Pagets Disease (1)

8/2/2019 Pagets Disease (1)

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A Case Report

Presented By

Dr. Kush Pathak


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Case description

Discussion

Pathophysiology

Lab Investigations

Differential Diagnosis

References


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Age/Sex: 35/m

Chief complaint:

History of present illness:

Patient complains of swollengums in upper gums since 5

-6 months.

Swelling present since 5-6 months associated withmobility of teeth. Pain was not present in the beginningbut at present since one month, pain is mild andcontinuous.


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Past medical history:

Personal history:Family history: Non Contributory

General physical examination:

Pt. was cooperative, moderately built, moderately nourished &presented with a normal gait.Pallor was seen

Extra - Oral Examination:Diffuse swelling present in relation to premaxillary region withobliteration of nasopalatine fold & elevation of ala of nose of left sideseen.


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Intra - Oral Examination:

Hard tissue examination: stains ++gen. severe attrition

gr. I mobility irt 11, 12, 13, 21, 23gr. III mobility irt 22


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Obliteration of ala of nose seen.

Lips are incompetent

Exophytic lesion firm to hard present in relation to premaxillary region

excluding the anterior part of hard palate.

Soft tissue examination:


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Provisional diagnosis:

Fibro osseous lesion in relation to anterior region of maxilla.

Differential diagnosis:

AOT

CEOT

Tenderness on palpation seen.


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Investigations :

Hematologic:

RBS- 76 mg/dl,

Hb 12.8 gm%,

BT 145, CT 500

HIV & HBsAg negative


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Cotton Wool appearance due to patchy areas.


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Generalized bone enlargement.

Increased density, trabeculae and cortical thickening .


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HISTOPATHOLOGIC EXAMINATION


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Connective

tissue

stroma


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Stroma

composed of

irregularly

shaped bone

fragments

withoutosteoblastic

rimming.

Resorption

lacunae are seenbut no

osteoclasts are

evident


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Irregularly

shaped bone

fragments

showingappositional

and reversal

lines

depictingtypical

mosaic

pattern


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FINAL DIAGNOSIS

PAGETS DISEASE


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Uncoordinated increase in the osteoclastic and osteoblastic activityof bone cells of older adults producing larger but weaker bones,extensive pain, high levels of serum alkaline phosphatase & urinaryhydroxyproline & an increased tendency to develop malignant boneneoplasms.

It is also called osteitis deformans.

Was first described by Sir James Paget in 1877.

Characterized by excessive and abnormal remodeling of bone

Discussion


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Leads to distortion and weakening of bones.

Common in middle aged and elderly patients


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Prevalence of Paget's disease increases with age.

Most commonly diagnosed after 50 years and rarely in peopleyounger than 20 years

Systemic findingsinclude: almost all bones can be involved The major characteristic is enlargement of affected bone.

Patient complains of bone pain perceived as a dull constant achingpain deep below the soft tissues.


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The involved bones become warm to touch because of the increasedvascularity.

Non specific headaches, impaired hearing and tinnitus are commonsymptoms of Paget's disease.

Bowed legs, Enlarged pelvis


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Skull: skull enlargement

bitemporally and frontally

(frontal bossing); Dilated scalp veins; headaches,

dizziness, loss of muscle strength

in the face (facial droop), orproblems with vision or hearing.


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ORAL MANIFESTATIONSinclude Involvement of jaws

Maxilla exhibits progressive enlargement, the alveolar ridgebecomes widened and palate is flattened.

If teeth are present, they become loose and migrate, producing somespacing.


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Osteolytic phase can produce osteoporosis circumscripta

(localized cranial osteoporosis) i.e. decreased radiodensity of boneand alteration of trabecular pattern.

Cotton Wool appearance due to patchy areas.

Bone softening can produce bowing, platybasia, protrusionacetabuli or greenstick fractures.

Mixed phase shows generalized bone enlargement.

Sclerotic phase shows increased density, trabeculae and corticalthickening .


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Paget's disease is characterized by enhanced resorption of bone by

giant multinucleated osteoclast with formation of disorganizedwoven bone byosteoblast. This process evolves through various phases of activity, followed by

a quiescent stage.

Hence, Paget's disease consist of following 3 phases:

Lytic

Mixed lytic and blastic

Sclerotic or burned out

Initial osteolytic phase is marked by disordered areas of resorptionby an increased number of overtly large osteoclasts (these abnormalosteoclast consist of as many as 100 nuclei)


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The next osteoblastic phase follows with haphazard laying of newbone matrix and formation of woven bone.

Repeated episodes of bone removal and formation results inappearance of many small irregularly shaped bone fragments thatappear to be joined injigsawormosaic patternwith deeply staining

hematoxyphilic reversal lines. This pattern is histologic hallmark ofPaget's disease.

The Paget's boneis coarse with an affinity for calcium andphosphorus


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Marrow spaces are filled with loose highly vascularized connectivetissue- this causes increase in the regional blood flow and thusleads to rise in skin temperature seen clinically.

Pagetic bone shows no tendency to form haversian systems or tocentre on blood vessels; the bones are very hard and dense.

Sclerotic / burned out phase Eventually osteoblastic activity diminishes and osteoporotic orburned out phasepredominates. The new bone thus formed is disordered, poorly mineralized and

lacks structural integrity.

The proliferation of bone and concomitant hypercementosissometimes results in obliteration of PDL.


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Histology of Paget's diseaseshows several bone spicules inhighly vascularized connectivetissue stroma

Higher magnification :A- osteoclast in howshiplacunaeB- osteoblast in process of bone

formation


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MOSAIC PATTERN IN PAGETS DISEASE


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Loss of normal trabeculation and appearance of irregular

osteoblastic activity gives rise to typical cotton wool appearance ofPaget's bone.

Teeth and adjacent bone also show radiographic changes :

pronounced hypercementosis and loss of well defined lamina Dura.

Root resorption is reported in some cases but it is unusual.


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Radiographic

image shows

typical cottonwool

appearance in

Paget's disease

Hypercementosis and

loss of lamina dura


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PATHOPHYSIOLOGY


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Etiology

Hormonal

Dysfunction

Autoimmune

States

Viral Causation

Chronic Infection

Genetic Factor(Sequestrosome 1

gene on

chromosome 5)

Ca ECF

Compensatory

Mechanism

Hyperactivity of

osteoclasts

Osteoclast destroys

lamellar bone

Increase extensiveresorption

osteoblast response


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Rapid disposition of

vascular connective tissue

Increase bone formation

Increase bone size and

thickness


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Bone pain

Spinal stenosis

NumbnessWeakness

(Skull)

headaches,

dizziness,facial droop

with vision or

hearing

impairment

Bowing of legs

Curve backbone

Skull

enlargement

bitemporally

and frontally

Enlargement

of pelvis

Compression of

nerves

Poorly mineralized

bones

Overgrown

bone


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- Hypervascular / Osteolytic Phase: Initial phase of disorder involves bone resorption byosteoclasts.

Subsequently there is vigorous osteoblastic response, producingexcessive, poorly organized, structurally weak, highly vascularwoven bone.

Disease causes significant increase in blood flowof involved bones.

This increase may be so extensive, due to small arteriovenousshunts, that cardiac output is significantly increased.

Degenerative arthritis is assoc. w/ hypervascularity of ends of bone.

After some time osteoclastic activity subsides & woven bone is

replaced by lamellar bone as the osteoblastic action persists.


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Intermediate Phase:In this phase osteoblastic activity predominates, but osteolyticactivity is also present and therefore, and bone structural changes

and bone deformity are manifest.

Quiescent stage:

Finally, osteoblastic activity diminishes & bone becomes quiescent,with bony sclerosis and no evidence of increased turnover of bone,bone enlargement and widening.

Vascular fibrous tissue replaces the marrow.

Haversian systems are absent.


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Complications of Paget disease depend on the site affected and theactivity of the disease. When Paget disease occurs around a joint,secondary osteoarthritis may ensue. Skull involvement may lead to

the following:

Deafness

Vertigo

Tinnitus

Dental malocclusion

Basilar invagination

Cranial nerve disorders


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Frequently, erythema is present over the affected bone area, whichis due to the increased hypervascularity.

In patients with Paget disease who have extensive bonyinvolvement, this increased bone vascularity may cause high-output cardiac failure and an increased likelihood of bleedingcomplications following surgery.

Vertebral involvement of Paget disease may be associated withserious complications, including nerve root compressionsand cauda equina syndrome. Fractures, which are the mostcommon complication of Paget disease, may occur and may have

potentially devastating consequences.

Rarely, Pagetic bone may undergo a sarcomatous transformation.


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Increase in alkaline phosphatase, which reflects increase in boneformation.

Serum calcium & phosphorus, & acid phosphatase are usuallynormal (unless the patient has been immobilized in which casehypercalemia may occur).

uric acid level may be increased.

Increased urinary & serum levels ofhydroxyproline levels ( elevatedurinary hydroxyproline is a reflection ofbone lysis and is seen inother conditions such as RA, hyperparathyroidism, and

osteomyelitis. Urinary pyridinium / pyridinoline peptides can also be used as

markers of increased activity.


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Levels of bone turnover markers (including markers of bone formationand resorption) are elevated.

Markers of bone turnover that are useful to monitor in persons withPagets disease include the following:

Deoxypyridinoline (marker of bone resorption).

N-Telopeptide of type I collagen (marker of bone resorption).

Alpha-alpha type I C-Telopeptide fragments.


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The juvenile form of Paget disease differs greatly from the adultversion.

Juvenile Paget disease is characterized by widespread skeletalinvolvement and has distinctly different histologic and radiologicfeatures.


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Paget's disease showing Paget cells with atypical round or oval nucleiand abundant basophilic, amphophilic or clear cytoplasm. The Pagetcells are present as single cells and located throughout all layers ofthe epidermis


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Paget's disease showing Paget cells with negativeimmunoreaction for ERs


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Paget's disease showing Paget cells with nuclear positivity forandrogen receptors in more than 10% of tumor cells.


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Paget's disease showing paget cells with nuclear positivity forARs in almost 100% of tumor cells.


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Rare example of mammary Paget's disease showing Paget cellswith nuclear positivity for ERs.


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Paget's disease showing Paget cells with intense complete membrane staining(3+) for Her2/neu in almost 100% of tumor cells.


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Incomplete stress fractures frequently occur in Pagets disease.

Mild injuries may cause acute true pathologic fractures which are

more common in women than men.

Degenerative joint disease is associated with Pagets disease.

Cardiovascular abnormalities such as increased cardiac output has

been observed.

Left Ventricular hypertrophy is an associated finding.


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Florid osseous dysplasia

Familial gigantiform cementoma,

Osteogenesis imperfecta.

Sclerosing osteitis,

These all present with similar localized clinico-radiographic

pictures as PDB without the generalized skeletal changes and no

changes in alkaline phosphatase levels.

Florid cemento osseous dysplasia


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y p

Seen in middle-aged black women.

Shows the cortical plate enlargement along with mixedradiopacities, in relation to the maxillary right quadrant and mayresemble Paget's disease of bone.

Pagets disease of bone may transform into Osteosarcomas.

The dysplastic lesion ofPagets is always polyostotic.

COD case do not show an increase in the serum alkaline.

Phosphatase level and in histopathology, there was no jigsaw puzzleor mosaic pattern of trabeculae seen.


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O t i I f t


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Osteogenesis Imperfecta:

Also called brittle bone disease, or "Lobstein syndrome, is a geneticbone disorder.

Caused due to small or no amount of bone collagen (a proteinfound in connective tissue)

Pagetic involvement of the bony labyrinth is often asymmetric, incontradistinction to the pattern of Osteogenesis Imperfecta .

The patients age (36 years) mitigates against Paget disease, whichaffects an older population.


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FAMILIAL GIGANTIFORM CEMENTOMA

Multiple, large cemental masses found in the maxilla and mandible.

Inherited as an autosomal dominant trait.

Pagets disease has similar features still the main difference is that it

does not begin at an early age.


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Increased bone deposition due to inflammation. This can beassociated with either reversible pulpitis or irreversible pulpitis. It

can also be associated with areas of inflammation such asperiodontitis.

Radiographic Features:

Location: Surrounding the source of inflammation a tooth or anarea of inflammation.

Edge: Well-localized.Number: May be single or multiple.Staphylococcus aureus culture is always positive.

Bone deposits symmetrically and concomitantly.


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Medication to help regulate bone remodelling Biphosphonates, Zoledronic acid, Calcitonin Medication to relieve painPain killers & Physiotherapy Surgery

Arthroplastywhere the damaged joint is removed and replacedwith an artificial joint; the most commonly performed arthoplasties

are hip replacements and knee replacements

Arthrodesiswhere the joint is fused into a in a permanent position


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Contemporary Oral & Maxillofacial Pathology J. Philip

Sapp Shafers textbook of Oral Pathology 6th edition.

Oral & Maxillofacial Pathology 3rd edition Neville

Clinical Outline of Oral Pathology: Diagnosis and Treatment-Lewis R. Eversole

http://www.wheelessonline.com/ortho/pagets_disease_etiology_a

nd_pathogenesishttp://emedicine.medscape.com/article/334607-overview#a0104


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http://www.wheelessonline.com/ortho/pagets_disease

http://www.dentistry.ucla.edu/pic/visitors/pdb/page1.html#dif_

diagJohn T. Anderson et al. Osteolytic form of Paget's disease -differential diagnosis. The journal of bone and joint surgery. vol.

58-a, no. 7, october1976 Karpagaselvi Sanjai, Jayalakshmi Kumarswamy, Vinod K

Kumar, and Archana Patil. Florid cemento osseous dysplasia inassociation with dentigerous cyst. J Oral MaxillofacPathol. 2010 Jul-Dec; 14(2): 6368.


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Heimert T. L., Li D. M., Yousem M. D. OsteogenesisImperfecta of the Temporal Bone. Radiology 2002; 224:166

170. A. J. Lyons & A. V. Babajews. Gigantiform cementomaanunusual incidental finding. 1986, The British Journal of

Radiology, 59, 277-279http://drgstoothpix.com/radiographic-interpretation/pulpalapical-findings/apical-findings-inflammatory/sclerosing-osteitis/

Pagets Disease (1)

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