Pagets Disease (1)
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Transcript of 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/