This document provides an overview of fibro-osseous lesions, specifically fibrous dysplasia and ossifying fibroma. It begins with the normal anatomy of bone and then discusses the classification, definition, etiology, clinical features, investigations, and treatment of fibrous dysplasia. It notes that fibrous dysplasia is caused by a mutation and can present as monostotic or polyostotic forms. The document then discusses the definition, epidemiology, pathophysiology, clinical features, investigations, histological features, radiological features, treatment and prognosis of ossifying fibroma. It notes that ossifying fibroma is a benign bone tumor most common in females involving the mandible. The document also provides a

1. FIBRO-OSSEOUS LESIONS
DINGISWAYO MAKOWANI & ANGETILE KASANGA
5TH YEAR MBCHB

2. OUTLINE
• NORMAL BONE ANATOMY
• INTRODUCTION
• CLASSIFICATION
• FIBROUS DYSPLASIA – DEFINITION
• ETIOLOGY
• CLINICAL FEATURES
• MONOSTOTIC FORM
• POLYOSTOTIC FORM
• HISTOLOGICAL FEATURES
• RADIOGRAPHIC FEATURES
• TREATMENT AND PROGNOSIS

3. NORMAL BONE ANATOMY
• Normal bone is a type of specialized connective tissue with a composition of about
60% inorganic component (hydroxyapatite), 10% water and 30% organic component
(bone matrix proteins).
• The inorganic component of bone (hydroxyapatite – mainly composed of calcium and
phosphate) makes bone hard and rigid, allowing for it to serve its function of
providing mechanical support for locomotion, protecting vital organs, and regulating
mineral homeostasis.
• The organic component of the bone matrix is called osteoid. It
contains proteoglycans, glycoproteins and collagen fibers. Without the organic
components of the matrix, the bone would be very brittle and it would break if
twisted or stretched. These organic molecules, especially the collagen fibers act like
reinforcing metal rods in concrete (the concrete here being the mineral salts). They
provide bone with great flexibility and tensile strength (resistance to being stretch
or torn apart).

4. HISTOLOGY OF NORMAL BONE

5. 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.
• Clinical, radiographic, and histopathologic correlation is usually most
beneficial in establishing a specific diagnosis.

6. CLASSIFICATION

7. FIBROUS DYSPLASIA (FD)

8. DEF.
• It is a rare bony disorder in which normal bone is replaced
by abnormal fibro-osseous tissue.
• A noninherited, benign intramedullary bone lesion in which
the normal bone is replaced by an excessive proliferation of
cellular fibrous connective tissue intermixed with irregular
bony trabeculae.

9. ETIOLOGY
• FD is caused by a post-zygotic mutation in the GNAS1 gene located on
chromosome 20q13.2-13.3, which encodes the alpha subunit of the
stimulatory G protein, Gsα. As a consequence of this mutation, there
is a substitution of amino acid arginine in position 201 of the genomic
DNA in the osteoblastic cells with amino acid cysteine or histidine.
• The abnormal G1 protein stimulates cyclic adenosine monophosphate
(cAMP), and the osteoblastic cells expressing this mutation have a
higher rate of DNA synthesis than normal cells. This abnormal
growth leads to the formation of a disorganized fibrotic bone matrix
with primitive bone formation and a lack of maturation to lamellar
bone.
• Can occur at 3 stages: Early, late, and post natally.

10. CONT.
• Manifestations of the condition will depend on the stage at which this
mutation occurs:
• 1. Early – Undifferentiated stem cells. Osteoblasts, melanocytes and
endocrine cells (progeny) will carry that mutation and express the
mutated gene. The clinical presentation of multiple bone lesions,
cutaneous pigmentation, and endocrine disturbances would result.
• 2. Late – Skeletal progenitor cells still migrating in skeletal
formation, resulting in multiple bone lesions of fibrous dysplasia.
• 3. Postnatal life – Progeny of mutated cell are essentially confined to
one site, resulting in fibrous dysplasia affecting a single bone.

11. TYPES OF FD
• 1. Monostotic FD: Where lesion is confined to a single bone
• 2. Craniofacial form: Various bones in the skull are affected
e.g FD involving the Maxilla, zygomatic, occipital and
sphenoid bones.
• 3. Polyostotic FD: Lesions in diverse places, about 75% of
skeleton usually affected

12. MONOSTOTIC FIBROUS DYSPLASIA (MFD)
• This type accounts for about 80% to 85% of all cases of FD, with the
jaws being among the most commonly affected sites.
• Can occur at any age. However, it is usually observed in children and
young adults with 75% of patients presenting before the age of 30.
• Monostotic lesions are mostly asymptomatic, but they may progress
during skeletal growth, and they tend to stabilize after puberty
• FD involves the maxilla almost two times more often than the
mandible and it frequently appears in the posterior region of the jaw
bone, usually unilaterally.

13. CLINICAL FEATURES OF MFD
• A painless swelling of the affected area is the most common feature.
• Growth is generally slow, and the patient or parents are often unable
to recall when the lesion was noted first. Occasionally, however, the
growth may be fairly rapid.
• Involvement of the mandible often results not only in expansion of the
lingual and buccal plates but also bulging of the lower border.
• When the maxilla is involved, the lesional tissue displaces the sinus
floor superiorly and commonly obliterates the maxillary sinus.

16. CRANIOFACIAL FORM
• FD involving the skull bones
• Although mandibular lesions are truly monostotic, maxillary lesions often
involve adjacent bones (e.g., zygoma, sphenoid, occipital) and are not strictly
monostotic.
• Usually very problematic - Depending on the type and location of FD, the
signs and symptoms vary and include facial deformity and asymmetry,
vision changes, hearing impairment, nasal congestion and/or obstruction,
pain, paresthesia, and malocclusion.
• Of worthy note, the craniofacial region is involved in 90% of the cases of
polyostotic FD and the anterior cranial base is involved in over 95% of these
cases.

20. POLYOSTOTIC FORM
• Involvement of two or more bones, a relatively uncommon condition.
• The number of involved bones varies from a few to 75% of the entire
skeleton.
• Can manifest in three (3) types of syndromes:
• 1. Jaffe-Lichtenstein syndrome – When seen with café au lait (coffee with
milk) pigmentation, melanocytes involved.
• 2. McCune-Albright Syndrome – Polyostotic fibrous dysplasia combined with
café au lait pigmentation and multiple endocrinopathies, such as sexual
precocity, pituitary adenoma, or hyperthyroidism.
• 3. Mazabraud syndrome – Characterized by fibrous dysplasia in combination
with intramuscular myxomas.

22. RADIOLOGICAL FEATURES OF FD
• The chief radiographic feature is a fine “groundglass” opacification that results from
superimposition of a myriad of poorly calcified bone trabeculae arranged in a
disorganized pattern. (Ground glass appearance – Hazy-like opacities not
completely obliterating the image before and after them)
• Radiographically, the lesions of fibrous dysplasia are not well demarcated. The
margins blend imperceptibly into the adjacent normal bone so that the limits of the
lesion may be difficult to define.

25. HISTOLOGICAL FEATURES
• The typical microscopic findings of FD consist of irregularly shaped trabeculae of
immature (woven) bone in a cellular, loosely arranged fibrous stroma. The bone
trabeculae are not connected to each other. They often assume curvilinear shapes,
which have been likened to Chinese script writing. The bone trabeculae are
considered to arise by metaplasia and are not surrounded by plump appositional
osteoblasts.
• In contrast to other fibro-osseous lesions, FD typically demonstrates a rather
monotonous pattern throughout the lesion rather than being a haphazard mixture of
woven bone, lamellar bone, and spheroid particles.
• The lesional bone fuses directly to normal bone at the periphery of the lesion so that
no capsule or line of demarcation is present.

26. CONT.

28. INVESTIGATIONS
LABORATORY INVESTIGATIONS
1. Biopsy
2. FBC and DC
3. ESR
4. Serum Calcium and phosphate levels
5. Genetic testing

29. IMAGING
1. X-Ray
2. OPG
3. CT Scan
4. MRI
5. Scintigraphy
- Difinative Dx of a fibro-osseous lesion is dependent on the clinical,
radiological, and histological findings.

30. TREATMENT AND PROGNOSIS
• Definite treatment of symptomatic lesions includes surgical excision, reduction and
recontourring of disfigured bone (in monostotic).
• The prevalence of regrowth after surgical reduction is difficult to determine, but it
has been estimated that between 25% and 50% of patients show some regrowth after
surgical shave-down of the lesion. The regrowth is more common in younger
patients, and many surgeons believe that surgical intervention should be delayed for
as long as possible.
• Patients with minimal cosmetic or functional deformity may not require or desire
surgical treatment but are advised to attend regular clinical check ups
• Medically, patients with polyostotic disease can be effectively managed with
bisphosphonate therapy, such as intravenous pamidronate and oral alendronate.
Bisphosphonates have been shown to provide pain relief and improve skeletal
strength.

31. CONT.
• Malignant change, usually development of an osteosarcoma,
has been rarely associated with fibrous dysplasia. Most
examples have been found in patients who had received
radiation therapy for FD, but a few examples of
spontaneous sarcomatous changes have been reported.
• Radiation therapy for FD is contraindicated because it
carries the risk for development of postirradiation bone
sarcoma.

33. OSSIFYING FIBROMA
(CEMENTIFYING FIBROMA/
CEMENTO-OSSIFYING
FIBROMA)

34. CONTENTS
CONVENTIONAL OSSIFYING FIBROMA
• DEFINITION
• CLASSIFICATION
• EPIDEMIOLOGY
• RISK FACTORS
• PATHOPHYSIOLOGY
• CLINICAL FEATURES
• INVESTIGATIONS
• TREATMENT AND PROGNOSIS
• COMPLICATIONS
• DIFFERENTIAL DIAGNOSIS
OVERVIEW ON JUVENILE OSSIFYING FIBROMA

35. CONVENTIONAL OSSIFYING
FIBROMA

36. WHAT IS OSSIFYING FIBROMA ?
•A well-demarcated, encapsulated, expansile
intraosseous lesion of the jaws composed of a
variable mixture of bony trabeculae, cementum-
like spherules, or both.

37. • Before the refining of the concept of focal cemento-
osseous dysplasia in the mid 1990s, ossifying
fibroma was thought to be a common neoplasm. In
reality, true ossifying fibromas are relatively rare,
with many previously reported examples actually
being focal cemento-osseous dysplasia.

38. EPIDEMIOLOGY
• Mostly occurs during the 3rd and 4th decades
• Definite Female predilection,
• Mandible involved far more often than the maxilla.
• The mandibular premolar and molar area is the most
common site

39. RISK FACTORS
• A mutation in a tumor suppressor gene HRPT2
• Hyperparathyroidism-jaw tumor syndrome(HPT-JT)
• Family history
• Female preponderance with a ratio of 5:1
• Can be Idiopathic

40. PATHOPHYSIOLOGY
• ossifying fibroma is a true neoplasm with a significant growth potential which primarily affects
the craniofacial region.
• Benign tumor whose origin is suggested to be odontogenic or from periodontal ligaments.
• Characterized by abnormal proliferation of fibroblasts and osteoblasts, leading to the formation
of immature woven bone.
• Etiology is unknown but it is believed to arise from genetic mutations in genes like the HRPT2
Tumor suppressor gene or alterations in signaling pathways involved in bone development and
remodeling.
• These genetic alterations may result in the dysregulation of cellular processes that control bone
formation and resorption.

41. CLINICAL FEATURES
• Small lesions rarely cause any symptoms and are only detected on
radiographic examination.
• The lesion is slow growing
• Bony hard mass
• Larger tumors result in a painless swelling of the affected bone causing
obvious facial asymmetry, which on occasion reaches grotesque size
• Pain and Paresthesia are rare in ossifying fibroma

44. INVESTIGATIONS
LABORATORY INVESTIGATIONS
Ossifying fibroma is diagnosed via clinical assessment, imaging studies
and biopsy. Biopsy is useful when confirming the diagnosis. Other
Laboratory investigations maybe performed to rule out other conditions
or assess the overall health of the patient. Laboratory tests include:
1. Biopsy
2. FBC and DC
3. ESR
4. Serum Calcium and phosphate levels
5. Genetic testing

45. HISTOLOGICAL FEATURES
• A few ossifying fibromas will show, grossly and microscopically, a fibrous capsule
surrounding the tumor
• Most are not encapsulated but are well demarcated grossly and microscopically from the
surrounding bone.
• They consist of fibrous tissue that exhibits varying degrees of cellularity and contains
mineralized materials.
• hard tissue portion may be in the form of trabeculae of osteoid and bone or basophilic
and poorly cellular spherules that resemble cementum. The typical finding is a mixture
of both types.
• Bony trabeculae vary in size and frequently demonstrate a mixture of woven and
lamellar patterns
• Peripheral osteoid and osteoblastic rimming are usually present.

46. • spherules of cementum-like material often demonstrate peripheral
brush borders that blend into the adjacent connective tissue
• Significant intralesional hemorrhage is unusual

48. IMAGING
Imaging studies play a crucial role in diagnosis and evaluation of
ossifying fibroma. These investigations include:
1. X-Ray
2. OPG
3. CT Scan
4. MRI
5. Cone Beam CT (CBCT)

49. RADIOLOGICAL FEATURES
• Lesion is often well defined and unilocular. Some examples show a sclerotic
border.
• May appear completely radiolucent depending on the amount of calcification in
the tumor. But more often varying patterns of radiopacity are seen.
• True ossifying fibromas that become largely radiopaque with only a thin
radiolucent periphery are uncommon.
• Root divergence or resorption of roots of teeth associated with the tumor may
be seen
• Large ossifying fibromas of the mandible often demonstrate a characteristic
downward bowing of the inferior cortex of the mandible.

51. TREATMENT AND PROGNOSIS
• Circumscribed nature of the ossifying fibroma generally permits
enucleation with ease.
• Surgical resection and bone grafting may be necessary for tumors
that are large and have destroyed considerable bone.
• The prognosis, however, is very good, and recurrence after
removal of the tumor is rarely encountered
• There is no evidence that ossifying fibromas ever undergo
malignant change.

52. COMPLICATIONS
• Potential complications of ossifying fibroma are generally dependent
on size, location and growth pattern. These complications include:
1. Vision impairment
2. Hearing impairment
3. Recurrence

53. DIFFERENTIAL DIAGNOSIS
• Fibrous dysplasia
• Ameloblastoma
• Osteitis deformans
• Osseous dysplasia
• Focal sclerosing osteomyelitis
• Diffuse sclerosing osteomyelitis

54. JUVENILE OSSIFYING FIBROMA
(JUVENILE ACTIVE OSSIFYING
FRIBROMA/ JUVENILE AGGRESSIVE
OSSIFYING FRIBROMA)

55. JUVENILE OSSIFYING FIBROMA
(JUVENILE ACTIVE OSSIFYING FRIBROMA/ JUVENILE
AGGRESSIVE OSSIFYING FRIBROMA)
• Controversial lesion that has been distinguished from larger group
of ossifying fibroma on the basis of age of the patient, most common
sites of involvement and clinical behavior
• PATTERNS
1. Trabecular
2. psammomatoid

58. 1. TRABECULAR
• The trabecular form is diagnosed initially in younger
patients. The mean age of trabecular juvenile ossifying
fibromas is approximately 11 years,
2. PSAMMOMATOID
• This form appears outside of the jaws, with over 70%
arising in the orbital and frontal bones and paranasal
sinuses and it is diagnosed in patients approaching 22 years

59. CLINICAL FEATURES
• Early to late childhood
• Affects Maxilla more than the Mandible
• Singular, slow-growing, painless swelling
• Overgrowth of tissue that occurs centrally in the jaws
• May involve impacted or unerupted teeth disfiguring
• Slight male predilection
• Severe malocclusion
• Ulceration or a maxillary lesion that interferes with sight and breathing may
be present, signifying an aggressive form of this condition.

60. INVESTIGATIONS
LABORATORY INVESTIGATIONS
Ossifying fibroma is diagnosed via clinical assessment, imaging studies
and biopsy. Biopsy is useful when confirming the diagnosis. Other
Laboratory investigations maybe performed to rule out other conditions
or assess the overall health of the patient. Laboratory tests include:
1. Biopsy
2. FBC and DC
3. ESR
4. Serum Calcium and phosphate levels
5. Genetic testing

61. HISTOLOGICAL FEATURES
• Abundant cellular fibrous connective tissue in a whorled pattern
• Proliferating fibroblasts form spicules of bone and cementum
• At maturity the bone may be somewhat normal
• Areas of hemorrhage and small clusters of multinucleated giant cells
• Trabecular variant shows irregular strands of highly cellular osteoid encasing
plump and irregular osteocytes.
• The psammomatoid pattern forms concentric lamellated and spherical ossicles
that vary in shape and typically have basophilic centers with peripheral
eosinophilic osteoid rims

62. IMAGING
Imaging studies play a crucial role in diagnosis and evaluation of
ossifying fibroma. These investigations include:
1. X-Ray
2. OPG
3. CT Scan
4. MRI
5. Cone Beam CT (CBCT)

63. RADIOLOGICAL FEATURES
• Radiolucent or mixed radiolucent and radiopaque appearance
(ground glass)
• Lamina dura is usually obscured and the cortical plates thinned

64. TREATMENT AND PROGNOSIS:
• Management and prognosis are uncertain.
• Smaller lesions, complete local excision or thorough curettage appears
adequate,
• Rapidly growing lesions, wider resection may be required
• Recurrence rates of 30% to 58%
• Malignant transformation has not been documented.

65. DIFFERENCES BETWEEN TRABECULAR AND
PSAMMOMATOID TYPES

68. REFERENCES
• Pimenta FJ, Gontijo Silveira LF, Tavares GC, Silva AC, Perdigao PF, Castro WH, Gomez MV,
The BT, De Marco L, Gomez RS. HRPT2 gene alterations in ossifying fibroma of the jaws. Oral
Oncol. 2006 Aug;42(7):735-9.doi:10.1016/j.oraloncology.2005.11.019.Epub 2006 feb 2.
PMID:16458039
• Neville B.W. (2016) Oral and Maxillofacial Pathology, 4TH Edition, Elsevier Canada.