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Part one : By Osama Yousef

Before we start talking about Pagets disease of bone, you have to know the following things : Osteoclast Bone resorption . OsteoblastBone deposition. Pagets disease of bone is of unknown etiology, there are hypothesis about the etiology of this disease, but most of the cases are of unknown etiology. Normally there is a balance between the activity of bone deposition and bone resorption and this is called normal bone remolding, but in Pagets disease of bone this balance is not kept. We have excessive or abnormal: bone resorption or in other words : Osteoclast function , either it is excessive ; hyperosteoclast function or abnormal.

In Pagets disease of bone there are three overlapping phases : 1. The first phase is called Predominantly osteolytic phase : there is excessive osteoclast activity (or excessive bone resportion) in this stage the radiograph will be radiolucent (more black in color).

2. The second phase will be a mix between osteolytic (bone resorption ) and osteoblastic ( bone deposition ) , all of which are taking place at the same time.

3. The third phase is the Sclerotic phase or Osteosclerotic bone where the osteoblastic activity is the predominant and the bone becomes osteoscleraotic the bone will show the following signs in this stage : Dense, hard, brittle, easily fractured upon extraction and with low blood supply, all of these signs might lead to osteomaliets and bone infection which will be discussed in later occasions The first phase and second phase, we will have excessive bleeding because of increases of vascularity in the marrow spaces, in fact we have too much vascularity the patient might have heart failure. The second phase could be also considered as a vascular phase. So the complications of the first and second phase is excessive bleeding and hemorrhage after extraction due to high vsacularity Deformity of bones will occur in the first and second phases. In the third phase itll fix the deformity and make it dense or; sclerotic.

It should be noted that Pagets disease of bone is a chronic disease . The disease is most common in areas such as United kingdom, Australia and North America, in fact in England because they wear hats, the patient will complain about their hats are getting smaller in size, but whats actually happing is that their skulls are getting bigger! We are going to talk about the sgins of Pagets disease in different areas of the human body .

The effects on the bones can be summed up as follows : 1. There is bony deformity, the head becomes large. 2. The femur in legs will have curved apperance 3. the sacrum in the vertebral column is also affected (giving the bend appearance). 3

Not all the bones are necessarily affected, the patient may have the disease but with only one bone deformed, or in other cases the patient may have the disease but there are no signs to tell ; it can be only discovered with biopsy from that patient , so either single bone , multiple bones or not discovered at all.

4. we can see raidographically ( the adjacent picture ) that the skull is very dense and we cant differentiate the outer cortex (dipole) of the skull nor we can differentiate the tables of the skull. One of the complications of the large skull is the pressure on nerves. This pattern of whitish you see is called cotton wool appearance.

The effects of Pagets disease on the oral area can be summed as follows : 1. What is important in this disease for us as a dentists is the maxilla, there is going to be changes in the maxilla. It will be affected it will be enlarged in size and when the maxilla is enlarged ,the teeth are going to be spaced and the denture will not fit as it used to be , so the patient might need occasional changes of the maxillary denture to make it fit. 2. Spaced teeth 3. The teeth may also be palatally inclined (retro inclaniaiton ) 4

4. hypercemntosis and the ankylosis , ankylosis as you already know is the fusion between cementum and bone without PDL space . 5. We also might have root resorption , which will occur mainly in the first phase . 6. We also might have Post-extraction hemorrhage and More prone to infection in sclerotic phase as we said earlier. 7. Widening of the alveolar ridges 8.Abnormal occlusion

Due to hypercemntosis and ankylosis in Pagets disease , there might be surgical complications because the tooth wont come out easily. 9. Loss of the lamina dura in teeth , what is the lamina dura ? It is the compact bone or dense bone it appears radiographically as white lines surroding the teeth, these white lines have spaces between them and the root and within this space we 5

have the PDL. Itll be lost in Pagets disease due to bone resorption and when there will be bone deposition there will be hypercemntosis as we said earlier , so it will be lost. Note that Pagets disease of bone is more cmmon in maxialla.

Now we come to the etiology part, what is the cause of all of these changes? Unknown cause : paramyxovirus infection affecting the osteoclasts Genetic predisposition : Chromosome 18q locus defect or might be genetically related to familial tendency

In the first osteolytic phase we can see hyperosteoclastic (multi-nucleated) , they are called scalloping of the margins of the bone . When reverse of the activity of resorption occurs, a thin scallop line with a different color compared to the bone will occur, why these lines are formed? Because these lines are not well mineralized as the rest of the bone, because there is a sudden change in the bone activity either resorpition or deposition or formation. As you can see in the pictures A and B (on next page ) these blue lines on the H&E stain, it is called reversal lines because there is a reverse in the activity between osteoblastic and osteoclastic . You will have to know that, this general pattern of bone is called Mosaic pattern , we call it mosaic because we have small piceses of bone surrounded by these blue lines. So this mosaic appearance will indicate the reversal activity. If you look at the picture A, you can see that we are on the 2nd phase and we are moving toward to the 3rd phase . How did I know that? Well, most of the bone are sclerotic and there are a few blood vessels (arrows), we say that these are blood 6

vessels because if you look closer you can see endothelial lining. You should note that determining the phases is a hard thing, because often they are overlapping.

Increased serum alkaline phosphatase this reflects the bone resorption or deposition Serum calcium and phosphorus occasionally increased usually within normal limits. (There is change in the calcium/phosphor but they are in the normal range) .

In order to treat Pagets disease patient we have to stop the osteoclastic activity, and we do this by giving Calcitonin and diphosphonates .

Pagets disease is usually not fetal, but it creates lesions inside the bones and these lesions might lead to increased incidence of malignant neoplasms , most common type of the malignat complications is osteosarcoma. Note that the incidence for this is <1%. You should also remember the default sings of pagets disease of bone which we discussed earlier as, skull enlargement and the maxilla denture problems related to this disease which may count also as complactions.

Question : Are each phase of the three phases with a fixed timing ? the answer was : no , they have no specific timing , they are overlapping but the least duration would be the first phase .

Question: You said that Pagets disease affects the maxilla; does it affect the mandible as well? Yes it does, but the maxilla rate is greater and it is more commonly involved, it depends on which bone the disease choose to infect .

As we said, one of the complications of Pagets disease is the lesions that are inside the bone , looking at this picture which phase is this picture indicating ? it is the first because we have too many osteoclasts activity and scalloped border of the bone. ( picture of gaint cell lesion , next page ) The doctor said that we have already talked about central giant granuloma and we have already compared it with hyper-para-thyrodism , honestly she just passed the slides without talking too much about it , it is up to you if you want to study it or not.

With this we finish our talk about Pagets disease of bone and we move our attention to another subject which is Exostoses .

Simply they are defined as Localized bony protuberances, non neoplastic Their etiology is : developmental or in response to chronic trauma, following surgery, hereditary factors (autosomal development AD ). These are not benging tumors, what is the difference between for example osteoma and for example buccal exostoses? The difference between them is that the exostoses will not keep growing as the true tumors; they might even either grow in size or reduce in size but not a continuous growth! (The doctor asked a question of osteoma and Buccal exostoses , you are not familiar with them for now, but once you finish this lecture you will be , so dont worry ). The examples about exostoses have been already disscuesed but for example like: Torus palatinus :which is more common than mandibular Torus mandibularis: above MH line, bilateral Buccal exostosis: molar maxillary region Palatal exostosis Lets start off with the first one , Torus Palatinus .

Torus : something exostoic ( from the word exostoses) and palatinus : something that is found on palate , this exostoses is hard because it is bony , It might be multilobular or it might be lobular torus.

It is not common in children and it is not of developmental cause , in the past they thought that it had a developmental connection to it , but it turned out not to be , because if it were developmental how come we cant see it more in children .

Some say it increases in size because of masticatory function, especially patients of burixsm habit , but if you think about it there isnt much of muscles movement going on the palate so it is just one of the theories , other causes is unknown of why it changes in size . But burixsim habit has a link to it. This change in size due to the muscles pull might be more evident in the torus mandibularis , which will be discussed next .

It is found at the lingual aspect, present above the mylohyoid line , it is found in 90% bilateral . Note that torus palatinus is more common than torus mandibularis

They are neither benign nor malignant tumors so they are not tumors at all! , still their significance comes from: The denture of the patient will not fit propbley as it used to be.

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 The dentist might not understand what are the raidopacity that are present (look the x-ray). The dentist might be confused with the diagnoses, until he meets the patient and discover these toruies , see picture A.

They occur in the Buccal aspect of the alveolar bone and mainly on the maxillary teeth, people with gum smile will be more concerned than normal people because these Buccal exostoses will be more shown . What you have to do is only reassurance you have to explain to them that these are just developmental changes and there is absolutely no need to worry, if they are too much worried, and then you can make a surgical removal for them.

Like the Buccal exostosis we can also have palatal exostosis (picture), they may occur palatal to the last molar area.

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We also have Subpontine exostosis which is after extraction of the tooth and constriction of a denture or a bridge there might be exostotic mass, why it formed there? Well maybe because it is reactive in the space provided by the denture or bridge.~ note this exostosis is not mentioned in the book.

It is composed of dense compact bone (look picture), you can notice the few bone marrow spaces. Most of the time the histopathology is dense compact bone.

Dense bone island is of idopathic cause , you may see that the tooth is, not having low grade infection ,it is not carious and the bone is not cemnto-ostasis dysplisa because it is not surrondeed by raidolucent area , it is not causing bone expanison so in this case you call it dense bone islnad or bone scar , as the scars in the skin. It might not be fused to the root or it might be fused to the root , looking at the picture above the doctor asked to give some dignoses for it . Some answered that it might be hypercemntosis the dr said no because hypercemntosis occuer in the root surface and the hypercemntosis will still show the PDL space , unlike the picture. Others said concrescence , again the dr said no because in the concrescence you cant find dense bone areas within the bone itself , the concrescence is just fusion of the roots between adjacent teeth with cemntum , here if you take a look you 12

dont see cemntum you see a bone that is present between the two teeth and this bone is connecting the two teeth to each other.

End of part one .

Part two : by Enas Y. Salameh

Bone Tumors in general may originate from:

1-Marrow cells (the cells that are in the bone marrow) 2- Bone cells{Osteoblast or Osteoclast} Osteosarcoma 3- Blood vessels Hemangioma of bones. 4- Fibrous tissue within the bone marrow Fibrosarcoma. 5- Cartilage remnants inside the bone Chondrosarcoma especially in the developing areas of bones.

Benign
Bone
Osteoma& Osteoblastoma

Malignant
Osteosarcoma

Cartilage

Chondroma

Chondrosarcoma

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It is a true benging tumor of bone meaning that it will keep enlarging in size slowly with time, it is usually not multiple like the Buccal exstosis and not present in the midline of the palate nor the above the mylohyoid line . It is usually found at the angle of the mandible. It could be sub periosteal (immediately below the perotisum) or diffused within the bone (central ). The ostoemoa may be compact or cancellous bone . Looking at picture A, what is this mass? Is it soft tissue ? No , it is a bony mass , that is found at the angle of the mandible and if you look at the radiograph you can notice that it is a bony mass , it is denser than the bone , so it is osteomoa. It requires surgical removal because it is continuosaly growing , unlinke buccal exoseosis they dont require surgical treatment expect when denture constriaction or cosmatic reasons.

Looking at picture B, what do you think this disease is if you knew it is continuously enlarging its size. Is it osteoma or Buccal exostosis ? The answer is osteomoa because it is continuously enlarging in size and because it is found as a single proturbrance , Buccal exosteosis is found multiple and not only one. But if the osteoma are multiple in a single patient we should think about Gardner syndrome (we discussed gardner syndrome in the middle exam material, we said that gadrnder syndrome had a relation with multiple supernumerary teeth).

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The patients of this syndrome will have premalagenit adenomas of the colon, and 100% of those patients will have adenocarcinoma of the intestine . What shall we do for these patients ? Actually they cut their colon as prohylaxis to make sure they dont get the worse case which is the adecnocarcinoma of the intestine.

It is Autosomal dominenet Polyposis coli marked tendency for malignant change Fibrous tumors Sebacous cysts of the skin Multiple impacted and supernumerary teeth

Looking at the picture A , you can see we have two osteomoma , so this person might have Gardner syndrome , so genetic analysis is important for this patient . Looking at picture B , you can notice that the osteomia is not below the bone it is actually wihtin the bone so it is of central type. It looks also cancilous bone , not very dense. A student asked a question from picture B , sometimes we might get confiused between exosteosis and osteomoa . The answer was as follows : No , this is osteomia because of two things : 1. In oral pathology we dont have a single exososs apperaing at the angle of the mandbile 2. The angle of the mandbile is a common place for osteoma

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A student asked another question The buccl exosteosis looks simillar to what we saw in the ginvial cysts . The answer was during the clinc trial , upon palpation the cyst will show fluid materials , while the osteoma will be a bony mass ; will not show fluid .

It is a true benign slow growing tumor of bone that consists of mature bone. It is more frequent in the mandible than the maxilla. It may arise as Sub periosteal or central. Multiple osteomas is a feature of Gardner Syndrome.

With this we finished talking about osteoma .

Is a benign tumor but locally aggressive. It may destroy the cortical plates of bone, and may reach big sizes and cause fracture to the mandible. Histologically ,, Osteoblastoma are totally different from Osteoma. The doctor didn't talk
about these differences.

Microscopically, may be confused with Osteosarcoma because it has active cells within it. Clinically and radiographically may look like Cementoblastoma. But the difference is that Osteoblastoma is separated from the cementum of the root.

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 Is a Benign tumor of cementum It is well demarcated from the surrounding bone It is fused with the cementum of the root. It's increasing in size because it's a true tumor of bone. Dense lesion that has mixed radiolucent and radiopaque according to the activity of the cells, with a surrounding radiolucent line. *** In the adjacent picture, Well defined rounded radilucent small area between the roots of mandibular premolars is Mental Foramena !!

Is a malignant tumor of bone The malignant cells in it are osteoblast . ** The normal product of osteoblast is bone, the immature bone is called woven bone, and the matrix of this immature bone is called osteoid ,which is not well mineralized yet. It will have malignant osteoblast that will form osteoid which will be malignant, too. Most common primary malignant tumor in jaws. *** Primary tumors come from the bone itself, but Secondary tumors come from metastasis NOT from the bone itself and it may come from the oral epithelium in the oral cavity.

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 The age of onset is around 30 a little bit later than osteosarcoma in other long bone in the body , May be central, or may start from under the periosteom which is easier to be diagnosed. The mandible will have better prognosis, because the maxilla may have many marrow spaces that the osteosarcoma may spread through them easily and early . Ostoesarcoma may increase in paget's deiseas of bones.

The arrow points to osteoid because it is homogenous; dense eosinophilic that will absorb eosin stain, so it will be red in color. Bone is mineralized in the center but at periphery it's still young "nonmineralized". The cells that form this dense bone is malignant osteoblast are polymorphic; they vary in shape (oval or irregular) ,size (small or big )and stain (hyperchromatic or not ). The problem is that it doesnt show bone formation ""In microscopic pictures ,when there is a sample with no bone formation then it's so difficult to say it's osteosarcoma,so it will need different stains and procedures"".

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Malignant tumors are rapidly growing, therefore they dont give time to the body to form a well defined corticated region; ill-defined radiolucent region. This lesion will eat everything (the roots, the bone). It may perforate through the cortex causing expansion of the bone. May go inside PDL causing symmetrical widening. It may go out the soft tissue and produce rapidly enlargement lesion with ulceration later on, because the epithelium will be thin which a secondary manifestation is and mastication of the above teeth will allow the enlargement, it fells bony. The lesion may be radiopaque or radiolucent or mixed according to the amount of osteoid that will be formed within the lesion; if it has more bone radiobaque but if it has less bone then it will be radiolucent.

Swelling Pain, toothache because the tumor may press on the nerves and it will resorb teeth. Loose or displaced teeth Bleeding Paresthesia because of pressure on nerves 19

*** Sun-ray pattern: due to formation of bony trabeculae in perpendicular angle to the bone .It is present only in 25% of all patients and it may present in other lesions. **Not unique to osteosarcoma** Early signs: localized symmetrical widening of PDL because it is easy to go through them. Treatment: Surgery, radiation thereby or chemotherapy.

***If the whole lesion was like this then it will appear radiolucent.

End of part two

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Part three : By Ali Al-Qudsi

Chondrosarcoma is a tumor of chondroblasts (cartiallage producing cells), classified as a primary bone tumor, due to remnants of cartilage in the jaw (Mandible = Head of the condyle / Maxilla = Close to the anterior part of the maxilla). Product of chondrobalsts = Chondroid Chondrosarcoma = Malignant, Chondroma = Benign. The more common of the two is the malignant form (Chondrosarcoma).

The chondroid matrix appearance is not completely pink/eosophillic it appears a mix of eosniphillic and basophilic, the chondoroblasts themselves are found in their lacuna but they are Pleomorphic (varying size), Mulit-loculated, can Be Binucleated, (highly cellular & Contains plump cells).

The appearance of Chondroma (benign form) closely resembles that of the chondrosarcoma except a few differences, mainly No bi-nucleation, no Hyperchromatism and minimal pleomorphisim (picture A in next page )

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Chondrosarcomas/Chondromas can appear radiographically as radio-opaque, radiolucent or mixed depending on the amount of chondroids found in the lesion. These chondroids may later ossify (turn into bone) with time which makes it difficult to differentiate between Chondrosarcomas and Osteosarchomas microscopically (each has a different treatment, therefore its critical to differentiate between the two. Mandibular lesions have a better prognosis (less dangerous) Chondrosarcomas are less aggressive than other sarcomas (slower growth rate).

Plasma cells (found in bone marrow) may become cancerous leading to a condition known as multiple myelomas (malignant tumor/neoplasm of plasma cells), may be present as a Single lesion/Multiple lesions. Multiple myeloma is most common in elderly patients, a common symptom of multiple myelomas is sever bone pain, upon radiographic investigation the patients skull appears to have a punched out appearance (present as well defined well rounded radiolucencies). Multiple myeloma may affect several bones (skull, vertebral column, mandible and other bones). The product of plasma cells are immunoglobulins (IgG, IgA, IgE) A single lesion of defected plasma cells is called Plasma-Cytoma

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Upon protein investigation of blood there will be a peak/spike in one of the blood proteins due to monoclonal proliferation of the plasma cells. This protein is the M Spike/Para-protein (M in relation to myeloma) this M spike represents the increase in the number of IGs.

Malignant tumors are usually accompanied by rapid growth and destruction accumulating in both bone and soft tissue. Radiographically the lesions appear IllDefined leading to a radiographical feature called floating in air teeth (teeth appear to be unsupported at all- very common in Langerhan Cell Disease) due to the destruction in bone (the tooth is only supported by abnormal soft tissue- hardly any bone left). The most commonly affected bones are the Skull, Vertebrae, Sternum and Pelvis; however its possible that the only clinical manifestation is lower back pain.

Electrophoresis to search for M Spike Protein Bence-Jones Proteins- light protein chains that may leak out in the urine (present in 50% of the cases) Blood may contain Increase in Calcium (due to increased bone resorption) Amyloidosis (Protein presence in tissue of chronic diseases) leads to Macroglossia or swelling. Sharply demarcated punched out radiolucencies (diploe of the skulls are evident- lost in Pagets disease)

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Within the bone you can see sheets of malignant plasma cells. Characteristics of these malignant plasma cells are: Pleomorphism, hyperchromatism and Monoclonal (Use Kappa/Lambda test to see if they are producing similar chains or nottype of diagnostic test), if the lesion is reactive and produces different types of chains then it is classified as polyclonal.

End of part three End of the lecture done by : Enas salameh , Ali Alqudsi and Osama Yousef

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