1Odontogenic Tumors and Cysts Dens 3702, Spring Semester Basic objectives for individual lesions: 1.

Identify the cause (etiology; pathogenesis), cell or tissue of origin, and frequency (prevalence rate) 2. List the predilection GAL (Gender predilection, Age predilection, Location predilection) 3. Describe the typical clinical appearance, unusual clinical variants, and look-alike lesions 4. Describe the basic microscopic features 5. Describe the usual biologic behavior (pathophysiology) and prognosis without treatment, and describe the typical treatment(s) and the prognosis with such treatment(s) 6. Describe unique variants, special features, or unique problems Ameloblastoma: 1. Etiology: Benign neoplasm of epithelial rests of dental lamina, basal cells of oral mucosa (alveolar only), or cyst epithelium. The most common of the aggressive odontogenic tumors. 2. GAL: None; any age, but usually 30-50 years of age; posterior mandible. 3. Clinical: Asymptomatic, multilocular (soap bubble), well demarcated radiolucency, may be unilocular. Expands and thins cortex. May extend far into ramus, or fill maxillary sinus. Often resorbs adjacent roots; may push roots and may be associated with crown of unerupted tooth. 4. Micro: Islands of odontogenic epithelium with peripheral palisading and hyperchromatism (peripheral cells look like preameloblasts). Islands are in a mature fibrous stroma and often show cystic degeneration, or centers with stellate reticulum, squamoid epithelium (acanthomatous type) or granular cells (granular cell type). Sometimes resemble basal cell carcinoma (basal cell type). Epithelial islands and sheets may have several patterns: follicular type (most common), with epithelium resembling enamel organ epithelium, and plexiform type, with intertwining, often thin strands of lesional epithelial cells. 5. Treat: Enucleation has high recurrence rate (>50%), so en bloc resection is often performed (<15% recurrence rate). Main problem: local destruction, may invade through base of skull or wrap around neck structures. Rarely: piece breaks off during surgery, is aspirated, and ameloblastoma grows in bronchial tree. The more cystic the original lesion, the better the prognosis. 6. Special variants: Unicystic ameloblastoma: 15% of all ameloblastomas; clinically resembles dentigerous cyst. In younger persons (average age = 23 years); much less aggressive; unilocular radiolucency only. Several microscopic types Peripheral ameloblastoma (Extraosseous ameloblastoma) : Same histology, but on attached gingiva. Minimal growth potential, but may cup out underlying cortex. Desmoplastic ameloblastoma: Dense fibrous stroma with squished epithelial islands, shows moth-eaten radiolucency, not multilocular. Ameloblastic carcinoma: Dysplastic ameloblastoma cells, often very aggressive, metastasizes Malignant ameloblastoma: routine ameloblastoma histology, but metastasizes

 Ameloblastoma implanted in lungs: tumor fragments get inhaled during surgery, with ameloblastoma growing in bronchial tree. Ameloblastic fibroma (juvenile ameloblastoma): 1. Etiology: Benign neoplasm of both epithelial and mesenchymal origin. Uncommon. 2. GAL: None; first two decades of life; posterior mandible. 3. Clinical: Asymptomatic, usually multilocular, well-demarcated radiolucency, often with thin sclerotic rimming and without calcifications centrally. Usually associated with crown of unerupted tooth. Expands cortex and moves teeth. 4. Micro: Double-layered strands and ameloblastoma-like islands of cuboidal odontogenic epithelium in a background of primitive mesenchymal tissues. Mesenchymal cells are plump oval or stellate cells. Islands may show peripheral palisading of epithelial cells at margins. Large islands have stellate reticulum-like appearance centrally. 5. Treat: Conservative surgical removal or curettage, but 40% risk of recurrence. May become very large. 6. Special variants: Ameloblastic fibrosarcoma: stroma shows evidence of malignancy; epithelial islands are unchanged. Ameloblastic fibro-odontoma: also has enamel and dentin features. May be early stage in odontoma; may become very large. Radiographically, has globular opacities centrally located, perhaps with tooth-like shapes. Adenomatoid odontogenic tumor (AOT, adenoameloblastoma): 1. Etiology: benign neoplasm of reduced enamel epithelium; some feel it is a hamartoma. 2. GAL: Female; second decade; anterior maxilla. Represents 5% of all odontogenic tumors. 3. Clinical: Asymptomatic, well-demarcated, unilocular radiolucency, often with thin sclerotic rimming. Eventually globular radiopacities develop, or small snowflake opacities. Around crown of impacted tooth; usually interferes with eruption. 1-2 cm. in size, may expand cortex. 4. Micro: Spindle-shaped epithelial cells form sheets and strands, with whorled masses and rosette structures. Ductal structures show peripheral palisading or polarization of nuclei toward the basement membrane. Amyloid may be produced. Small dystrophic calcifications; thin fibrous capsule. 5. Treat: Surgical curettage; almost no recurrence risk. 6. Special variant: Peripheral AOT: very mild behavior; no recurrence. Calcifying Epithelial Odontogenic Tumor (Pindborg tumor; CEOT): 1. Etiology: Benign but aggressive neoplasm of tooth bud cells, probably stellate reticulum 2. GAL: None; 30-50 years; posterior mandible. Represents less than 1% of all odontogenic tumors. 3. Clinical: Asymptomatic, well-demarcated unilocular or multilocular radiolucency, often with globular calcified structures. Frequently associated with crown of impacted tooth. Expands cortex. 4. Micro: Islands and clusters and strands of polyhedral epithelial cells, often with intercellular bridges, in a background fibrous stroma. Often large and dysplastic, but not true dysplasia. No mitotic activity. Globular calcifications with Liesegang rings (onion skinning) are seen, as are masses of hyalinized material (amyloid). Need congo red staining or thioflavin T immunostaining to prove amyloid. 5. Treat: Less aggressive than ameloblastoma. Conservative local resection with narrow rim of

surrounding normal bone; 15% recurrence rate. 6. Special variant: Peripheral Pindborg tumor: Develops in attached gingiva; low biological behavior, may erode underlying bone; anterior region. Odontoma: 1. Etiology: Developmental hamartomas. 2. GAL: None; first two decades of life; compound variant = anterior maxilla, complex variant = molar regions (both jaws). Most common odontogenic tumor, prevalence exceeds all others combined. 3. Clinical: Asymptomatic, well-demarcated, unilocular radiolucency, usually with thin sclerotic rimming. Central opacities are either amorphous, globular or tooth-like. Usually associated with crown of unerupted tooth; often prevent eruption. 4. Micro: Mature fibrous stoma containing irregular masses of dentin with areas of enamel matrix along some edges, and occasionally with cementum and pulp tissue. Masses may be tooth-like. Encapsulated. 5. Treat: Enucleation or curettage; almost no recurrences. 6. Special subtypes: Complex odontoma: Unorganized calcified tooth-related tissues Compound odontoma: Tooth-like structures are present Combined odontoma: Mixture of complex and compound Cystic odontoma: Develops in wall of dentigerous cyst Odontoameloblastoma: Collision of two tumors, ameloblastoma and odontoma. Behaves like an ameloblastoma. Odontogenic myxoma: 1. Etiology: Benign neoplasm of odontogenic ectomesenchyme. Rare 2. GAL: None; second - fourth decades; found exclusively in the jaws, not in other bones. 3. Clinical: Asymptomatic, well-demarcated, multilocular radiolucency. Expands and thins cortex, can push teeth or resorb roots. May be unilocular; often associated with crown of impacted tooth. 4. Micro: Background stroma of rather acellular fibromyxoid material with few stellate or bipolar mesenchymal cells; similar to primitive pulp tissue. Not encapsulated. 5. Treat: Small lesions: curettage. Larger lesions: resect with margin of normal bone. 25% recurrence rate, but usually no recurrence after second surgical removal. 6. Special variants: Odontogenic fibromyxoma: in teenagers, around crown of impacted tooth, much less aggressive than routine myxoma. Fibrous stroma is more dense. Odontogenic fibromyxosarcoma: stroma is malignant. Odontogenic fibroma: 1. Etiology: Benign neoplasm of odontogenic mesenchymal tissues. 2. GAL: Females; second - fourth decades of life; anterior maxilla and posterior mandible. Rare tumor. 3. Clinical: Asymptomatic, well-demarcated unilocular radiolucency, often surrounding crown of impacted tooth. May resorb roots and expand cortex. May move teeth. Larger lesions are often multilocular. 4. Micro: Background stroma of mature fibrous tissue with stellate and spindled fibroblasts, often

with whorled pattern. Focal areas may show odontogenic epithelial rests and dystrophic calcifications or globules of cementum-like or dentin-like calcified material. Stroma may be quite loose, like odontogenic myxoma. Encapsulated. Caution: must distinguish from hyperplastic dental follicle. 5. Treat: Enucleation or curettage; recurrence is rare. 6. Special variants: Simple odontogenic fibroma: almost all fibrous, with only small epithelial islands and dystrophic calcifications WHO type of odontogenic fibroma: many epithelial islands and calcified structures Peripheral odontogenic fibroma: innocuous gingiva mass. Cementoblastoma (Benign cementoblastoma): 1. Etiology: Benign neoplasm of cementum (attached to tooth); the cementum counterpart to the osteoblastoma of bone. 2. GAL: Female; second-fourth decades; mandibular molar 3. Clinical: Well-demarcated rounded or irregular radiopaque enlargement of root tip, with thin capsule around it and continuous with periodontal ligament. May have areas of mixed radiolucency-radiopacity. May be tender or painful. Tooth remains viable, even as tumor destroys the root. 4. Micro: Globular cementoid, sometimes osseous calcified masses extending from cementum surface of root tip. Small spaces are filled with fibrous tissue, and cementoblasts are commonly present. Encapsulated. 5. Treat: Conservative surgical removal of affected tooth; recurrences are rare. Dentigerous cyst: 1. Etiology: Cystic degeneration from separation of reduced enamel epithelium of follicle from crown. Usually developmental, may originate from inflammation 2. GAL: None; second and third decades; third molar areas, especially mandible. 3. Clinical: Well-demarcated radiolucency, usually unilocular, often with thin sclerotic rimming, around the crown of an unerupted tooth. Lesional periphery is at least 1.5 mm. from the surface of the crown (arbitrary number). Tooth can be pushed great distance from origin; occasionally will resorb roots of adjacent teeth. Often prevents eruption. Three types by location: central, lateral, circumferential. 4. Micro: Atrophic, sometimes hyperplastic stratified squamous epithelial lining (perhaps with parakeratin surface layer) overlying moderately dense fibrous or fibromyxomatous stroma. Stroma may be inflamed, ulceration of epithelium may lead to cholesterol deposits in ulcer bed, with proliferative granulation tissue and foreign body giant cells (cholesterol granuloma). Reduced enamel epithelium is thought by some to be part of a normal follicle, not a cyst. Waldron type of dentigerous cyst, however, refers to a radiographically obvious cyst with minimal or no squamous epithelium lining. Lining may show respiratory or mucus metaplasia. Some linings have thick orthokeratin (orthokeratinized odontogenic cyst). 5. Treat: Enucleation, perhaps with extraction or orthodontic guidance of involved tooth; large lesions may be marsupialized. 6. Special cases: Eruption cyst (Eruption hematoma): Classical dentigerous cyst but with overlying cortex completely missing, allowing a blue or bluish-red color to be seen clinically. Only fibrous stroma separates cyst epithelium from surface epithelium. No treatment needed unless infected, in which case marsupialization is done. Tooth erupts normally. May erupt into

pericoronitis, in which case is sometimes called paradental cyst. Some dentigerous cysts are odontogenic keratocysts. 7. Special problem: Carcinoma arising from odontogenic cyst: A very small proportion of odontogenic cysts, usually dentigerous cysts, have transformation of epithelial lining into malignancy. Usually this produces a moth-eaten lesional periphery in the area of cancer; may be painful. Odontogenic keratocyst: 1. Etiology: Developmental cystic degeneration of odontogenic epithelial rests, sometimes triggered by inflammation. 2. GAL: None; second through fourth decades; posterior mandible, including ramus. 3. Clinical: Asymptomatic, well-demarcated radiolucency, multilocular or unilocular, often with thin sclerotic rim. Seldom expands cortex facially, but may do so in a superior-inferior direction. May be very large. May push teeth great distances, or resorb adjacent roots. Several types according to radiographic presentation: primordial cyst type (replaces undeveloped tooth bud; not all primordial cysts are keratocysts); dentigerous cyst type (around crown of unerupted tooth; most common type), lateral periodontal cyst type (adjacent to or between roots, especially mandibular premolars; rare), periapical cyst type (appears to be much less aggressive than other types; rare). 4. Micro: Unique epithelium: uniform 4-7 cell thickness, loss of rete ridges, thin corrugated layer of surface parakeratin, polarized and hyperchromatic basal cell nuclei, pulling away from basement membrane. May be many islands of benign odontogenic epithelium in fibrous or fibromyxomatous stroma, may be many daughter cysts. 5. Treat: Enucleation and curettage = up to 62% recurrence (usually within 5 years); peripheral ostectomy and/or chemical cauterization of bony cavity (Carnoys solution). Large lesions may be marsupialized before removal. Rarely: malignant transformation of epithelium. 6. Special disease association: Nevoid basal cell carcinoma syndrome (Gorlin syndrome): Mutation of PATCH (PTCH, patched) tumor suppressor gene at chromosome 9q22.3-q31 Multiple keratocysts, often dentigerous cyst type, may be huge Multiple basal cell carcinomas and nevi Palmar/plantar pits Bifid ribs, splayed ribs, fused ribs, missing ribs Calcified falx cerebri Spina bifida occulta, cervical or thoracic vertebrae 7. Special associated cyst: Orthokeratinizing odontogenic cyst: Old name: orthokeratinizing odontogenic keratocyst May be histologically similar, but lining is covered by orthokeratin, not parakeratin May have no microscopical similarity to odontogenic keratocyst, but produces great excess of orthokeratin Prognosis is same a dentigerous cyst; low recurrence rate Gingival cyst of newborn (wrongly called Epstein pearls, Bohn nodules): 1. Etiology: Developmental cyst formation from remnants of dental lamina. 2. GAL: none; infancy/congenital; alveolus, posterior hard palate and soft palate. Prevalence: may be seen in up to 50% of newborn infants. 3. Clinical: Small, superficial whitish blebs of alveolar mucosa. May be single or may have dozens. Similar papules of posterior hard and soft palate midline are called Epstein pearls or Bohn

nodules. 4. Micro: Cyst lining of stratified squamous epithelium, with lumen filled with sloughed keratin. 5. Treat: None required, cysts rupture spontaneously within days (may last until teeth start erupting); do not interfere with eruption. Gingival cyst of adult: 1. Etiology: Degenerative cyst development from long-standing embryonic rests of squamous epithelial cells in gingival stroma (rests of Serres) 2. GAL: none; fifth-sixth decades; attached gingiva of facial surface, mandibular cuspid/premolar area (70% of cases) 3. Clinical: Painless, dome-shaped (sessile) fluctuant mass <.5 cm; may have blue color. May show saucerize underlying cortex, to create well-demarcated radiolucency. 4. Micro: Stratified squamous epithelial cyst lining over dense fibrous stroma, sometimes with focal areas of epithelial thickening protruding into lumen. Lumen filled with fluid, perhaps some keratin. 5. Treat: Enucleation; no recurrence. Lateral periodontal cyst, developmental type: 1. Etiology: Developmental cystic degeneration of odontogenic epithelial rests of dental lamina. 2. GAL: None; fifth - seventh decades; mandibular premolar area (80% of all cases). Represents <2% of all odontogenic cysts. 3. Clinical: Asymptomatic, well-demarcated radiolucency with midpoint halfway between adjacent premolars. May push roots out of way; teeth are viable. Usually < 5 mm. diameter. 4. Micro: Thin stratified squamous epithelium with focal nodular thickening extending into lumen or into underlying fibrous stroma. 5. Treat: Enucleation; small recurrence rate. 6. Special type: Botryoid odontogenic cyst: multilocular radiographic appearance, like grape cluster. Higher recurrence rate; may become larger than routine lateral periodontal cysts. 7, Caution! Check vitality of adjacent teeth. Laterally located radicular cysts can look like this. Buccal bifurcation cyst: 1. Etiology: Inflammatory stimulation of epithelial rests in the furcation region of mandibular molar 2. GAL: None, middle-aged; first molar area. 3. Clinical: Asymptomatic or tender, poorly demarcated furcation radiolucency, without being about to probe a periodontal pocket in the region; tooth is viable. Sessile, moderately firm gingival mass facing toward the facial; < 8 mm. diameter. 4. Micro: Degenerated, often hyperplastic stratified squamous epithelium over fibrous stroma with numerous chronic inflammatory cells; PMNs in and beneath epithelium. 5. Treat: Enucleation, but may have to extract tooth. 6. Caution! Check vitality of the tooth, since radicular cyst can form beneath pulp floor. Also, probe for periodontal pocket. Calcifying odontogenic cyst (Gorlin cyst; calcifying ghost cell odontogenic cyst): 1. Etiology: Cross between developmental cyst and benign neoplasm 2. GAL: None; anterior maxilla and mandible (65% of cases); 3. Clinical: Unilocular, well-demarcated radiolucency, often with thin sclerotic rimming. May be multilocular. Eventually shows irregular radiopacities or tooth-like structures centrally. Around

crown of unerupted tooth in 1/3 of cases. Usually 2-4 cm., may be much larger. 4. Micro: Stratified squamous epithelium lining with keratin production and eosinophilic ghost cells (epithelial cells with shadow of nucleus), with dystrophic calcification. Basal cells might be cuboidal and look like preameloblasts. Epithelium may greatly proliferate into lumen or into underlying fibrous stroma. 5. Treat: Enucleation; few recurrences. 6. Special variants: Peripheral Gorlin cyst: Located on attached gingiva, not clinically aggressive. May represent as much as 30% of all Gorlin cysts. Epithelial odontogenic ghost cell tumor : No cyst formation; solid tumor. Represents 2-14% of all Gorlin cysts, and are thought to be more aggressive. Gorlin cyst phenomenon: small rests of same histology, associated with odontoma, adenomatoid odontogenic tumor, ameloblastoma, and other odontogenic tumors. No aggressive clinical behavior. Rarely: Odontogenic ghost cell carcinoma (very rare malignancy ; 73% 5-year survival)