Bone Neoplasms and Related Disorders

Question 1

What is Paget’s disease and what is the aetiology

Answer 1

• Disturbance of bone turnover that causes resorption, softening and sclerosis of bones
• Unknown cause but 30% pts have several genes recognised (SQSTM1 and RANK genes) important in osteoclast function
• Possible due to environmental factors or virus

Question 2

What are the clinical features of Paget’s disease

Answer 2

• Affects the elderly, with onset of 45+ years
• Incidence and severity declining
• Irregular resorption, softening and then sclerosis of bone
• Bones frequently affected: sacrum, spine, skull, fear and pelvis
• In severe cases: thickening of long bones which bend under stress, and tenderness or aching bone pain
• Often radiographic finding. Less common as clinical disease
• Maxilla occasionally, but mandible rarely affected
• Teeth may show gross irregular hypercementosis
• Serum alkaline phosphatase markedly raised; serum calcium and phosphorus levels usually normal

Question 3

What is the pathology of Paget’s disease

Answer 3

• A focus of diseased bone gradually enlarges, spreading along a bone like a wave, leaving an enlarged central zone of bone sclerotic and distorted
• Bone resorption and replacement becomes rapid, irregular, exaggerated and the ultimate result is diffuse thickening of affected bones
• Closely adjacent parts of the bone may show different stages of the disease; a common result is patchy areas of osteoporosis and of sclerosis
• In the late stages, affected bones are thick, the cortex and medulla are obliterated and the whole bone is spongy in texture. There is fibrosis of marrow spaces and increased vascularity with large vessels. These shunt the majority of the blood flow direct from arterial to venous circulation, reducing perfusion of bone and peripheral resistance, This place strain on the heart and may lead to eventual high-output cardiac failure

Question 4

How is the skull affected in Paget’s disease

Answer 4

• Most frequently affected bone
• Softened skull vault deforms under the weight of brain and sags down around the sides to produce a radiological sign of tam o’shanter skull
• Involvement of skull base narrows foramina and can lead to cranial nerve deficits

Question 5

How are the jaws affected in Paget’s disease

Answer 5

• 20% of pts (in severe cases)
• Maxilla more frequently and severely than mandible
• Alveolar process becomes symmetrically and grossly enlarged => spacing and denture no longer fits
• Sinus obliterated
• Nasal airway reduced
• Orbits pushed laterally
• May be gross and irregular hypercementosis of teeth that can extend through the apex into the pulp. The lamina dura around the teeth is lost, and teeth may be ankylosed if the hypercementosis becomes fused to sclerotic areas of the bone. Attempts to extract teeth may only work by tearing bone away and severe bleeding from vascular bone may follow. In the long term, the dense cemental and bone sclerosis are prone to osteomyelitis and heal slowly. AB cover is necessary for xla

Question 6

How is Paget’s disease diagnosed

Answer 6

• Serum alkaline phosphatase

- Radiological appearance

Question 7

What is the radiographic appearance of Paget’s disease

Answer 7

• Patchy sclerosis and resorption gives cotton wool appearance
• Lower density of bone in the early stages and sclerosis in the later stages
• Loss of normal trabeculation

Question 8

What is the histological appearance of Paget’s disease

Answer 8

• Repeated bone resorption and deposition is marked histologically by blue staining resting and reversal lines => leaves jigsaw puzzle pattern of reversal lines
• Both osteoclasts and osteoblasts are more prominent than that in normal bone
• Osteoclasts abnormally large and with more nuclei than usual

Question 9

How is Paget’s disease managed

Answer 9

• Bisphosphonates: oral or IV infusion
• Calcitonin can also be used to inactivate osteoclasts and limited to 3 months of tx as it has small risk of cancer
• Ca and vitamin D supplementation required

Question 10

What is an osteoma

Answer 10

• Genine osteomas are benign neoplasms and thus show progressive growth. They must be differentiated from exoduses and tori for this reason.
• Osteomas are relatively rare in the jaws, but the sinuses are a site of predilection and they occasionally grow in the jaw

Question 11

What are the types of osteoma

Answer 11

• Compact osteoma: nodule of dense lamella bone, sometimes in parallel layers like bone cortex rather than in Haversian systems. This dense bone containers occasional vascular spaces and grows very slowly
• Cancellous osteomas: have a peripheral cortical layer and central zone of medullary bone with marrow spaces. Osteomas are easily excised if they become large enough to cause symptoms or interfere with a fitting of a denture

Question 12

What are the clinical features of osteomas

Answer 12

• More common in mandible than maxilla
• Bony hard, sometimes pedunculated lump, occasionally lobulated
• Histologically normal bone and indistinguishable from this

Question 13

What is Gardener’s syndrome and what does it carry a high risk of

Answer 13

• Variant of familial adenomatous polyposis (FAP) caused by mutation in the APC gene and inherited as an autosomal dominant trait
• This has additional signs of multiple osteomas of the jaw/facial bones/skull, fibromas and epidermal cysts, together with range of other less frequent abnormalities
• Carries a high risk of colon carcinoma
• Osteomas and dental features are visible radiographically before colonic polyposis so early recognition could save a life

Question 14

What are exostoses and tori

Answer 14

• Localised swellings of bone are thought to be developmental and are very common
• Extensions of the normal bone structure, with a surface of cortical compact bone layer and, if large, a core of normal medullary bone
• Small exostoses are occasionally seen, usually on surface of alveolar processes of maxilla buccally (sometimes multiple forming row)
• Thin mucosal covering on tori are prone to damage and their prophylactic removal has been suggested to prevent MRONJ which develops more commonly in areas of mucosal trauma

Question 15

What types of tori are found

Answer 15

• Torus mandibularis: develops on the lingual aspect of mandible above mylohyoid muscle and floor of mouth mucosa
• Torus palatines: commonly forms toward the posterior of the midline of the hard palate

Question 16

What is an osteochrondroma. Where is it usually found and how is it treated?

Answer 16

• Small columns of bone with a cap of hyaline cartilage or fibrocartilage (similar to condyle) at the outer growing end. Lesion is subperiosteal and progressively ossifies with time
• Form hard bony protuberance, usually from anteromedial aspect of the condyle that limits mouth opening or causes displacement
• In the jaw, these benign bony growths cease to grow after skeletal maturation. Removal is therefore curative
• Characteristic radiographically and maybe diagnosed with reasonable certainty on CBCT, although cartilage cap cannot be seen on CBCT

Question 17

What is a chondroma, what should be suspected and how is it treated?

Answer 17

• Rare, and chondrosarcoma should always be suspected (as low-grade chondrosarcoma has similar histological features as chondroma)
• Chondromas consist of hyaline cartilage but the cells are irregular in size and distribution. Calcification or ossification may develop
• Most arise in maxillary bones or base of skull
• Treated by excision including wide margin of normal tissue

Question 18

What is an osteosarcoma

Answer 18

• Malignant neoplasm that forms bone or osteoid
• Most arise in long bones of children and adolescents, are highly malignant, metastasise early to lunch and are frequently fatal
• Osteosarcomas of jaws arise 30-50y, seem to grow slowly and have a better prognosis
• Typically firm swelling that grows noticeable in few months and becomes painful. Teeth may be loosened, and there may be paraesthesia or loss of sensation in the mental nerve area

Question 19

What is the radiographic appearance of osteosarcomas

Answer 19

• Bone formation is seen in a soft tissue mass
• Appearances are variable but irregular bone destruction with a poorly defined moth-eaten margin is usual
• Bone formation within osteosarcomas varies in extent, but when the sarcoma extends beyond bone into soft tissue, even small amounts of bone can be seen clearly and aid diagnosis
• Rapid enlargement pushes the periosteum away from the bone and triggers formation of the periosteal new bone layer over the tumour, giving rise to a sun-ray appearance and Codman’s triangles at the margin

Question 20

What is the pathology of an osteosarcoma

Answer 20

• Unknown cause, though causative mutations in the retinoblastoma gene RB1 and p53 are recognised in long bone lesions
• The mass comprises disorganised neoplastic osteoblasts that vary in size and shape, from spindle cells to angular or large and hyperchromatic. Bone formation is not necessarily prominent, and a search must be made for diagnostic zones of osteoid and disorganised woven bone
• Mitoses may be seen
• Cartilage and clusters of osteoclasts may also be found
• May develop in skull and facial bones affected by Paget’s disease, and also occasionally many years after head and neck irradiation for another cancer

Question 21

How are osteosarcomas managed

Answer 21

• Treated by radical surgery (resection including any soft tissue extension) - hemimandibular or total maxillectomy
• Common to also have additional chemotherapy and/or radiotherapy
• Prognosis depends mainly on the extent of the tumour and deteriorates with spread to the soft tissue, to lymph nodes or to the base of the skull
• In ~50% of cases, there is local recurrence within a year of treatment. the 5-year survival rate may range from 70% for tumours less than 5cm in diameter to zero for tumours greater than 15cm, and death usually follows local recurrence rather than distance metastasis

Question 22

What is a chondrosarcoma and what are the clinical features

Answer 22

• Malignant neoplasms that form cartilage are chondrosarcomas. [Those that form both cartilage and osteoid or bone are considered osteosarcomas]
• Chondrosarcomas of the jaws behave in a similar fashion to those in the commoner sites in the vertebrae, ribs and skull
• Chondrosarcomas of the jaws are even rarer than osteosarcomas and affect people ~45y old
• The anterior maxilla is the most frequent site
• A painless swelling or loosening of teeth associated with a radiolucent area are typical
• The radiolucency can be well or poorly circumscribed, or may appear Multilocular
• Calcifications are frequently present and may be widespread and dense

Question 23

What is the pathology of chondrosarcomas

Answer 23

• Chondrosarcomas are graded on the basis of how well the cartilage is differentiated and how pleomorphic and mitotically active the cells are
• Jaw osteosarcomas are usually at the low-grade end of the spectrum
• The cartilage is comparatively well formed, with mild atypica in chorocytes and only occasional mitosis

Question 24

What is the management of chondrosarcomas

Answer 24

• Widely excised as early as possible as radiotherapy and chemotherapy have no effect on low-grade tumours
• Greater margins are required with increased grade
• Survival is good: 75% 5y survival
• Metastasis is unusual

Question 25

What is a mesenchymal chondrosarcoma

Answer 25

• Rare but highly malignant variant
• Highly cellular tumour in which there are only small foci of tissue recognisable as poorly formed cartilage
• The jaws are common sites, and pts are younger than for other chondrosarcomas

Question 26

What are the clinical features of myelomas

Answer 26

• Multiple myeloma is a malignant neoplasm of plasma cells. The malignant plasma cells localise in the bone marrow, multiply to displace the normal marrow and cause multiple foci of bone destruction
• Myeloma is a systemic disease from the outset
• It is rare for a jaw lesion to cause the initial symptoms, but the skull is a common site of involvement and a third of pts may have a focus in the jaws. Myeloma is usually diagnosed in pts older than 60y
• Clinically, myeloma lesions may be asymptomatic or cause bone pain and tenderness, weakening of bones and pathological fracture
• The malignant plasma cells secrete immunoglobulin is detectable by serum electrophoresis for diagnosis
• Radiologically myeloma lesions are radiolucencies, traditionally multiple ‘punched out’ radiolucencies in the vault of the skull
• Presentation with jaw lesions is uncommon, but multiple small foci of bone destruction is a common presentation in those under tx or in relapse

Question 27

How does myeloma arise genetically?

Answer 27

• Arses by one of several mechanisms involving chromosomal translations
• These bring together one of a variety of oncogenes (often the cell cycle regulator cyclin D1 with genes from immunoglobulins), both transforming the cell and inducing the excessive immunoglobulin synthesis
• Myeloma arises from a single cell, and so all the malignant plasma cells are monoclonal; they all secrete antibody of the same immunoglobulin class and antigen specificity

Question 28

What is the management of myeloma

Answer 28

• Considered incurable, but treatment has developed to the stage that life can be extended for many years
• Initially, most pts will be treated with combination of chemotherapy including steroids and a thalidomide analogue and the proteasome inhibitor bortezomib, and there is frequently a good response
• Remission is maintained and prolonged with a progression of drug regiments selected to match disease progression and avoid adverse effects
• Autologous stem cell transplants provide best survival
• Localised lesions treated with radiotherapy or surgery if they threaten adjacent important structures
• When bone metastases are widespread or symptomatic, treated with Bisphosphonates to reduce bone resorption and bone pain

Question 29

What are the dental affects of myeloma

Answer 29

• Myeloma deposit in the jaws or amyloid deposition in the oral soft tissues can be the first manifestation of the disease
• Complications of disease and its treatment affect delivery of dental treatment
• Bone marrow replacement causes thrombocytopenia, anaemia, bleeding and purpura
• Immunosuppression from steroids and loss of normal lymphocytes cause opportunistic infections arise
• AB prophylaxis may be required for surgery depending on stage of disease
• High-potency Bisphosphonates given intravenously include pamidronate and zoledronic acid, and this treatment carries a risk of MRONJ

Question 30

Which bones are most affected by blood-borne metastasis and where are blood-borne metastasis to bone usually from?

Answer 30

• Metastasis to bone affects those bones with the greatest medullary volume, the spine, pelvis, ribs and femur
• Jaw metastases are relatively unusual and almost always signify late-stage disease and widespread bony and other metastases
• Blood-borne metastasis to bone is almost always from a carcinoma, usually an adenocarcinoma

Question 31

How common is jaw metastases compared to primary malignant neoplasm of bones

Answer 31

• Jaw metastases are much more common than primary malignant neoplasms of bone (osteosarcoma, chondrosarcoma)

Question 32

What are the common key features of jaw metastasis

Answer 32

• Common symptoms are pain or swelling of jaw, trismus and paraesthesia or anaesthesia of the lip
• A non-healing tooth socket in an important presentation for dentists
• There is typically an area of radiolucency with a hazy outline. This sometimes stimulates infected cyst or may be quite irregular and simulate osteomyelitis
• One key features is that metastases seen in the marrow spaces and, in the mandible, most other marrow lies below the inferior dental canal. This localisation helps distinguish potential metastases from lesions associated with the teeth. However, it is important to be alert for metastases mimicking infection or dental disease if the radiographic features are unusual or treatment is ineffective

Question 33

What is langerhans cell histiocytosis

Answer 33

• Langerhans cells are dendrites antigen-presenting cells that derive from the bone marrow and migrate to function within epithelia. In this group of conditions, they proliferate excessively and localise in bone, organs and skin
• Cause is unknown
• Three main forms are recognised: chronic unifocal, chronic multifocal and acute disseminated which all fall on a spectrum of severity

Question 34

What are the key oral lesions of langerhans cell histiocytosis

Answer 34

• Isolated or multifocal tumours of langerhans cells
• Eosinophilic granulomas form sharply demarcated radiolucencies
• Alveolar bone around teeth may be destroyed (teeth floating in air appearance)
• May also mimic juvenile periodontitis radiographically
• Solitary lesions repsond to curettage or resection