Fibro osseous lesion

Contents
1. Introduction
2. Various classification criteria
3. Fibrous dysplasia
a) Introduction
b) Etiology/Pathogenesis
c) Clinical features of each type
d) Radiological features
e) Histological features
f) Differential diagnosis
g) Treatment and prognosis
4. Cherubism
a) Introduction
b) Genetics

Introduction
• Fibro-osseous lesions are a diverse group of processes that are
characterized by replacement of normal bone by fibrous tissue containing a
newly formed mineralized product.
• The designation fibro-osseous lesion is not a specific diagnosis and
describes only a process.
• Fibro-osseous lesions of the jaws include developmental (hamartomatous)
lesions, reactive or dysplastic processes, and neoplasms.

• These group of lesions are known to encompass common characteristics
that include common clinical, radiographic and microscopic features.
• Fibro-Osseous lesions [FOL] regarded as very confusing area in diagnostic
pathology .
• Various classification systems have been put forward by various authors.

Classification Schemes of Fibro-Osseous
Lesions
1. Charles Waldron Classification Of The Fibro-Osseous Lesions Of The Jaws
(1985)
2. Working Classification Of Fibro-Osseous Lesions By Mico M. Malek (1987)
3. Peiter J. Slootweg & Hellmuth Muller (1990)
4. WHO Classification (1992)
5. Waldron Modified Classification Of Fibro-Osseous Lesions Of Jaws (1993)
6. Brannon & Fowler Classification (2001)
7. WHO Classification Of Fibro-Osseous Lesions Of Jaws (2005)
8. Paul M. Speight & Roman Carlos Classification (2006)
9. Eversole Classification (2008)

Charles Waldron Classification Of The Fibro-Osseous
Lesions Of The Jaws (1985)
1. Fibrous Dysplasia
a. Monostotic
b. Polyostotic
2. Fibro-Osseous (Cemental) Lesions Presumably Arising In The Periodontal Ligament
a. Periapical Cemental Dysplasia
b. Localized Fibro-Osseous-Cemental Lesions (Probably Reactive In Nature)
c. Florid Cement-Osseous Dysplasia (Gigantiform Cementoma)
d. Ossifying & Cemenifying Fibroma
3. Fibro-Osseous Neoplasms Of Uncertain Or Detectable Relationship To Those Arising In The Periodontal
Ligament (Category II)
a. Cemetoblastoma, Osteoblastoma & Osteoid Osteoma
b. Juvenile Active Ossifying Fibroma & Other So Called Aggressive, Active Ossifying /Cementifying Fibromas.

Working Classification Of Fibro-Osseous Lesions By
Mico M. Malek (1987)
In 1987 from the viewpoint of
diagnostic pathologist, a
working classification of fibro-
osseous lesions was given by
Mico M. Malek which is as
follows

Peiter J. Slootweg & Hellmuth Muller (1990)
In 1990 Peiter. J. Slootweg & Hellmuth Muller gave a classification that laid
emphasis primarily on the histopathological features, and they underscore that this
classification requires inclusion of adjacent normal bone to make diagnosis.
However in the absence of this, the clinical & radiological features have to be taken
in to consideration.
Group I: Fibrous Dysplasia
Group II: Juvenile Ossifying Fibroma
Group III: Ossifying Fibroma
Group IV: Periapical Cemental Dysplasia & Florid Osseous Dysplasia

Waldron Modified Classification Of Fibro-
Osseous Lesions Of Jaws (1993)
Later on, to overcome the demerits of his own classification, Waldron
reviewed the subject of benign fibro-osseous lesions of jaws (BFOL) in
1993 and suggested a modification of his earlier classification.

Brannon & Fowler Classification (2001)
In 2001, Brannon & Fowler
gave another classification
which was quite different
from that of Waldron & WHO
classification. This was done
to include more number of
lesions which were also
showing features like FOL.

WHO Classification Of Fibro-Osseous Lesions
Of Jaws (2005)
1) Ossifying Fibroma (OF)
2) Fiberous Dysplasia
3) Osseous Dysplasia
a. Periapical Osseous Dysplasia
b. Focal Osseous Dysplasia
c. Florid Osseous Dysplasia
d. Familial Gigantiform Cementoma
4) Central Giant Cell Granuloma
5) Cherubism
6) Aneurismal Bone Cyst
7) Solitary Bone Cyst
COD HAS BEEN THEREFORE CALLED
OSSEOUS DYSPLASIAS (BARNES ET AL.). BECAUSE
THE DISCUSSIONS DURING THESE LAST DECADES
ABOUT WHETHER CEMENTUM-
LIKE TISSUES IS PRESENT, IT HAS BEEN DECIDED TO
GIVE UP THE TERM OF “CEMENT”. The core of this
classification is the
concept of a spectrum of clinicopathological
entities in which the diagnosis can only be made
on the basis of a
full consideration of clinical, histological and
radiological features.

Paul M. Speight & Roman Carlos Classification
(2006)
THIS NEW CLASSIFICATION
CONCENTRATED ON THE
HISTOPATHOLOGICAL FEATURES that
may guide the working surgical
pathologist towards a diagnosis.

Eversole 2008 Classification
The basis of this classification
Definitive diagnosis can rarely be rendered on the basis of histopathological features alone rather;
PROCUREMENT OF A FINAL DIAGNOSIS IS USUALLY DEPENDENT UPON ASSESSMENT OF MICROSCOPIC, CLINICAL AND IMAGING

Fibrous Dysplasia --Introduction
Defect in osteoblastic differentiation and maturation.
• Remodeling in which the normal medullary bone and cortices are
replaced by a disorganized fibrous woven bone.
• The resultant fibro‐osseous bone is more elastic and structurally
weaker than the original bone.
• It is caused by the deletion of a bone maturation protein during
embryogenesis.
• There is no evidence to suggest a hereditary influence.

Etiology
• Exact cause of fibrous dysplasia is not known.
• Usually caused by a mutation in the GNAS1 gene
• Gene encodes a G-protein that stimulates the production of cAMP.
• Continuous activation of the G-protein leading to overproduction of
cAMP in affected tissues.
• Hyperfunction of affected endocrine organs, frequently giving rise to
precocious puberty, hyperthyroidism, growth hormone and cortisol
overproduction.

• Increased proliferation of melanocytes resulting in large café-au-lait
spots with irregular margins as opposed to the regular outlined café-
au-lait spots in neurofibromatosis.
• cAMP is thought to have an effect on the differentation of osteoblasts
leading to fibrous dysplasia.

THREE disease patterns are recognized
1. Monostotic form
2. Polyostotic form
3. Craniofacial form.

THREE disease patterns
• Each type usually presents as an asymptomatic, slowly expanding portion of one or
more bones.
• The condition develops in children and teenagers primarily, with few if any cases
beginning after the age of 25 years.
• Two-thirds of patients with polyostotic disease are asymptomatic before they are aged
10 years.
• With monostotic disease, patients as old as 20 or 30 years are asymptomatic.
• No specific racial predilection exists.
• The incidence is equal in males and females.
• Clinical findings of increasing pain and an enlarging soft tissue mass suggest malignant
change.

• All types of fibrous dysplasia result from a defect in bone maturation
that begins in the embryo.
• At certain times in the histodifferentiation phase of the embryo,
a genetic mutation or deletion occurs in the gene that encodes for an
intracytoplasmic transducer protein required for bone maturation.
• Consequently, all the daughter cells of this original aberrant cell will
lack this signal transducer, and therefore a certain population of cells
in the individual will be able to
• Produce only fibrous dysplastic bone rather than mature bone.

• If the genetic defect occurs early in embryonic development, a large
number of daughter cells will be affected, some of which may not yet
have migrated to their eventual skeletal site.
• When such early term‐altered cells migrate into several skeletal sites,
they produce polyostotic fibrous dysplasia.
• If the genetic defect occurs in an even earlier phase of embryonic
development, the original cell may produce daughter cells of divergent
differentiation that is, some that will migrate into bone primordia,
some into skin primordia, and some into endocrine gland primordia
and thus produce either the McCune‐Albrightsyndrome or the Jaffe‐
Lichtenstein type of polyostotic fibrous dysplasia.
• The time at which these genetic alterations occur is thought to be
before the sixth week of fetal life.

• When the embryo is in its sixth week of development, most
histodifferentiation and cell migration have already occurred.
• If the same genetic defect occurs around this time, the daughter cells
will be localized to one region and thus may produce the craniofacial
type of fibrous dysplasia, which involves several contiguous bones in a
broad area.
• If the genetic defect occurs slightly later, the daughter cells will be
even more localized and will thus produce monostotic fibrous
dysplasia.

MONOSTOTIC FIBROUS DYSPLASIA
• Monostotic fibrous dysplasia, which involves a single focus in one
bone, accounts for about 75% of fibrous dysplasia cases.
• Frequently occurs in the rib (28%), femur (23%), tibia, craniofacial
bones (10–25%), and humerus.
• Seen most frequently in the body of the mandible or in the premolar‐
molar regions of the maxilla.
• Degree of bone deformity is relatively less severe compared with that
of the polyostotic type.

Clinical Features
• Equal predilection for males and females
• More common in children and young adults than in older
• Mean age of occurrence is 27-34 years.
• The first clinical sign of the disease is a painless swelling or bulging of
the jaw.
• The swelling usually involves the labial or buccal plate, seldom the
lingual aspect, and when it involves the mandible it sometimes causes
a protuberant excrescence of the inferior border.

• Tipping or displacement of the teeth due to the progressive expansile
nature of the lesion
• Mucosa is almost invariably intact over the lesion.

Fibrous dysplasia of the maxilla
• Serious form of the disease since it has a marked predilection for
occurrence in children and is almost impossible to eradicate without
radical, mutilating surgery
• These lesions are not well circumscribed, commonly extend locally to
involve the maxillary sinus, the zygomatic process and the floor of the
orbit, and even extend back toward the base of the skull.
• Severe malocclusion and bulging of the canine fossa or extreme
prominence of the zygomatic process, producing a marked facial
deformity, are typical sequelae of this disease.

Radiographic Features
Three basic patterns
• In one type, the lesion is generally a rather small unilocular radiolucency or a
somewhat larger multilocular radiolucency, both with a rather well-
circumscribed border and containing a network of fine bony trabeculae.
• In the second type, the pattern is similar except that increased trabeculation
renders the lesion more opaque and typically mottled in appearance.
• The third type of quite opaque with many delicate trabeculae gives a ‘ground-
glass’ or ‘peau d’orange’ appearance to the lesion. This latter type
characteristically is not well circumscribed but instead blends into the adjacent
normal bone

• In all types, generally the cortical bone becomes thinned because of
the expansile nature of the growth, but seldom is this bony plate
perforated, or is periosteal proliferation obvious.
• Roots of teeth in the involved areas may be separated or moved out
of normal position but only occasionally exhibit severe resorption.

Polyostotic fibrous dysplasia
• Approximately 20–30% of fibrous dysplasias are polyostotic.
• more frequently involves the skull and facial bones, pelvis, spine, and
shoulder girdle.
• Although the polyostotic variety tends to occur in a unilateral
distribution, involvement is asymmetric and generalized when disease
is bilateral.
• Often, the initial symptom is pain in the involved limb associated with a
limp, spontaneous fracture, or both.

• The structural integrity of the bone is
weakened, and the weight-bearing
bones become bowed.
• The curvature of the femoral neck and
proximal shaft of the femur markedly
increase causing a Shepherd’s crook
deformity, which is a characteristic
sign of the disease.

Two apparently separate types of
polyostotic fibrous dysplasia
1. Fibrous dysplasia involving
a variable number of
bones, although most of
the skeleton is normal,
accompanied by
pigmented lesions of the
skin or ‘café-au-lait’ spots
(Jaffe’s type).

• An even more severe fibrous dysplasia involving nearly all bones in
the skeleton and accompanied by pigmented lesions of the skin, and
in addition, endocrine disturbances of varying types (Albright’s
syndrome).

Cutaneous pigmentation
• Most common extraskeletal manifestation in fibrous dysplasia and occurs in
more than 50% of cases of the polyostotic form.
• Cutaneous pigmentation in polyostotic fibrous dysplasia is ipsilateral to the side
of bony lesions, a feature that differentiates this disease from pigmentation in
neurofibromatosis.
• The macules or café-au-lait spots are related to increased amounts of melanin
in the basal cells of the epidermis. They tend to be arranged in a linear or
segmental pattern near the midline of the body, usually overlying the lower
lumbar spine, sacrum, buttocks, upper back, neck, and shoulders. Similar
lesions may occur on the lips and oral mucosa. Pigmentation may occur at birth,
and in fact, they occasionally precede the development of skeletal and
endocrine abnormalities.

Mc Cune Albright syndrome Neurofibromatosis
Never cross the midline and Cross the midline.
Irregular borders
(coast of Maine)
Smooth borders
(coast of California)

McCune-Albright syndrome
• Association of polyostotic fibrous dysplasia, precocious puberty,
café-au-lait spots, and other endocrinopathies due to hyperactivity of
various endocrine glands.
• Fuller Albright first described this syndrome in 1937.
• McCune-Albright syndrome has been shown to be due to a
postzygotic activating mutation of the GS alpha gene in the affected
tissues. The GS alpha subunit is the component of the G-protein
complex, which couples hormone receptors to adenylate cyclase (the
intracellular second messenger) in a submembrane site. It then
mediates the cellular effects of hormone binding.

Clinical Features
• Precocious puberty
associated with the
condition is
gonadotrophin-
independent.
• Hyperthyroidism
• Acromegaly
• Hyperprolactinemia
• Cushing syndrome
• Hyperparathyroidism
Precocious puberty as evidenced by
mature breast development and pubic
hair growth in this 6‐year‐old girl with
the McCune‐Albright type of polyostotic
fibrous dysplasia.

Mazabraud’s syndrome
• The association of fibrous dysplasia and intramuscular myxoma is a
rare disease known as Mazabraud’s syndrome.
• Both lesions tend to occur in the same anatomical region. The
relationship between fibrous dysplasia and myxoma remains unclear,
whereas an underlying localized error in tissue metabolism has been
proposed to explain this occasional coexistence.
• Patients with soft tissue myxomas should be thoroughly examined for
fibrous dysplasia. The greater risk of sarcomatous transformation in
fibrous dysplasia with Mazabraud’s syndrome has been reported.

A.Multi-loculated expansile
intramedullary fibrous
dysplasia lesions in the ileum
and proximal part of the
femur (straight arrows).
C. Coronal CT with a soft tissue
window showing the low-
density myxomas in the medial
thigh muscles (curved arrow).

Typical histological
appearance of
intramuscular myxoma:
well-circumscribed,
paucicellular lobulated
myxoid tumour with
skeletal muscle
involvement

Craniofacial form
• 25% of patients with the monostotic form and in 50% with the polyostotic
form. It also occurs in an isolated craniofacial form.
• Sites of involvement most commonly include the frontal, sphenoid,
maxillary, and ethmoidal bones.
• The occipital and temporal bones are less commonly affected.
• Hypertelorism, cranial asymmetry, facial deformity, visual impairment,
exophthalmos, and blindness may occur because of involvement of orbital
and periorbital bones.
• Involvement of the sphenoid wing and temporal bones may result in
vestibular dysfunction, tinnitus, and hearing loss.
• When the cribriform plate is involved, hyposmia or anosmia may result.

Craniofacial fibrous dysplasia
• Craniofacial fibrous dysplasia involves two or more bones of the jaw‐
midface‐skull complex in continuity.
• This type of fibrous dysplasia is seen relatively often in dental and oral
and maxillofacial practices.
• It is frequently underestimated and thought to be a monostotic
fibrous dysplasia of the maxilla, yet it often includes the zygoma,
sphenoid, temporal bone, nasal concha, and clivus.

RADIOGRAPHIC PRESENTATION
• Nearly all cases of fibrous dysplasia will show a diffuse, hazy
trabecular pattern that has been called the ground‐glass appearance
pattern as radiolucent
• CT scan pictures of fibrous dysplasia show a homogeneous, finely
trabecular bone pattern replacing the medullary bone and both
cortices and often the lamina dura as well. Its shape is fusiform and
its margins are indistinct, showing a gradual blend into normal bone.
It shows greater buccal than lingual expansion and does not d
isplace the inferior alveolar canal.

• In fibrous dysplasia, the medullary bone is replaced by fibrous tissue,
which appears radiolucent on radiographs, with the classically
described ground-glass appearance.
• Woven bone contain fluid-filled cysts that are embedded largely in
collagenous fibrous matrix, contributes to the generalized hazy
appearance of the bone.

An occlusal view of fibrous dysplasia will show
its diffuse "ground‐glass"
appearance, expansion, and fibrous dysplasia
replacement of the cortical outline.

• Usual appearance of fibrous
dysplasia in long and short tubular
bones includes a lucent lesion in the
diaphysis or metaphysis, with
endosteal scalloping and with or
without bone expansion and the
absence of periosteal reaction.
• The lucent lesion has a thick
sclerotic border and is called the
rind sign.

• Among skull and facial bones the frontal bone is involved more
frequently than the sphenoid, with obliteration of the sphenoid and
frontal sinuses.
• Most commonly, maxillary and mandibular involvement has a mixed
radiolucent and radiopaque pattern, with displacement of the teeth
and distortion of the nasal cavities.

Histologic Features
• Considerable microscopic variation
• Fibrous one made up of proliferating fibroblasts in a compact stroma
of interlacing collagen fibers
• Irregular trabeculae of bone are scattered throughout the lesion with
no definite pattern of arrangement.
• Characteristically, some of these trabeculae are C-shaped, or as
described by one author, chinese character-shaped. These trabeculae
are usually coarse woven bone but may be lamellar, although not as
well organized as normal lamellar bone.

Fibrous dysplasia (right of image) jutxaposed with unaffected
bone (left of image)

. Fibrous dysplasia consisting of a fibrous stroma
with haphazardly arranged
trabeculae of woven bone.
Fibrous dysplasia showing woven bone with no
osteoblastic rimming and
numerous osteocytes.

A mature lesion of fibrous dysplasia with
parallel arrangement of lamellar osseous
trabeculae.
The same fibrous dysplasia lesion shown revealing
osteoblastic rimming.

• Large lesions may show variation from area to area and sometimes
present a greater bony reaction around the periphery of the lesion
than in the central portion.
• Histologic features alone, however, are unreliable for diagnosis;
therefore, clinical and radiographic correlation is imperative.

Laboratory Findings
• No consistent significant changes in the serum calcium or
phosphorus, although the serum alkaline phosphatase level is
sometimes elevated.
• Premature secretion of pituitary follicle-stimulating hormone has
been reported, as well as moderately elevated basal metabolic rate.

Calcium
• Primary hyperparathyroidism, which produces excessive PTH, creates
significant hypercalcemia.
• Secondary hyperparathyroidism, which is related to renal failure and cause
excessive urinary calcium loss, produces hypocalcemia.
• The hypocalcemia in turn signals the normal parathyroid glands to produce
elevated levels of PTH, which is ineffective in elevating serum calcium level
because of the constant renal loss.
• In both situations, PTH levels are elevated.
• In primary hyperparathyroidism, elevation is caused by an autonomous
overproduction of PTH.
• In secondary hyperparathyroidism, it is caused by constantly stimulated
parathyroid glands.

Phosphate
• Phosphate, like calcium, is absorbed in the gut and is controlled by
vitamin D.
• It is also excreted in the kidneys, but unlike calcium its excretion is
enhanced by PTH, which prevents phosphate reabsorption.
• Serum phosphate concentrations are the inverse of serum calcium
concentrations in each type of hyperparathyroidism.

• In primary hyperparathyroidism, the excess PTH produces a
hypophosphatemia by increasing renal loss.
• In secondary hyperparathyroidism, urinary phosphate loss is reduced
by the lack of glomerular filtration of phosphate and the ineffective
response to PTH, resulting in hyperphosphatemia.

Alkaline Phosphatase
• Bone‐related alkaline phosphatase is an enzyme secreted by
osteoblasts that hydrolyzes organic phosphates for bone
mineralization.
• Elevations are a rough index of new bone formation.
• In Paget disease, serum calcium and phosphate levels are normal
because a dynamic equilibrium exists (the same amount of each
ion enters bone as it is released). However, as the new bone
formation tries to keep pace with bone resorption, alkaline
phosphate levels are markedly increased.

• In ossifying fibroma, fibrous dysplasia, and cherubism, the bone
aberrations are not systemic and therefore do not affect serum
calcium or phosphate levels.
• However, cherubism and fibrous dysplasia mostly occur during active
growth years in which there is a physiologic (normal) elevation of
alkaline phosphatase.

DIFFERENTIAL DIAGNOSIS
• Most important differential diagnosis for fibrous dysplasia is to
distinguish it from an ossifying fibroma.
• Other entities that may resemble fibrous dysplasia include
1. Chronic sclerosing osteomyelitis,
2. Paget disease, and
3. Sometimes osteosarcoma.

• Fibrous dysplasia arises and is established by the age of 20 years. Although
some ossifying fibromas also develop in youth, most begin at an older age.
Radiographs and/or CT scans of axial views show an ossifying fibroma to be
spherical to egg shaped, heterogeneous, and well demarcated from normal
bone. Also shown are an expanded or a thinned residual uninvolved cortex
and displacement of the inferior alveolar canal.
• The radiographs and scans support the concept advanced by worth that an
OSSIFYING FIBROMA IS A DISEASE WITHIN BONE while
fibrous dysplasia is a disease of bone.

A CT scan of fibrous dysplasia shows the same features,
especially the fibrous dysplasia replacement of the cortical outline as
well as its generally homogeneous internal structure.
This CT scan of an ossifying fibroma can be
contrasted to that of fibrous dysplasia.
Its expansion is well demarcated, retains a
thinned cortical outline, and has a generally
heterogeneous
internal structure.

• Chronic diffuse sclerosing osteomyelitis resembles fibrous dysplasia in
its diffuse and poorly demarcated radiographic appearance.
• May occur in teenagers and preteens, but it is more common in adults
• Usually severely and constantly painful; there is frequently a history of
endodontic therapy, an abscessed tooth, or some other infection; and
appropriate cultures may yield actinomyces species and eikenella
corrodens

• Paget disease can be distinguished from fibrous dysplasia by its onset
in individuals older than 40 years and its increased alkaline
phosphatase levels.
• Osteosarcoma may be difficult to distinguish from fibrous dysplasia
radiographically and certainly must be ruled out by histopathologic
studies if the diagnosis is not clear. In general, osteosarcomas do not
remodel but rather resorb a cortex and expand outward from a
destroyed cortex.

A CT scan of an osteosarcoma often
shows formation of irregular
endosteal and
extracortical bone as well as a
destroyed or obliterated cortex.
A CT scan of diffuse chronic sclerosing
osteomyelitis will show endosteal
sclerosis
within which small areas of
radiolucency may be seen.
An occlusal view radiograph or CT
scan of osteomyelitis with
proliferative
periostitis (Garre osteomyelitis) will
show some expansion and
extracortical bone formation
outside a normal cortex. Here the
extracortical bone formation is layer
ed to produce a so‐called onion‐skin
effect. Extracortical bone outside a
normal cortex is inconsistent with
osteosarcoma.

TREATMENT AND PROGNOSIS
• Preferred approach to maxillofacial monostotic fibrous dysplasia and
craniofacial fibrous dysplasia is no treatment.
• Most children adapt well to the facial expansion and do not desire
osseous contouring surgery.
• If osseous contouring surgery is desired, it is ideal to defer it until
adulthood (ages 18 to 21 years)
• Like cherubism, fibrous dysplasia shows less growth and its activity is
reduced as adulthood approaches, although occasional late expansions and
regrowth have occurred in adulthood.
• Regrowth is most commonly seen when surgeries are performed on
patients younger than 21 years.

• If, because of symptoms or psychologic needs, surgery is required during
this time period, it is important to remember that fibrous dysplasia
undergoes episodic growth, unlike cherubism, which undergoes a slow and
steady growth.
• Although the surgery itself does not stimulate regrowth, the earlier in life a
surgery is performed, the more likely it is that a natural episode of growth
will occur postsurgically.
• Therefore, surgery should be avoided during a period of active expansion
even though that is often the time that pain or peer pressure forces its
consideration.
• In such cases, the active phase should remit for a period of 3 months
before osseous contouring is performed.

• Resection is not usually indicated, even for severe craniofacial fibrous
dysplasia unless neural compression threatens vision or hearing.
• In such cases, local resection only around the area of the nerve
compression or around the involved foramen is often necessary.
• Monostotic fibrous dysplasia or a focus of polyostotic fibrous dysplasia of
the skull does lend itself to a local en‐bloc resection.
• The structural weakness of fibrous dysplasia does not functionally impair
the jaws to a great extent.
• Therefore, jaw resection with subsequent bony reconstruction is not
justified unless it is an unusual situation in which the patient's function
and appearance are significantly altered and osseous contouring is not an
option.

• Radiotherapy is contraindicated in the treatment of fibrous dysplasias
Numerous cases of radiation sarcomas arising from radiotherapy have
been documented.
• The time from radiation to sarcoma ranges from 10 to 35 years, with a
mean at about 20 years.
• To date, repeated biopsies and surgeries have not been shown to be
stimulus for malignant transformation.
• About 0.8% of long‐standing, usually polyostotic fibrous dysplasias
spontaneously transform into sarcomas.

• Radiographic features suggestive of malignant degeneration include a
rapid increase in the size of the lesion and a change from a previously
mineralized bony lesion to a lytic lesion.
• Clinical findings of increasing pain and an enlarging soft tissue mass
suggest malignant change.
• Osteosarcoma and fibrosarcoma are the most common tumors.

Fibrous dysplasia in a 17‐year‐old
patient shows an expansion, which has
been stable for more than 6 months.
Osseous contouring of fibrous dysplasia
should include the lateral and inferior
border. The bone of fibrous dysplasia
will have a cancellous noncortical
texture. The surgeon should
attempt to contour the expansion to
match the opposite side.
Ten years after the osseous
contouring, the fibrous dysplasia
has remained stable and a near
symmetry has been retained.

Content
1. Cherubism
2. Paget’s disease
3. Cemento-osseous dysplasia
a) Introduction

CHERUBISM
(Familial fibrous dysplasia of jaws, disseminated
juvenile fibrous dysplasia, familial multilocular
cystic disease of jaws, familial fibrous swelling of
jaws)
An autosomal dominant fibro-osseous lesion of the jaws
involving more than one quadrant that stabilizes after the
growth period, usually leaving some facial deformity and
malocclusion.

• Affect the jaws of
children bilaterally
and symmetrically,
usually producing
the so-called
cherubic look

• The disease was first described in 1933 by Jones, who called it familial
multilocular disease of the jaws.
• The term ‘cherubism’, was introduced by Jones and others to describe
the clinical appearance of affected patients.
• According to the WHO classification, cherubism belongs to a group of
non-neoplastic bone lesions affecting only the jaws.
• 100% penetrance in males and only 50–70% penetrance in females.

Genetics
• The gene related to Cherubism was located on chromosome 4p16.3.
• Mutations in the SH3BP2 (SH3 domain binding protein 2) gene have
been identified in about 80% of people.
• The SH3BP2 gene provides instructions for making a protein whose
exact function is still unclear.

SH3BP2 gene Protein Replacement of old bone
tissue with new one
(bone remodeling)
Inflammation in the
jaw bones
Overactivity
Triggers the production of
osteoclasts
Breakage of bone tissue
while remodeling

• Typically, the jaw lesions of cherubism remit spontaneously when
affected children reach puberty, but the reason for this remission is
unknown.
Facial expansion of cherubism at age 9 years. Here the
asymmetry is the result of
attempted osseous contouring of the left side.
The facial expansion of cherubism is usually
symmetric.
The high school graduation photograph
of the individual shown at age
17 years shows involutional clinical
remodeling without further surgery.

Possible explanation
Sex steroids and the increase in plasma
concentrations of estradiol and testosterone at
puberty
Reduction in osteoclast formation

Clinical Features
• Affected children are normal at birth and are without clinically or
radiographically evident disease until 14 months to 3 years of age.
• At that time, symmetric enlargement of the jaws begins.
• Typically, the earlier the lesion appears, the more rapidly it progresses.
• The self-limited bone growth usually begins to slow down when the
patient reaches five years of age, and stops by the age of 12–15 years.

• At puberty the lesions begin to regress. Jaw remodeling continues
through the third decade of life, at the end of which the clinical
abnormality may be subtle.
• The signs and symptoms depend on the severity of the condition and
range from clinically or radiographically undetectable features to
deforming mandibular and maxillary overgrowth with respiratory
obstruction and impairment of vision and hearing.

The jaw lesions are usually painless and symmetric and have florid
maxillary involvement.

• The lesions, which are firm to
palpation and non-tender, most
commonly involve the molar to
coronoid regions, the condyles
always being spared, and are
often associated with cervical
lymphadenopathy.

• Enlargement of the cervical lymph nodes contributes to the patient’s
full-faced appearance and is said to be caused by lymphoid
hyperplasia with fibrosis.
• The lymph nodes become enlarged before the patient reaches 6 years
of age, decrease in size after the age of 8 years and are rarely enlarged
after the age of 12 years.

• Intraoral swelling of the
alveolar ridges may occur.
When the maxillary ridge
is involved, the palate
assumes a V shape.

• A rim of sclera may be visible beneath the iris, giving the classic ‘eye
to heaven’ appearance.

Oral Manifestations
• Expansion and deformity of the jaws, and the eruption pattern of the
teeth is disturbed because of the loss of normal support of the
developing teeth.
• The endocrine disturbance also may alter the time of eruption of the
teeth.

Oral Manifestations
Numerous dental abnormalities
• Agenesis of the second and third molars
of the mandible,
• Displacement of the teeth,
• Premature exfoliation of the primary
teeth,
• Delayed eruption of the permanent teeth,
and
• Transpositions and rotation of the teeth.
• In severe cases, tooth resorption occurs.

Cherubism has occurred in association with these syndromes:
1. Noonan syndrome,
2. Ramon syndrome and

Noonan syndrome
• Short stature,
• Cherubic facies,
• Congenital heart defects,
• Chest deformity and
• Mild mental retardation
• Sporadic or inherited as an
autosomal dominant trait and
• Occurs between one in 1000-
2500

Laboratory findings
• Only significant laboratory abnormality is an elevated alkaline
phosphatase level.

Grading System
Arnott (1978) suggested the following grading system for the lesions of
cherubism:
• GRADE I is characterized by involvement of both mandibular
ascending rami,
• GRADE II by involvement of both maxillary tuberosities as well as the
mandibular ascending rami, and
• GRADE III involvement of the whole maxilla and mandible except the
coronoid process and condyles.

Type I cherubism involves just the bilateral
rami of the mandible and may go
unnoticed.
Subtle and mild expan
sion of the rami in a
type I cherubism.
Despite the absence of obvious clinical
expansion, type I cherubism will show
bilateral multilocular radiolucencies in the
rami and posterior body of the mandible
.

Type II cherubism involves the
bilateral rami and the posterior
body of the mandible
as well as a small portion of the
maxillary tuberosities.
More obvious clinical expansion in
an individual with type II
cherubism.
Type II cherubism will also have
bilateral multilocular radiolucencies
but will also
show clinical expansion and may
expand forward to the area of the
mental foramen.

• Involve mandible to an advanced degree as compared to type II and
also includes the maxilla.
• The involvement of the maxilla's contribution to the orbital floor and
orbital rim displaces the globes upward, causing a scleral show. This
feature, combined with the expansion of the maxilla, gives a child
with cherubism the chubby‐faced appearance and the "upward‐to‐
heaven"‐looking eyes of a cherub.

• The maxillary involvement includes the alveolar bone and palate but
does not extend beyond the maxillary sutures. Therefore, the
adjacent palatine bones, vomer, zygomas, and nasal bones are
completely normal.

• Radiographically, the involved bones show a dramatic multilocular
radiolucency with thin and expanded cortices, including the inferior
border. The condyle and condylar neck appear normal.

Type III cherubism involves the ent
ire mandible symmetrically across
the midline
except the condyles. It also
involves all the components of
the maxilla and will not cross
suture lines.
Type III cherubism will show obvious
symmetrical clinical expansion of
the mandible
and the maxilla. The maxillary
expansion will produce a scleral
show and will rotate the globes
upward, producing the "eyes turned
toward heaven" appearance of a
cherub.
Type III cherubism will show the classic
bilateral multilocular radiolucent lesions
of both the mandible and the maxilla.
In the mandible, the condyles will be
spared. In the maxilla, the
radiolucencies will not extend past the
maxillary sutures.

Grading (Seward and Hankey)
• Grade I: Involvement of bilateral mandibular molar regions and
ascending rami, mandible body, or mentis.
• Grade II: Involvement of bilateral maxillary tuberosities (in addition to
grade I lesions) and diffuse mandibular involvement.
• Grade III: Massive involvement of entire maxilla and mandible, except
the condyles.
• Grade IV: Involvement of both jaws, including the condyles.

• Radiologically, cherubism is characterized by bilateral multilocular cystic
expansion of the jaws.
• Early lesions occur in the posterior body of the mandible and the ascending
rami.
• Maxillary lesions may occur at the same time but escape early radiographic
detection because of overlap of the sinus and nasal cavities.
• Displacement of the inferior alveolar canal has been reported.
• The presence of numerous unerupted teeth and the destruction of the
alveolar bone may displace the teeth, producing a radiographic appearance
referred to as floating tooth syndrome

• With adulthood, the cystic areas in the jaws become re-ossified,
which results in irregular patchy sclerosis. There is a classic (but
nonspecific) ground glass appearance because of the small, tightly
compressed trabecular pattern.

Panoramic radiograph shows derangement of the teeth, many
cyst like lesions, and expansion of the cortical plates.

The facies of type III cherubism reflects
expansion of the mandible and maxilla.
Note the upward‐turned eyes caused by
maxillary expansion into the orbital
volume and the open bite
caused by nasal obstruction and
subsequent mouth breathing.
Radiographically, type III cherubism is mostly symmetric. It is a
multilocular radiolucency that spares the condyle and the upper
condylar neck.

This CT scan of type III cherubism shows symmetric maxillary expansion
and asymmetric expansion into the orbital volume, which had clinically
displaced the left eye more upward than the right eye.

• Histologically similar to central giant cell granuloma,

HISTOPATHOLOGY
• The lesions of cherubism consist of a vascular fibrous stroma,
extravasated erythrocytes, and scattered multinucleated giant cells.
• An increase in the amount of fibrous tissue and a corresponding
decrease in the number of giant cells is probably associated with
regressing lesions.
• Clinical and radiographic correlation is necessary, as the histologic
features strongly resemble those seen in central giant cell tumors
and the lesions of hyperparathyroidism.

Cherubism with histologic features similar to
those seen in hyperparathyroidism and
central giant cell tumors. The stroma is fibrous
with haphazardly arranged multinucleated
giant cells
and some hemorrhage.
High‐power view of showing multinucleated giant
cells in a fibrous stroma.

• Cherubism, like most fibro‐osseous diseases, requires a clinical and
radiographic diagnosis rather than a histopathologic diagnosis.
• Other entities that may mimic this presentation are
1. Primary hyperparathyroidism,
2. multiple odontogenic keratocysts, perhaps as part of the basal cell
nevus syndrome.

• The specific clinical and radiographic features that permit a diagnosis
of cherubism are
1. Symmetric presentation,
2. Radiographic evidence of multilocular contiguous lesions,
3. Sparing of the condyle,
4. Lack of involvement of adjacent bones,
5. Middle concha enlargement (variable) in the maxilla, and
6. Emergence and expression of the disease between the ages of 2 and 5 years

• As with any genetic disease, cherubism currently is not curable.
• However, the natural course of cherubism is one of gradual
enlargement that continues until the onset of puberty.
• After puberty, a gradual involution begins and is often complete by
age 18 to 20 years, and almost never lasting beyond age 30 years.
• The result is a nearly complete reversal of the facial expansion, which
is usually very well accepted by the individual

Facial expansion of cherubism at
age 9 years. Here the asymmetry
is the result of
attempted osseous contouring of
the left side. The facial expansion
of cherubism is usually
symmetric.
The high school graduation ph
otograph of the individual
shown at age
17 years shows involutional
clinical remodeling without
further surgery.
Although cherubism will clinically involute
to near‐normal facial contours, residual
radiolucencies containing giant cell lesions
are usually present, as are unerupted teeth
and therefore
edentulous areas.

• Radiographs show only partial bony regeneration as residual
radiolucent areas persist. There also may be unerupted and displaced
teeth. This eruption disturbance, which occurs throughout the
childhood years, may cause the patient to be partially edentulous.

• The general clinical approach is to avoid surgery altogether and allow
natural involution to take place or defer surgeries until after puberty.
• If reduction of the expanded bone (osseous contouring) is required
because of pain or psychologic needs, it is done with the knowledge
that the operated bone will re‐expand at the same or a higher rate of
expansion as before surgery.

• If osseous contouring is required, especially on a young patient, the
surgeon must be aware of the vascular nature of the bone and
proceed with the same intraoperative hemorrhage control procedure
as would be used in treating a central giant cell tumor (i.e,an elevated
head position, hypotensive anesthesia, an accessible supply of
hemostatic packs, and a preparation of autologous blood or
"designated donor" blood available for transfusion).

• Nasal obstruction is caused by enlargement of the middle concha.
Because the genetic defect is expressed on the embryologic maxilla or
mandible only, the other conchae—
the inferior concha, which is an independent bone, and the superior
concha, which is part of the ethmoid bone—are not involved.
• On occasion, the nasal obstruction can become severe, leading to air
way concerns or to significant mouth breathing and an open‐bite
deformity. In such cases, removal of the middle concha and turbinates
is a reasonable and beneficial procedure.

• Surgical therapy with curettage and replacement of the bone defect
with autograft or allograft usually results in resorption of the graft at
the surgical site.
• Use of allograft or cortical autograft usually delays this conversion, as
it is more resistant to resorption and replacement by dysplastic bone.

Paget Disease
(OSTEITIS DEFORMANS)

Introduction
• Osseous dysplasia
• Rapid turnover remodeling of bone throughout the skeleton.
• Elderly--older than 50 years
• Most prevalent in the Britain and New Zealand—Classic paget’s.
• Men : women = 3:2
• The bones most commonly affected are the spine, femurs, skull,
pelvis, sternum, and jaws.
• Maxilla is affected twice as frequently as the mandible.

• Defective function of the osteoprotegerin/ TNFRSF11A or
B/RANKL/RANK pathway, a molecular regulator of osteoclastogenesis
• Classic Paget’s disease
1. Inactivation mutations in the TNFRSF11B gene that encodes
osteoprotegerin.
2. Mutations in SQSTM1 (p62), the sequestosome gene that encodes a scaffold
protein for the NFKappaB signaling pathway

Virus theory
• Many reports that have described viral particles and arrays in the
osteoclastic cells of CPDB
• Paramyxoviruses (measles in particular), canine distemper virus and
respiratory syncytial virus.
• Develop a pagetic osteoclastic phenotype with increased numbers
and increased nuclei per cell.
• RT-PCR do not support the presence of viral transcripts.
• Active virus has not been recovered from Paget bone.

Paget Disease -- PATHOGENESIS
• The pathogenesis begins with overactive osteoclasis of bone.
• The bone responds by osteoblastic differentiation in which these
osteoblasts lay down haphazard bone in many different directions.
• An increase in vascularity to cope with the demands of so much new
bone formation develops
• Dense, sclerotic, end‐stage bone that has reduced cellularity and
vascularity.

Classic Paget Disease of Bone (CPDB)
• Late adult onset
• Rapid turnover of bone
• Osseous expansion with progressive skeletal deformities
• Tubular bones show bowing and spinal curvature, vertebral collapse
occur in the later stages of the disease.
• Markedly elevated serum alkaline phosphatase is a constant feature,
• Calcium and phosphate levels are normal.

Paget's disease of bone (osteitis deformans), which has resulted in bowing of the legs
and consequent wearing of the lateral soles & heels of the shoes

• All bones of the cranio-facial complex can be affected
• Foramina narrowing  cranial nerve neuropathies  deafness being
the predominant ﬁnding
• Osteitis circumscripta-- in early stages of disease, radiolucent
‘‘coin shaped’’ lesions appear in the ﬂat bones of the skull.
• Affected area will often feel warm with visibly enlarged veins or a
bluish hue because of the increased vascularity.
• Skull enlargement that necessitated ever‐increasing hat sizes.

The optic canals are narrowed, explaining the optic nerve compression
and the visual loss.

Cross sectional view of CT scan showing growth in the intercorticol spaces of maxilla and occipital bones

Saggital section of CT scan showing growth in the intercorticol spaces of saggital and occipital bones

Cotton wool opaciﬁcation in the maxilla

DIAGNOSTIC WORK‐UP
• Elevated serum alkaline phosphatase level.
• Serum calcium and phosphate values are normal.

Histopathology
• Repeated destruction and repair of bone with no functional
organization.
• Process continues in random fashion.
• Irregular cemental lines that mimics a mosaic.
• Marked vascularity is of surgical significance because there may be
profuse bleeding during operative procedures.

Marked osteoclastic as well as osteoblastic activity is
evident in Paget disease.
An abnormally large osteoclast is present, as are
many active osteoblasts.

Histology
Mosaic pattern of resting and reversal lines in
sclerotic bone regions
Normal bone histology

Radiographic appearance
• Pagetic bone appears as a mottled mixture of radiopacities and
radiolucencies.
• Ratio of these elements depends on the duration of the disease.
• Ground glass trabecular pattern in early stage disease.
• With progression, diffuse sclerosis is seen radiographically yielding
the so-called ‘‘cotton wool’’ appearance of conﬂuent nodular
opaciﬁcations.
• “Cotton wool" appearance because it is characterized by a fluffed,
radiodense, cloud‐like aggregation.

A mixture of irregular radiopacities, bone
expansion, and radiolucencies give
pagetic bone a so‐called cotton wool appearance
.
A skull radiograph of pagetic calvarium will often
show the same cotton wool
appearance. There is thickening of the inner and
outer tables and widening of the diploe.

Lateral skull film shows marked
enlargement of the cranium with new bone formation
above the
outer table ofthe skull and a patchy, dense, "cotton wool"
appearance.
Periapical film showing the
"cotton wool" appearance of the bone.

Nuclear medicine bone scan of an elderly male, showing marked uptake in the mandible, especially on the left.
The bearded-appearance is known as the “Abraham Lincoln” sign, after the famous American president.

Dental ﬁnding
• Generalized hypercementosis which is most advanced on premolar
and molar teeth.
• Diastemas and lingual inclinations because of dental compensations
in response to the slow expansion
• Denture wearer may present with the classic complaint of a denture
that has become too small and may even have had several appliances

Paget disease produces a slow expansion of the invol
ved bone; in the jaws, it creates
diastemas between teeth and malocclusions. Note the
increased vascularity of the area.
.Paget disease will expand the jaws so that dentures w
ill no longer fit in edentulous
individuals. The tissue will be warm because of the
excessive vascularity of pagetic bone.

• Radiopaque, painful expansion of the jaws in an adult may be suggestive
of osteomyelitis, particularly chronic diffuse sclerosing osteomyelitis.
• Osteosarcoma is another consideration.
• Fibrous dysplasia may resemble paget disease radiographically but would
have been present from early life.
• Radiopacities of florid cemento‐osseous dysplasias also mimic the
"cotton wool" appearance of paget disease and may be painful from
secondary infection.

• Mild cases require no treatment.
• Paget disease is currently incurable, but the pain and deformity can be cont
rolled with treatment.
• Anti‐osteoclastic actions of calcitonin or the bisphosphonates.
• 200‐mg oral dose of disodium etidronate may be given twice daily.
• prolonged use of etidronate will adversely affect bone mineralization in the
rest of the skeleton.
• Pamidronate is another drug effective in Paget disease, but it must be
given intravenously in 500 mL of normal saline at a dosage of 30 mg over
4 hours. Response to this therapy lasts for 3 to 6 months, then the dosage
must be repeated.

Mechanism of action of bisphosphonates

• Results in a reduction in pain and bony expansion.
• Alkaline phosphatase levels as well as urinary hydroxyproline levels
fall in response to this therapy
• Long‐Standing disease develop renal failure or nephrocalcinosis
caused by hypercalcemia.
• Radiation in paget disease is Contraindicated because it has been
proven to incite malignant transformation.

• Osteosarcomas in CPDB are seen in the elderly with severe advanced
disease
• Occur primarily in the pelvis., Proximal femur, tibia and in the
calvarium
• High grade and have already metastasized at the time of discovery.
• Only 14% survive beyond 2.5 years.

Juvenile Paget disease
(Idiopathic hyperphosphatasia)
• Inherited as an autosomal recessive trait
• Clinically by deformities in the long bones,
kyphosis, acetabular protrusion.
• Patho-physiologically by rapid bone
turnover
• Begins in infancy or early childhood

• Long bone widening with propensity for pathologic fracture and
thickening of the skull.
• Serum alkaline phosphatase is elevated.
• Extremely rapid bone turnover is accompanied by osteopenia and
skeletal deformity with bowed limbs.

Cemento‐Osseous Dysplasia
• A spectrum of dysmorphic bone and cementum
• Periapical cemento‐osseous dysplasia (a localized form of dysplasia found
in the anterior mandible)
• Florid cemento‐osseous dysplasia (a widespread form of dysplasia)
• Focal cemento‐osseous dysplasia (a localized form of dysplasia found in
single areas other than the anterior mandible).

PATHOGENESIS
• Mesenchymal stem cells that seem to have lost their ability to
maintain their structural morphology and, therefore, produce what is
termed DYSPLASTIC BONE.

Periapical Cemento‐Osseous Dysplasia
Clinical presentation
• Asymptomatic set of lesions that form around the apex of mostly
mandibular, vital anterior teeth
• Radiolucent to mixed radiolucent‐radiopaque to completely
radiopaque without a change in the root structure or tooth vitality
• Black women of AFRICAN heritage around the age of 40 years
• Usually an incidental radiographic finding because these lesions do
not induce tooth mobility or bony expansion.

DIFFERENTIAL DIAGNOSIS-- radiologically
• During the radiolucent stage,
1. Apical periodontal granuloma,
2. Radicular cyst
3. Primordial odontogenic keratocyst
4. Early phase of an ossifying fibroma.
• Chronic osteomyelitis---
It is, therefore, imperative that all anterior teeth undergo pulp testing a
nd that serial radiographs are taken over time.

• During the mixed radiolucent‐radiopaque and completely radiopaque
phases,
1. Odontoma,
2. Sequestrum from a case of chronic osteomyelitis,
3. Ossifying fibroma,
4. Osteoblastoma

HISTOPATHOLOGY
• Initially, the lesions consist of vascular fibrous tissue with no capsule.
• Over time, an increasing quantity of mineralized tissue develops,
which may take the form of rounded, cementum‐like material and/or
osseous trabeculae.
• Eventually, there is coalescence of this material with formation of a
sclerotic, avascular, and acellular mass.

A fibrous stroma within which rounded and trabecular cemento‐osseous tissue is randomly arranged.

A sclerotic area with little fibrous stroma
Ultimately a solid sclerotic mass of tissue
is formed.

DIAGNOSIS AND TREATMENT
• Biopsy is not usually required. The clinical history, age, race, sex, and
radiographic findings are sufficient to diagnose most cases.
• Because this phenomenon is not progressive, symptomatic, or
particularly damaging, no treatment is required.

FLORID Cemento‐Osseous Dysplasia
• Refers to a set of radiolucent‐radiopaque periapical and interradicular
lesions involving the mandible bilaterally and sometimes the maxilla.
• Basically an extended form of periapical cemento‐osseous dysplasia
• Asymptomatic dysmorphic bone‐cementum complexes.
• About 10% become exposed to the oral flora because of tooth
removal, periodontal disease, or pulpal disease and become painful
because of secondary infection.

Florid cemento‐osseous dysplasia will have radiopacities in several quadrants, which
will obliterate tooth root outlines. Involvement is limited to the tooth‐bearing
alveolar bone and spares the rami and basilar bone.

• Highest incidence in women of african heritage around the age of 40
• Large radiolucent, mixed, or most often dense radiopaque masses
• Do not involve the inferior border
• Do not occur in the rami.
• Not always limited to the periapical alveolar bone; often, they also
involve the interradicular bone

• Diffusely positioned, radiopaque masses in the jaws may suggest a
systemic etiology, most importantly Paget disease or the multiple
endosteomas in Gardner syndrome.
• If it cannot be distinguished from Paget disease radiographically, an
alkaline phosphatase determination is needed.
• If Gardner syndrome is a strong consideration, a skull series and other
radiographs to search for osteomas elsewhere, as well as a
colonoscopy, are recommended.

• A large ossifying fibroma or chronic osteomyelitis
• Chronic diffuse sclerosing osteomyelitis is very painful, involves the
inferior border or ramus, and is seen more commonly in Caucasians
and Asians.

HISTOPATHOLOGY
• Unencapsulated fibroblastic tissue with irregular osseous trabeculae
and acellular cementum‐like material
• Over time, sclerotic, acellular, avascular masses develop.

Florid cemento‐osseous dysplasia showing a fibrous stroma with
trabecular and rounded cemento‐osseous tissue.

The Cemento-osseous
Dysplasias.
(a) Early stage lesion
with hemorrhagic foci,
(b). Early region with
ﬁbro-
osseous pattern,
(c). Mid stage lesion with
progressively more
trabeculae,
(d). Late stage lesion
with sclerotic bone.
(e) Late stage lesion with
‘‘ginger root’’ curvilinear
conﬂuent trabeculae

• Requires a clinical‐radiographic diagnosis.
• should not treat asymptomatic florid cemento‐osseous dysplasia that
is covered with mucosa.

• If tooth removals, the roots are ankylosed to the bone‐cementum
complex, which has poor cellularity and vascularity;
wound that remains exposed and does not heal--
secondarily infected wound and the onset of pain and drainage

Cases of symptomatic, secondarily infected
• Local wound care and antibiotic therapy.
• Hyperbaric oxygen
• Although these treatments often improve the symptoms, the exposed
bone‐cementum complex usually does not heal completely, and
symptomatic exacerbations often recur
• An alveolar resection of the symptomatic area only

Surgery for florid cemento‐osseous dysplasia will identify avascular
discolored bone with some granulation tissue. The diseased bone is usually separated from normal
bone by granulation tissue. When it is not, it is more difficult to remove.

Curetted material consisting of multiple small gritty and hemorrhagic
fragments

PROGNOSIS
• Most individuals can live with the radiographically apparent lesions
without difficulties.
• Those with an exposed bone‐cementum complex are often helped by
non-surgical therapy.
• IMPORTANT----
In areas of focal resections, normal bone that does not develop the dysm
orphic features of florid cemento‐osseous dysplasia will regenerate, finding
that supports the concept that this entity arises asa dyscementogenesis.
• Bone graft remains normal as well.

After curettage of the cemento‐osseous dysplasia, the regenerated bone will be
radiographically and histologically normal.

Focal Cemento‐Osseous Dysplasia
• An incomplete form (forme fruste) of florid cemento‐osseous
dysplasia that is much less common.
• Develops in a single focus in the alveolar bone of one or both jaws

Focal cemento‐osseous dysplasia will present as a single area or as two close‐
together areas representing a less severe form of florid cemento‐osseous dysplasia but making it less
distinguishable from other radiopaque lesions.

Melrose RJ, Abrams AM, Mills BG. Florid osseous dysplasia. A clinical-
pathologic study of thirty-four cases. Oral Surg Oral Med Oral Pathol.
1976 Jan;41(1):62-82.
Describe one additional feature that had not been reported previously:
the simultaneous occurrence of simple bone cysts in approximately
40% of their series of 34 cases of florid osseous dysplasia.
The suggested cause for the occurrence of these cysts is obstruction of
the normal interstitial fluid by the fibroosseous proliferation.

• Odontoma,
• Cementoblastoma,
• Osteoblastoma,
• Ossifying fibroma,
• Osteosarcoma.
• Condensing osteitis, a residual tooth root, or a bone scar from a
previous injury

FCOD OF
An irregular mixed radiolucent-opaque
pattern (69%) with slightly more than
half of cases showing well-deﬁned
borders.
More than half of OF present as a pure
radiolucency with signiﬁcantly larger size
and typically cause jaw expansion
clinically.
FCOD shows a close association with
tooth apices (70.6%) or with previous
extraction sites (21%).
Majority of OF (86%) shows no
relationship with either.
Benign nonneoplastic process OF is a true neoplasm

• Focal cemento‐osseous dysplasia is a radiographic diagnosis that,
once made, should not require treatment unless a non-
healing bone exposure or significant symptoms develop.
• In such cases, removal of the affected bone and teeth in the area will
resolve the disease.

Content
1. Hyperparathyroidism
2. Osteopetrosis
3. Ossifying fibroma
a) Introduction

Primary Hyperparathyroidism
• Caused by hypersecretion of parathyroid hormone (PTH)
• Hyperplastic glands
• Identified by hypercalcemia ≥10.5 mg/dl [2.6 mmol/L], after correction for serum
albumin (8.5 to 10.2 mg/dL)
• <5% of cases are recognized by the presence of an osteolytic defect with giant cells,
a condition referred to as a brown tumor.
• Some cases are suspected by the presence of renal "stones" (nephrocalcinosis).

• More common in women and in those older than 50 years.
• Most gland hyperplasias are of unknown cause, but some are related to the
multiple endocrine neoplasia syndrome of familial inheritance types i and iia
(MEN I AND MEN IIA).
• Because most cases are due to an idiopathic hyperplasia of each gland, a
neck mass is usually not palpable.
• Most cases are asymptomatic. However, as serum calcium levels increase,
symptoms may occur that are related to the hypercalcemia per se or to the
disease's effects on bone and on the urinary tract.

Pathogenesis of Hypercalcemia
• Over-secretion of active PTH.
• Increases serum calcium levels by the following three mechanisms
(in order of decreasing effect):
(1) Increasing osteoclastic bone resorption;
(2) Reducing renal excretion of calcium; and
(3) Increasing calcium absorption in the small intestines.

Pathogenesis of Hypercalcemia
Resultant abnormal laboratory test results,
• Hypercalcemia,
• Compensatory hypophosphatemia, and
• Alkaline phosphatase level is usually normal, may increase in
widespread lytic disease

Hypercalcemia‐Related Signs and Symptoms

Bone‐Related Signs and Symptoms
• Bone pain is the main symptom and occurs primarily in the vertebrae, tibias,
and joints.
• Long‐standing disease can produce kyphosis and multiple small vertebral
fractures that can lead to loss of height.
• Radiolucencies (brown tumors) may develop in bones, commonly in the jaws
or a diffuse demineralization, sometimes called osteitis fibrosa cystica, may
result.

• Both entities evidence a fibrovascular stroma replacing mineralized
bone. These areas appear as a friable, red‐brown mass, hence the term
BROWN TUMORS.
This mandibular radiolucency was asymptomatic
and caused a slight expansion. It was thought to be
another entity but was confirmed to be a brown
tumor by biopsy and a serum calcium
determination, which identified a 14.1 mg/dL value
This known brown tumor of hyperparathyroidism
was identical to the more common giant cell
tumor. It was friable, hemorrhagic, and reddish
brown.

Subperiosteal erosion along the shafts of the
phalanges

“Salt and pepper” appearance of the skull

75-year-old woman with right mandible cystic lesion
and primary hyperparathyroidism. Axial unenhanced CT
image shows a well-circumscribed, expansive lytic
lesion within the right angle and body of the mandible,
with cortical expansion and incomplete internal septa
but without internal osteoid or calcified matrix.
75-year-old woman with right mandible cystic
lesion and primary hyperparathyroidism. MR
imaging

Urinary Tract ‐Related Signs and Symptoms
• Polyuria and a resultant increase in thirst (polydipsia) are related to
hypercalcemia.
• Renal calculi in the calyces or ureters or calcifications within the renal
parenchyma (nephrocalcinosis) are deposits of calcium oxalate or calcium
phosphate.
• Obstructive nephropathy or nephrocalcinosis leading to renal failure may
develop in long‐standing disease.

"STONES, BONES AND ABDOMINAL GROANS"
• Stones refers to the fact that marked tendency to develop renal calculi (kidney
stones, nephrolithiasis) because of the elevated serum calcium levels.
• Bones -- osseous changes that may occur in conjunction with
hyperparathyroidism--subperiosteal resorption of the phalanges of the index
and middle fingers. Generalized loss of the lamina, A decrease in trabecular
density and blurring of the normal trabecular pattern occur; often a "ground
glass" appearance results.
• Abdominal groans refers to the tendency for the development of duodenal
ulcers.

HISTOPATHOLOGY
• Jaw lesions of hyperparathyroidism exhibit a picture that is virtually
identical to that of the central giant cell tumor. A proliferation of
spindle cells with extravasated blood and haphazardly arranged,
variably sized multinucleated giant cells is seen.
• These are osteoclasts, the action of which is influenced by PTH. Osteoid
formation may also occur. All types of hyperparathyroidism present
similar histologic findings.

A lesion of hyperparathyroidism showing
resorption of bone with deposition of
osteoid and a fibrous stroma with
multinucleated giant cells.
The fibrous stroma and scattered osteoclasts.
Both the osteoclasts and hemorrhage occur
haphazardly throughout the lesion.

Scattered multinucleated giant cells within a
vascular and proliferative
fibroblastic background.
This periapical radiograph
reveals the "ground glass" appearance of the
trabeculae and loss
of lamina dura in a patient with
hyperparathyroidism.

H&E staining shows multinucleated giant cells and abundant
hemosiderin deposition.

TREATMENT
• Medical treatment for primary hyperparathyroidism is indicated only in
those in whom surgery is contraindicated and in those with mild
hypercalcemia (< 11 mg/dL [2.75 mmol/L], albumin corrected) who show
no evidence of organ dysfunction.

TREATMENT
• Treatment consists of increased fluids, exercise, avoidance of prolonged
inactivity, and avoidance of thiazide diuretics, because these drugs
decrease calcium excretion and raise serum calcium levels.
• For postmenopausal patients, estrogen hormone therapy also may be
considered.

• Most patients with primary hyperparathyroidism require surgery.
• Surgery involves removal of at least three of the four glands and, in
some cases, a subtotal resection of the fourth.
• If the disease has been isolated to a specific adenoma or carcinoma,
excision of only that particular tumor is the rule.

• After surgery, most patients are expected to become hypocalcemic
within 12 to 24 hours.
• Checked with determination of serum calcium and serum albumin
levels as well as eliciting a positive Chvostek sign.
• Rapid fall in serum calcium to subnormal levels may produce a
hypocalcemic tetany.

• Some patients require large amounts of calcium, vitamin D3
(cholecalciferol), and increased dietary magnesium in the first 1 week
to 1 month following surgery while the residual parathyroid gland
responds to the hypocalcemia with its own hyperplasia.
• Efforts should be made to keep serum calcium levels above 8.0 mg/dL
(2 mmol/L).

PROGNOSIS
• Prognosis after surgery is very good as the remaining parathyroid gland
adapts to the Increased demands placed on it.
• Supplemental calcium, vitamin D, or magnesium is rarely needed.
• The disease may recur, often many years after surgery.
• Recurrences are hyperplasias of glands not excised at surgery.

DIFFERENTIAL DIAGNOSIS AND WORK‐UP
• Most common presentation is one of hypercalcemia without
radiographic evidence of bone lesions.
• Other entities that cause hypercalcemia are:
• Multiple myeloma, hypercalcemia of malignancy, sarcoidosis, over-
ingestion of calcium and/or vitamin D.

• Primary hyperparathyroidism should be confirmed by
radioimmunoassays (RIAs) ofthe circulating parathyroid levels. Such RIA
are sufficiently specific to determine levels of normal PTH.
• If necessary, multiple myeloma can be ruled out by serum protein
electrophoresis
• Sarcoidosis by an incisional parotid biopsy,
• Overingestion of calcium or vitamin D by history.

CLINICAL PRESENTATION AND PATHOGENESIS
• Occurs secondary to renal failure.
• Most patients on dialysis have some element of secondary
hyperparathyroidism.
• The patient is hypocalcemic and has hyperphosphatemia, which are
conditions opposite to those seen in primary hyperparathyroidism.
• In both, alkaline phosphatase enzyme levels are normal.

Renal loss of calcium
Hypocalcemia
Continuously secreting PTH in
response by normal
parathyroid glands

• Lack the symptoms related to hypercalcemia
• Do have PTH‐related signs, such as brown tumors and osteitis fibrosa
cystica, which is termed renal osteodystrophy
• These symptoms are usually coupled with the signs and symptoms of
their existing renal failure.

• Secondary hyperparathyroidism is suspected when a patient presents
with a history of dialysis and/or renal failure. It is confirmed by
demonstrating hypocalcemia, hyperphosphatemia, and elevated PTH
levels.
• Radiographs may show involvement of all bones with a
patchy and mottled radiolucent/radiopaque appearance. Expansion in
the areas of brown tumors also is seen.

• Loss of the lamina dura and
tooth mobility are seen more
commonly in secondary hyper
parathyroidism than in
primary hyperparathyroidism

Secondary hyperparathyroidism will affect all
bones with a moderate expansion and
a diffuse mottled radiopacity.
Secondary hyperparathyroidism also affects the
mandible with a moderate
expansion and a diffuse mottled radiopacity.

TREATMENT
• Secondary hyperparathyroidism is managed by closely controlled
dialysis or by a renal transplant.
• Significant bone disease associated with the condition may be
prevented or reduced by medical management.
• Phosphate binders such as calcium carbonate and aluminum hydroxide
antacids can reduce the hyperphosphatemia. A reduction in the excess
phosphate will raise serum calcium levels, while compensatory
mechanisms attempt to maintain the product of serum calcium and
serum phosphate at a constant level.
• vitamin D may be administered

PROGNOSIS
• Secondary hyperparathyroidism may be totally incurable even with
renal transplantation and effective dialysis.
• Most patients with renal failure have some element of chronic
disease and undergo more active therapy to treat symptoms as they
occur.

Osteopetrosis
CLINICAL PRESENTATION AND PATHOGENESIS
• Inherited defect in osteoclasts.
• Defective osteoclasts fail to resorb bone in the normal (0.7% per day)
resorption‐remodeling cycle of the skeleton.
• All bones progressively become more dense, less cellular, and less
vascular.
• Foramen and the marrow cavity spaces, these areas become
compromised and compressed in osteopetrosis.

• Therefore, fractures, anemia, thrombocytopenia, and nerve
dysfunction ranging from hearing loss to visual disturbance to facial
palsy are possible.
• Three inheritance patterns
• Severe autosomal‐recessive osteopetrosis, which is also known as
albers‐schonberg disease;
• Mild autosomal‐recessive osteopetrosis; and
• Benign autosomal‐dominant osteopetrosis.

• Each of these inheritance patterns may produce a similar
presentation clinically and will have overlapping signs.
• Distinguishing the conditions requires genetic testing and long‐term
clinical observation.
• Exposed bone with granulation tissue and a low‐grade osteomyelitis.
• Increased radiographic density is seen on panoramic radiographs or
skull radiographs and unerupted teeth are present.

Due to the presence of teeth or the removal of teeth,
osteopetrosis patients frequently have exposed bone
of the alveolar ridges with granulation tissue, a finding
that is not usually seen in other bones.

• The vertebrae may appear to have the "sandwich" look, an early sign
that is caused by an increased density in the superior and inferior
cortices in contrast to the less dense cancellous marrow area
between them
Early or less severe cases of
osteopetrosis may be identified
on a cervical‐ (C‐) spine radiograph
which will show an increased
density of the vertebral cortices,
called sandwich appearance.

Since osteopetrosis involves all skeletal
tissues, radiographs showing extreme
bone densities can be astonishing.

• Exposed dense and discolored bone is common and almost always
follows tooth extraction.
• Cutaneous fistulae also are frequently seen.
• Defective vision and nystagmus are common.
• Any of the cranial nerves may be compressed at several foramina and,
therefore, can present with a varied group of paresthesias and p
areses.

• Because osteopetrosis begins in the cortex of long bones and
progresses inward, significant marrow cavity obliteration is a later
finding.
• Anemia and thrombocytopenia may be seen but are uncommon.

RADIOGRAPHIC APPEARANCE
• The skull in particular will show an extreme density.
• The mandible should be assessed for fractures, unerupted teeth, and
areas of past debridement.
• The maxillary sinuses may be smaller than usual and the frontal sinus
obliterated altogether.
• Radiographs of the cervical spine in early stages will show the
"sandwich" appearance.
• Subluxations and a fracture of the odontoid process.

• Enamel hypoplasia, defects in mineralization of dentin, and abnormal
pulp chambers.
• Unerupted teeth show areas of ankylosis between cementum and
bone with absence of periodontal membrane

Panoramic radiograph of osteopetrosis showing defects from previous surgery, a
pathologic fracture, a retained tooth, and a bone sequestrum, all of which are typical of
the disease.

Erlenmeyer flask deformity
Relative constriction of the diaphysis and
flaring of the metaphysis.

• A fully expressed case of osteopetrosis is radiographically
pathognomonic by its involvement of all bones.
• If the presentation is one of only clinically exposed dense bone and
no radiographs have been taken, the clinician should be concerned
about florid cemento‐osseous dysplasia,
• Osteoradionecrosis if there is a history of radiotherapy,
• Early cases may also produce a radiographic picture resembling the
bony changes seen in severe anemias, such as severe sickle cell
anemia and beta thalassemia.

• Most commonly confirmed by history because the patient is usually
well aware of his or her condition.
• Skull radiographs
• Cervical spine radiographs
• Panoramic radiograph
• Complete blood count is recommended either to document anemia/
pancytopenia or to establish a reference point for future comparisons

HISTOPATHOLOGY
• Osteoclasts lack ruffled border
which normally release
lysosomal enzymes at the bone
‐osteoclast interface.
• Therefore, these defective
osteoclasts fail to resorb bone
in the
normal resorption‐remodeling
cycle. medulla has been replaced by material that
looks like primary spongiosa

mandibular osteomyelitis, and multiple draining fistulae are
present on his face

Draining sinus extraorally in
mandibular right posterior region
large area of denuded bone in
45, 46 region

Resected mandible Healing intraorally after 2 weeks

BIOLOGIC BEHAVIOR AND TREATMENT
• Unlike in other diseases involving exposed nonviable bone,
debridement is not the focus of therapy in osteopetrosis.
• Avoid bony surgery and to limit the degree of surgery as much as
possible
• Involvement of the entire skeleton does not allow the surgeon to debride
to "healthy bone,"
• Bone grafts are not available from any site.
• Therefore, almost all surgeries in which bone is debrided and a soft tissue
closure is obtained result in re‐exposure of a greater amount of bone and
further risk of fracture.

• Tooth removal should be avoided if possible.
• Frequent dental visits with prophylaxis and prompt restorative and en
dodontic care are recommended.
• A removed tooth often initiates the development of persistently
exposed bone and low‐grade infection.
• Mostly nonsurgical management even when fractures occur.
• Chlorhexidine gluconate oral rinses, and frequent irrigations
• Culture‐directed antibiotics

OSSIFYING FIBROMA (CEMENTIFYING
FIBROMA; CEMENTO-OSSIFYING FIBROMA)
• Ossifying fibroma is a true neoplasm with a significant growth
potential.
• True ossifying fibromas are relatively rare
• Focal cemento-osseous dysplasia
• Variable mixture of bony trabeculae, cementum-like spherules, or
both.
• Same progenitor cell produces the different materials.
• All of these variations will be combined under the term, ossifying
fibroma.

Clinical features
• Cases encountered during the third and fourth decades of life.
• Female predilection
• Mandible > maxilla
• Mandibular premolar and molar area is the most common
• Painless swelling of the involved bone
• May cause obvious facial asymmetry
• Rarely pain and paresthesia

Radiographic features
• Well defined and unilocular
• Depending on the amount of calcified material, may appear
completely radiolucent , or more often varying degrees of radiopacity.
• Large ossifying fibromas of the mandible often demonstrate a
characteristic downward bowing of the inferior cortex of the
mandible.

Enlargement of the posterior maxilla caused
by a large ossifying fibroma
Mixed radiolucent and radiopaque lesion
expanding the posterior maxilla

Histopathologic Features
• Well demarcated from the surrounding bone,
• Permitting relatively easy separation of the tumor from its bony bed.
• Few show grossly and microscopically a fibrous capsule surrounding
the tumor.
• Most are not encapsulated but are well demarcated

Gross specimen showing a
well-circumscribed tumor that shelled out in one piece.

Histological view showing a fibrous stroma with calcifications
and osteoid material.

Treatment and Prognosis
• Circumscribed nature of the ossifying fibroma generally permits
enucleation of the turnor with relative ease
• Prognosis is very good, and
• Recurrence after removal of the tumor is rarely encountered
• No evidence that ossifying fibromas ever undergo malignant change.

Differential diagnosis
• Fibrous dysplasia
• Focal cemento-osseous dysplasia

JUVENILE OSSIFYING FIBROMA
(JUVENILE ACTIVE OSSIFYING FIBROMA;
JUVENILE AGGRESSIVE OSSIFYING FIBROMA
• Distinguished from the larger group of ossifying fibromas on the basis
of the age of the patients, most common sites of involvement, and
clinical behavior.
• Two patterns: (1) trabecular, (2) psammomatoid.

Clinical and Radiographic Features
• No significant sexual predilection
• Well-circumscribed. And lack continuity with the adjacent normal
bone.
• Trabecular form is diagnosed initially in younger patients; mean age =
11 years.
• Psammomatoid variant approaches 22 years.
• Reveal a maxillary predominance.
• Cortical expansion facial enlargement

Computed tomography (CT) scan showing a
large tumor involving the left maxilla and
maxillary sinus of a 12-year·old girl.
Clinically, the tumor was growing rapidly.

• nonencapsulated but well demarcated from the surrounding bone.
• tumor consists of cellular fibrous connective tissue that exhibits areas
that are loose and other zones that are so cellular that the cytoplasm
of individual cells is hard to discern because of nuclear crowding.
• Mitotic figures can be found but are not numerous.
• mineralized component in the two patterns is very different

• Trabecular variant shows irregular strands of highly cellular osteoid
encasing plump and irregular osteocytes

• Psammomatoid pattern forms
concentric lamellated and
spherical ossicles that vary in
shape and typically have
basophilic centers with
peripheral eosinophilic osteoid
rims

• Many tumors demonstrate slow but progressive growth, some
juvenile ossifying fibromas demonstrate rapid enlargement.
• For smaller lesions, complete local excision or thorough curettage
appears adequate.
• For some rapidly growing lesions, wider resection may be required.
• Recurrence rates of 30% to 58% have been reported for juvenile
ossifying fibromas.
• Malignant transformation has not been documented .

FAMILIAL GIGANTIFORM CEMENTOMA
• Hereditary disorder
• Formation of massive sclerotic masses of disorganized mineralized
material.
• Autosomal dominant disorder- high penetrance and variable
expressivity.
• Caucasians
• No sexual predilection

• Develop radiographic alterations during the first decade of life.
• By adolescence, clinically obvious alterations are typically noted.
• Rapid and expansive growth pattern
• Limited to the jaws
• Multifocal involvement of both the maxilla and mandible.
• Significant facial deformity, as well as impaction, malposition, and
malocclusion of the involved dentition.
• Osseous enlargement eventually ceases during the fifth decade.

• Radiographically, features resemble those seen in cemento-osseous
dysplasia.
• Radiolucent Mixed pattern  radio-opaque
Same spectrum of changes seen in florid cemento-osseous dysplasia,
and the two cannot be distinguished microscopically.

Massive mixed radiolucent/
radioopaque expansile lesions in both jaws.

Fibro-osseous pattern
with cementicles and boney trabecuae, the former oftern appearing
much larger that those seen in cemento-ossifying ﬁbroma

• Before the final sclerotic stage, attempts to improve aesthetics by
shave-down surgical procedures have not been successful because
the dysplastic tissue rapidly regrows.
• Once sclerotic, extensive resection of the altered bone and
reconstruction have been recommended and can produce acceptable
functional and aesthetic results.

Summarize
Fibrous dysplasia
• Expansion of bone
• Unilateral, painless
• Alk phosphatase
• Mono or Polyostotic
• Diffuse radiolucent or ground glass
• Trabecular ‘‘Chinese/Hebrew’’

Osteitis deformans
Expansile lesions
Alk phosphatase
Cranial neuropathies
Polyostotic
Ground glass
Cotton wool
Mosaic bone

Cemento-osseous Dysplasia
Non-expansile
Painless
African descent
3 patterns
MELROSE et al

Hyperparathyroidism
Parathormone, Ca
Renal disease
Ground glass
Multilocular Brown tumors
Massive opaque jaw lesions
Trabecular
Giant cell lesions

Ossifying ﬁbroma
Expansile, painless
Circumscribed lucent
Floccular opacities
Similar to cemento-osseous

Fibro osseous lesion

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