Fibrous dysplasia is a benign bone lesion characterized by the replacement of normal bone by fibrous tissue containing irregularly shaped bone trabeculae. It can involve single bones (monostotic) or multiple bones (polyostotic). The lesion is caused by a mutation in the GNAS1 gene leading to abnormal bone formation. Clinically, it presents as swelling or deformity and radiographically as a "ground-glass" opacity. Histologically, there are irregular bone trabeculae in a cellular fibrous stroma. Treatment involves surgery for functional or cosmetic reasons, while some severe cases may be treated with bisphosphonates. Malignant transformation is rare.

1. Anitha N, Sankari SL, Malathi L, Karthick R. Fibrous dysplasia-recent
concepts. J Pharm Bioallied Sci. 2015;7(Suppl 1):S171-S172.

2. CONTENTS
 INTRODUCTION
 CLASSIFICATION OF FIBRO-OSSEOUS LESIONS
 DEFINITION
 ETIOLOGY
 PATHOPHYSIOLOGY
 CLINICAL FEATURES
 RADIOLOGICAL FEATURES
 HISTOPATHOLOGICAL FEATURES
 DIFFERENTIAL DIAGNOSIS
 MALIGNANT TRANSFORMATION
TREATMENT

3. ABSTRACT
Fibrous dysplasia (FD) is a benign intramedullary fibro-osseous
lesion. FD is a bone developmental anomaly characterized by
replacement of normal bone and marrow bone by fibrous tissue.
It involves any of the bones as single lesion (monostotic) or in
multiple bone lesions (polyostotic) or all of the skeletal system
(panostotic). Long bones are most commonly involved, which
mostly identified incidentally and clinically appears
asymptomatic. Clinical, radiographical and histopathological
findings will help in confirming the lesion. There are many
treatment option available, but still management of FD remains
challenging.

4.  Fibro-osseous lesions are a diverse group of processes that characterized by
replacement of normal bone by fibrous tissue containing a newly formed
mineralized product.
 The commonly included fibro-osseous lesions are fibrous dysplasia (FD),
cemento-osseous dysplasia and ossifying fibroma.

5. WHO CLASSIFICATION 1992
1. Osteogenic Neoplasms
a. A.Cemento-Ossifying Fibroma (Cementifying Fibroma, Ossifying Fibroma)
2. Non-Neoplastic Bone Lesions
a. Fibrous Dysplasia Of Jaws
b. Cemento-Osseous Dysplasia
I. Periapical Cemental Dysplasia (Periapical Fiberous Dysplasia),
II. Florid Cemento-Osseous Dysplasia (Gigantiform Cementoma, Familial Multiple
Cementomas)
III. Other Cemento-Osseous Dysplasia
c. Cherubism (Familial Multilocular Cystic Disease Of The Jaws)
d. Central Giant Cell Granuloma
e. Aneurismal Bone Cyst
f. Solitary Bone Cyst (Traumatic, Simple, Hemorrhagic Bone Cyst)

6. Waldron Modified Classification Of Fibro-
Osseous Lesions Of Jaws (1993)
1. Fibrous Dysplasia
2. Cement-Osseous Dysplasia
a. Periapical Cement-Osseous Dysplasia
b. Focal Cement-Osseous Dysplasia
c. Florid Cement-Osseous Dysplasia
3. Fibro-Osseous Neoplasm
A. Cementifying Fibroma,
B.Ossifying Fibroma,
C. Cement-Ossifying Fibroma
David S. Macdonald, classification and nomenclature of fibro-osseous lesions, volume 131, issue 4, p385-389, april 01, 2021

7. WHO CLASSIFICATION 2005
1) Ossifying Fibroma (OF)
2) Fibrous 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
David S. Macdonald, classification and nomenclature of fibro-osseous lesions, volume 131, issue 4, p385-389, april 01, 2021

9. DEFINITION
 FD is a developmental tumor like a condition characterized by
replacement of normal bone by an excessive proliferation of cellular
fibrous connective tissue intermixed with irregular trabeculae.
 A benign lesion, presumably developmental in nature, characterized by
the presence of fibrous connective tissue with a characteristic whorled
pattern and containing trabeculae of immature non lamellar bone.
(Waldron 1985)
 Reeds definition : fibrous dysplasia is an arrest of bone maturation in
woven bone with ossification resulting from metaplasia of a non specific
fibro-osseous type

10. ETIOLOGY
 Fibrous dysplasia is not hereditary in nature and it caused by mutation in
the GNAS1 (guanine nucleotide binding protein, alpha stimulating
activity polypeptide) gene and this gene encodes a G-protein which
results in overproduction of cAMP in the affected tissues.
 Further more,there is increased the proliferation of melanocytes thus
results in cafe-au-lait spots.
 The cAMP have effect on the differentiation of osteoblasts

11. PATHOPHYSIOLOGY
 Bianco et al demonstrated that FD is a disease of bone marrow stromal cells
(BMSC)
 The BMSCs form structural framework upon which hematopoiesis occurs
in the bone marrow and a subset of BMSC are multipotent stem cells
capable of differentiating into multiple cells including osteoblasts,
osteocytes, chondrocytes, bone marrow adipocytes and other cells.
 In FD BMSC differentiate along osteogenic lineage, but differentiation is
arrested and instead undergo proliferation giving rise to fibro-osseous
masses of tissue.
 Arrest in differentiation is by mutation in GNAs gene.

15. POST ZYGOTIC MUTATION OF
GNAS 1 GENE
ACTIVATION OF G PROTEIN OVERPRODUCTION OF CAMP
HYPERFUCTION OF
ENDOCRINE SYSTEMS &
INCREASED PROLIFERATION
OF MELANOCYTES
PRECOCIOUS PUBERTY
OVERPRODUCTION OF
GROWTH HORMONE,
CORTISOL, HYPERTHYROIDISM
LARGE CAFÉ AU LIT
SPOTS

16. UNDIFFERENTIATED STEM CELLS
DURING EARLY EMBRYOGENESIS
OSTEOBLASTS
MELANOCYTES
ENDOCRINE
CELLS
MULTIPLE
BONE LESIONS
CUTANEOUS
PIGMENTATION
ENDOCRINE
DYSFUNCTION

17. LATER STAGE OF
EMBRYOGENESIS
MANIFESTATION IS RESTRICTED
TO OSTEOBLAST
FIBROUS
DYSPLASIA
POST NATAL LIFE
MUTATED CELLS ARE
CONFINED TO ONE
SITE
FIBROUS
DYSPLASIA OF
SINGLE BONE

18. CLINICAL FEATURES
 Fibrous dysplasia has three clinical patterns namely monostotic, polyostotic,
craniofacial form.
 incidence of Fd 1:4000 to 1:10,000.(Young population)
 About3% of lesions associated are ,with skin pigmentation and hyper-functioning
endocrine disorders known as the McCune–Albright syndrome.
 FD in infancy is rare and heralds severe widespread disease with multi organ
involvement.
 Pain, fracture and deformity are common clinical features.

19.  The pain complaint is less in children and more in adults.
 The skull base and proximal metaphysic of femoral, are two sites most
commonly involved.
 In childhood in the skull, FD involves skull bases and facial bones.
 FD presents as facial asymmetry or a bump, but symmetric expansion of
malar prominences and/or frontal bosses may be seen.
 Due to abnormal growth and deformity of craniofacial bones may result in
encroachment on cranial nerves.

20.  Female patients experience increased pain level during pregnancy
and during the menstrual cycle because of estrogen receptors found
in FD.

21.  Monostotic fibrous dysplasia is diagnosed most often during the second and
third decades of life.
 Males and females are affected with about equal frequency.
 Commonly involved sites include the ribs, femur, and tibia, craniofacial bones,
humerus.
 70% to 85% of patients with fibrous dysplasia have disease limited to a single
bone.
 If it is occurring in craniofacial bones, Maxilla is affected more often than the
mandible.
 There is a predilection for the posterior region.
MONOSTOTIC FIBROUS
DYSPLASIA

22. 25-year-old man with leontiasis ossea as a complication
of polyostotic fibrous dysplasia

23. Painless, unilateral swelling is the most common clinical finding .
Growth is generally slow, and it is common for the patient to be
aware of the condition for several years before seeking professional
evaluation.
Occasionally, however, the growth may be fairly rapid.
Maxillary lesions often involve adjacent bones (eg. Zygoma
,sphenoid, occipital). These lesions are often called as craniofacial
fibrous dysplasia.
Adjacent teeth may be displaced by the bony mass but usually
remain firm.

24.  Mandibular lesions often exhibit buccolingual expansion and bulging of the
inferior border.
 There may be superior displacement of the inferior alveolar canal.
 The classic radiographic finding is a fine “ground-glass”opacification with
poorly defined margins.
 Periapical radiographs of the adjacent dentition may demonstrate narrowing of
the periodontal ligament space and an ill-defined lamina dura.

25.  Involvement of two or more bones is termed as polyostotic fibrous dysplasia.
 Less common and more severe.
 Sites- femur, tibia ,pelvis ,ribs, skull ,facial bones, upper extremity ,lumbar,
cervical
 Age – before 10 years
 Sex- female> male
 The number of involved bones varies from a few to 75% of the entire
skeleton.
 Patient usually complain of pain, pathologic fracture, limping, leg length
discrepancy, and bowing deformity.

26. Shepherd’s crook deformity - refers
to a distinctive abnormal contour of
the proximal femur in the setting of
fibrous dysplasia. As the bone
deforms the angle made between the
neck of the femur and shaft of the
bone.
RADIOLOGICAL FEATURES
Periapical radiograph showing a
diffuse “ground-glass”
radiographic appearance.
Occlusal radiograph showing
localized expansion of the
mandible and the “ground-glass”
radiographic appearance. The
margins of the lesion are not
well defined and blend into the
adjacent bone.

27. SYNDROMES ASSOCIATED
McCune-Albright syndrome, characterized by polyostotic
fibrous dysplasia, café au lait pigmentation, and multiple
endocrinopathies
Jaffe-Lichtenstein syndrome, characterized by polyostotic
fibrous dysplasia and café au lait (coffee with milk)
pigmentation.
Mazabraud syndrome, characterized by fibrous dysplasia and
intramuscular myxomas.
Neville, Damm, Allen, Bouquot. Oral & maxillofacial pathology ,1st south asia edition

28. LAB FINDINGS
No significant change in serum
calcium/phosphorus
Elevated Alkaline phosphatase
Moderate increase in Basal
Metabolic Rate

29. HISTOPATHOLOGIC FEATURES
 Irregularly shaped trabeculae of immature (woven) bone in a cellular fibrous
stroma.
 The lesional bone fuses with normal bone, without a capsule or line of
demarcation.
 Abnormal bony trabeculae tend to be thin and disconnected, with curvilinear
shapes likened to Chinese characters.
 Osteoblastic rimming is usually absent or minimal, and peritrabecular clefting
Neville, Damm, Allen, Bouquot. Oral & maxillofacial pathology ,1st south asia edition

30. Irregularly shaped trabeculae of
woven bone in a fibrous stroma.
Neville, Damm, Allen, Bouquot. Oral & maxillofacial pathology ,1st south asia edition

31.  In later stages, the woven bone is replaced by lamellar bone with roughly
parallel trabeculae.
long-standing lesion shows separate, broad
trabeculae of bone within fibrous connective
tissue
Maturation of lamellar
bone
Neville, Damm, Allen, Bouquot. Oral & maxillofacial pathology ,1st south asia edition

32.  Microscopic variations include a pagetoid pattern (characterized by
thick, interconnected bone trabeculae) and a hypercellular pattern by
parallel bone trabeculae with numerous osteocytes and polarized
osteoblastic rimming).
 Secondary aneurysmal bone cyst formation has been reported as
well.

33. OSSIFYING FIBROMA
PERIAPICAL CEMENTO-OSSEOUS DYSPLASIA
PAGETS DISEASE
OSTEOSARCOMA
HYPERPARATHYRIDISM
CHRONIC OSTEOMYELITIS

34. OSSSIFYING FIBROMA CEMENTO-OSSEOUS
DYSPLASIA
PAGETS DISEASE
RADIOGRAPHIC
FINDINGS
Well defined UNILOCULAR
radiolucency with sclerotic border.
Depending upon the amount of
calcified material in the tumor ,it
can be radiolucent to
radiopaque(varying degree).
lesion varies from
completely
radiolucent to densely
radiopaque with a thin
peripheral radiolucent rim.
Most commonly, however,
there is A MIXED
RADIOLUCENT AND
RADIOPAQUE PATTERN
Affected bone exhibits decreased
radiodensity and a coarse
trabecular pattern. Particularly in
the skull, large circumscribed
radiolucencies may be present.
The patchy sclerotic areas
characteristically exhibit a
“COTTON WOOL”
APPEARANCE
HISTO-
PATHOLOGICAL
FINDINDS
Mixture of woven bone and
cementum like material. Basophilic
spherules have brush borders that
blends in the connective tissue
In c.t, mixture of woven
bone ,lamellar bone and
cementum like particles
(basophilic spherules).With
maturation bony trabeculae
become thick curvilinear
structure resembling ginger
root.
Uncontrolled resorption
and formation of bone.
Osteoblasts form osteoid rims
around the bone trabeculae, and
the bone lacks an organized
lamellar pattern. Basophilic
reversal lines, which indicate the
junction between alternating bone
resorption and formation, result
in a characteristic
“JIGSAW PUZZLE” OR
DIFFERENCE BETWEEN DIFFERENT BONY LESIONS ON THE BASIS OF HISTOPATH & RADIOGRAPHIC FINDINGS

35. MALIGNANT TRANSFORMATION
 Malignant transformation is rare about 0.4% - 4%.
 Osteosarcoma
 Fibrosarcoma
 Chondrosarcoma
 Malignant transformation may be more common in Mazabraud's syndrome
(FD in association with intramuscular myxomas).
 Useful biomarkers such as serum ALP and urinary hydroxyproline can be
used to monitor response in nonsurgical treatment of the disease rather than
diagnosis.
Dua N,Singla N, Garg S . Fibrous dysplasia of maxilla:Report of two cases.J Indian Acad Oral Med Radiol 2015;27:472-5

36. TREATMENT
 Conservative treatment-prevent deformity.
 Management requires a multidisciplinary approach -polyostotic.
 Bisphosphonate therapy may help to improve function, decrease pain,
& lower fracture risk -some patients.
 Surgery-complete resection, restoring function &improving facial
aesthetics

37. REFERNCES
 Shafer’s textbook of oral pathology 7th Edition
 Burkitt’s oral medicine,11th edition.
 Neville, Damm, Allen, Bouquot. Oral & maxillofacial pathology ,1st south asia
edition.
 David S. Macdonald, classification and nomenclature of fibro-osseous lesions,
volume 131, issue 4, p385-389, april 01, 2021
 Dua N,Singla N, Garg S . Fibrous dysplasia of maxilla:Report of two cases.J
Indian Acad Oral Med Rsdiol 2015;27:472-5