Bone PathologyTopics: Fibrous Dysplasia, Cemento-Osseus Dysplasia

Submitted By: Pooja Chaturvedi

Bone PhysiologyBone is a connective tissue composed of ground substance, cells and fibers.

Classification

A). Based on Morphology:

Long bonese.g. upper and lower limbs; Have marrow cavity filled with yellow marrow

Short bonese.g. carpels and tarsals;

Have marrow but lack marrow cavity

Flat bonese.g. skull and facial bones;Spongy bone is present between upper & lower layer of compact bone

Irregular bonese.g. sphenoid and ethmoid;

Spongy bone covered with a thin layer of compact bone and has marrow without any marrow cavity

Sesamoid bonese.g. patella;

Develop in areas of pressure or tension

Morphologic classification :

a. Long bonesb. Short bonesc. Irregular bonesd. Flat bones

B). Based on Development:

Endochondral Replacement of hyaline cartilage with bony tissue.e.g. bones of trunk and extremities

IntramembranousReplacement of sheet like connective tissue with bony tissuee.g. cranial & facial flat bones of skull, mandible and clavicle

C). Based on Microscopic Structure:

Mature Bone Immature Bone-first formed bone-rarely seen after birth-seen in alveolar bone & during healing of fractures.

Compact/Lamellar/Cortical Bone-well formed concentric lamellae around haversian canal

Cancellous/Spongy/Trabecular Bone:-irregular bony spikules called ‘Trabeculae’ around marrow spaces.

Compact bone v/s Spongy bone

Composition• Mineral Content• Hydroxyapatite crystals

with carbonate content & low Ca/P ratio.

• Bone crystals as ‘leaf like’ structures aligned parallel to collagen fibres.

• Narrow gaps between crystals is associated with water and organic macromolecules.

• Organic Content• Mainly type I collagen• Also type V• Alveolar bone = type I +

type III + type V + type XII collagen

• Sharpeys fibres contain type III with type I collagen

• Type III & type XII are produced by fibroblasts during production of periodontal ligament.

• Type I, V and XII are expressed by osteoclasts.

Non Collagenous Proteins1). Osteocalcin:-Has amino acid – gamma carboxy glutamic acid-Demonstrated in alveolar bone-Carboxy terminal is chemo-attractant to osteoclasts precursors.

2). Osteopontin:-Present in alveolar bone-Heavily glycosylated & phosphorylated-Aspartate is predominant -Inhibits hydroxyapatite crystal growth

3). Bone Sialoprotein:-Glutamic acid is predominant-Initiation of mineral crystal formation

4).Osteonectin:-Calcium binding glycoprotein

Bone Histology

• Periosteum

• Endosteum• Circumferential lamellae• Concentric lamellae• Haversian canal• Haversian canal + Concentric Lamellae = OSTEON• Reversal Line: sharply delineated by cement lines which is highly

basophilic(due to rich content of glycoproteins & proteoglycans) and marks the limit of bone erosion prior to osteon formation.

• Resting Line• Volksmann canal connects the osteons and the periosteum.• Lacunae containing osteocytes at the junction of lamellae• Canaliculi radiating from lacunae; helps in exchange of nutrients and

wastes between lacunae (osteocytes).• Interstitial lamellae: present between osteons; remnants of osteon, left

behind during remodelling.

Fibrocollagenous layer(outer)

Inner layer with bone cells with rich vascular supply

Histopathology of bone

Fibrous Dysplasia Skeletal developmental anomaly of the bone forming mesenchyme that manifests as a defect in osteoblastic differentiation & maturation.

•Non heridetary disorder of unknown cause.

•Can occur in any part of the skeleton but the bones of skull, thigh, ribs, upper arms and pelvis are most commonly involved.

•It is not a form of cancer.

•Most lesions are monostotic, asymptomatic & identified incidentally & can be treated with clinical observation.

Etiology • Post zygotic mutation in GNAS 1 gene(20q.13.2)• GNAS 1(Guanine Nucleotide Binding Protein- alpha

stimulating activity polypeptide)gene encodes a G-protein that stimulates the production of cAMP.

• Continuous activation of G-protein leading to over production cAMP in the affected tissues.

• Hyperfunctioning of the affected endocrine organs.• Leading to

i. Precocious pubertyii. Hyperthyroidismiii. GH & cortisol overproductioniv. Increased proliferation of melanocytes resulting in large

Cafe-au-lait spots with irregular margins.v. cAMP affects the differentiation of osteoblasts leading to

fibrous dysplasia

Pathophysiology• Medullary bone is replaced by fibrous tissue which

appears radiolucent on radiographs-”Ground Glass Appearance ”.

• Trabeculae of woven bone contains fluid filled cysts that are embedded largely in collagenous fibrous matrix.

• Bony trabeculae are abnormally thin & irregular & often described as “Chinese Characters”

.• Fibrous Dyspalsia is characterised by “Shepherd’s

Crook” deformity which refers to coxa varus angulation of proximal femur.

• Cause of transformation is not completely known, however levels of transcription factor C-fos are raised which leads to gene over expression & tumor formation.

Types

•Monostotic: Involvement of a single bone.

•Polyostotic: Many bones are involved. Most severe form is McCune Albright

Syndrome

Clinical Features• Four disease patterns are recognised:

i. Monostotic ii. Polyostoticiii. Craniofacial formiv. Cherubism

Age : 3-15 years2/3 of patients with polyostotic disease are asymptomatic

before they are aged 10 years.

Monostotic patients as old as 20-30 years are asymptomatic.Males and females are equally affected.

Clinical findings of increasing pain & an enlarging soft tissue mass suggest malignant change.

Monostotic Fibrous Dysplasia70-80% of the lesions.Most frequently occurs in the ribs(28%), femur(23%) and humerous in decreasing order of frequency.The clinical term ‘Leontiasis Ossea’ has often been applied to cases of fibrous dysplasia which affect the maxilla or facial bones & give the patient a leonine appearance.

Clinical Features• Age: children & young

adults.• Sex: equally affects males &

females

• Painless swelling or bulging of jaws.

(usually involves labial/buccal plate; when it involves mandible, sometimes it causes a protruberant excrescence of inferior border)

• Malalignment, tipping of teeth due to progressive expansile nature of lesion & tenderness may develop.

• Malocclusion

• Mucosa over the lesion is invariably intact.

(Fibrous Dysplasia of maxilla is a serious form of disease since it has marked predilection for occurrence in children & is impossible to eradicate without radical, mutilating surgery).

• lesions extend locally to involve maxillary sinus, zygomatic process & floor of orbit & base of skull.

• Bulging of canine fossa• Extreme prominence of

zygomatic process• Marked facial deformity

Radiographic Features• Has 3 basic patterns:

i. Small, unilocular/large, multilocular with well circumscribed border containing a network of fine bony trabeculae.

ii. Increased trabeculations render the lesion more opaque-Mottled Appearance

iii. Many delicate trabeculations-Ground Glass or peau d’ orange appearance; it is not well circumscribed and blends into adjacent normal bone.

• In all types, cortical plate is thinned because of expansile nature of growth.

Monostotic Fibrous Dysplasia showing ground glass appearance

Histopatholgy

•Lesion is fibrous composed of proliferating fibroblasts in compact stroma of interlacing collagen fibres.

•Irregular bony trabeculae are scattered throughout the lesion without any definite pattern- ‘Chinese Character’ shaped.

•Trabeculae are of coarse, woven bone.

Treatment

•Surgical removal of lesion.

•Lesions with type III radiographic findings should be block resected.

•Malignant transformation into osteosarcoma.

Mc Cune Albright SyndromeorPolyostotic Fibrous DysplasiaDefined as association of polyostotic fibrous dysplasia, precocious puberty, café-au-lait spots & other endocrinopathies due to hyperactivity various endocrine glands.

Etiology

•Post zygotic activation mutation of GS alpha gene in affected tissues.

•GS alpha subunit is a component of G-protein complex, which couples hormone receptors to Adenylyl Cyclase (intracellular second messenger) in a submembrane site.

Clinical Features• Precocious puberty associated with the condition is

gonadotrophin-independent.• Acromegaly• Gonadotrophin-McCune Albright Syndrome• Hyperprolactinemia• Some severely affected patients may present with

associated hepatic, cardiac and GI dysfunction.• Cutaneous pigmentation is the most common extraskeletal

manifestation & is ipsilateral to side of bony lesions.• Café-au-lait spots are related to amount of melanin in

basal cells of epidermis.• Pigmentation may occur at birth & may precede the

development of skeletal & endocrine abnormalities.

Café-au-lait spots

Laboratory Findings

•Serum alkaline phosphatase level is elevated.

•Premature secretion of pituitary follicle stimulating hormone.

•Moderately elevated basal metabolic rate.

Histopathology• Areas of fibrous metaplasia within flat and

tubular bones.

• Progressively expanding fibrous lesion of bone forming mesenchyme.

• Concentric expansion in an outward direction within the medullary bone.

• Well-defined, non-encapsulated.

• Lesions are rich in spindle shaped fibroblasts with a swirled appearance within the marrow space.

Treatment

•Mild cases: surgical radiation•Severe cases: X-ray radiation•Prognosis depends on the degree of

skeletal involvement.•Malignant transformation into

osteosarcoma can also occur.

Cemento-Osseous DysplasiaorOsseus DysplasiaMost common fibro-osseous lesion which occurs in tooth bearing areas of the jaws.

Pathogenesis

•Periodontal origin; or

•Defect in extraligamentary bone remodelling that maybe triggered by local factors or possibly by hormonal imbalance.

Types

•Based on clinical and radiographic features, it is divided into three groups:

i. Focal cemento-osseus dysplasiaii. Periapical cemento-osseus dysplasiaiii. Florid cemento-osseus dysplasia

Focal Cemento-Osseus Dysplasia

•Exhibits a single site of involvement.•Most commonly in black females with a

predilection for 3-6 decade.•Posterior mandible is the commonest site.•Usually asymptomatic with a positive

vitality test of the affected teeth. •Most of the lesions are smaller than

1.5cm in diameter.

Radiographic Features

• Lesions vary from being completely radiolucent to densely radiopaque with a thin peripheral radiolucent rim.

• Most common is a mixed radiolucent and radiopaque pattern.

• Well defined lesion with a slightly irregular border.

• Occurs in both dentulous and edentulous areas.

Focal cemento-osseus dysplasia

Periapical Cemento-Osseus Lesions

•Also called as ‘Cementoma’, ‘Fibrocementoma’, ‘Periapical Fibro Osteoma’.

•Teeth associated with lesion is invariably vital.

• Involves periapical region of anterior mandible.

•Generally occurs between 30-50 yrs of age.

Radiographic Features

•Early lesions appear as circumscribed areas of radiolucency involving periapical areas of tooth.

•Mature lesions create a mixed radiolucent and a radiopaque appearance.

•Periodontal ligament is intact.

•There is no fusion to the teeth.

Periapical cemento-osseus dysplasia

Florid Cemento-Osseus Lesions• Most clinically extensive form of cemento-osseus dysplasia,

thus the term – ‘Florid’.

• Common in black females with marked predilection for middle aged to older adults.

• Multifocal involvement, not limited to anterior areas.

• May involve all the 4 quadrants.

• Asymptomatic.

• Dull pain and an alveolar sinus tract maybe present.

• Some degree of expansion maybe seen.

• Bilateral and symmetric involvement.

Radiographic Features•Initially, lesion is predominantly

radiolucent, with time, becomes mixed and then predominantly radiopaque with a thin peripheral rim.

•Maybe totally radiopaque and blend with adjacent normal appearing bone.

•Both, edentulous and dentulous areas are affected.

Florid cemento-osseus dysplasia

Histopathology • All 3 variants present a similar histopathologic

picture.• Tissue consist of fragments of cellular

mesenchyme composed of spindle shaped fibroblasts and collagen fibres with numerous blood vessels.

• Free hemorrhage is typically noted interspersed throughout the lesion.

• Within the fibrous connective tissue background is a mixture of woven bone, lamellar bone & cementum like particles.

• As the lesions mature and become more sclerotic, the ratio of fibrous connective tissue to mineralised material decreases.

• With maturation, the bony trabeculae become thick, curvilinear structures that have been said to resemble the shape of ‘ginger roots’.

Treatment

•For asymptomatic patients: regular recall examinations with prophylaxis and reinforcement of good home hygiene care.

•For symptomatic patients: •Antibiotics•Sequestration of sclerotic cement like

masses and is followed by healing.•Saucerisation of dead bone.