Neoplasms of the Oral Cavity

Clinical

• Most common benign neoplasm of the oral cavity

• No gender predilection; most commonly seen in the third to fifth decades of life:

  • May occur in pediatric ages

• Any site can be affected but most frequently involves tongue, palate, buccal mucosa, tonsil, and uvula

• Symptoms relate to a painless mass.

• Majority are solitary but may be multiple:

  • Multiple papillomas may occur in association with focal dermal hypoplasia syndrome or in focal epithelial hyperplasia (Heck disease)

  • Focal dermal hypoplasia:

    • –

      Autosomal dominant disorder with incomplete penetrance

    • –

      Predominantly occurs in women

    • –

      Features include:

      • ▪

        Multiple papillomas

      • ▪

        Dermal hypoplasia with fatty penetrance

      • ▪

        Syndactyly

      • ▪

        Colobomas of the iris and choroids

      • ▪

        Strabismus

      • ▪

        Ductal hypoplasia

  • Focal epithelial hyperplasia or Heck disease includes:

    • –

      Multiple oral papillomas

    • –

      Caused by HPV types 13 and 32

    • –

      Papillomas may occur anywhere in the oral cavity but most common on the labial and buccal mucosa and the tongue

  • Florid oral papillomatosis:

    • –

      Clinical term for diffuse papillomatous change but not a defined clinicopathologic entity

    • –

      May be associated with:

      • ▪

        Cowden syndrome:

        • □

          Autosomal dominant disease characterized by facial trichilemmomas associated with GIT, CNS, musculoskeletal, and thyroid abnormalities

      • ▪

        Down syndrome, nevus unis lateris syndrome (ichthyosis hystrix), acanthosis nigricans, tuberous sclerosis, and focal dermal hypoplasia syndrome (Goltz-Gorlin syndrome)

      • ▪

        Immunosuppressed patients, in particular HIV infection, may be associated with florid oral papillomas/papillomatosis (immunodeficiency and papillomas/papillomatosis):

        • □

          Entire oral mucosa may be papillo­matous.

        • □

          Lesions tend to be larger than nonimmunosuppressed-related lesions and may be multiple; lesions may coalesce to form extensive mucosal patches.

        • □

          Multiple HPV subtypes, including unusual ones, may be identified.

• Cause:

  • Human papillomavirus (HPV) proposed as causative:

    • –

      Many HPV subtypes have been detected, but most common are HPV types 6 and 11.

    • –

      HPV DNA identified in greater than 80% of cases

    • –

      No definitive association between HPV type and the type of papilloma

Pathology

Differential Diagnosis

• Verruca vulgaris

• Syringocystadenoma papilliferum

• Verrucous carcinoma

• Exophytic squamous cell carcinoma

• Inflammatory papillary hyperplasia:

  • Benign, reactive oral epithelial hyperplasia often associated with an intraoral inflammatory process (e.g., stomatitis)

  • Relatively common oral lesion

  • More common in men than in women; typically occur in the third through fifth decades of life

  • May occur in any intraoral site but is most often found on the palate

  • Painless, appearing as multiple warty or papillary, red-appearing lesions

  • Development linked to:

    • –

      Patients with stomatitis, the result of ill-fitting dentures or dental prostheses, especially in those people who retain their prosthesis while sleeping and who exhibit poor oral hygiene

    • –

      Candida

  • May also occur in dentulous patients without known history of dental prosthesis use

  • Histologically:

    • –

      Similar to pseudoepitheliomatous hyperplasia with hyperkeratosis, parakeratosis, and an absence of epithelial dysplasia

    • –

      Edematous change and a mixed chronic in­­flammatory cell reaction can be seen in the submucosa.

    • –

      Secondary reactive or degenerative changes of seromucous glands, including squamous metaplasia, fibrosis, atrophy, mucin pool formation, and mixed inflammation may be present in areas overlying minor salivary glands; despite these findings the lobular configuration of the seromucous glands is retained.

    • –

      Fungi (i.e., Candida albicans ) may be present.

  • Resolution may occur by initial treatment approach that includes:

    • –

      Replacement of prosthesis with a better fitting one and education in the proper oral hygiene indicated

    • –

      Topical antifungal (e.g., miconazole) used to treat presence of fungi

  • Failure for lesions to regress/resolve after conservative (nonsurgical) approach may require surgical excision

  • Not considered to be a premalignant lesion

Treatment and Prognosis

• Complete surgical excision usually is curative.

• Recurrences occur infrequently and relate to inadequate excision.

• Malignant transformation does not occur.

Clinical

• Uncommon tumor

• No gender predilection; occurs over wide age range including first to eighth decades of life; median age of 32 years

• Asymptomatic, slow-growing, painless, submucosal nodular lesion of the anterior dorsal tongue

Pathology

Differential Diagnosis

• Monomorphic adenoma of salivary glands:

  • Myoepithelioma:

    • –

      Myoepithelioma of the anterior dorsal tongue is rare.

    • –

      Immunohistochemical findings would be compatible with myoepithelial cells, but presence of chondromyxoid stroma and absence of plasmacytoid and/or spindle-shaped myoepithelial cells by light microscopy weigh against this diagnosis.

• Pleomorphic adenoma:

  • Rarity of salivary gland tumors localized to the anterior dorsal tongue and absence of identifiable glandular differentiation by light microscopy weigh against this diagnosis.

• Extraskeletal myxoid chondrosarcoma:

  • Location is rare for chondrosarcomas of any type

  • Presence of cytokeratin and glial fibrillary acidic protein are not features seen in chondrosarcomas.

Treatment and Prognosis

• Conservative but complete excision is curative

• Rarely (<10%) recur; recurrence likely a function of inadequate excision

General Considerations

• Benign peripheral nerve sheath tumors include neurilemoma and neurofibroma (see Section 4, Neck).

• Other benign tumors of nerve sheath or presumed peripheral nerve sheath origin include:

  • Granular cell tumor

  • Mucosal neuroma

  • Palisaded encapsulated neuroma (solitary circumscribed neuroma)

  • Dermal nerve sheath myxoma (neurothekeoma) (see Section 4, Neck)

  • Perineurioma (see Section 4, Neck)

• See Section 5, Larynx, for discussion of mucosal granular cell tumor.

Clinical

• More common in females than males; occurs exclusively in newborns (at or immediately after birth)

• Identified on gum pads in oral cavity on the crest of the alveolar ridge in the incisor region:

  • Localizes to labial aspect of the dental ridge with a predilection of the upper jaw

• Affects the maxilla more often than the mandible but can occur in both locations simultaneously

• Approximately 10% are multiple.

• Radiology:

  • May be diagnosed prenatally by ultrasound:

    • –

      Ultrasound examination shows marked blood flow in the tumor.

• Histogenesis:

  • Owing to absence of S100 protein reactivity, this tumor is felt to originate from a non-neural cell of origin but the histogenesis remains uncertain.

  • Some authorities believe it to be a nonneoplastic (hamartomatous) lesion.

Pathology

Treatment and Prognosis

• Usually require complete surgical excision

• May regress spontaneously

Clinical

• Slightly more common in females than males; noted at birth or during first few years of life

• Common sites of involvement include lips, tongue, and eyelids:

  • Oral cavity:

    • –

      Vermilion border of the lips, anterior third of the ventral or dorsal tongue, buccal mucosa

  • Ocular:

    • –

      Eyelids

• Clinical appearance includes the presence of multiple small, sessile, mucosal-covered nodules.

Pathology

Differential Diagnosis

• Traumatic (amputation) neuroma:

  • Exuberant, non-neoplastic proliferation of nerves occurring in response to injury or surgery

  • Presents as firm nodule occasionally tender or painful

  • Circumscribed nodule(s) located in continuity with proximal end of injured or transected nerve

  • Unencapsulated lesion consisting of haphazard proliferation of nerve fascicle including axons Schwann cells and fibroblasts:

    • –

      Less well-myelinated than parent nerve

    • –

      Enveloped in collagen

    • –

      May be embedded in mucoid matrix

  • Immunoreactivity present for neurofilament protein (axons), S100 protein (Schwann cells), and EMA (perineurial cells)

• Plexiform neurofibroma

• Palisaded encapsulated neuroma (solitary circumscribed neuroma) ( Fig. 6-7 ):

  • Distinct form of true neuroma consisting of Schwann cells as well as axons within a perineurial-derived capsule

  • No association with NF-1 or MEN 2B

  • Usually a cutaneous lesion

  • May occur in the oral cavity (palate, lips)

  • Small asymptomatic solitary circumscribed nodule

  • No gender predilection; occurs in adults

  • Histology:

    • –

      Submucosal circumscribed nodular or multinodular, solid proliferation of Schwann cells lacking stromal alterations, including hyalinization or myxoid change often associated with schwannomas or neurofibromas

    • –

      Most are small, measuring approximately 3 mm, and localized to the reticular dermis or submucosa.

    • –

      In spite of its description most do not show “palisading” and are not encapsulated but often are incompletely encapsulated.

    • –

      Composed of bland-appearing spindle cells set in a variably fibrous stroma and focally separated by artifactual clefts or cracking artifact:

      • ▪

        Clefts or cracks likely related to fixation

      • ▪

        Surrounds or results in slit-like spaces between cell bundles

    • –

      Schwann cells are diffusely and strongly S100 protein positive.

    • –

      Presence of axons traverse the lesion in close association with Schwann cells:

      • ▪

        Not evident on hematoxylin and eosin staining

      • ▪

        Best seen with silver stains

      • ▪

        May be highlighted by neurofilament protein (NFP) immunostaining

  • Simple surgical excision is curative.

  

Treatment and Prognosis

• Surgical excision may be performed for cosmetic purposes.

• Diagnosis should prompt work-up for possibility of MEN 2B:

  • Early diagnosis of MEN 2B, especially evaluation for the possibility of medullary thyroid carcinoma, allows for initiation of earlier treatment.

Clinical

• Myofibromas:

  • Most common type occurring three times more often than multicentric form

  • More common in males than females; occurs over a wide age range, including infants and adults but represents the type most commonly seen in adults

  • Tend to occur in the head and neck region:

    • –

      Most common in bone (mandible and skull) followed by the oral cavity, especially the buccal mucosa and tongue; less common intraoral sites of involvement include the gingival, palate, lip, retromolar trigone

    • –

      May rarely involve other head and neck sites, including sinonasal tract and neck

  • Presents as a painless mass usually measuring less than 3 cm

• Myofibromatosis may occur with or without visceral involvement:

  • Without visceral involvement:

    • –

      More common in males than females; majority (up to 90%) occurs within the first 2 years of life with many presenting at birth

    • –

      Sites of involvement include skin, subcutis, soft tissue, and bone:

      • ▪

        Multiple lesions may be limited to a single general anatomic site (e.g., only head and neck) or may be generalized in distribution

      • ▪

        Absence of visceral involvement

    • –

      Presents as a painless mass usually measuring less than 3 cm

    • –

      Possible but not definitive for familial inheritance

  • With visceral involvement:

    • –

      Up to 40% have visceral involvement

    • –

      More common in males than females; majority (up to 90%) occur within the first 2 years of life with many presenting at birth

    • –

      Sites of involvement include skin, subcutis, soft tissue, and bone as well as visceral involvement, the latter including:

      • ▪

        Lungs, heart, gastrointestinal tract, liver, kidney, pancreas, and rarely central nervous system

    • –

      Present with symptoms related to the organs involved

    • –

      Possible but not definitive for familial inheritance

• Radiology:

  • Osseous lesions appear as circumscribed radiolucent lesions often with sclerotic margin

  • Central mineralization may be present.

• Familial occurrence has been reported:

  • Inherited in autosomal dominant manner

Pathology

NOTE: Pathologic findings remain similar, whether solitary or multifocal.

Differential Diagnosis

• Fibromatosis

• Nodular fasciitis

• Smooth muscle neoplasms (leiomyoma, leiomyo­sarcoma)

• Sarcomas:

  • Due to increased cellularity, rich vascularity, and presence of necrosis, myofibromas/myofibromatosis may be mistaken for a sarcoma.

Treatment and Prognosis

• Spontaneous regression may occur in solitary or multifocal (without visceral involvement) lesions.

• Simple excision of solitary lesions is curative.

• Surgical resection of multiple lesions may be indicated in cases in which there is functional impairment or involvement of vital organs.

• Recurrence rates after surgery usually are less than 10% of cases.

• Prognosis less favorable in newborns and infants with multiple visceral lesions:

  • Increased morbidity and mortality:

    • –

      Mortality rates >70% reported

  • Death may be due to cardiopulmonary or gastrointestinal complications.

  • Low-dose chemotherapy (methotrexate and vinblastine) may be effective in treating patients with multicentric visceral involvement.

Clinical

• More common in women than men; occurs over a wide age range but is most frequently seen in the second to fourth decades of life

• Most common site of occurrence is the mandible, especially molar or posterior area followed by the premolar area, incisor area, and cuspid area

  • May also occur in association with the maxilla, but maxillary involvement occurs much less often as compared with the mandibular region

• Generally asymptomatic unassociated with pain or swelling and diagnosed incidentally after radiographic examination; symptomatic tumors manifest by displacement of teeth or as an expansile mass that may include facial asymmetry.

• Typically presents as solitary mass but infrequently may be multifocal:

  • Multifocal tumors can occur in the mandible, in the maxilla, or in both regions.

  • Polyostotic involvement of extragnathic bones as seen in fibrous dysplasia is not a finding associated with ossifying fibromas.

• Radiology:

  • Well-circumscribed lesion with smooth contours having a variation in appearance based on the maturity of the tumor, including:

    • –

      Completely radiolucent:

      • ▪

        Immature lesion

    • –

      Completely radiopaque:

      • ▪

        Mature lesion

    • –

      Mixed radiolucent and radiopaque:

      • ▪

        Increased mineralization with age results in radiopaque foci admixed with radiolucent areas

• Presumptive origin is from the periodontal ligament, which:

  • Is a layer of fibrous connective tissue surrounding and attaching the roots of teeth to alveolar bone

  • Is capable of forming cementum, bone, and fibrous tissue

  • Supports close relationship to cementifying fibroma and cemento-ossifying fibroma; in fact, all of these lesions are considered variants of ossifying fibroma

Pathology

Differential Diagnosis

• Primarily with fibrous dysplasia (see below and Table 6-1 )

  • Differentiation of ossifying fibroma from fibrous dysplasia is important because the therapeutic rationale differs for these lesions.

Treatment and Prognosis

• Surgical excision is the preferred treatment:

  • Well-circumscribed nature of this lesion allows for relatively easy removal.

• Prognosis is excellent after complete excision.

• Recurrences are rare.

General Clinical Features

• Monostotic type:

  • No gender predilection or slightly more common in women

• Polyostotic type:

  • More common in women than men

• Regardless of type, majority of patients affected are under 30 years of age, although older individuals may be affected:

  • In monostotic type most common in second to third decades of life

  • In polyostotic type and McCune-Albright syndrome tend to occur in the first decade of life

• Craniofacial symptoms include:

  • Painless, asymmetric, nonmobile swelling associated with functional disturbances

  • Displacement or malocclusion of teeth, failure of tooth eruption in children

  • Headaches, proptosis, nasal obstruction, especially for sinonasal tract lesions

  • Hearing loss (conductive)

• Laboratory findings:

  • Serum calcium and phosphorous levels are normal; alkaline phosphatase may be elevated.

• May be associated with:

  • Oncogenic osteomalacia

  • Cholesteatoma

• Radiology:

  • Poorly defined expansile osseous lesion with a thin intact cortex

  • Predominantly fibrous lesions are radiolucent.

  • Predominantly osseous lesions are radiodense.

  • Equal admixture of fibrous and osseous components results in a ground glass appearance.

  • Usually no periosteal reaction is seen unless there is an associated fracture.

• Cause remains unknown:

  • No familial or hereditary origin

  • Cherubism is congenital form of fibrous dysplasia:

    • –

      Autosomal dominant disease with variable expressivity

    • –

      Characterized by lateral swelling of the jaws:

      • ▪

        Bilateral symmetric involvement is almost pathognomonic.

      • ▪

        Usually involves the mandible with the ramus always involved.

      • ▪

        Patients have characteristic upturned appearance of the eyes, resulting in a cherubic expression.

• Rarely may be associated with soft tissue myxomas referred to as Mazabraud syndrome:

  • Defined as combination of one or more intramuscular myxomas and fibrous dysplasia of bone

  • Association is more common with polyos­totic fibrous dysplasia and McCune-Albright syndrome

  • Myxomas tend to appear years (decades) after bone lesions

  • Soft tissue myxomas most common in the thigh (intramuscular)

  • Often multiple and tend to occur near to abnormal bones

  • These patients are at increased risk for malignant transformation:

    • –

      Risk is greater than in those with fibrous dysplasia alone

    • –

      Risk increases when patient has both McCune-Albright and Mazabraud syndromes

Pathology

Differential Diagnosis

• Ossifying fibroma (see Table 6-1 ):

  • Gnathic fibro-osseous lesions (fibrous dysplasia and ossifying fibromas) may be histologically indistinguishable; therefore the diagnosis and differentiation rest on the clinical–radiologic–histopathologic correlation.

  • Differentiation of ossifying fibromas from fibrous dysplasia is important because the therapeutic rationale differs for these lesions.

Treatment and Prognosis

• Conservative surgical excision is the preferred treatment and is indicated only in cases with compromise of function, progression of deformity, pain, associated pathologic fracture(s), or the development of a malignancy.

• Disease may stabilize at puberty and, in children, therapy should be delayed if possible until after puberty.

• Radiation treatment is not used because of the risk of inducing malignant change.

• Recurrence rates are low and death due to extension into vital structures rarely occurs.

• Malignant transformation:

  • Occurs in less than 1% of cases but is most feared complication

  • When it occurs is most often an osteosarcoma > chondrosarcoma > fibrosarcoma:

    • –

      Also associated with angiosarcoma, Ewing sarcoma, and malignant mesenchymoma, including osteosarcomatous, chondrosarcomatous, and rhabdomyosarcomatous elements

  • Most common in craniofacial bones (maxilla and mandible) followed by femur and tibia

  • Peaks in third and fourth decades

  • May occur spontaneously or in patients treated by prior radiation

  • Identified more often in association with the monostotic type:

    • –

      Risk increases when patient has both McCune-Albright and Mazabraud syndromes

    • –

      Risk is greater than in those with fibrous dysplasia alone

  • Tends to occur years to decades after development of fibrous dysplasia

  • Treatment is similar to that of a primary malignant bone tumor.

  • Prognosis is poor with tendency to metastasize to lungs and short survival periods.

Clinical

• Most occur at ends (epiphyses) of long bones with distal femur the most common site followed by proximal tibia

• Rare in the head and neck:

  • Less than 2% of all giant cell tumors occur in head and neck.

  • Propensity to affect sphenoid, temporal, and ethmoid bones

• More common in women than in men; occur over a wide age range

• Symptoms vary per site of involvement:

  • • –

      Sphenoid and ethmoid bones

    • –

      Headaches, diplopia, visual disturbances, proptosis

  • Middle ear, temporal bone, petrous bone:

    • –

      Conductive hearing loss

    • –

      Vertigo and sensorineural hearing loss

• Laboratory:

  • No abnormalities of serum calcium

• Radiology:

  • Lytic lesions with or without involvement/destruction of adjacent bones

Pathology

Differential Diagnosis

• Giant cell granuloma:

  • Share histologic similarities with giant cell tumor:

    • –

      Divergent opinion whether giant cell tumor and giant cell granuloma represent spectrum of a single entity

  • Features in giant cell granuloma differing from giant cell tumor include:

    • –

      Predilection to the gnathic bones, especially the mandible

    • –

      Overall fewer numbers of giant cells with less even distribution of the giant cells

    • –

      Frequent areas of hemorrhage and tendency for giant cells to cluster in areas of hemorrhage, as well as in proximity to vascular spaces

    • –

      Greater amount of stromal collagenization

• Brown tumor of hyperparathyroidism:

  • Absence of abnormalities of serum calcium in giant cell tumor assists in differentiating these lesions.

• Chondroblastoma

Treatment and Prognosis

• Surgical excision (i.e., curettage) is the preferred treatment:

  • Treatment recommendation is based on the more common giant cell tumors of long bones.

  • In long bones recurrence rates vary from 20% to 50% after surgical curettage.

• Radiation is not recommended because:

  • These tumors are not felt to be radiosensitive.

  • There is believed to be increased risk of malignant transformation after radiation treatment.

• Medical therapies include diphosphonates and denosumab (RANKL inhibitors):

  • May be used in patients with untreatable disease, including refractory, recurrent, or metastatic giant cell tumor

• Rarely (less than 10%) morphologically benign giant cell tumors may metastasize:

  • May be referred to as benign metastasizing giant cell tumor

  • No reliable predictors of which lesions may metastasize

  • Metastasis may be solitary or multiple.

  • Metastatic disease most often to lungs; less often to lymph nodes and other visceral sites

  • If solitary surgical resection is achievable (metastasectomy), prognosis is good.

  • Rarely, more diffuse metastatic disease occurs and may result in death.

• Malignant transformation of giant cell tumors is uncommon, representing presence of histologically benign giant cell tumor in association with sarcomatous component:

  • Malignant giant cell tumors, primary and secondary:

    • –

      Primary malignant giant cell tumor represents a de novo malignancy (i.e., at presentation).

    • –

      Secondary malignant giant cell tumor represents malignant transformation of a previous tissue-verified benign giant cell tumor:

      • ▪

        Most occur secondary to radiation treatment.

      • ▪

        Could be considered postirradiation sarcoma

    • –

      For primary and secondary malignant giant cell tumors, malignancy includes osteosarcoma, undifferentiated pleomorphic sarcoma, and fibrosarcoma.

    • –

      Metastatic disease is most often to the lungs.

    • –

      Poor prognosis with greater mortality associated with secondary as compared with primary malignant giant cell tumor

  • Rare malignant giant cell tumor of the sphenoid arising in setting of Paget disease.

Clinical

• Represent approximately 1% to 4% of all benign tumors of bone

• Most common site of occurrence is in the vertebra:

  • Uncommon tumor of head and neck

  • In head and neck occurs most commonly in gnathic (jaw) bones:

    • –

      More common in the mandible (body) than maxilla

    • –

      Less common sites of occurrence include the cervical vertebrae, skull, sinonasal tract, and middle ear/temporal bone.

• More common in men than in women; overwhelming majority of cases (greater than 90%) occur in patients under 30 years of age

• Presentation is usually that of localized pain to involved site:

  • Unlike osteoid osteoma, pain is not nocturnal and aspirin does not typically assist in resolving the pain.

  • In addition to pain, other symptoms related to site of occurrence may include:

    • –

      Jaws: swelling, loosening of teeth

    • –

      Sinonasal tract: epistaxis, nasal obstruction

    • –

      Middle ear/temporal bone: conductive hearing loss

• Radiology:

  • Well-defined or sharply circumscribed to poorly defined radiolucent/radiopaque lesion with variable mineralization:

    • –

      Depending on the degree of mineralization may appear:

      • ▪

        Predominantly lytic

      • ▪

        Predominantly sclerotic

      • ▪

        Mixed lytic and sclerotic

  • Expansion of bone with cortical erosion and extension into adjacent soft tissue may be identified

  • Usually measure more than 2 cm but rarely larger than 10 cm

  • Absence of a nidus as seen in osteoid osteoma

  • In gnathic bones may be intimately associated with roots of teeth

  • Significant percentage of cases may radiographically show features similar to those identified in osteosarcoma.

Pathology

Differential Diagnosis

• Osteoid osteoma:

  • Benign bone forming tumor with limited growth potential

  • Represents approximately 14% of all benign bone tumors

  • More common in men than in women; most common in the first to third decades of life

  • Majority occurs in femur and tibia

  • Rare in head and neck sites, where most common sites of occurrence include mandible and cervical vertebrae

  • Pain, especially occurring at night (nocturnal pain), is most common presenting complaint; pain typically responds (i.e., pain relief) to nonsteroidal anti-inflammatory drugs.

  • Radiology:

    • –

      Circumscribed dense cortical radiolucency surrounding marked sclerosis (nidus)

  • Usually measures 1 cm or less

  • Essential identical histology to osteoblastoma:

    • –

      Exception is presence in osteoid osteoma of a nidus representing interconnecting mass of osteoid and immature (woven) bony trabeculae of variable length and thickness rimmed by osteoblasts

    • –

      Because of shared histologic features (except for the nidus), differentiation may not be achievable in curetted material, thereby requiring radiographs to assist in differentiating osteoid osteoma from osteoblastoma.

  • Complete surgical excision or ablation of the nidus (en bloc) is curative:

    • –

      Depending on the site of occurrence may require multiple procedures

    • –

      Medical management (nonsteroidal anti-inflammatory drugs) may be an option if surgical treatment is contraindicated.

• Aneurysmal bone cyst

• Fibrous dysplasia

• Giant cell tumor

• Odontogenic lesions/neoplasms:

  • Cementoblastoma, cemento-ossifying fibroma, cemento-osseous dysplasia

• Osteosarcoma:

  • Features in osteoblastoma that assist in excluding osteosarcoma include:

    • –

      Sharp circumscription with no permeation or entrapment of surrounding host bone

    • –

      Bony trabeculae embedded in loose connective tissue; lining of trabeculae by a single layer of osteoblasts

  • Features in osteosarcoma that contrast to those of osteoblastoma include:

    • –

      Greater nuclear pleomorphism and hyperchromasia

    • –

      Greater number of mitoses with atypical mitotic figures

    • –

      More compact stromal component

    • –

      Penetration of neoplastic cells between existing bone/bony trabeculae

    • –

      Presence of sheets of osteoblasts without osteoid production

Treatment and Prognosis

• Conservative but complete surgical resection by curettage or local excision is the preferred treatment and is curative in majority of cases.

• Recurrent tumor is uncommon.

• Features potentially associated with aggressive behavior include:

  • Location of lesion:

    • –

      Tumors of the central neuroaxis associated with increased morbidity and mortality

  • Presence of secondary aneurysmal bone cyst component:

    • –

      Associated with more destructive behavior

  • Local control of disease:

    • –

      Ability to completely resect tumor associated with excellent long-term prognosis

  • Histology alone is not predictive of aggressive behavior.

• Metastatic disease rarely, if ever, occurs.

Clinical

• Second most common odontogenic tumor (odontoma is considered the most common odontogenic tumor)

• Most common type of ameloblastoma, representing greater than 80% of all cases

• No gender predilection; occurs over a wide age range but most commonly occurs in the fourth to sixth decades of life; rare under 20 years of age

• Greater than 80% involve the mandible with predilection for the posterior mandibular region (molar-ramus area > premolar area > symphysis); often associated with unerupted third molar teeth:

  • Predilection to the molar-ramus area is thought to be the result of:

    • –

      Aberrant tooth germs often found in this region

    • –

      Posterior end of the dental lamina proliferates continuously.

• Maxillary ameloblastomas occur primarily in the posterior (molar) region

• May occur as a primary sinonasal tract neoplasm; see Section 1, Sinonasal Tract, for detailed discussion.

• Most common clinical presentation is a painless swelling of the affected area; pain or paresthesia is rare

• Radiology:

  • Unilocular or multilocular radiolucent lesion resembling cysts with a honeycomb appearance and scalloped borders

  • Extensive thinning of cortical bone can often be seen.

  • Desmoplastic type may present as mixed radiolucent/radio-opaque lesions

Pathology

Differential Diagnosis

• Dentigerous cyst: see earlier in section

• Odontogenic keratocyst: see later in section

• Ameloblastic fibroma

• Squamous odontogenic tumor:

  • Rare benign odontogenic epithelial neoplasm thought to arise from epithelial rests of Malassez of the periodontal membrane

  • Most common in third to fourth decades of life

  • Occur most often in the anterior maxilla or posterior mandible

  • Radiology: well-demarcated radiolucent lesion with sclerotic, osseous border

  • Histologic features include:

    • –

      Irregular-shaped islands of bland-appearing mature squamous epithelium without nuclear pleomorphism, nuclear hyperchromasia, increased mitotic activity, or dyskeratosis

    • –

      Flattened peripheral cells with smoothly contoured connective tissue interface

    • –

      Absence of stellate reticulum and peripheral nuclear palisading with reverse polarity:

      • ▪

        Assists in differentiating from acanthomatous variant of ameloblastoma

    • –

      Cystic change may be present.

    • –

      Abundant fibrous stroma

    • –

      Epithelial islands may contain spherical eosinophilic hyaline material (reminiscent to Rushton bodies) that stain strongly with PAS

  • Absence of significant cytologic atypia allows for differentiation from intraosseous carcinoma or metastatic squamous cell carcinoma

  • Simple excision (enucleation or curettage) considered preferred treatment and is curative

Treatment and Prognosis

• Complete surgical resection is preferred treatment:

  • For small tumors that are well delineated, conservative but complete excision can be performed.

  • For larger tumors that have spread to adjacent tissues (e.g., bone, other) en bloc resection may be required to include at least 1 cm of normal tissue beyond radiographic margin.

• Surgical curettage not an acceptable form of therapy

• Considered radioresistant; chemotherapy has no proven efficacy.

• Recurrence is not uncommon and may lead to extensive local destruction with facial disfigurement or may pose life-threatening complications as a result of extension into vital structures.

• Metastases are rare and are generally related to long-standing tumors associated with multiple surgical procedures or radiation treatment.

• Prognosis for ameloblastomas depends on tumor size, extent of disease, and location of the tumor:

  • Mandibular ameloblastomas tend to be confined tumors, due to the inherently thick cortical mandibular bone

  • Maxillary ameloblastomas are more likely to demonstrate extension beyond the bone, due to the absence of a thick cortical bone and the intimate association with the sinonasal cavity.

• Malignant ameloblastoma:

  • Represents ameloblastomas with benign features yet metastasize

  • Diagnosis can be rendered only after identification of metastatic tumor:

    • –

      Also referred to by designation metastasizing ameloblastoma

  • Rare occurrence

  • Lung followed by regional lymph nodes represent most common sites for metastases:

    • –

      Other reported metastatic sites include bone, brain, kidney, intestine, and liver.

  • Interval between diagnosis of primary tumor and metastasis can be years

• Ameloblastic carcinoma ( Figs. 6-20 and 6-21 ):

  • Represents rare malignant transformation of a benign ameloblastoma characterized by cytomorphologically malignant epithelial cells with marked nuclear pleomorphism, increased nuclear-to-cytoplasmic ratio, increased mitotic activity, necrosis, and lymph-vascular invasion:

    • –

      Predilection for the mandible

    • –

      Presentation may include pain, swelling, tris­mus, and odynophagia

    • –

      Treated by surgical resection

    • –

      May metastasize to regional lymph nodes and distantly to lungs, bone, and liver

    • –

      Poor prognosis

  
  

• Ameloblastic fibrosarcoma (ameloblastic sarcoma) ( Fig. 6-22 ):

  • Rare malignancy in which there is mixed epithelial-mesenchymal odontogenic neoplasm composed of a sarcomatous mesenchymal component arising:

    • –

      De novo

    • –

      From pre-existing odontogenic mixed neoplasm such as an ameloblastic fibroodontoma or ameloblastic fibroma

  • Histology includes foci of ameloblastoma most often in a follicular pattern surrounded by sarcomatous proliferation with fascicular to herringbone pattern composed of malignant spindle-shaped cells with marked nuclear pleomorphism, increased mitotic activity including atypical mitoses and necrosis

  • Biomarker analysis showed alterations of p53 and c-KIT genes restricted to the sarcomatous component

  • Treatment follows that for other sarcomas, including radical extirpation and chemotherapy.

  

Clinical

• From 5% to 15% of all ameloblastomas are of the unicystic type

• No gender predilection; tends to occur at a younger age than solid/multicystic ameloblastoma primarily in the second to third decades of life

• Greater than 90% involve the mandible, usually the posterior portion of the mandible.

• May be asymptomatic or present as a painless swelling of affected area

• Often associated with an impacted tooth, making it indistinguishable from a dentigerous cyst

• Radiology:

  • Well-delineated unilocular radiolucency

  • Occasionally may show demarcated, perilesional corticated rim

  • Radiolucency often associated with an unerupted tooth, making it indistinguishable from a dentigerous (follicular) cyst