Uncertain but genetic, inflammatory, and endocrine factors may contribute; risk of dev PD is approx 7X greater in first degree relatives of affective pts than in unaffected pts

15-40% of PD pts have family hx of auto dom inheritance

- Relatively common; 1/100-150 older than 45 y/o

- More common in men and caucasians

- May be subclinical & discovered on routine radiographs or from unexpected increase in serum alkaline phosphatase

- May be monostotic but usually polyostotic (lumbar vertebrae, pelvis, skull and femur)

- Affected bones become thickened enlarged and weakened

- Weight bearing bone involvement often causes bowing deformity (simian  appearance)

- Skull involvement causes progressive increase in circumference of head

- Symptoms may include bone pain and limited joint mobility

Jaw involvement in 17% of cases

Max>>mand causes enlargement of middle third of face (leontiasis ossea) w/ nasal obstruction, enlarged turbinates, obliterated sinuses, etc.

Alveolar ridges enlarge symmetrically but grossly, causing spacing of teeth or need for larger dentures

- Early osteolytic stage shows decreased radiodensity + enlarged, irregular trabeculation

- Later osteoblastic stage produces patchy areas of sclerotic bone in pre-existing lucent background "cotton wool" appearance

- Teeth often show severe widespread hypercementosis

- Combined and disorganized resorption and formation of bone

- Interlacing trabeculae numerous OCs in some areas & OBs in others, sometimes on same trabecula

- Numerous reversal lines indicating much alternating bone resorption and formation resulting in mosaic appearance to bone

Depends on severity of signs and symptoms and progression of disease

Mild cases may not need much treatment aside from symptomatic and supportive

Severe cases treated medically to reduce bone turnover: PTH antagonists (calcitonin, BPs)

- Most commonly inherited (auto dom), due to a defect in CBFA1 gene of chrom 6p21 (Gene normally guides osteoblastic differentiation, approp bone formation; also affects odontogenesis through role in odontoblast differentiation, enamel organ formation and dental lamina proliferation)

- Spontaneous in up to 40% of cases

- Clavicles absent unilaterally or bilaterally in ~10% of cases, more commonly hypoplastic and/or malformed

- Muscles assoc w/ malformed clavicle undeveloped

- Neck appears long, shoulders narrow and drooping

- Short stature, large head, pronounced frontal and parietal bossing, ocular hypertelorism, broad-based nose, depressed nasal bridge

Closure of skull sutures and fontanelles delayed and may never close; secondary ossif centers in sutures: wormian bones

Abnormal temporal bone and eustachian tube dev may lead to hearing loss

- Palate is high, narrow, and arched w/ increased incidence of cleft palate

- Prolonged retention of deciduous teeth and delayed or failed eruption of permanent teeth

- Some studies have found lack of secondary cementum on unerupted permanent teeth; other studies throw some doubt on this as poss etiology

- Numerous unerupted permanent and also supernumerary teeth, many malformed

- Maxilla often underdeveloped, contributing to a class III malocclusion (prognathism)

- May be abnormal spacing of mandibular teeth due to widening of alveolar bone

- No treatment available or necessary for skull, clavicular and other bone anomalies

- Oral and dental treatment may include removal of many supernumerary teeth, selective prosthetic replacement, ortho

- Prognosis generally good, but oral condition may be problematic

- Abnormal bone regeneration following tooth extraction

- Persistent fetal bone marrow

- marrow hyperplasia in response to increased demand for erythrocytes

Must biopsy to confirm diagnosis and rule out many other lesions; no other treatment necessary

Excellent

- Eosinophilic granuloma of bone - monostotic or polystotic (no visceral involvement)

- Chronic disseminated histiocytosis involving bone, skin, and viscera (including Hand-Schuller-Christian disease)

- Acute disseminated histiocytosis w/ widespread prominent cutaneous, visceral and bone marrow involvement, mainly in infants (letterer-siwe disease)

Most well defined and most likely to be encountered in jaws and skull

Lesions may be found in almost any bone, but skull, ribs, vertebrae, and mandible are amongst the most freq sites

Jaws are affected in 10-20% of all cases, often accompanied by dull pain and tenderness

- Appear most commonly as punched out radiolucencies w/out corticated rim, but occasionally ill-defined radiolucency is seen

- Mandible usually occurs in posterior and characteristically presents w/ "scooped out" appearance, teeth in area "floating in air" or resembling severe periodontitis

- EG may also occur in body of mand or max situated so as to radiographically mimic periapical granuloma/cyst

- Ulcerative or proliferative mucosal lesions or gingival mass may form if EG breaks out of bone

- Sheets of histiocyte looking Langerhans cells, often w/ abundant cytoplasm and cleaved nuclei

- Characteristically accomp by signif #s of eosinophils and sometimes other inflammatory cells (plasma cells, lymphocytes, multinucleated giant cells)

- Areas of necrosis and hemorrhage often seen

- Langerhans cells can be identified through ultrastructural observation of Birbeck granules; now through cellular immunoreactivity w/ specific antibodies (CD-1a, CD-207 and S-100)

Solitary lesions of bone: curettage if accessible, low-dose radiation if not

Multiple lesions of bone: thorough medical evaluation and look for other lesions of bone, soft tissue, viscera: if so, consider chemo

- Dependent on extent of involvment

Solitary lesion: generally good, close followup for possible recurrences and spread locally or to other sites

Multiple site invovlement consider systemic chemo

Wide age range but >60% under 30

Female gender predilection 2:1

70% in mand

Most common in anterior jaws, can cross midline

Most cases asymptomatic, detected on routine exam

Less commonly --> pain, paresthesia, swelling, tooth (root) displacement, mucosal ulceration

- Great majority relatively slow-growing; occasionally rapidly growing and more destructive

Well-circumscribed unilocular or multilocular radiolucency, may cross midline

Radiographically may mimic periapical granuloma/cyst chronic periodontitis or ameloblastoma

- Varying #s of multinucleated giant cells distributed throughout a background of ovoid to spindle-shaped mesenchymal cells and monocyte-macrophages

- Giant cells may resemble osteoclasts, each showing numerous uniform nuclei distributed centrall or diffusely throughout eosinophilic cytoplasm; GCs may be clustered or diffusely distributed throughout spindle cell background

- Numerous extravasated RBCs, hemosiderin

- CGCG & some bone lesions of hyperparathyroidism ("brown tumor") are histologically indistinguishable. Accordingly pts who experience what appear histologically to be CGCG, esp if they are older than 30, should be evaluated medically w/ possibility of hyperparathyroidism in mind

- Standard treatment: thorough curettage; in some instances sacrifice of involved teeth may be ncessary

- More aggressive lesions treated in recent years w/ steroids, calcitonin or interferon alpha-2a

- Significant incidence of recurrence: most studies indicate 15-20%; otherwise prognosis is good

- Benign but aggressive neoplasm typically occurring in epiphyses of long bones

- Histologically diff from CGCG of jaws (giant cells as well as background)

- In all probability occurs rarely if ever in jaws

Most cases inherited as autosomal dominant trait with high penetrance but variable expressivity

Recent responsible gene identified as SH3BP2 located on chrom 4p16 (encoded protein linked to activation of OCs and OBs)

 - Onset usually between 2 and 5 y/o; may not be detected until later in childhood

- Typically involves jaws bilaterally, almost always mandible (including angles and ascending rami) & often max as well

- Enlargement is painless but causes widening and distortion of alveolar ridges; often significant interference w/ tooth dev and position, w/ attendant difficulties w/ occlusion, mastication, speech and esthetics

- Enlargement may progress through puberty but then slows down, stops or may regress

- Variable # of mutlinucleated giant cells set in a background of fibroblast-like spindle cells and collagen fibers, w/ mnay years of more edematous rather than highly cellular appearance

- Can also show eosinophilic cuffing of small blood vessels

- Looks somewhat like central giant cell granuloma

Depends on presentation of disease:

- Slowly progressing disease may not need treatment except for careful followup to detect sudden new growth

- Rapidly progressing lesion may require attempt at intervention

Lesions tend to slow down, stop and sometimes even regress around puberty

- By 4th decade facial features approach normalcy in most pts

- Trauma-hemorrhage theory: blood clot following trauma fails to organize and heal by bone regeneration; instead breaks down and resorbs

- Inadequate venous drainage --> buildup of interstital fluid

- Local disturbance in bone growth

- Ischemic marrow necrosis

- Any bone in body, common in jaws

- Most comon b/t 10-20 y/o

- In jaws vast majority in mand; can be bilateral

- Males>females

- 80% asymptomatic; incidental radiographic finding

- 20%: painless swelling

- Occasionally pain, paresthesia

- Most common in premolar/molar area

Generally well-circumscribed radiolucency, usually unilocular; occasionally less well defined and/or multilocular

Generally non-expansile

- When involving dentulous area characteristically scalloped b/t roots of the teeth (highly suggestive of dx)

- Often cone-shaped outline anteroposteriorly

- Cavity surrounded by thin layer of vascular fibrous tissue or somewhat myxomatous CT, either devoid of contents or containing small amounts of serosanguinous fluid and occassionally a few erythrocytes

- Periphery of cavity may show some reactive bone

- Thorough surgical curettage, scraping walls to encourage bone bleeding

- Always submit tissue for histologic exam, however meager the amount

- In jaws almost always heals w/ bone fill in 6 mos to a year

classic (or standard) form (95%) has blood filled clefts among bony trabeculae. Osteoid tissue is found in stromal matrix

olid form (5%) shows fibroblastic proliferation, osteoid production and degenerated calcifying fibromyxoid elements.

- Fibrous dysplasia

- Cemento-osseous dysplasia (focal cemento-osseous dysplasia, periapical cemento-osseous dysplasia, florid cemento-osseous dysplasia)

- Cemento-ossifying fibroma

- FD is sporadic condition resulting from a postzygotic mutation in GNAS1 (guanine nucleotide-binding protein, alpha-stimulating activity polypeptide 1) gene

- Whether a given patient manifests monostotic, polyostotic or polyostotic plus cutaneous and endocrine forms presumably depends on when in development the mutation occurs, earlier the mutation the more broad its effects

- FD limited to a single bone: 80-85% of all cases

- Jaws most commonly affected sites: max > mand

- Most cases diagnosed in 2nd decade of life

- Males and females affected w/ equal freq

- Generally painless, slowly growing swelling (although occasionally growth rapid and destructive)

- Maxillary involvement may spread to adj skull and facial bones: craniofacial FD

- Poorly circumscribed alteration most commonly "ground glass" appearance (superimposition of many poorly calcified bony trabeculae) - blends w/ adjacent bone (earlier stages may be radiolucent or mottled)

- Mand involvement may produce not only buccolingual expansion, but bulging of inferior border, displacement of mand canal

- Max involvement may displace sinus floor superiorly, and/or obliterate max sinus

- Max involvement may also be accompanied by increased radiodensity at base of skull involving occiput, sphenoid, roof of orbit and frontal bones (most characteristic radiographic feature of FD of skull)

- Irregularly shaped trabeculae of immature (woven) bone, in a cellular, loosely arranged fibrous stroma, trabeculae may be curvilinear ("Chinese character") in shape

- Trabeculae generally not surrounded by distinct OBs (metaplastic rather than neoplastic)

- Lesional bone fuses directly to normal bone at periphery - no capsule or demarcation

- Once diagnosis is made using clinical, radiographic and histologic correlation, tx depends upon degree of deformity and functional deficit

- In condition is slowly growing, not cosmetically significant and does not interfere with function, may wait for skeletal maturation to occur w/ slowdown or stopping of lesional grown

- If lesion is rapidly growing, cosmetically objectionable or interferes w/ function, surgical reduction is treatment of choice; not attempt usually made to completely resect due to the difficulty in identifying the margins

- Radiation contraindicated due to possibility of post-radiation osteosarcoma (although occasional cases have been report of OS arising in FD w/out radiation)