immortalization of cells
Risk factors: fair complexion, tendency to burn, outdoor occupation, elderly, immunosuppression, arsenic
exposure, genetic abnormalities and syndromes
Incidence: ~50% Caucasian adults with h/o signficiant sun exposure
o Increases with age
Age: > 40 yo
Site: skin – face and neck, dorsum hands, forearms, scalp (bald)
Clinical features: white, gray, brown, scaly plaques; rough, “sandpaper” – like texture, erythematous base, may
peel off
Histology: hyperkeratosis, epithelial acanthosis, varying grades of dysplasia
o Bowenoid AK = dysplasia involving full thickness of epidermis
o Solar elastosis = basophilic change in superficial CT (dermis)
o ± chronic inflammation in dermis
o ± melanosis
Treatment: complete ablation – topical chemotherapeutic agents, photodynamic therapy
o Encourage use of sun protection, long-term follow-up – monitor for additional lesions
o Malignant transformation – 10% AK cases progress to squamous cell carcinoma over 2-yr period
What is this?
Actinic cheilitis (cheilosis)
Premalignant lesion of epithelium
Etiology: cumulative UV exposure
o UV light  mutations p53 tumor suppressor gene, mutations of telomerase gene
Risk factors: same as actinic keratosis, fair complexion, tendency to sunburn, outdoor occupation
(“farmers”, “sailor’s” lip) immunocompromise, etc.
Gender: M>>F (10:1)
Age: >45 yo
Site: lower lip
Clinical features: slow-progressing, atrophy of lower lip vermillion, pale, smooth blotchy areas,
blurring of margin between vermilion and skin
o Older – rough, scaly; may peel off, leukoplakic areas, chronic ulceration (worrisome for SCC)
Histology: hyperkeratosis, epithelial atrophy, varying grades of dysplasia, solar elastosis, chronic
inflammation in CT, ± melanosis
Treatment: Biopsy worrisome areas – thickened, firm/indurated, ulcerated, leukoplakic
o Lip shave (vermilionectomy), other therapies as listed in actinic keratosis section
o Encourage use sun protection (sunblock, sunscreen)
o Long-term follow-up – monitor for additional lesions
o Malignant transformation – 6-10% of actinic keratoses progress to SCC
What is this?
Keratoacanthoma
Self-limiting, epithelial neoplasm Histology: **Overall architecture key to dx
Controversial o Downward proliferation of epithelium
o ? very well-differentiated variant of squamous o “lateral lipping” between normal and neoplastic
cell carcinoma (SCC, keratoacanthoma type) ep – acute angle
Etiology: Unknown cause – arise form o Epithelial hyperplasia, dyskeratosis, keratin-
infundibular epithelium of hair follicle, ?UV filled crater, chronic inflammation
exposure, HPV, immunosuppression, trauma? Treatment: Despite involution, surgical excision
o Genetic predisposition – rare syndrome (Muir- recommended to minimize scarring
Torre syndrome) o Recurrence unusual (~2% of cases)
Gender: M>F o Aggressive behavior, malignant transformation
reported - ?true SCC from outset?
Age: >45 yo
Site: Sun-exposed skin - ~8% occur on lip
vermilion (upper and lower)
Clinical features: firm, well-demarcated, sessile
nodule, central keratin plug – yellow, brown,
black, irregular surface
o 3 phases of development:
 1. Growth phase – rapid enlargement of lesion (1-
2 cm in 6 wks)
 2. Stationary phase – lesion stabilizes
 3. Involution phase – spontaneous regression (6-
12 months), scarring
What is this?
Keratin
pearls
Squamous cell carcinoma
Malignant neoplasm of squamous cells  Heavy drinkers may also have concurrent nutritional deficiencies
Incidence: oral cancer <3% of all cancers in US, 94% of oral cancers are o 5. Radiation (ultraviolet [UV], x-irradiation)
 UV radiation, greater risk (lip SCC)
SCC, 21,000 new cases diagnosed annually  Prior x-irradiation to H&N, greater risk (oral, lip SCC)
Groups at risk:  Risk is dose-dependent – higher dose, greater risk
o Caucaion males, >65 yo  X-irradiation – reduced immune reactivity, chromosomal
o AA males, middle-aged abnormalities
o Risk increases with increasing age o 6. Iron deficiency
Etiology: multifactorail  Severe iron deficiency, greater risk
 SCC esophagus, oropharynx, posterior mouth
o 1. Extrinsic factors
 SCC develops at younger age
o 2. Intrinsic factors  Iron deficiency – impaired cell-immunity, abnormally rapid turnover
o Most preceded by a premalignant (precancerous) lesion of epithelial cells
 Mostly leukoplakia o 7. Vitamin-A deficiency
 Other precancerous conditions  Low serum retinol and dietary betacarotene, greater risk
o 1. Tobacco smoking  Vitamin-A deficiency – changes in skin, mucous membranes
 Proportion of smokers with oral SCC 2-3x greater than general o 8. Syhpilis
population  Tertiary syphilis, greater risk SCC of dorsal tongue (RR of 4)
 Pipe and cigar smoking, greater risk  Possibly related to carcinogenic treatment agents used in past
 More cigarettes, greater risk
o 9. Oncogenic viruses
 Reverse smoking, greater risk
 HPV, high risk strains (16, 18, 31, 33) greater risk
 SCC that occurs in non-smokers
Female, young age
 HPV – degradation of p53 (E6), degradation of pRb (E7)
Cancer of oral cavity vs. pharynx, larynx o 10. Candida
Mutations of p53, other tumor suppressor genes  Discussed previously, ? role in oral carcinogenesis
o 2. Smokeless tobacco o 11. Immunosuppression
 Relative risk (RR) of 2-26  AIDS patients, greater risk
 Dry snuff > moist snuff > chewing tobacco, greater risk  Transplant patients, greater risk
 Oral SCC develops in site where tobacco habitually placed  Risk further increased with tobacco and alcohol use
o 3. Betel quid (paan)  Immunosuppression – loss immune surveillance, inability to
 8% lifetime risk of developing oral SCC recognize and destroy malignant cells
 Significant risk of developing precancerous lesions o 12. Oncogenes and tumor suppressor genes
o 4. Alcohol  Activation of oncogenes, inactivation/mutation of tumor suppressor
 Historically, potentiator for other causative factors genes, greater risk
 Use of tobacco and alcohol together, greater risk (RR of 15)  Oncogenes: ras, myc, EGFR, tumor suppressor genes: p53, pRb, p16,
 Risk is dose and time dependent E-cadherin
 1/3 males w/ oral SCC are heavy drinkers
 20% males with oral SCC develop cirrhosis
Squamous cell carcinoma
Metastasis: largely through lymphatics to ipsilateral cervical lymph nodes resection w/ excellent results
o Cervical lymph node w/ metastatic carcinoma – usually firm to stony hard, non-tender, and enlarged.  Only 8% recur
 5-year survival rate – 95-100% In one study that evaluated all vermilion cancers, diagnosed in a population
o If malignant cells have perforated the capsule of the node and invaded into surrounding tissues, node
over 6 decades, not one patient died of his or her disease.
will feel “fixed” or not easily movable
o SCC – Upper lip vermilion
o 2-22% of patients have distant (“below the clavicles”) metastasis at diagnosis  Has a different biologic behavior than those of lower lip
 Lungs, liver, bones – most common sites  5-year survival rate – 58%
o Not an early event for carcinomas of the oral cavity proper  25% of lesions recur after treatment
o Tumors in the posterior oropharynx are prone to early metastasis  Fortunately – considerably less common than lower lip carcinoma
 >50% of affected persons have positive cervical nodes at diagnosis o Intraoral SCC – treatment guided by clinical stage of the disease
 1/10 already have distant metastasis by that time  Wide surgical excision, radiation therapy, combination of surgery and radiation therapy
Staging: Tumor size and extent of metastatic spread of oral squamous cell carcinoma o Location may influence treatment plan – oropharyngeal lesions usually receive radiation
o Best indicator of patient’s prognosis o Chemotherapeutic agents are used as adjunctive therapy
o Quantifying thee clinical parameters = staging the disease o Small intraoral carcinoma – single treatment modality is usually chosen
o Tables on slides 11 and 12 – summarize most popular staging protocol – tumor-node-metastasis o Patients w/ larger lesions or clinically palpable lymph nodes, typically require combined therapy
(TNM) system. o Prognosis depends on tumor stage
o Staging protocol depends on three basic clinical features: o 5-year disease-free survival rate for intraoral carcinoma
 T = size of primary tumor (in metrics)  76% if metastasis has not occurred at time of diagnosis (stage I and II)
 N = involvement of local lymph nodes  41% when cervical nodes are involved (stage III)
 M = distant metastasis  9% when metastasis below the clavicle – present (stage IV)
o Higher stage classification – worse prognosis  Some patients die of disease as many as 10 years after initial treatment
o Most head and neck staging protocols – do not use histopathologic or immunohistochemical findings  Majority of deaths occur w/in first 5 year
beyond those needed for a determination of the diagnosis o Various molecular markers associated w/ carcinoma:
 Mutation of tp53 tumor suppressor gene – shown equivocal results as prognostic indicators
Histopathologic features:  Presence or absence of HPV – including subtypes 16 and 18 – also does not seem to affect prognosis
o Arises from dysplastic surface epithelium o Overall 5-year survival rate for intraoral carcinoma in whites in United States and Europe – increased
o Characterized by invasive islands and cords of malignant squamous epithelial cells from 40% in 1950’s to 58% today
o Invasion: irregular extension of lesional epithelium through the basement membrane and into o During same period, however, rate f or black Americans decreased from 36% to 32%
subepithelial connective tissue.  Due to: delayed diagnosis, inadequate initial therapy, responsible for an 8% increase in H&N cancer-
o Lesional cells may surround and destroy blood vessels, invade the lumin of veins or lymphatics related mortality rate in black Americans since 1960
o Strong inflammatory or immune cell response – focal areas of necrosis may be present  Oral cancer mortality rate for whites has decreased by 20% since that time.
o Lesional epithelium – capable of inducing formation fo Multiple carcinomas:
 New small blood vessels - angiogenesis o Patients with one carcinoma of mouth or throat is at increased risk for additional concurrent or later
 Occasionally – dense fibrosis – desmoplasia, or scirrhous change primary surface epithelial malignancies of upper part of body
o Lesional cells generally show:  Risk estimated to be 6-44% in affected individuals
 Abundant eosinophilic cytoplasm w/ large, often darkly staining nuclei (hyperchromatic)  Highest figures in male patients who continue to smoke and abuse alcohol after therapy
 Increased nuclear-to-cytoplasmic ratio  9-25% of patients w/ oral carcinoma – additional mouth or throat malignancies develop
 Varying degrees of cellular and nuclear peomorphism o In patients w/ more than one malignancy, ~1/3 of tumors arise simultaneously
o Keratin – normal product of squamous epithelium o Rest – second lesion usually develops w/in 3 years after initial cancer
 Keratin pearls (round foci of concentrically layered keratinized cells) may be produced w/in lesional
o “Field Cancerization” – tendency toward development of multiple mucosal cancers
epithelium
 May reflect diffuse exposure to local carcinogens
 Single cells also may undergo individual cell keratinization
 Increases malignant transformation potential of all exposed epithelial cells
o Grading: histopathologic evaluation of the degree to which these tumors resemble their parent tissue o Positive tp53 reactivity for all synchronous tumors of upper GI tract – reported to indicate common
(squamous epithelium), produce their normal product (keratin)
predisposition toward malignant development – not clones of original, did not migrate
o Lesions are graded on a three or four-point scale – less differentiated tumors receive higher numerals
o Histopathologic grade of a tumor – related somewhat to its biologic behavior
 Mature tumor (low-grade or well-differentiated):
Closely resembles tissue of origin
Grows at a slightly slower pace
Metastasizes later in its course
 Immature tumor (high grade, poorly differentiated):
Much cellular and nuclear pleomorphism
Little or no keratin production
Becomes difficult to identify tissue of origin
Tumor often enlarges rapidly, metastasizes early
o Grading is a subjective process:
 Depends on area of tumor sampled, individual pathologists criteria
 Clinical staging seems to correlate much better w/ prognosis than microscopic grading
 Diagnosis of SCC almost always made w/ routine light microscopy
o Carcinoma of vermilion zone of the lower lip – usually treated by surgical excision – typically a wedge
What is this?
Verrucous carcinoma
Etiology: A low-grade variant of oral SCC o Characterized by wide and elongated rete ridges that appear to
o Reported first by Ackerman in 1948 – spit tobacco-associated “push” into underlying CT
malignancy o Lesions show abundant keratin (parakeratin) production and a
o Tumors at anatomic sites other than the mouth are unrelated to papillary or verruciform surface
tobacco  Parakeratin fills clefts or crypts b/w the surface projection
o HPV subtypes 16 and 18 identified in some, significance unclear o Lesional epithelial cells generally show a normal maturation pattern
o Verrucous carcinoma = 1-10% of all oral SCC w/ no significant degree of cellular atypia
 Depends on local popularity of spit tobacco use o The histopathologic diagnosis of verrucous carcinoma requires an
o Many lesions arise from the oral mucosa in people who chronically adequate incisional biopsy
use chewing tobacco or snuff – typically in the area where the  ~20% of these lesions have a routine squamous cell carcinoma
tobacco is habitually placed developing concurrently w/in the verrucous carcinoma
o Cases also may occur in nonusers – patients may deny tobacco habit Treatment and prognosis:
o In spit tobacco users – regular SCC is 25x more likely develop than o Metastasis – an extremely rare event in verrucous carcinoma
low-grade variant o TOC: surgical excision w/out radical neck dissection
o Men, >55 yo, avg age 65-70 o 90% of patients are disease free after 5 years – some may require
o Areas where female spit tobacco use predominates – elderly females another surgical procedure during this time
o Most common sites of oral mucosal involvement: o Treatment failures occur in patients w/ extensive involvement,
 Mandibular vestibule, buccal mucosa, hard palate inability to tolerate extensive surgery, inability to identify a focal
o Site often corresponds to placement of chronic tobacco use squamous cell carcinoma
 Maxillary vestibule or under the tongue o Radiotherapy is effective – been less popular because of published
Clinical features: reports of poorly differentiated or anaplastic carcinoma developing
o Extensive by the time of diagnosis w/in the lesion after radiotherapy
o May be present for 2-3 years before diagnosis  Over-exaggerated
o Diffuse, well-demarcated, painless, thick plaque w/ papillary or  Can happen in lesions treated surgically
verruciform surface projections o Chemotherapy may temporarily reduce the size of verrucous
o Lesions are typically white but also may appear erythematous or pink carcinoma – not definitive
o Color depends on amount of keratin produced and host inflammatory
response
o Leukplakia or tobacco pouch keratosis may be seen on adjacent
mucosal surfaces
 Proliferative verrucous leukoplakia (PVL)
 Oral florid papillomatosis
o As a deceptively benign microscopic appearance
What is this?
Carcinoma of the maxillary sinus
An uncommon malignancy of unknown cause Treatment and Prognosis:
o Does not appear to be related to sinusitis, nasal polyps, or o If confined in maxillary sinus – treated by
tobacco use hemimaxillectomy
o Most lesions remain asymptomatic for long periods while o If perforated through surrounding bone – treated by
the tumor grows to fill the sinus radiotherapy, combined radical surgery and radiotherapy
 Dx may not be made until lesion has perforated o Even w/ radical treatment – prognosis is poor
through the surrounding bone  10-30% of patients survive 5 years after therapy
Clinical and radiographic features:  Presence of metastatic deposits in local lymph nodes
o Second division of trigeminal nerve involvement: reduces survival rate <8%
 Intense pain or paresthesia of midface or maxilla may  Involvement of pterygo-palatine fossa reduces survival
occur rate
 Simulates a toothache o W/ or w/out cervical nod involvement, death usually
 Teeth in area of tumor may become loosened occurs from local destruction and the inability to control
 Dental radiographs often reveal a “moth-eaten” the primary disease
destruction of the lamina dura and surrounding bone o Aggressive multimodal therapy, including complete
o Panograph shows: surgical excision when feasible – treatment of choice for
 Cloudy sinus, destruction of its bony wall sino-nasal undifferentiated carcinoma
 Best visualized by computed tomography CT, MRI o Prognosis – extremely poor
o If tumor perforates lateral wall of sinus unilateral facial o Life of the patient may be extended w/ cisplatin
swelling and pain usually present chemotherapy or bone marrow transplantation
o If extension is medial, nasal obstruction or hemorrhage
usually occurs
o Extension superiorly results in displacement of protrusion
of the eyeball
o ~4% of patients have cervical or submandibular lymph
node metastasis at time of diagnosis
o Distant metastasis – uncommon until late in progression
of disease
What is this?
Nasopharyngeal carcinoma
A group of malignancies arising from the lining epithelium of the patterns
lymphoid tissue-rich nasopharynx  1. SCC
 2. Differentiated non-keratinizing carcinoma
o Similar tumors – found in the palatine tonsil and base of tongue
 3. Undifferentiated non-keratinizing carcinoma
o These three anatomic sites are collectively called Waldeyer’s tonsilar
o More than one histopathologic type may be present in the same
tissue or Waldeyer’s ring
biopsy sample
o Nasopharyngeal carcinoma – rare in most areas of the world  Classified according to predominant type
o Average annual incidence rate in United States - <1 case/100,000 o Lymphoepithelioma:
population  A term used to describe this lesion because it was once thought to be
In southern Chinese males – rate = a startling 20-55 cases per 100,000 a malignancy that originated from both epithelial and lymphoid
o Among southern Chinese males who migrate to the US, the rate is tissue
intermediate  Term should be discouraged – not part of the neoplastic process
o Suggests an environmental causative agent o Some undifferentiated tumors are currently classified as sinonasal
Implicated as contributory factors include: undifferentiated carcinomas (SNUC).
 Occasional neoplasms show neuroendocrine differentiation
o Epstein-Barr virus, diets deficient in Vit. C, consumption of salt fish
 Less-differentiated lesions tend to occur in younger individuals
that contains potentially carcinogenic N-nitrosamines  Virtually all nasopharyngeal carcinomas in people <40 years of age
Clinical features: are poorly differentiated
o Occurs in all age groups – most commonly affects 40-60 years old Treatment and Prognosis:
o 3x more common in men o Because of inaccessibility and frequency of metastasis – most
o Primary lesion frequently treated with radiotherapy to the nasopharynx and neck
 Usually arises from lateral nasopharyngeal wall, often is small and o May be combined with chemotherapy
difficult to detect – even when the area is examined endoscopically
o Prognosis ranges from good to poor – depends on stage of disease
o First sign of disease for 50-60% of patients – an enlarged, firm to hard,
o Overall 5-year disease-free survival rate reported in one large series of
cervical lymph node:
cases in US – 45.5%
 Represents metastatic tumor
 Stage I patients – 100% 5-year survival
 Often in the posterior triangle
 Stage II patients – 67%
o Symptoms related to the ear – described by 50% of these patients  Stage III patients – 44%
o Epistaxis, nasal obstruction, and pharyngeal pain may be present  Stage IV patients – 34%
o Tumor may invade through the forame lacerum into the brain o Patients with 2 or more clinical symptoms tend to have a worse
o Signficiantly: 5-10% of patients also have distant metastasis at time of prognosis
diagnosis • Persons treated for nasopharyngeal carcinoma – increased risk for
Histopathologic features: developing a second primary malignancy of head and neck mucosa
o Surgeon often has difficulty finding primary lesion clinically
o Microscopic examination typically shows one of three histopathologic
What is this?
Basal cell carcinoma (rodent ulcer)
Etiology: Histopathologic features:
o Most common skin o Considerable diversity of appearances
o Most common of all o Actinic damage in the form of solar elastosis almost always is seen in adjacent stroma
o Locally invasive, slowly spreading primary malignancy o Occasionally seen admixed with an independent primary SCC of the skin
o Arises from basal cell layer of the skin and its appendages  Resulting “collision” tumor – called baso-squamous carcinoma
o ~85% - found on the skin of H&N Treatment and prognosis:
o >800,000 new cases diagnosed annually in USA o Depends on size and site of lesion
 80% of all skin cancers, new cases increase 3-7% annually o Small lesions (<1cm) - treated by routine surgical excision, laser ablation, or electro-
o Incidence increases with age dessication and curettage w/ 5 mm margins of clinically normal-appearing skin beyond
o Results from chronic exposure to UV radiation visible lesion
o Oral lesions reported – usually considered cases of misdiagnosed salivary or odontogenic  Cure rate of 95-98%
neoplasms o Large or aggressive lesions – surgical excision AND radiation therapy recommended
Clinical and radiographic features: o Mohs micrographic surgery should be used for sclerosing-type lesions, recurrent lesions,
o Disease of adult whites – especially those w/ fair complexsions or lesions situated near embryonic planes of fusion
o Most patients >40 yo when diagnosed  Uses frozen-section evaluation of specifically mapped and marked surgical specimens to
 Some detected as early as second decade of life determine whether tumor tissue has been left behind
 Particularly in patients w/ red hair and blue eyes o Recurrence – uncommon
o Nodular (nodulo-ulcerative) basal cell carcinoma o Metastasis – exceptionally rare, death usually a result of local invasion into vital structures
 Most common form of this lesions o Patients w/ history of basal cell carcinoma must be evaluated periodically – 30% chance
 Starts as a firm, painless papule of second lesion developing w/in 3 years of treatment of initial tumor
 Slowly enlarges – gradually develops a central depression and umbilicated appearance
 Telangiectatic blood vessels
 Pearly, opalescent quality
 Expanding ulceration, patient may give history of intermittent bleeding followed by healing
 Rodent ulcer – untreated lesions continue to enlarge slowly over months and years – w/
ulceration and destruction of underlying structures
 Destruction of underlying bone or cartilage may occur, metastasis extremely rare
o Other varieties:
 Pigmented basal cell carcinoma
Seen occasionally, represents a nodulo-ulcerative tumor colonized by benign melanocytes
Melanin production  tan, brown, black or blue lesions
Pigment – not distributed uniformly
 Sclerosing (morpheaform) basal cell carcinoma
Insidious lesion – often mimics scar tissue
Overlying skin appears pale, atrophic
Firm to palpation, poorly demarcated borders
Slight elevation
Often a great deal of invasion has occurred before the patient becomes aware of problem
 Superficial basal cell carcinoma
Primarily on trunk
Multiple and appear well-demarcated erythematous, scaly patches
May be mistaken clinically for psoriasis
Fine, elevated, “threadlike” border at margins
o Some investigators believe that basal cell carcinoma associated w/ nevoid basal cell
carcinoma syndrome should be placed in a separate category
 Lesions develop in both sun-exposed and protected areas of skin
 May number in hundreds
 Tumors associated w/ this syndrome do not produce a significant degree of tissue
destruction
What is this?
Etiology:
o Malignant neoplasm of melanocytic origin
Malignant melanoma 

5-10% of cutaneous melanoma
Develops from precursor – lentigo maligna (Hutchinson’s freckle)
 Occurs almost exclusively on sun-exposed skin of fair complexioned elderly persons
o Arises from a benign melanocytic lesion or de novo from melanocytes w/in otherwise normal skin or  Particularly in mid-facial region
mucosa  Represents a melanoma in situ – purely radial growth phase
o Most occur on the skin – may develop at any site where melanocytes are present  Large, slowly expanding macule w/ irregular borders
o Damage from UV radiation considered major causative factor  15 years duration of radial growth
o Chronic sun exposure: does not seem to be as significant as it is for other cutaneous cancers – such as  Appearance on nodularity signals onset of invasive or vertical growth, transition to lentigo maligna
melanoma
basal and SCC, Lesions of intraoral mucosa – not related to sun exposure
o Acral lentiginous melanoma (mucosal lentiginous melanoma)
o Acute sun damage: may be of greater causative importance than chronic exposure in melanoma
 Most common melanoma in blacks, least common in whites
o Risk of melanoma development – 2-8x greater when a relative has a history of the cancer  Most common oral melanoma
o Additional risk factors:  Develops on: palms of hands, soles of feet, subungual area, mucous membranes
 Fair complexion, light hair, tendency to sunburn easily, history of painful or blistering sunburns in  Often separated into acral lentiginous melanoma, mucosal lentiginous melanoma
childhood, indoor occupation w/ outdoor recreational habits, personal history of melanoma, personal o Oral melanoma often nodular at time of diagnosis
history of dysplastic or congenital nevus  Early lesions may be flat
o 1/3 most common skin cancer, 5% of all skin cancers o Affected persons are usually in 6-7th decade of life, 2/3 are male patients
o Most deaths due to skin cancer, however, are caused my melanoma o 80% of oral melanomas are found on hard palate or maxillary alveolus
o US: 48,000 new cases/year, 7,700 persons die of disease o Oral lesions begins as a brown/black macule with irregular borders
o 1/75 caucasians born in 2000 will develop cutaneous melanoma in his/her lifetime  Ulceration may develop early – many lesions are dark, lobulated, exophytic masses
o ~25% of cutaneous melanomas arise in the head and neck area o More than 20% contains so little pigment that they essentially have normal mucosal tint
 40% occur on extremities o Pain not common, most lesions remain soft to palpation, radiographs may show irregularities
o Oral mucosal melanoma rare in the US 1 per 2 million annually, comprises <1% of all melanomas Histopathologic features:
o More frequent in other countries
o Superficial – pagetoid spread
o Mucosal melanoma – appears at higher stage, much more aggressive than cutaneous o Spreading of lesional cells along basal layer constitutes the radial growth phase of the neoplasm
o ~33% of patients w/ oral melanoma have a history of a pigmented macule in region of tumor for
o When malignant melanocytes are observed invading the CT, vertical phase has taken place
some time before melanoma diagnosis o Oral lesions tend to show invasion of lymphatic and blood vessels more readily than skin lesions
 Melanoma occasionally affects the parotid gland
o Can mimic a variety of undifferentiated tumors due to lack of melanin
Clinical features: o Clark system of measurement
o Most melanomas are seen in white adults  Assigns a “level” to the lesion that depends on the deepest anatomic cutaneous region that has been
o Average age of affected persons – 50-55 years invaded by tumor cells
o A few melanomas occur in the second and third decades of life o Breslow classification
o Four clinicopathologic types of melanoma have been described:  More recent, appears to show a more accurate correlation w/ the prognosis
 1. Superficial spreading melanoma  Based on actual measurement of distance from top to deepest point of tumor invasion
 2. Nodular melanoma Treatment and prognosis:
 3. Lentigo maligna melanoma
o Surgical excision only curative treatment, 1 cm margin adequate for small , early tumors
 4. Acral lentiginous melanoma
o Melanomas exhibit two directional patterns of growth: o Radiation therapy has no significant impact on survival – adjunct chemotherapy and immunotherapy
 1. Radial growth phase – early stages of melanoma development of lentigo maligna melanoma, superficial are showing promise
spreading melanoma, acral lentiginous melanoma o 10-year survival rate – 79% - patients usually die from distant metastasis
 2. Vertical growth phase – eventually malignant cells begin to invade underlying connective tissue – o Areas w/ worse prognosis are designated “BANS”
predominates in nodular melanoma  Intrascapular area of the back, posterior upper arm, posterior and lateral neck, scalp
o Many clinical similarities exist between melanoma and its benign counterpart – melanocytic nevus o Prognosis better for young, women
 Asymmetry – uncontrolled growth pattern o Prognosis for oral melanoma is extremely poor, younger survive better than old
 Border irregularity – often w/ notching o Patient w/ nonpigemnted or amelanotic lesions appear to have a particularly poor prognosis
 Color variation – varies from brown – blue
 Diameter > 6mm – pencil eraser
 Elevation – lesion rises above mucosal or cutaneous surface
o Superficial spreading melanoma
 Most common form
 70% of cutaneous lesions
 Most common sites of origin – intrascapular area of males, back of legs of females
 Appears as a macule w/ a variety of potential colors
 < 3 cm, many are elevated, satellite macules may develop
o Nodular melanoma
 Represents 15% of cutaneous melanomas
 33% develop in H&N
 Begins almost immediately in vertical growth phase
 Nodular elevation that rapidly invades into the connective tissue
 Usually a deeply pigmented exophytic lesion
Sometimes melanoma cells are poorly differentiated, non-pigmented amelanotic melanoma
o Lentigo maligna melanoma
What is this?
Morsicatio buccarum
Etiology: scientific term for chronic cheek chewing, suction, glassblowers
o Prevalent in people who are under stress or exhibit psychological conditions
o May pts aware of their habit or deny it
o Women 2:1, 3:1 after age 35 – 1/800 adults has active lesions
Clinical features: lesions frequently bilaterally on buccal mucosa, may be unilateral, combined with
lesions of lips or tongue, isolated to lips or tongue
o Thickened, shredded white areas, white mucosa demonstrate irregular ragged surface
o Mid-portion of anterior buccal mucosa
Histolpathologic features: biopsy reveals extensive hyperparakeratosis
o Extremely ragged surface with numerous projections of keratin
o Clusters of vacuolated cells may be present in the superficial portion of the prickle cell layer
o Not pathognomic of morsicatio
o May bear a striking resemblance to oral hairy leukoplakia
o Betel chewer’s mucosa – similar histopathologic pattern
Diagnosis: clinical presentation – sufficient for a strong presumptive diagnosis
o Clinicians familiar w/ these alterations rarely perform biopsy
o Further investigate in patient’s at high risk for HIV infection w/ isolated involvement of the lateral border
of the tongue.
o No treatment required, oral acrylic shield for patients who desire treatment, psychotherapy
What is this?
Traumatic ulcerations/granuloma
Etiology: acute and chronic injuries of oral mucosa are frequently observed. Injury can result from mechanical damage, some are self-induced and
clinically obvious or subtle and difficult to diagnose.
o Acute or chronic trauma to oral mucosa may result in surface ulcerations
o Eosinophilic ulceration (traumatic granuloma, traumatic ulcerative granuloma w/ stromal eosinophilia (TUGSE).
 Eosinophilic granuloma of the tongue – histopathologically unique type of chronic traumatic ulceration of the oral mucosa, pseudoinvasive inflammatory reaction,
slow to resolve
o Atypical eosinophilic ulceration (atypical histiocyte granuloma)
 Rare, eosinophilic ulceration not associated with trauma, inflammatory infiltrate that suggests a neoplastic process, often are T-lymphocytes – not histiocytes
o Lesions may undergo spontaneous remission after incisional biopsy, most cases there is an adjacent source of irritation,
o Many cases resemble early ulcerative squamous cell carcinoma – biopsy is performed to rule out that possibility
Clinical features:
o Simple chronic traumatic ulcerations occur most often on tongue, lips, and buccal mucosa – sites that may be injured by dentition
o Lesions of gingiva, palate, and mucobuccal fold may occur from other sources of irritation
o Overzealous toothbrushing can create linear erosions along free gingival margins
o Individual lesions: areas of erythema surrounding a central removable, yellow fibrinopurulent membrane. May develop – rolled white border of
hyperkeratosis immediately adjacent to area of ulceration
o Occurs at all ages, significant male predominance, most reported on the tongue
o Lesion may last from 1 week to 8 months
o Occasionally, underlying proliferative granulation tissue can result in a raised lesion similar to a pyogenic granuloma
Riga Fede Disease
o Etiology: sublingual ulcerations may occur in infants as a result of chronic mucosal trauma from adjacent anterior primary teeth – often associated with
nursing
o Clinical features: typically appears b/w 1 wk – 1 yr of age, develops in associated with natal teeth (maxillary incisors), anterior ventral surface of tongue
most common.
o Treatment and prognosis: extraction of anterior primary teeth is not recommended – teeth should be retained if stable
Atypical eosinophilic ulceration occurs in older people >40, tongue most common site
o Simple traumatic ulcerations are covered by a fibrinopurulent membrane that consists of fibrin intermixed with neutrophils
 Membrane of variable thickness, adjacent surface epithelium may be normal or slightly hyperplastic.
o Ulcer bed consists of granulation tissue – supporting a mixed inflammatory infiltrate or lymphocytes, histiocytes, neutrophils, plasma cells – occasionally
Treatment and prognosis: use of corticosteroids in management of traumatic ulcerations – controversioal
o Patients with atypical eosinophilic ulcerations should be thoroughly evaluated for evidence of lymphoma elsewhere
o Recurrence frequently seen
What is this?
Electrical burns
Etiology: electrical burns to the oral cavity – fairly common
o ~5% of all burn admissions to hospitals
o Two types of electrical burns can be seen: 1. Contact, 2. Arc
 1. Contact burns - Require good ground, electrical current passing through the body from point of
contact to the ground site. Electric current can cause cardiopulmonary arrest, may be fatal
 2. Arc burns – most electrical burns affecting the oral cavity, saliva acts as conducting medium,
electrical arc flows between electrical source and the mouth. Extreme heat, up to 3000:C – possible
w/ resultant significant tissue destruction. Most result from chewing on female end of extension cord,
bit through a live wire
Clinical features: most occur in children >4 years of age, lips most frequently
affected
o Significant edema, after 4 days affected area becomes necrotic and sloughs
o Adjacent teeth may become non-vital, malformation of developing teeth may occur, facial
nerve paralysis infrequently reported – resolves in time
o Tetanus immunization if not current is required, prophylactic antibiotic
o Primary problem with oral burns is contracture of mouth opening during healing
o Without intervention, significant microstomia may develop
o Extensive scarring and disfigurement
o In most cases, splinting is maintained for 6-8 months to ensure proper scar maturation
What is this?
Thermal burns
Etiology: Thermal burns of the oral cavity arise from
ingestion of hot foods or beverages
o The microwave has been associated w/ an increased
frequency of thermal burns
Clinical features: injuries related to thermal food burns
usually appear on palate, posterior buccal mucosa
o Lesions appear as zones of erythema and ulceration –
remnants of necrotic epithelium at the periphery
o Are of little consequence, resolve w/o treatment
What is this?
Chemical injuries
Etiology: Aspirin, sodium perborate, hydrogen peroxide, gasoline, turpentine, rubbing alcohol, battery acid, drugs when held long in the mouth –
psychoactive drugs, aspirin
o Improper use of aspirin, hydrogen peroxide, silver nitrate, phenol, and certain endodontic materials deserve further discussion because of frequency of
misuse, severity of related damage, lack of adequate documentation of these materials as harmful agents
o Aspirin: necrosis from aspirin being held in the mouth is not rare
o Hydrogen peroxide: concentration at >3% associated most often w/ adverse reactions, epithelial necrosis noted w/ dilutions as low as 1% - many over-the-
counter oral medications exceed this concentration
o Sliver nitrate: popular treatment for aphthous ulcerations (chemical cautery = pain relief with nerve-end destruction), use should be discouraged – mucosal
damage increased by use
o Phenol: cavity-sterilizing agent, extremely caustic, judicious use required
o Endodontic materials: some endodontic materials are dangerous because of the possibility of soft tissue damage, injection into hard tissue – deep spread
and necrosis
 Paraformaldehyde – gingival and bone necrosis from leakage of material, use should be discouraged
 Sodium hypochlorite – use rubber dam, avoid excessive pressure, keep away from apex
Clinical features:
o Affected mucosa exhibits superficial white, wrinkled appearance, increased exposure causes necrosis to proceed, epithelium becomes separated from
underlying tissue
o Use of rubber dam dramatically reduces iatrogenic mucosal burns
o Cotton roll burn (cotton roll stomatitis):
 Oral mucosa can adhere to dry cotton rolls
 Rapid removal of rolls from mouth  stripping of area epithelium
o Caustic materials injected into bone during endodontic procedures can result in significant bone necrosis, pain, perforation into soft tissue
Histopathologic features: microscopic examination of the white slough removed from areas of mucosal chemical burns reveals coagulative necrosis
of epithelium
o Necrosis begins on surface and moves basally – outline of individual epithelial celsl and nuclei remain
o Amount of epithelium affected depends on duration of contact, concentration of the offending agent
o Best treatment – prevention of exposure of oral mucosa to caustic materials
o Children should not use chewable aspirin immediately before bedtime – rinse after use
o Superficial areas of necrosis resolve in 10-14 days after discontinuation of offending agent
o Temporary protection: cover area, topical dyclonine HCl, (Sugrets) temporary pain relief
o Large areas – surgical debridement, antibiotic coverage.
What is this?
Foreign body tattoos (amalgam)
Etiology: Several pigmented materials can be implanted within the oral o Clinical features:
mucosa  clinically evident pigmentations  Rarely documented – most likely occurs w/ a higher frequency than
indicated by the number of cases reported
o Implantation of dental amalgam (amalgam tattoo)
 Gray areas of mucosal discoloration of the hard palate, the most
 Occurs most often, frequency far outdistances that for all other
likely site for pencil-related trauma
materials
 “Localized argyrosis” another name for amalgam tattoo. Histopathologic features:
 Floss related, amalgam falling into extraction site o Microscopic examination of amalgam tattoos reveales:
 Endodontic-related amalgam implantation  Pigmented fragments of the metal w/in the CT
o Intetional tattooing  Scattered, large, dark solid fragments or numerous find, black, or
 Found in ~25% of the world’s population, may be performed in the dark-brown granules may be seen
oral cavity  The silver salts of the dental amalgam preferentially stain the
 Some cases are culturally related reticulin fibers, especially those encircling nerves and vascular
channels
Clinical features: intentional intraoral tattoos not placed by health
 Biologic response to amalgam appears related to: particle size,
professionals occur most frequently on – anterior maxillary facial elemental composition of amalgam
gingiva of East African individuals (most commonly from Ethipia or o Large fragments often become surrounded by dense fibrous CT with
Eritrea) mild inflammation
o Anterior maxillary facial gingiva  a heavy blue-black discoloration o Smaller particles – associated with MORE significant inflammatory
o Amalgam tattoos appear as macules or, rarely, as slightly raised response
lesions  May be granulomatous or a mixture of lymphocytes and plasma cells
 May be black, blue, gray o Graphite implantation appears similar microscopically to amalgam
 Borders can be well defined, irregular, or diffuse  Differentiated by birefringence after treatment w/ ammonium
 Lateral spread may occur for several months after the implantation sulfide and lack of staining of the reticulin fibers
 In most cases, only one site is affected, although multiple tattoos in a Treatment and Prognosis:
single patient may be present o To confirm diagnosis of amalgam tattoo – radiographs may
o Any mucosal surface can be involved – most common sites: demonstrate metallic fragments
 Gingiva, alveolar mucosa, and buccal mucosa
o No treatment required – Biopsy may be needed to rule out
Radiographic features: possibility of melanocytic neoplasia
o Periapical radiographs, when taken, are negative in many cases
o When metallic fragments are visible radiographically:
 Clinical area of discoloration typically extends beyond the size of the
fragment
o Fragments are densely radiopaque
o Vary from several millimeters to pinpoint in size
Mucosal graphite implantation:
What is this?
Lead intoxication
 Little is known about prevalence of lead poisoning (plumbism) – one of the most widespread environmental toxins
affecting children in the USA
 One of the primary causes of lead intoxication in infants – formula preparation using tap water tainted by the metal, lead-
based paint
 PICA syndrome:
Children may ingest paint chips in older homes, may be exposed to fumes or dust during sanding and renovation
Paint w/ high lead content was not restricted until 1977
Still remains in many older homes
 Adult exposure also occurs – often related to industry
Handling lead oxide batteries, lead processing industries, illicit alcohol production, welding, contaminated food and drink
containers
 Nonspecific systemic signs and symptoms – ultimate diagnosis very difficult
 Determined by type of lead, patient’s age
 Acute cases often have: abdominal colic w/ anemia, fatigue, irritability, weakness, encephalopathy, renal dysfunction
 Chronic exposure causes: dysfunction of nervous system, kidneys, marrow, bone and joints
Symptoms include – fatigue, musculoskeletal pain, and headache
Bones and teeth represent a major reservoir in patients w/ chronic plumbism – 90% of the body’s desposition being w/ in
bone
 Oral manifestations include:
Ulcerative stomatitis
Gingival lead line – blue line along the marginal gingiva, results from the action of bacterial hydrogen sulfide on lead in the
gingival sulcus  precipitation of lead sulfide (similar for bismuth)
Gray areas may be noted on buccal mucosa and tongue
Additional manifestations: tongue tremor on thrusting, advanced periodontal disease, excessive salivation, metallic taste
What is this?
Mercury – acrodynia (pink, swift
disease)
 Elemental mercury – poorly absorbed, its ingestion is relatively harmless
 Inhalation of mercury vapor – very hazardous, high rate of absorption and systemic retention
 Ingestion of mercury salts – associated w/ significant adverse reactions
 Attention has been directed toward mercury released from dental amalgams
No well-documented adverse health effects have been identified
Level of mercury released from amalgams does not appear sufficiently high
 Mercury poisoning may be acute or chronic
Acute: abdominal pain, vomiting, diarrhea, thirst, pharyngitis, gingivitis
Chronic cases: GI upset, numerous neurologic symptoms
 Oral changes include:
Metallic taste, ulcerative stomatitis, inflammation and enlargement of salivary glands, gingiva, and tongue
Gingiva may become blue-gray to black – mercuric sulfide can be generated by the bacterial action on the metal –
can cause significant destruction of the alveolar bone w/ resultant exfoliation of teeth
 Chronic mercury exposure in infants and children:
Cold, clammy skin – especially on hands, feet, nose, ears, cheeks
Erythematous and pruritic rash
Severe sweating, insomnia, weakness, increased lacrimation, photophobia, tachycardia, irritability, hypertension,
GI upset
May tear out patches of hair
Excessive salivation, ulcerative gingivitis, burxism, premature loss of teeth
Silver- argyria
 Systemic administration of silver was once common – especially in treatment of GI ulcers
 Current examples of silver poisoning are usually restricted to industrial exposure or
secondary to misuse of silver containing medications or so-called supplements
 A number of colloidal silver proteins continue to be marketed in health food stores –
their continued use cannot be supported because they have no known physiologic
function.
 A number of silver nitrate and silver sulfadiazine formulations remain available by
prescription – use of these products should be minimized
 Generalized argyria – seen secondary to long-term use of silver nitrate in dental
treatment of aphthous ulcerations, dental sores
 Systemic silver intoxication – silver disseminated throughout the body w/ substantial
amounts accumulating as subepithelial deposits in the skin
These deposits result in diffuse grayish-black discoloration, develops primarily in the sun-
exposed areas, sclera and nails may be pigmented
 One of the first signs occurs in the oral cavity – appears as a slate-blue silver line along
gingival margins, secondary to deposition of metallic silver, silver sulfide pigments
Oral mucosa often exhibits a diffuse bluish-black discoloration
What is this?
Bismuth and arsenic
 In the United States – exposure to bismuth and arsenic – currently rare
 Medical use of these metals has diminished dramatically
 Most current cases arise from occupational exposure
Bismuth – used in the past for treatment of venereal disease and dermatoses
o Chronic exposure  diffuse blue-gray discoloration of the skin
o Conjunctiva and oral cavity also may be involved
 Blue-gray line along the gingival margin similar to that seen from lead intoxication – most
common intraoral presentation
o Combines with bacterial hydrogen sulfide to from bismuth sulfide – locally irritating but not as destructive
as mercuric sulfide
o The following may be seen – ptyalism, burning, stomatitis, ulceration
Arsenic – used to treat many conditions – asthma, dermatoses
o Prolonged ingestion often results in a diffuse macular hyperpigmentation
o Discoloration due to – presence of the metal, increased melanin production
o Palmar and plantar hyperkeratosis
o Arsenical keratoses – tumerous premalignant skin lesions
o Development of basal cell carcinoma and cutaneous squamous cell carcinoma has been seen after years
of exposure
o Oral manifestations are rare – excessive salivation, painful areas of necrotizing ulcerative stomatitis
o In the past – extensive dorsal hyperkeratosis of the tongue was seen in patients w/ syphilis – may be
related to arsenic therapy used before the advent of antibiotic therapy
What is this?
Gold
 Used today in selected cases of – active rheumatoid arthritis, other immunologically mediated
diseases
 Side effects – well known, patients are closely observed by their physician
 Most common complications of gold therapy is dermatitis
Often preceded by warning of pruritis
 Second most common adverse reaction to gold is severe oral mucositis
Buccal mucosa, lateral border of tongue, palate, pharynx
 A metallic taste often precedes development of oral lesions
 Chrysiasis – therapy w/ gold can rarely bring about a slate-blue discoloration of sun-exposed skin
o Management of heavy metal intoxication involves:
 Removal from further exposure to the agent, supportive care, decontamination, use of chelating
agents
o In the past, first-line therapy in treatment of lead poisoning = two chelators
 EDTA
 BAL – used to treat arsenic and mercury intoxication
 These medications may have significant side effects – less toxic alternatives are now available – DMSA,
DMPS
 No antidote exists for silver intoxication – treatment limited to supportive measures
What is this?
Smoker’s melanosis
Etiology: exert a synergistic effect when combined w/ smoking
o Oral pigmentations are increased significantly in HEAVY o Tobacco smoking appears to be most common cause for
SMOKERS mucosal pigmentation in light skinned adult populations
o In one study of >31,000 caucasians Diagnosis:
 21.5% of tobacco smokers exhibited areas of melanin o Made by correlating smoking history w/ clinical
pigmentation presentation and medical history
 3% among those not using tobacco o Rule out other causes of melanin pigmentation such as –
 In a study of an ethnically pigmented population – trauma, neurofibromatosis, etc.
smokers had more oral surfaces exhibiting melanin
pigmentation Histopathologic features:
o Melanin pigmentation in skin exerts a protective effect o Increased melanin pigmentation of basal cell layer –
against UV damage similar to a melanotic macule
o Exposure to polycyclic amines (nicotine, benzpyrenes) – o Collections of incontinent pigmentation are free w/in
shown to stimulate melanin production by melanocytes superficial CT and in scattered melanophages
that also are known to bind strongly to nicotine Treatment and Prognosis:
o Melanin production in oral mucosa of smokers may o Cessation of smoking  gradual disappearance of areas
serve as a protective response against some harmful of related pigmentation over a 3-year period
substances in tobacco smoke o Biospy should be considered when – pigmentation in
 Supported findings in “reverse” smokers unexpected locations such as hard palate
Clinical features:
o Although any mucosal surface may be affected –
smoker’s melanosis most commonly affects anterior
facial gingiva
o Most are cigarette users
o Areas of pigmentation significantly increase during the
first year of smoking, appear correlated to the number of
cigarettes smoked/day
o Higher frequency seen in females – female sex hormones
What is this?
Drug-related discoloration of the oral
mucosa
Etiology:
o An expanding number of medications – implicated as a cause of oral mucosa discolorations
 Many medications stimulate melanin production by melanocytes
 Deposition of drug metabolites – responsible for color changes in others
o Pigmentary alterations have been associated w/ use of:
 Phenolpthalein, minocycline, tranquilizers, antimalarial medications, estrogen, chemotherapeutic agents, meds to treat AIDS
Anti-malarial Medications or Tranquilizers
o Etiology:
 Antimalarial agents – most frequently implicated – chloroquine, hydrochloroquine etc.
Used for many other disorders including: Lupus erythematosus, rheumatoid arthritis
 Classic presentation of intraoral pigmentation – bluish-black discoloration, limited to hard palate
 Intake of antimalarial medications may occasionally cause more diffuse brown melanosis of oral mucosa and skin
Chemotherapeutic agents
o Etiology:
 Most commonly associated with doxorubicin, busulfan, cyclophosphoamide
 Idiopathic hyperpigmentation also may occur
 Increased melanin pigmentation demonstrated w/ AIDS patients receiving AZT, clofazimine, or ketoconazole
Clinical features:
o Presentations of pigmentations vary related to drug use
o Most agents produce a diffuse melanosis of the skin and mucosal surface – may cause a unique pattern
o Females are more sensitive – most likely as a result of interaction with sex hormones
o Use of phenolphthalein as a laxative has been associated w/ numerous small, well-circumscribed areas of hyperpigmentation on the skin – similar areas of
oral mucosal melanosis also can occur.
o Minocycline
 Clinical features:
Long-term use of minocycline results in discoloration of bone and developing teeth – affect bone is dark green but creates a blue-gray discoloration through mucosa.
Most common presentations – linear band above facial attached gingiva near mucogingival junction – broad zone of discoloration on the hard palate
Rare: soft tissue pigmentation of lips, tongue, eyes, and skin
o Estrogen, chemotherapeutic agents, and medications used in the treatment of AIDS patients may result in a diffuse brown melanosis of the skin and
mucosal surfaces
o Although discolorations of oral mucosa may be aesthetically displeasing – they cause no long-term problems
• In most instances, discontinuing medication results in gradual fading of areas of hyperpigmentation.
What is this?
Mucocele
Etiology: Rupture of salivary duct and spillage of mucin into soft tissues
Age: Any age; children and young adults
Site: Lower lip >> FOM, ventral tongue, buccal mucosa, almost never involves
upper lip
o FOM = ranula
o Soft palate, retromolar pad = superficial mucocele
Clinical features: bluish, translucent, dome-shaped, fluctuant to firm to palpation,
recurrent swelling, ↑ and ↓ in size
o Superficial mucocele
 Single or multiple
 Clear vesicles  shallow ulcers, can be mistaken for viral vesicle, vesiculobullous disorder
Histology: spilled (extravasated) mucin, surrounded by a “wall” of granulation
tissue, foamy histiocytes, ± adjacent salivary ducts and salivary glands with
inflammation
Treatment: some may rupture and heal, most require conservative surgical
excision with removal of adjacent (feeding) salivary glands, recurrences common
What is this?
Ranula
Mucocele involving floor of mouth
Etiology: same as mucocele, arises from sublingual gland, submandibular duct,
minor salivary glands
Gender and age: same as mucocele
Site: Floor of mouth, lateral to midline
Clinical features: bluish, dome-shaped, fluctuant swelling, can become very large,
can elevate tongue
o Plunging (cervical) ranula
 Ranula that dissects through mylohyoid muscle
 Swelling of neck
 Imaging studies may be needed
Histology: Same as mucocele
Treatment: removal of feeding gland (usually sublingual gland), marsupialization
(exteriorization)
o “Deroofing” of lesion
o For superficial ranulas
o Associated with higher recurrence rates
What is this?
Salivary duct cyst
AKA: Mucous retention cyst
True developmental cyst
Etiology: uncertain, ?cystic dilatation 2: to obstruction – likely not true salivary duct cyst
Age: Adults
Site: Major salivary glands – parotid gland; minor glands – FOM, Bu mucosa, lips
Clinical features:
o Major glands: slow growing swelling, asymptomatic
o Minor glands: mucocele, bluish, amber-hued; translucent, dome-shaped, fluctuant to firm to palpation
Histology: **True cyst
o Epithelium
 Cuboidal, columnar, stratified squamous
 ± oncocytes (large cells with granular, eosinophilic cytoplasm), mucous in lumen, ± papillary infoldings
o Cyst wall – fibrous CT
Treatment:
o Major glands: excision of cysts with partial or total removal of major gland
o Minor glands: conservative excision of cyst and adjacent glands
What is this?
Sialolithiasis
AKA: Salivary stones, salivary calculi  Submn, parotid – panorex or periapical
Superimposed over mandible, ramus
Etiology: Deposition of calcium salts in salivary Difficult to distinguish from other soft tissue
ducts calcficiations (calcified LN, tonsilloliths,
phleboliths)
o Calcium surrounds nidus of debris (mucous,
o Minor glands – soft tissue radiograph,
bacteria, ductal epithelial cells, foreign bodies)
sialography, ultrasound, CT scans
Gender: Not specified Histology:
Age: Young and middle-aged adults; any age o Calcified mass – concentric, calcified
Site: Submandibular ducts laminations
o 1. Long, tortuous, upward ductal system o Inflammation, granulation tissue, ±surrounding
o 2. Thicker, mucoid secretion ductal epithelium
 Parotid duct far less common
 Minor salivary glands (upper, lip, bu mucosa)
Treatment:
o Small sialoliths – milk stone towards duct orifice,
Clinical features: surgical removal
o Major gland: Episodic pain, swelling at
o Larger sialoliths – surgical removal
mealtimes
o Removal of feeding gland
o Major and minor glands: Hard, palpable mass if
o Sialogogues (stimulate salivary flow), increased
close to exit of duct ± tenderness
fluid intake, moist heat
Radiographic features: o Salivary gland endoscopy, shock wave lithotripsy,
o May see radiopaque mass corresponding to basket retrieval
sialoth
o Major glands:
 Submandibular – occlusal radiograph (submn)
What is this?
Sialadenitis
Etiology: Inflammation of salivary glands  Etiology: ductal obstruction, decreased flow –
usually infectious
o 1. Infectious  Site: Mostly parotid (acute parotitis) – may be
 Viral – poxvirus (mumps), coxsackie A, etc.
bilateral
 Bacterial – staph. Aureus, streptococci
 Clinical features: swelling, pain, erythema of
1. Obstruction (sialolith, duct strictures,
tumors) overlying skin, purulent drainage from duct
2. Decreased flow (dehydration, meds, etc.) Histology:
o (e.g.) “surgical mumps” (acute o Chronic sialadenitis
parotitis) – NPO, atropine
 1. Patchy chronic inflammation of glands
intraoperatively
Retrograde spread of bacteria  2. Acinar atrophy
 3. Ductal dilatation
o 2. Non-infectious  ± fibrosis
 Sjogren syndrome
 Sarcoidosis o Acute sialadenitis
 Radiation therapy  Neutrophilic infiltration of glands
 Various allergens Treatment:
Gender and age: depends on predisposing o Chronic sialadenitis
 Antibiotics, analgesics, glandular massage
condition  Elimination of cause (obstruction)
2 types:  Advanced cases – may require ductal dilatation,
o 1. Chronic sialadenitis removal of gland
 Etiology: Usually, recurrent/persistent ductal o Acute bacterial sialadenitis
obstruction – infectious, non-infectious  Antibiotic therapy, increased hydration, surgical
 Site: Minor, major glands drainage of abscess
 Clinical features: periodic swelling, pain  Mortality: uncontrolled spread of infection, sepsis
(mealtimes)
o 2. Acute sialadenitis
Sialorrhea
Excessive salivation
Etiology: Local irritation – apthous ulcers, mucosal ulcers, ill-fitting
dentures
o new dentures, GERD, heavy metal poisoning, rabies, medications
(lithium, cholinergic agonists)
Age: depends on predisposing condition
Clinical features: excessive saliva, choking, sores on mouth, perioral
skin, chin, neck
Treatment:
o Treat underlying cause (e.g. GERD)
o Anticholinergic agents, Botox (!), surgical approaches (e.g.
duct/relocation/ligation, gland excision)
What is this?
Xerostomia
Subjective sensation of dry mouth – frequently Clinical features: reduction in salivary secretion
associated with salivary gland hypofunction o Saliva thick, foamy, “ropey”
Etiology: o Mucosal dryness, “cracker” test
o Developmental: salivary gland aplasia o Tongue – atrophy of filiform papillae, fissured
o Water/metabolite loss: impaired fluid intake, o Secondary candidiasis
hemorrhage, vomiting/diarrhea o Cervical and root caries (“xerostomia-related
o Iatrogenic: medications, radiation therapy to caries” – variable severity
H&N Treatment: adequate hydration, artificial saliva,
 Medications – common cause of xerostomia saliva substitutes, OH products with
>500 meds produce xerostomia
~63% of commonly prescribed meds lactoperoxidase, lysozyme, lactoferrin
Risk increased with increasing # meds (Biotene), sugarless lozenges, gums –
Common culprits: antihistamines,
antihypertensives, antidepressants, discontinuation/substitution of meds after
antipsychotics consult with physician
o Systemic diseases: Sjogren syndrome, diabetes o Sialogogues
mellitus, diabetes insipidus, sarcoidosis, HIV  Pilocarpine [Salagen], cevimeline HCl [Evoxac])
infection, Graft vs. Host disease, psychogenic  Side-effects: excessive sweating; increased heart
disorders rate, blood pressure
 Contraindications: narrow-angle glaucoma
o Local factors: decreased mastication, smoking,
o Frequent dental evaluation (caries)
mouth breathing
o Topical fluoride treatment
Prevalence: ~25% older adults o CHX rinse
Gender and age: depends on predisposing
condition
What is this?
Sjogren syndrome
Etiology: autoimmune disorder  3. Ocular signs – schirmer test, ocular dye
o Chronic inflammation of salivary and lacrimal glands  4. Histopathology
 1. Dry eyes (xeropthalmia)  5. Salivary gland involvement by test – Lashley cup measurement,
 2. Dry mouth (xerostomia) sialography
 6. Autoantibodies – antibodies to Ro(SS-A), La(SS-B), or both
o Unknown cause
 Genetic influence, viruses o Primary SS
 1. 4 of 6 criteria met – including histopathology and/or serology
2 forms:  2. 3 of 4 objective criteria met – ocular signs, histopathology, salivary
o 1. Primary Sjogren syndrome (sicca syndrome) gland involvement, serology
 Dry eyes and dry mouth o Secondary SS
o 2. Secondary Sjogren syndrome  Either of subjective criteria AND at least 2 of objective criteria AND
 Dry eyes, dry mouth, another autoimmune dz (e.g. rheumatoid other autoimmune dz
arthritis (15%), SLE (30%)
Histology:
Prevalence: 0.2=3.0% o Minor salivary glands: Lymphocytic infiltration = ≥2 aggregates of
Gender: F>>M (9:1) ≥50 lymphocytes, acinar destruction
Age: Middle-aged, elderly o Major glands: lymphocytic infiltration, acinar destruction,
Clinical Features: lymphoepithelial lesions = “islands” of ductal epithelium surrounded
o Eyes: dry eyes (“keratoconjunctivitis sicca”) – scratchy, gritty by dense lymphocytic infiltrate
sensation; blurred vision, pain Treatment:
o Oral: Xerostomia – variable severity o Supportive care
 Difficulty swallowing, wearing dentures; altered taste (dysgeusia), o Eyes – artificial tears
mucosal dryness, tongue – atrophy of papillae, fissured; secondary o Oral – tx recommendations for xerostomia
candidiasis (atrophic candidiasis, angular cheilitis); cervical and root
o Increased risk for lymphoma
caries
 40x normal population
o Salivary glands (mostly parotid): firm enlargement, usually bilateral  Usually low-grade, non-Hodgkin’s lymphoma
 Slightly tender, enlargement may be intermittent or persistent  Molecular pathology techniques helpful
o Other: dry skin, dryness of other mucosae, fatigue
Imaging:
o Sialography – abnormal ductal system, “fruit-laden, branchless tree”
o Salivary scintigraphy – delays in uptake, excretion of tracer
Diagnosis: Revised International Classification Criteria
o Subjective:
 1. Ocular symptoms
 2. Oral symptoms
o Objective:
What is this?
Sialadenosis (sialosis)
Etiology: Non-inflammatory disorder of parotid glands –
enlargement of parotid glands
o Underlying systemic problem
 1. Endocrine (DM)
 2. Nutritional (alcoholism, anorexia, bulimia)
 3. Neurogenic
Gender and age: Depends on predisposing condition
Site: Parotid gland, bilateral
Clinical features: swelling of parotid gland ± decreased
salivation
Histology: hypertrophy of acini, lack of significant
inflammation
Treatment: Manage underlying cause
What is this?
Acinar atrophy Sq. metaplasia
Necrotizing sialometaplasia
Locally destructive inflammatory disorder of salivary glands
Etiology: likely, ischemia of salivary tissues  localized infarction
Predisposing factors/conditions:
o 1. Local trauma
o 2. Dental injections
o 3. Ill-fitting dentures
o 4. Upper respiratory infections
o 5. Adjacent tumor
o 6. Previous surgery
Gender: M>F
Age: Adults
Site: Hard or soft palate, unilateral>bilateral
Clinical features:
o Early: non-ulcerated swelling, pain, paresthesia
o Later: deep, crater-like ulcer – rarely, destruction of underlying bone
Histology:
o 1. Acinar necrosis (“necrotizing”)
o 2. Squamous change (metaplasia) of salivary ducts (“sialometaplasia”)
o ± PEH of epithelium
o May be mistaken for SCC or mucoepidermoid carcinoma histologically and clinically
Treatment: Biopsy to rule out neoplastic process, resolves spontaneously in 5-6 weeks
Salivary gland neoplasms
Primary epithelial neoplasms, soft tissue neoplasms, lymphoma, metastatic tumors
Incidence: 1.0-6.5 cases/100,000 people
Frequency of tumors by site:
o Parotid: 64-80% all salivary gland tumors
o Submandibular: 8-11%
o Sublingual: <1%
o Minor salivary glands: 9-23%
Tumors by site:
o Parotid
 2/3 – 3/4 rule
 2/3-3/4 of salivary gland tumors occur in parotid
 2/3-3/4 of parotid tumors are benign
 2/3-3/4 of parotid tumors are pleomorphic adenomas
 Benign: pleomorphic adenoma, Warthin tumor
 Malignant: mucoepidermoid carcinoma
o Submandibular
 37-45% malignant
 Benign: pleomorphic adenoma
 Malignant: adenoid cystic carcinoma
o Sublinual
 70-90% malignant
o Minor salivary glands
 ~50% malignant (except upper lip)
 Palate > lips > bu mucosa
 Benign: pleopmorphic adenoma
 Malignant: mucoepidermoid carcinoma, adenoid cystic carcinoma, polymorphous low-grade adenoca
What is this?
Ductal
epithelial
cells
Myoepithe
lial cells
Pleomorphic adenoma
AKA: Benign mixed tumor dome-shaped mass; ± secondary ulceration; movable if
involves lip, buccal mucosa
Benign neoplasm of ductal epithelial and
Histology:
myoepithelial cells o Well-circumscribed, mostly encapsulated
**Most common salivary gland tumor o 1. Ductal epithelial cells – cuboidal cells forming small
**Most common salivary gland tumor of childhood ducts, islands
Prevalence: o 2. Myoepithelial cells – variable appearance, angled,
o PAs account for: 53-77% of parotid tumors – mostly, spindled, “plasmacytoid”
superficial lobe o 3. Chondromyxoid stroma - ± fat, bone
o 44-68% submandibular tumors Treatment:
o 38-43% minor salivary land tumors o Complete surgical excision
Gender: F slightly > M o Parotid, superficial lobe: superficial parotidectomy,
Age: 30-60 yo; any age preservation CN VII
Site: o Parotid, deep lobe: total parotidectomy, preservation
CN VII
o Parotid gland: superficial lobe>deep lobe, rarely occurs
o Submandibular: excision tumor and submn gland
bilaterally
o Minor glands: excision tumor
o Minor salivary glands: palate>upper lip> bu mucosa
o Recurrence, multifocality can occur if incomplete
Clinical features: excision
o Delays in diagnosis common o Malignant transformation rate of 5% (ca ex PA)
o Parotid
 Swelling over ramus anterior to ear, angle of mn
(superficial lobe)
 Mass of lateral pharyngeal wall, soft palate (deep lobe)
 Slowly growing, mostly movable, can become very
large, usually asymptomatic
o Minor salivary gland
 Slowly growing; mucosal colored; smooth-surfaced,
What is this?
Oncocytoma
Benign neoplasm of oncocytes (epithelial cells)
Oncocytes – salivary gland, thyroid, parathyroid, kidney – common finding in older
pt
Prevalence: rare; ~1% all salivary tumors
Age: Older adults (8th decade)
Site: Parotid, superficial lobe (85-90% cases), rare in minor glands
Clinical features: slowly growing, painless, firm mass
Histology:
o Well circumscribed
o Oncocytes: large cells; abundant granular, eosinophilic cytoplasm (mitochondria); central
nuclei, ± clear cells, minimal stroma, lymphocytic infiltrate
Treatment:
o Complete surgical excision
 Varies according to site
 Parotidectomy (partial or total), excision of tumor and submandibular gland, local excision
o Low recurrence rate
o Malignant transformation rare (oncocytic carcinoma) – poor prognosis
What is this?
Oncocytosis
AKA: Nodular oncocytic metaplasia
Metaplastic proliferation of oncocytes in salivary gland tissue
Likely not a true neoplasm – Oncocytic metaplasia of ducts and acinar
cells
May be associated with other salivary gland tumors
Age: Older adults
Site: parotid>>submn, minor
Clinical features: May be discovered incidentally, may produce a clinical
swelling
Histology: multifocal, nodular proliferations of oncocytes ± clear cells
Treatment: No treatment necessary after diagnosis, periodic evaluation
What is this?
Warthin tumor
AKA: Papillary cystadenoma lymphomatosum
Benign neoplasm of ductal epithelium, secondary formation of lymphoid tissue
Prevalence: 5-14% of parotid neoplasms, 2nd most common benign parotid tumor
Predisposing factors: Smoking (8-fold risk)
Gender: M slightly > F
Age: Older adults (6th-7th decades)
Site: Parotid gland, especially tail – bilateral in 5-14% of cases; rarely, submn and
minor glands
Clinical features: slowly growing, painless, firm or doughy mass, angle of mandible
– parotid tail
Histology:
o 1. Oncocytic ductal epithelium: bilateral arrangement, surround cystic spaces, papillary
infoldings
o 2. Stroma with prominent lymphoid component: germinal centers
Treatment: surgical excision – superficial parotidectomy
o Recurrence rate: 6-12%
o Malignant transformation very rarely reported
What is this?
1 1
2
Monomorphic adenoma
Historically, benign salivary gland tumors with more o Prevalence: 1-2% of all salivary gland tumors
“uniform” pattern than pleomorphic adenoma o Gender: F>M
o Age: Middle-aged to older adults
Historically, encompassed a variety of tumors o Site: parotid, superficial lobe (75%); upper lip, bu mucosa
2 main neoplasms o Clinical features: slow growing, painless, freely movable,
o 1. Canalicular adenoma mass
o 2. Basal cell adenoma  Membranous basal cell adenoma
1. Canalicular adenoma Hereditary, multiple, bilateral BCAs of parotid, in
association with skin tumors (dermal cylindromas,
o Benign neoplasm of ductal epithelial cells trichoepitheliomas)
o Gender: F>M o Histology: well-circumscribed, usually encapsulated,
o Age: older adults (7th decade) islands and cords of epithelial cells
o Site: Upper lip (75% of cases) – one of most common  Inner cells pale; Outer cells darker, cuboidal/columnar,
tumors of upper lip, bu mucosa palisaded; Minimal stroma, fibrous
o Clinical features: slow growing, painless, normal to  Membranous BCA
bluish, mass, firm to fluctuant, freely movable – may be Closely-arranged epithelial islands (“jigsaw” puzzle)
Surrounded by pink, hyaline material
mistaken for a mucocele – but mucoceles of upper lip o Treatment: complete surgical excision, recurrence rare –
rare; may be multifocal except membranous BCA (25-37%)
o Histology: well-circumscribed, encapsulated, columnar or  Malignant transformation reported (basal cell
cuboidal cells adenocarcinoma)
 Single-layer or bilayered
 Enclose ducts, long canals (“canalicular”)
 Large, cystic spaces
 Stroma loose and vascular – “watery”
o Treatment: complete surgical excision, multifocal cases
described
2. Basal cell Adenoma
o Benign neoplasm of ductal epithelial and myoepithelial
cells
What is this?
Squamous
cells
Mucous
cells
Clear
cells
Mucoepidermoid carcinoma
Malignant neoplasm of mucous and squamous cells  Graded based on various features
Prevalence: One of most common salivary gland o 3 histologic grades:
 1. Low-grade, 2. Intermediate grade, 3. High-grade
malignancies o Dependent on:
o 10% all major gland tumors in US  1. % intracystic cmpnt – more, lower grade
o 15-23% all minor gland tumors in US  2. Neural invasion – absent, lower grade
Gender: F slightly>M  3. Necrosis – absent, lower grade
Age: Wide age range (2nd-7th decades) – most  4. Mitotic activity – absent, lower grade
 5. Degree cytologic atypia – less, lower grade
common malignant salivary gland tumor in children  6. Invasion pattern – bony, lymphovascular invasion
Site: Parotid gland – Palate>lower lip, FOM, tongue, Treatment: depends on location, histologic grade,
retromolar bone stage of tumor
Clinical features: o Parotid – partial or total parotidectomy ± facial nerve
o Parotid: Swelling over ramus anterior to ear, angle of resection/sacrifice
mandible (superficial lobe) o Submandibular – excision of tumor and gland
 Mass of lateral pharyngeal wall, soft palate (deep lobe) o Minor glands – excision of tumor, assess involvement of
 Asymptomatic, fixed over time ± pain, underlying bone
paralysis/paresthesia of CN VII o Neck dissection – mets; large; high-grade tumors
o Minor glands: blue to red, smooth-surfaced, dome- o Post-op radiation therapy (RT) – aggressive tumors
shaped mass (~mucocele), may be fluctuant, ± secondary Prognosis: dependent on grade and stage of tumor
ulceration
o Low grade = better prognosis
Histology: o Poor prognostic factors: higher grade, submandibular
o 1. Mucous cells (“muco”) tumors, tongue, FOM tumors
o 2. Squamous cells (“epidermoid”)
o 3. Intermediate cell – progenitor cell of mucous,
squamous cells
 ±clear cells, ±cystic spaces, ±lymphoid infiltrate in
stroma
What is this?
Intraosseous mucoepidermoid
carcinoma
AKA: Central mucoepidermoid carcinoma
Malignant neoplasm of mucous and squamous cells – intraosseous mucoepidermoid carcinoma =
mucoepidermoid carcinoma that arises within jaws
Source: debated; likely odontogenic epithelium
Prevalence: Rare
Age: Middle-aged
Site: Mn>Mx – molar/ramus area
Clinical features: cortical swelling ± pain, trismus, paresthesia
o Borders: well- to ill-defined
o Shape: Unilocular or multilocular
o Location: May be assoc. with unerupted tooth – may arise from odontogenic cyst
Histology: same as mucoepidermoid carcinoma – most are low-grade
Treatment: surgical excision, recurrence rates vary depending on surgery
o Conservative therapy (enucleation, curettage) – 40% recurrence
o Resection – 13% recurrence
o Metastasis in 12% of cases
o Prognosis fairly good
o Death: 10% of patients – due to local recurrence
What is this?
Acinic cell adenocarcinoma
Malignant neoplasm of serous acinar cells
Low-grade malignancy
Age: 2nd-7th decades
Site:
o Parotid – 85% of acinic cell adenocarcinom, 1-3% of parotid neoplasms
o Submandibular gland – 2.7-4%
o Minor salivary glands – 9% (bu mucosa, lips, palate)
Clinical features: slowly growing, mass, often long-standing, ± pain-tenderness, rarely facial nerve
paralysis
Histology: well circumscribed or infiltrative growth. Serous acinar cells – abundant, granular,
basophilic cytoplasm, ± ductal epithelial cells, ± clear cells, several growth patterns
Treatment:
o Parotid – partial or total parotidectomy ± facial nerve resection
o Submandibular – excision of tumor and gland
o Minor glands – excision of tumor, assess bone involvement
o Neck dissection – if metastatic disease
Prognosis: Good, recurrence in ~30% of pt, metastasis in ~10-15% of pt
What is this?
Carcinoma ex PA
Malignant transformation of epithelial component of a PA
Risk factors: long-standing, untreated PA – risk of PA undergoing malignant
transformation increases with duration of tumor
Age: ~15 yrs older than benign Pas – 6th-8th decades
Site: major glands (80%) – mostly parotid, minor glands – mostly palate
Clinical features: long-standing mass, recent h/o rapid growth, pain, ulceration, ±
h/o PA in area, ± facial nerve palsy (parotid tumor)
Histology:
o 1. Malignant epithelial component (“carcinoma”)
 cytologic atypia, mitotic activity
 adenocarcinoma, rarely PLGA, mucep. ca, ACC
 Invasion of tumor capsule, infiltration of soft tissues
o 2. Areas of atypical PA
Treatment: wide surgical excision ± neck dissection, radiation therapy
Prognosis: guarded
o 5 yr survival – 25-65%, decreases over time
o Poorer if: 1. Poorly differentiated carcinoma, 2. Capsular invasion >8mm
What is this?
Adenoid cystic carcinoma (ACC)
Malignant neoplasm of ductal epithelial and myoepithelial cells
High-grade malignancy
Prevalence: 2-3% of salivary gland tumors
Age: Middle-aged adults
Site: Minor salivary gland (50-60%), mostly palate, parotid, submandibular, maxillary sinus
Clinical features: slowly growing, mass, pain common, increases in intensity over time, facial nerve paralysis (parotid tumors), ± ulceration, ±
destruction of underlying palatal bone
Histology: ductal epithelial and myoepithelial cells in various patterns – 3 patterns:
o 1. Cribriform
o 2. Tubular
o 3. Solid
o Combination of patterns common
o **perineural invasion – tumor surrounds/ invades nerve bundles
o Cribriform
 1. Basaloid myoepithelial cells – uniform, dark, angular nuclei
 2. Ductal epithelial cells
 3. Cells surround cysts-like spaces (“swiss cheese”) – mucoid, hyalinized eosinophilic material in spaces, surrounding cells ± perineural invasion
Treatment: wide surgical excision-with underlying bone if palatal ± post-operative radiation therapy
Prognosis: Poor – aggressive tumors; local, late recurrence, distant metastasis
o Survival rates: 5-yr, 70%, 20-yr – 25%
o Poorer if:
 1. Solid subtype
 2. Submandibular, maxillary sinus location
o Distant metastasis: lungs, bones
o Death: local recurrence, invasion vital structures, distant metastasis
What is this?
Targetoid
infiltration
Single-file
infiltration
Polymorphous low-grade
adenocarcinoma (PLGA)
Malignant neoplasm of ductal epithelial cells – de novo, as malignant component of carcinoma ex
PA
Only recently recognized (1983)
Prevalence: Unknown, common
Gender: F>M
Age: Older adults (6th-8th decades)
Site: mostly minor glands – H and S palate (65%), upper lip, buccal mucosa, rarely, major glands
Clinical features: slow growing, painless, mass, can erode/invade underlying palatal bone ± pain
Histology:
o Ductal epithelial cells – pale-staining, uniform, cords, ducts
o Infiltrates in a “targetoid” pattern, single file infiltration
o Cells in varied growth patterns (“polymorphous”) – solid islands, cords, ducts, cribriform
o Basophilic, mucoid stroma
o ± perineural invasion
Treatment: Complete, wide surgical excision – with underlying bone if palatal
Prognosis: relatively good (“low-grade”), regional and distant metastasis rare, recurrences seen –
controlled by re-excision
o Death: uncommon, direct invasion vital structures
What is this?
Fibroma
Etiology:
o Most common soft tissue tumor of oral cavity
o In most cases – doubtful that it represent a true neoplasm – rather a reactive hyperplasia of fibrous
connective tissue in response to local irritation or trauma
Clinical features:
o Usually presents as a well-defined, smooth-surfaced pink nodule – may be sessile or pedunculated
o Most are <2cm in diameter – sometimes become larger
o Adults > Children
o Most commonly located on buccal mucosa along bite line – irritation from teeth
o Slow-growing, asymptomatic – unless secondary trauma occurs
Histopathology:
o Nodular mass of fibrous connective tissue covered by stratified squamous epithelium
o CT is dense and collagenized
o Lesion is not encapsulated – fibrous tissue instead blends gradually into surrounding connective tissues
o Surface may exhibit hyperkeratosis from secondary trauma
o Scattered inflammation may be seen – beneath epithelial surface
o Local surgical excision, lesions rarely recur
What is this?
Giant cell fibroma
Clinical features:
o Fibrous CT tumor, distinct entity from typical fibroma
o When compared to irritation fibroma:
 Giant cell fibroma occurs at a younger average age
 ~60% - seen in first 3 decades of life
 Most common location – gingiva – tongue, palate, bu mu, less frequently
o Lesions <1cm in diameter, often exhibit rough surface – may be mistaken for
papilloma
o Large stellate fibroblasts, occasionally multinucleated
o Mass of vascular fibrous CT, loosely arranged
o Hallmark – presence of numerous large, stellate fibroblasts w/ in superficial
CT – may contain several nuclei
o Surface is pebbly
o Conservative surgical excision, recurrences rare
What is this?
Retrocuspid papilla
Clinical features:
o Similar developmental lesion to giant cell fibroma
o Occurs on gingival lingual to mandibular cuspid
o Frequently bilateral, appears as small, pink papule
o <5 mm in diameter
o Common lesion – 25-99% of children/young adults
 Prevalence in adults and elderly drops to 6-19%
o Represents normal anatomic variation, disappears
with age
What is this?
Epulis fissuratum
Etiology:
o Reactive hyperplasia of fibrous CT and epithelium
o Occurs in alveolar vestibule, associated with long-standing irritation from poorly fitting denture
Clinical features:
o Growth of single or multiple folds of redundant tissue – denture flange often fits into depth of one fold
o More common in anterior areas, occurs more frequently on facial aspects
o Women > Men
o Often asymptomatic – tender if ulceration occurs at base
o Hyperplasia of fibrous CT
o Multiple folds and grooves
o Overlying epithelium frequently – hyperparakeratotic – demonstrates irregular hyperplasia of rete ridges –
epithelium may show inflammatory papillary hyperplasia or pseudoepitheliomatous
(pseudocarcinomatous) hyperplasia (PEH).
o Focal areas of ulceration, chronic inflammatory infiltrate present, minor salivary glands – chronic sialadenitis
o Surgical removal of excess tissue, construction of new dentures
What is this?
Inflammatory papillary hyperplasia
Etiology:
o Benign proliferation of ora mucosa – associated w/ wearing dentures 24 hours/day
o Usually develops on palate – occasionally on alveolar ridge, top of epulis fissuratum
Clinical features:
o Multiple, broad-based papillary projections that closely approximate one another
o May be normal or erythematous – erythematous lesions indicated possibility of secondary candidiasis
o Rarely – may occur on palate of patient without denture – mouth-breather, high palatal vault
o May be misdiagnosed as SCC
o Mucosa in inflammatory papillary hyperplasia exhibits – numerous papillary growths on surface covered by
hyperplastic stratified squamous epithelium
o In advanced cases, hyperplasia is pseudoepitheliomatous in appearance – should not be mistaken for
carcinoma
o CT loose or dense
o Chronic inflammatory cell infiltrate – lymphocytes, plasma cells, sclerosing sialadenitis
o Partial regression if patient discontinues wearing denture for short time
o Mild cases improve w/ antifungal agents, fabrication of new denture
o Surgical stripping, electrocautery, laser excision for severe cases
What is this?
Fibrous histiocytoma
Clinical features:
o Diverse group of tumors exhibit both fibroblastic and histiocytic differentiation
o Cell of origin uncertain – may arise from histiocytes which assumes fibroblastic properties
o Variable nature – different terms have been used including:
 Dermatofibroma, fibroxanthoma, sclerosing hemangioma, nodular subepidermal fibrosis
o Fibrous histiocytoma generally considered to represent a true neoplasm
o Can develop almost anywhere in the body – most common site – skin of extremities –
dermatofribroma
o Uncommon – tumors of oral and perioral region
o Oral tumors occur at any site – most common is buccal mucosa and vestibule
 Intrabony lesions of jaws are rare
 Oral fibrous histiocytomas occur in middle-aged and older adults, painless nodular mass
 Deeper tumors tend to be larger
o A cellular proliferation of spindle-shaped fibroblastic cells with vesicular nuclei
o Margins not sharply defined
o Storiform pattern – short, intersecting fascicles, irregular whorled appearance of straw mat
o Local surgical excision – treatment of choice
o Recurrence uncommon, larger lesions of deeper soft tissues tend to recur
What is this?
Fibromatosis
Etiology:
o Broad group of fibrous proliferations
o Have a biologic behavior and histopathologic pattern intermediate between those of benign fibrous lesions and fibrosarcoma.
o A number of different forms of fibromatosis are recognized throughout the body
o In soft tissues of the head and neck – frequently called juvenile aggressive fibromatosis or extra-abdominal desmoids
o Similar lesions in bone have been called desmoplastic fibromas
Clinical and radiographic features:
o Soft tissue fibromatosis of head and neck is a firm painless mass – may exhibit rapid insidious growth
o Most frequently occur in children or young adults – juvenile fibromatosis
o Most common oral site – para-mandibular soft tissues
o Destruction of adjacent bone may be observed on radiographs and other imaging studies
o Soft tissue fibromatosis – characterized by cellular proliferation of spindle-shaped cells arranged in streaming fascicles –
associated w/ a variable amount of collagen
o Lesion is usually poorly circumscribed and infiltrative in adjacent tissues
o Hyperchromatism and pleomorphism of cells should NOT be observed
o Locally aggressive – preferred treatment – wide excision that includes a generous margin of adjacent normal tissues
o 23% recurrence rate for oral and paraoral fibromatosis
o Metastasis does NOT occur
What is this?
Myofibroma
Etiology:
o Rare spindle cell neoplasm that consists of myofibroblasts – cells with both smooth muscle and fibroblastic
features
o Although myofibromas are rare neoplasms, they demonstrate a predilection for the head and neck region
o Occurs most frequently in first 4 decades of life – avg age 27 years
o Most common oral location – mandible
o A painless mass that sometimes exhibits rapid enlargement
o Intrabony tumors create radiolucent defects that usually tend to be poorly defined
o Multicentric myofibromatosis primarily affects neonates and infants who may have tumors of skin,
subcutaneous tissue, muscle, bone, viscera
o Composed of interlacing bundles of spindle cells w/ tapered or blunt-ended nuclei and eosinophilic
cytoplasm
o Centrally, lesion is often more vascular with a hemangiopericytoma appearance
o Tumor cells are positive for smooth muscle actin and musle-specific actin w/ immunohistochemistry –
negative for desmin
o Solitary myofibromas – treated by surgical excision
 Small percentage will recur
o Multifocal tumors – soft tissues and bone rarely recur after surgical excision
 Spontaneous regression may occur
o Myofibromatosis in viscera or vital organs in infants act more aggressively, may be fatal
What is this?
Pyogenic granuloma
Etiology:
o Relatively common reactive, tumor-like growth of the oral cavity
o Occurs as a result of local irritation
Clinical features:
o Occurs at any age – most common in teenagers and young adults
o Can develop almost anywhere in oral cavity – gingiva most common site
o Presents as pedunculated or sessile mass – ranges in size, mm-cm
o Characteristically red and highly vascular mass – shows tendency to bleed in some cases
o Epithelial surface is usually ulcerated – lesion is typically not painful
o May exhibit rapid growth
o More common in females – especially during pregnancy
o “pregnancy tumor” or “granuloma gravidarum” – identical to lesions in non-pregnant individuals
Histopathological features:
o Shows a highly vascular proliferation that resembles granulation tissue
o Vessels sometimes arranged in lobular aggregates
o Surface is usually ulcerated and replaced by a thick fibrinopurulent membrane
o Mixed inflammatory cell infiltrate of neutrophils, plasma cells and lymphocytes
 Neutrophils most prevalent near ulcerated surface
 Chronic inflammatory cells – found deeper
o Older lesions may have areas w/ a more fibrous appearance – many gingival fibromas represent pyogenic granulomas that
have undergone fibrous maturation
o Treatment – local surgical excision
o For gingival lesions – advisable to excise the lesion down to periosteum, scale adjacent teeth
o Recurrence occasionally seen
o If not removed may undergo fibrous maturation and resemble a fibroma
o Pregnant women – wait till after birth before surgical removal, may regress following birth
What is this?
Peripheral giant cell granuloma
Etiology:
o Tumor-like growth of gingiva or alveolar ridge – soft tissue counterpart of central giant cell
granuloma
Clinical features:
o Similar to pyogenic granuloma
o Presents as a sessile or pedunculated mass – often w/ an ulcerated surface
o Usually red – frequently exhibits somewhat deeper bluish-purple hue
o May occur at any age – most common in young and middle-aged adults
o F>M, more common in mandible, superficial bone erosion may occur
o Proliferation of multinucleated giant cells w/ in a background of plump ovoid and spindle-
shaped mesenchymal cells
o Some may have large, vesicular nuclei – others demonstrate small, pyknotic nuclei
o Mitotic figures common – abundant hemorrhage found throughout mass
o Overlying mucosal surface is ulcerated in ~50% of cases
o Surgical excision down to underlying bone
o Scaling of adjacent teeth to remove irritation and reduce chance of recurrence
o ~10% of cases recur
What is this?
Peripheral ossifying fibroma
Etiology:
o Relatively common tumor-like growth of gingiva
o May be reactive rather than neoplastic in nature
Clinical features:
o Teenagers and young adults – can be seen at any age
o F>M
o Maxillary or mandibular gingiva
o Most common in incisor/cuspid region
o Well-circumscribed nodular mass – smooth, pink surface, may be ulcerated
o Proliferation of fibrous connective tissue arising from periodontal ligament
o Associated with formation of bone, dystrophic calcification, cementum-like product
o Surgical excision to underlying bone
o Adjacent teeth should be scaled to remove source of irritation, stimulate redevelopment of
lesion
o Recurrence 16-20% cases
What is this?
Lipoma
Clinical features:
o Benign tumor of fat
o Common in subcutaneous tissues but relatively uncommon in the oral cavity
o May occur almost anywhere in mouth – buccal mucosa most common location, tongue
o Most common in adults
o Usually presents as a soft nodular mass – may be sessile or pedunculated
o Often appears yellow – deep-seated mass
o Multiple subcutaneous tumors occur in some patients
o Most oral lipomas are composed mature fat cells – differ little from surrounding normal fat
o Distinct lobular arrangement of cells often is seen
o Rarely – central cartilaginous or osseous metaplasia may occur
o Many microscopic variants have been described:
 Most common – fibrolipoma – significant fibrous component intermixed w/ lobules of fat cells
 Remaining variants rare
o Surgical removal, recurrence rare
What is this?
Traumatic neuroma (Amputation
neuroma)
Etiology:
o Not a true neoplasm
o Reactive hyperplasia of nerve elements following damage or severance of nerve bundle
 Distal portion of bundle undergoes degeneration
 Proximal nerve axons attempt to regenerate along axis cylinders and reestablish innervations
o If sprouting nerve elements encounter scar tissue or otherwise cannot reestablish
innervations – tumorlike mass of disorganized nerve and scar tissue may develop
o Oral traumatic neuromas typically present as nodules that are small, smooth, pink
o Frequently, but not always, painful
o Mental foramen – most common location – due to extraction, mandibular denture
o Haphazard proliferation of mature, myelinated nerve bundles within a fibrous CT stroma that
ranges from densely collagenized to myxomatous in nature
o Associated mild chronic inflammatory cell infiltrate may be present
o Traumatic neuromas w/ inflammation – more likely to be painful that those without
inflammation
o Surgical removal, recurrence uncommon
What is this?
Palisaded encapsulated neuroma
o Etiology:
 Benign neural tumor
 Represents one of the more common superficial nerve tumors of H&N
 Cause is uncertain
 Reactive lesion rather than true neoplasm
 Striking predilection for face
90% of reported cases
Nose and cheek are most common specific sites
 5th-7th decades of life
 Smooth-surfaced, dome-shaped papule or nodule - <1cm in diameter
 Painless, no sex predilection
 Most frequently appears on hard palate, maxillary labial mucosa
 Appear well circumscribed and often encapsulated
 Lobulated appearance
 Consists of moderately cellular interlacing fascicles of spindle cells that are consistent w/ Schwann cells
 Nuclei are characteristically wavy and pointed, no pleomorphism or mitotic activity
 More definite palisading and Verocay bodies typical of Antoni A tissue of a neurilemoma are usually not seen
 Special stains reveal presence of numerous axons w/in tumor and cells show positive immunohistochemical reaction for
S-100 protein
 Solitary circumscribe neuroma may be better description for this lesion
 Conservative local surgical excision
 Recurrence is rare
 Specific recognition of lesion is important because it is not associated with neurofibromatosis or multiple endocrine
neoplasia (MEN) type 2B.
What is this?
Neurilemoma (Schwannoma)
 Benign tumor of Schwann cell origin – uncommon in oral cavity
 Presents as solitary, slow-growing encapsulated nodular mass, usually painless
Pain or tenderness may occur in some instances
 Tongue most common oral location – can occur anywhere in oral cavity
 Rare intrabony tumors of jaws have been reported – usually in mandible
 Occasionally seen in patients w/ neurofibromatosis
 Encapsulated tumor that demonstrates two microscopic patterns in varying amounts:
Antoni A: characterized by streaming fascicles of spindle-shaped Schwann cells
o Often form palisaded arrangement around central acellular, eosinophilic area known as
Verocay bodies – consist of reduplicated basement membrane and cytoplasmic
processes
Antoni B:
o Less cellular and less organized
o Spindle cells are randomly arranged w/in a loose, myxomatous, watery stroma
 Tumor cells will show a diffuse, positive immunohistochemical reaction for S-100 protein
 Degenerative changes can be seen in some older tumors, tumors are still benign
 Surgical removal, recurrence rare
What is this?
Neurofibroma
o Etiology:
 A relatively common, benign tumor of nerve origin that contains:
Schwann cells, Perineural cells, neuritis
 May occur as a solitary neoplasm or in associate w/ neurofibromatosis
 Solitary oral neurofibroma is typically a nodular mass that is: painless, slow-
growing, soft nodular mass, usually non-ulcerated, similar to adjacent mucosa
 Unlike neurilemoma – neurofibroma is usually nonencapsulated histologically
 Oral tumors may occur at almost any site – rarely even in bone
 Solitary neurofibroma – local surgical excision
 Further clinical evaluation to rule out neurofibromatosis should be performed
What is this?
Neurofibromatosis
Etiology:  Actual intraoral neurofibromas are seen in only about 25% of
o Refers to a group of genetic disorders that are characterized by affected patients
Enlargement of fungiform papillae of tongue, mandibular canal,
development of multiple neural tumors – especially neurofibromas occlusal plane distortion, impacted teeth
o At least 8 forms of neurofibromatosis have been described – most o Diagnostic criteria for Neurofibromatosis Type I:
common form of the disease is neurofibromatosis type I (von  Criteria met if patient has two or more of following features:
Recklinghausen disease of skin) – 85-90% of cases 6+ café au lait macules >5mm in prepubertal persons and over
o Type I neurofibromatosis: 15mm in greatest diameter in postpubertal persons
Two or more neurofibromas of any type or one plexiform
 Inherited as an autosomal-dominant trait neurofibroma
 One of the most common hereditary diseases – 1/3000 births Freckling of axillary or inguinal regions
 About half of all affected individuals have no family history of Optic glioma
disorder – represent new mutations Two or more lisch nodules
o Clinical and radiographic features: Distinctive osseous lesion
 “Café au lait” spots: First degree relative w/ neurofibromatosis type I
Early clinical manifestations o Histopathologic features:
Flat, yellow-brown skin lesions, usually evident w/in first few years  Solitary neurofibroma is well circumscribed
of life  Tumor composed of interlacing bundles of spindle-shaped cells,
Begin as a freckle-like areas, gradually gets larger often exhibit wavy nuclei
Unexposed areas of body  Mast cells tend to be numerous
Present in more than 90% of patients with neurofibromatosis
o 6+ spots greater than 1.5 cm in diameter is
 Immunohistochemically, turmor cells show a scattered, positive
considered pathognomonic reaction for S-100 protein
 Crowe’s sign: site is the axilla, multiple spots may result in axillary o Treatment and prognosis: no effective treatment, surgery for large or
freckling painful tumors
 “Lisch nodules”:  Malignant transformation in 5% of cases, neurofibromasarcoma,
Presence of small pigmented spots on iris malignant schwannoma
 Usually begin to appear during childhood/adolescence after café au Most common on trunk and extremities, head and neck
lait spots involvement occasionally
 Usually slow growing, may occur in almost any location Prognosis for malignant peripheral nerve sheath tumors
 Some exhibit few, some exhibit hundreds associated w/ neurofibromatosis is poor – 15% 5-year survival rate
 Tumors sensitive to hormonal influence – often accelerated growth
during pubery/pregnancy
 May present as discrete soft nodules, larger-diffuse pendulous
masses
 Unilateral involvement rare
 Skeletal abnormalities are not uncommon
 Other neural tumors, including pheochromocytomas may be seen
 Mental deficiency seen in small percentage
 Oral lesions may be found in 72-92% of cases
What is this?
Multiple Endocrine neoplasia Type 2B
Etiology:
o Multiple endocrine neoplasia (MEN) syndromes are a group of rare conditions characterized by tumors or hyperplasias of neuroendocrine tissues
 MEN type 1, MEN type 2A (Sipple syndrome), MEN 2B
 MEN type 1: characterized by benign tumors of pancreatic islets, adrenal cortex, parathyroid glands, pituitary gland
 MEN type 2A (Sipple syndrome): characterized by development of adrenal pheochromocytomas, medullary thyroid carcinoma
 MEN 2B: in addition to pheochromocytomas and medullary thyroid carcinoma patients have mucosal neuromas that especially involve oral mucous membranes
o MEN 2B is inherited as autosomal dominant – 50% of cases are thought to represent spontaneous mutations
o Condition is caused by a mutation of RET protooncogene on chromosome 10 – detected in 95% of affected individuals
Clinical features:
o Marfanoid body build – think elongated limbs, muscle wasting
o Face is narrow
o Lips characteristically thick, protuberant due to diffuse proliferation of nerve bundles
o Upper eyelid sometimes is everted because of tarsal plate thickening
o Oral mucosal neuromas are usually the first sign of condition
 Soft painless papules or nodules on lips and anterior tongue
 Bilateral neuromas of commissural mucosa are highly characteristic
o Pheochromocytomas of adrenal glands develop in at least 50% of all patients
 More prevalent w/ age
 Secrete catecholamines  profuse sweating, intractable diarrhea, headaches, flushing, severe hypertension
o Most significant aspect of this condition is the development of medullary carcinoma of the thyroid gland
 >90% of cases
 Aggressive tumor arises from parafollicular cells (C cells ) – responsible for calcitonin production
 Most often diagnosed in patients 18-25, marked propensity for metastasis
 Average age at death 21 years
Laboratory values:
o If medullary carcinoma of thyroid gland present – serum or urinary levels of calcitonin are elevated
 Increase in calcitonin levels may herald the onset of tumor
o Pheochromocytomas may result in increased:
 Increased levels of urinary vanillylmandelic acid (VMA)
 Increased epinephrine to norepinephrine ratios
o Mucosal neuromas are characterized by marked hyperplasia of nerve bundles in otherwise normal or loose CT background
o Prominent thickening of perineurium is typically seen
o Prognosis centers on early recognition of oral features
o Prophylactic removal of thyroid gland at early age advocated
o Once developed, tumor often exhibits aggressive behavior with poor prognosis
o Observe for pheochromocytomas – may result in life-threatening hypertensive crisis
What is this?
Melanotic neuroectodermal tumor of
infancy
o Rare neoplasm – primarily occurs in anterior maxilla
o Convincing evidence, including elevated urinary vanillylmandelic acid levels in many patients
 Indicates tumor is of neural crest origin
o Most cases occurred in infants <9 months
o Lesions present as a mass of the anterior maxillary alveolar ridge that is rapidly growing and nonulcerated
o Tumor frequently pigmented because of presence of melanin-containing cells
o Underlying bone destruction – displacement of primary teeth
o Lesion is usually benign despite rapid growth and local destruction
Laboratory values:
o High urinary levels of vanillylmandelic acid (VMA) often are found in patients w/ melantoic neuroectodermal tumor of infancy
o Neural crest origin support
o Tumor consists of biphasic population of cells that form nests, tubules or alveolar structures w/ in a dense, collagenous stroma
 Alveolar and tubular structures are lined by cuboidal epitheliod cells that demonstrate
Vesicular nuclei, granules of dark-brown melanin pigment
 Second cell type is neuroblastic in appearance
Small, round cells w/ hyperchromatic nuclei and little cytoplasm
Cells grow in loose nests and frequently surrounded by larger pigment-producing cells
Mitotic figures are rare
o Conservative surgical excision
o Recurrence 10-15% of cases
o Some have acted in malignant fashion  metastasis and death
What is this?
Granular cell tumor
Clinical features:
o Uncommon neoplasm
o Shows oral cavity predilection – especially tongue
o Formerly called granular cell myoblastoma because of suspected skeletal muscle origin – most investigators
now believe it arises from either the Schwann cell or undifferentiated mesenchymal cell.
o Slow-growing, nonulcerated nodular mass, usually pink, sometimes yellow
o Most common in young and middle-aged adults
o F 2x > M
o Multiple lesions occasionally occur
o Large, polygonal cells w/ abundant pale eosinophilic, granular cytoplasm and small, vesicular nuclei
o Cells arranged in sheets, may be found in cords and nests
o Syncytial appearance – borders often indistinct
o Not encapsulated – sometimes appears to infiltrate adjacent connective tissues
o Immunohistochemical analysis reveals positivity for S-100 protein w/in cells
 Supportive, but not diagnostic, of neural origins
o Local surgical excision, recurrence uncommon
What is this?
Congenital epulis (of newborn)
Clinical features:
o Rare, benign tumor of uncertain histiogenesis
o Occurs on alveolar ridge of newborn infants
o Bears some histopathologic resemblance to granular cell tumor – seems to be separate entity
o ~90% of reported cases – in females
o Twice as common on maxillary ridge
o More common on anterior alveolar ridge – pedunculated smooth-surfaced mass
o Multiple tumors develop in 10% of cases
o Ranges in size, may interfere w/ feeding or breathing
o Large, rounded cells w/ abundant granular, eosinophilic cytoplasm and round to oval, lightly
basophilic nuclei
o In older tumors:
 Cells may become elongated, separated by fibrous CT
 In contrast to granular cell tumor
Overlying epithelium never shows pseudoepitheliomatous hyperplasia (PEH)
Typically demonstrates atrophy of rete ridges
Immunohistochemical analysis – tumor cells negative for S-100 proteins
o Surgical excision, spontaneous regression has been reported in a few cases
What is this?
Hemangioma
o Hemangioma:  Blue color, easily compressible, often grows proportionately w/ the patient –
 A variety of developmental vascular anomalies may swell when dependent or w/ increased venous pressure
Currently considered benign tumors of infancy  Secondary thrombosis and phlebolith formation can occur
Rapid growth phase w/ endothelial cell proliferation, followed by gradual Clinical features:
involution
Most cannot be recognized at birth – arise during first 8 weeks of life o A reltively common benign tumor of blood vessels
o Vascular malformations: o Some cases congenital – present on skin, birthmark
 Structural anomalies of blood vessels w/o endothelial proliferation o Others – develop during childhood, lateri n life
 Present at birth and persist throughout life o Hemangioma, especially congenital variety – considered a hamartoma rather
 Categorized according to: than a true neoplasm
Type of vessel involved: capillary, venous, arterial o Head and neck – most common site for hemangiomas - >50% of cases are seen
Hemodynamic features: low flow or high flow
there
o Arteriovenous malformations:
 High-flow lesions: result from persistent direct arterial and venous o F>M
communication o Oral tumors can occur at any site, flat or raised, blue-purple
 Present from birth: may not become noticeable until later in childhood or o Range in size from small to massive
adulthood o Often asymptomatic – may exhibit hemorrhage when traumatized
 Because of fast vascular flow through these lesions: a palpable thrill or bruit – Histopathologic features:
often noticeable o Early: numerous plump endothelial cells, often-indistinct vascular lumina
 Overlying skin typically feels warmer to touch  Juvenile or cellular hemangiomas
 Presenting symptoms may include – pain bleeding, skin ulceration
o Lesion matures: endothelial cells become flattened, small, capillary-sized
o Intrabony vascular malformations:
vascular spaces become more evident
 Intrabony “hemangiomas” also may occur – represent venous or arteriovenous
malformations o As hemangioma undergoes involution – vascular spaces become more dilated,
 Affect jaws in patients between 10-20 y/o widely spaced
 F>>M o Vascular malformations do not show active endothelial cell proliferation and the
 2x more common in mandible channels resemble vessel of origin
 May be completely asymptomatic – some associated with pain/swelling o Capillary malformation may be similar to capillary stage of hemangioma
 Mobility of teeth or bleeding gums from the gingival sulcus may occur o Venous malformation may show dilated vessels that resemble the cavernous
 A bruit or pulsation may be apparent on auscultation and palpation stage of hemangioma
 Radiographic appearance variable
Most commonly a multilocular radiolucent defect
o Many vascular malformations are incorrectly categorized as hemangiomas
Small – honecombe or large – soap bubble Treatment and prognosis:
 Large malformations may cause cortical expansion – occasionally a “sunburst” o Most hemangiomas undergo involusion – management consists of “watchful
radiographic pattern is produced. neglect”
 Angiography – helpful in demonstrating vascular nature of lesion  Educate parents, surgical resection rarely warranted during infancy
o Port wine stains:  For problematic or life-threatening hemangiomas:
 Relatively common capillary malformations Pharmacologic therapy, systemic corticosteroids, interferon-α-2a
 Occur in 0.3%-1% of newborns o Treatment of arteriovenous malformations is more challenging – depends on
 Most common on the face – along distribution of trigeminal nerve size of lesion and location to vital structures
 In Sturge-Weber angiomatosis – associated with intracranial lesions o Severe bleeding for vascular malformation of jaws during surgical manipulation
 Pink or purple macular lesions
o Needle aspiration of an undiagnosed intrabony lesion before biopsy – a wise
 Grow commensurately w/ the patient – patient gets older, lesion darkens
precaution to rule out the possibility of a vascular malformation
o Low-flow venous malformations:
 A wide spectrum of lesions – small isolated ectasias, complex growths that o Sever often fatal hemorrhages have occurred after incisional biopsy or
involve multiple tissues and organs extraction of teeth in area of such lesions
 Present at birth – may not always be immediately apparent.
What is this?
Surge-Weber Angiomatosis
o Congenital anomaly characterized by hemangiomatosis involving the facial skin, oral mucosa, eyes, and meninges
o Typically unilateral – skin and mucosal lesions following distribution of one or more divisions of the trigeminal nerve – occasionally – patient will have
bilateral involvement
o Cutaneous lesion – usually flat and pink to purple-red
o Often referred to as “port-wine nevus” or “nevus flammeus”
o ~10% of patients w/ facial port-wine nevi have Sturge-Weber angiomatosis:
 Unless the lesion involves the distribution of the ophthalmic branch of the trigeminal nerve – the patient is typically not at risk for the full condition
 These angiomatous skin lesions can be treated using flashlamp-pulsed dye lasers
o The meningeal angiomatosis is most common in the temporal and occipital regions
o May be associated w/ cerebral cortical atrophy, seizures, mental retardation, contralateral hemiplegia
o Gyriform intracranial calcifications resembling a tram-line or railroad tracks may be seen radiographically
o Neurosurgical removal of angiomatous meningeal lesions or hemispherectomy may be necessary in some cases
o Ocular lesions – often associated w/ development of glaucoma
o Oral involvement similar to that of cutaneous lesion, presenting as a flat, bluish-red hypervascularity of ipsilateral mucosa
o Gingiva may exhibit slight vascular hyperplasia or massive hemangiomas or pyogenic granuloma-like enlargement
 Gingival hyperplasia may be a result of increased vascular component, phenytoin therapy used to control epileptic seizures, or both
o Port wine nevus: characterized by excessive numbers of dilated blood vessels in the middle and deep dermis
o Intraoral lesions show a similar vascular dilatation
o Proliferative gingival lesions may resemble pyogenic granuloma
o Depends on nature and severity of clinical features
o Faical port wine nevi can be improved with lasers
o Neurosurgical removal of angiomatous meningeal lesions may be necessary in some cases
o Port wine nevi that affect the gingiva can make flossing and dental prophylaxis difficult
o Great care must be taken when performing surgical procedures in affected areas of the mouth – severe hemorrhage may be encountered
What is this?
Nasopharyngeal angiofibroma
o A rare vascular and fibrous tumor like lesion that occurs only in the nasopharynx
o Microscopically benign, but frequently exhibits locally destructive and aggressive behavior
o May represent a vascular malformation rather than a true neoplasm
o Occurs almost exclusively in males – exceedingly rare in females
o Predilection for adolescents b/w 10-17 y/o, often called juvenile nasopharyngeal angiofibroma
o Because of its almost exclusive occurrence in adolescent boys, hormonal influence seem likely
 However, no endocrine abnormalities have been detected
o Nasal obstruction and epistaxis are common early symptoms
o Lesion presumed to arise in the pterygopalatine fossa, expands medially into nasal cavity via sphenopalatine foramen
o Anterior bowing of posterior wall of maxillary sinus is characteristic feature
o Consists of dense fibrous CT that contains numerous dilated, thin-walled blood vessels of variable size
o Typically, the vascular component is more prominent at the periphery of the tumer
o The primary treatment – surgical excision
o Depending on extent of lesions – may be accomplished via a transpalatal approach, Le Fort 1 approach, medial maxillectomy,
midfacial degloving procedure
o Preoperative embolization of tumor is helpful in controlling blood loss
o Radiation therapy – usually reserved for recurrent lesions and extensive tumors w/ unusual vascular supplies or intracranial
extension
o Recurrence rate 20-40%
o Malignant transformation into fibrosarcoma – rarely been reported, probably associated w/ prior radiation therapy
What is this?
Lymphangioma
Clinical features:
o Benign tumor of lymphatic vessels
o Majority of cases – congenital or arise during early childhood – suggests that the lesion represents a hamartoma rather than a
true neoplasm
o Like the hemangioma – H&N area is most common location of lymphangioma
o Anterior two-thirds of tongue – most common oral site, often resulting in macroglossia
o Superficial tumors – usually exhibit a pebbly surface resembling a cluster of amber vesicles
o Deeper tumors – present as soft, ill-defined mass
o Trauma or infection may produce episodes of rapid, massive engorgement
o Composed of lymphatic vessels that may show marked dilation (cavernous lymphangioma), macroscopic cyst like structures
(cystic hygroma)
o Endothelium lining typically thin
o Some channels also may contain red blood cells, which creates uncertainty as to whether they are lymphatic or blood vessels
o In intraoral tumors:
 Lymphatic vessels are located just beneath the epithelial surface
 Often replace the CT papillae – superficial location results in translucent, vesicle like appearance
o Most often consists of surgical excision
o Common recurrence due to diffuse infiltrative nature of tumor
o If total removal is not possible in large tumor surgical debulking may be performed
o Lymphangiomas do not respond to sclerosing agents as hemangiomas.
 Intralesional injections of OK-432 success has been reported
What is this?
Rhabdomyoma
Clinical features:
o Benign tumors of skeletal muscle origin – extremely rare
o Excluding examples of cardiac rhabdomyoma – these tumors show a striking predilection for the head and neck region
o Extracardiac rhabdomyomas – divided into adult and fetal varieties:
 Adult rhabdomyomas:
Occur primarily in middle-aged and older patients
~70% of cases seen in men
Most common in pharynx, larynx, and oral cavity
May grow to considerable size before discovery
Multiple tumors not unusual
 Fetal rhabdomyomas:
Usually occur in young children
Most common on face, preauricular region
o Adult:
 Composed of well-circumscribed lobules of large, polygonal cells, which exhibit abundant granular, eosinophilic cytoplasm
 Cells often demonstrate peripheral vacuolization – “spider web” appearance
 Focal cells w/ cross striations can be identified
o Fetal:
 Has less mature appearance
 Consists of haphazard arrangement of spindle-shaped muscle cells that sometimes are found in myxoid stroma
 Some tumors show considerable cellularity and mild pleomorphism
Makes them easily mistaken for rhabdomyosarcomas
o Both treated with local surgical excision
o Recurrence uncommon
What is this?
Osseous and Cartilaginous Choristoma
Clinical features:
o Tumor-like mass of histologically normal tissue occurring in an abnormal
location
o Choristomas are rare in the oral cavity – most common locations is posterior
dorsum of tongue in region of foramen cecum and circumvallate papillae
o Most common types are: osseous, cartilaginous, mixed osteocartilaginous
choristomas
o Clinically a sessile or pedunculated mass that may produce dysphagia or
gagging
o Well-circumscribed mass of dense lamellar bone or mature cartilage
o Surrounded by dense fibrous CT
o Combination of bone and cartilage sometimes
o Bone has well-developed haversian canal system
o Local surgical excision, recurrence not reported
Soft tissue sarcomas in the head and
neck
• See Printout notes
What is this?
Metastases to oral soft tissues
Metastatic tumors to the oral cavity are uncommon
Represent 1% of oral malignancies
o Such metastases can occur to bone or to oral soft tisseus
Clinical features:
o Most common site for oral soft tissue metastases – gingiva – accounts for slightly >50% of cases
o 2nd most common site for oral soft tissue metastases – tongue
o Adjacent teeth may become loosened by an underlying destruction of alveolar bone
o Presence of teeth may play an important role in preference of metastases for the gingiva
o Oral soft tissue metastases more common in males – middle-aged, older adults
o Lung cancer – responsible for >33% of oral soft tissue metastases in men
 Followed by renal carcinoma and melanoma
o Metastases from prostate tumors have an affinity for bone and rarely occur in soft tissues – when appear
in maxilla or mandible – often opacities rather than radiolucencies
o For women – breast cancer accounts for 25% of cases
o In some cases oral lesions is the first sign of malignant disease
o Microscopic appearance of metastatic neoplasm should resemble the tumor of origin
 Most cases represent carcinomas
o Palliative treatment – prognosis poor

Oral Pathology I Review

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Oral Pathology I

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