Gnathic Bone Tumors Flashcards
Craniofacial fibrous dysplasia
May be mono-ostic (~80% of cases) or poly-ostic (associated with McCune Albright syndrome, ie activating GNAS mutation). Benign.
Irregularly contoured bony spicules, some with a “hooked” shape embedded in a moderately cellular fibrous matrix. “C” and “S” shapes are classic. Spindled and stellate stromal cells are uniform in size and appearance.
Basically all cases involve GNAS mutations, germline or somatic, 95% involving residue R201.
Osteoma
Usually in 10’s-30’s.
Benign tumor of mature compact or cancellous bone.
Multiple lesions of the mandible and calvaria can be associated with Gardner syndrome, called exostosis.
Ossifying fibroma
70% of cases are mandibular. May be rapidly growing in children.
Mineralized, woven bone admixed with lamellar bone, cementum-like bodies, and cellular fibrous tissue. May be mostly fibrous tissue with some bone, or mostly bone with some fibrous tissue (like the psammomatoid variant, shown below). “Juvenile-type” presents at a younger age (usually in children) and has highly cellular stroma with large, mitotically active osteoblasts and psammomatous ossicles.
May be seen in hyperparahtyroidism jaw-tumor syndrome, with CDC73 mutations, resulting in premature truncation of parafibromin protein product. May also be seen in Gnathodyaphysial dysplasia, caused by mutations in GDD1 (aka TMEM16E). Sometimes sporadic mutations in CDC73 will cause acquired tumorigenesis.
Ameloblastoma
Benign (despite being a “blastoma”), but locally aggressive odontogenic neoplasm that demonstrates ameloblast differentiation. Associated with unerupted teeth.
Cells usually display reverse polarization with pallisading in a cystic or follicular arrangement. Sometimes a “granular cell variant” resembling ganular cell tumor and having rhabdoid-like eccentric nuclear placement may be seen (shown here). There are many other variants, so have high suspicion.
X-ray: Soap bubbles in the molar region of the mandible (less likely maxilla).
IHC: CK5, calretinin, p63, p40
Molecular: BRAF V600E in ~60%, RAS and FGFR2 also common in MAPK pathway, SHH pathway sometimes implicated with PTCH1 or similar.
Calcifying epithelial odontogenic tumor, aka Pindborg tumor
Benign neoplasm, although it looks mean. Affects a broad range of ages. 50% associated with an impacted tooth, 66% affect the mandible. The tumor usually arises in the gingiva.
An epithelial odontogenic neoplasm characterized by the formation of calcific deposits and amyloid material, which stains Congo red positive (apple red-green birefringent). The tumor looks like sheets of irregularly contoured islands of large, polygonal cells with randomly scattered marked anisonucleosis and hyperchromasia; moderate-abundant eosinophilic cytoplasm with intercellular bridges. Notably, there should be an absence of mitoses.
“Incomplete” squamous differentiation is sometimes described, given the bridges.
Molecular: AMBN (Ameloblastin) gene is commonly found mutated, as in ameloblastoma and some other odontogenic tumors. One case of malignant transformation associated with TP53 mutation has been described.
Odontogenic keratocyst
Very common odontogenic tumor/cyst.
Cyst lined by benign squamous epithelium (5-9 layers) with a thin corrugated parakeratotic layer and perpendicularly palisading cells in the basal layer; multiple “daughter” cysts may co-occur. Detachment of the cyst epithelium is not uncommon, secondary inflammation and pseudoepitheliomatous hyperplasia possible. Rete ridges are usually absent and the cysts are usually filled with keratin.
May rupture, causing giant cell reaction, may recur locally, and may even be locally infiltrating, but not aggressively so.
Odontogenic myxoma (myxofibroma if abundant collagen)
70% involve the mandible.
Histologically, randomly scattered, small, bland stellate and spindle cells in a myxoid stroma. There should be an absence of necrosis and minimal vascularity.
Associated with mutations in PRKAR1A. Many yet uncharacterized.
Odontoma, Complex Type
Benign lesion that consists of mineralized cementum-like material, dentin, and enamel in a haphazard arrangement. Most common of all odnotogenic mass lesions.
Occurs in children and young adults.
Considered hamartomatous by many.
Craniofacial osteosarcoma
Type of osteoid or bone-producing sarcoma of the head and neck. Peak incidence in the 30’s-40’s. Associated with Paget’s disease or prior radiation therapy.
“Sunburst” pattern on X-ray, similar to osteoblastoma.
Histologically, composed of highly cellular tissue containing markedly hyperchromatic spindle and pleomorphic cells with irregular nuclear contours, easily identifiable mitoses, and variable amounts of malignant osteoid (which is lace-like and densely hyalinized enveloping individual cells or cell clusters). Many will also have hypercellular cartilagenous lobules. May or may not have osteoclastic giant cells.
Drivers include NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A.
Odontoma, Compound Type
Essentially supernumary teeth with dentin and enamel. All layers are there and are organized.
Ameloblastic fibro-odontoma
Regarded as developing ondontomas rather than as a distinct clinical entity by the WHO.
