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BONE PATHOLOGY Eugene Vlodavsky MD Pathology Institute RAMBAM Medical Center.

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Presentation on theme: "BONE PATHOLOGY Eugene Vlodavsky MD Pathology Institute RAMBAM Medical Center."— Presentation transcript:

1 BONE PATHOLOGY Eugene Vlodavsky MD Pathology Institute RAMBAM Medical Center

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5 MICROSCOPIC STRUCTURE OF BONE Osteoprogenitor cells – pluripotential mesenchymal cells. Under appropriate stimulation can differentiate into osteoblasts Osteoprogenitor cells – pluripotential mesenchymal cells. Under appropriate stimulation can differentiate into osteoblasts Osteoblasts – located on the surface of bone, “build” the bone and initiate process of mineralization. Have receptors for PTH, vit D and estrogen. Osteoblasts surrounded by bone matrix – osteocytes. Osteoblasts – located on the surface of bone, “build” the bone and initiate process of mineralization. Have receptors for PTH, vit D and estrogen. Osteoblasts surrounded by bone matrix – osteocytes. Osteocytes are less active than osteoblasts but play important role in control of the fluctuations in serum Ca and Ph levels. Osteocytes are less active than osteoblasts but play important role in control of the fluctuations in serum Ca and Ph levels. Osteoclasts – responsible for bone resorption, multinucleated giant cell,derivate of granulocyte-monocyte precursor cell from bone marrow Osteoclasts – responsible for bone resorption, multinucleated giant cell,derivate of granulocyte-monocyte precursor cell from bone marrow

6 MICROSCOPIC STRUCTURE OF BONE Osteoblasts produce proteins of bone,pred. collagen type 1 (90%of organic component - matrix) Osteoblasts produce proteins of bone,pred. collagen type 1 (90%of organic component - matrix) Woven bone – irregular nonmineralized bone, normally seen only in fetus. In adult is always sign of pathologic process Woven bone – irregular nonmineralized bone, normally seen only in fetus. In adult is always sign of pathologic process Lamellar bone – gradually replaces woven bone during growth and is stronger than woven bone Lamellar bone – gradually replaces woven bone during growth and is stronger than woven bone Osteoblasts and osteoclasts act in coordination as “basic multicellular unit” performing bone formation and resorption during skeletal growth (modeling) and maintenance of mature skeleton (remodeling) Osteoblasts and osteoclasts act in coordination as “basic multicellular unit” performing bone formation and resorption during skeletal growth (modeling) and maintenance of mature skeleton (remodeling)

7 NON-TUMOROUS DISEASES OF BONE NON-TUMOROUS DISEASES OF BONE

8 PAGET’S DISEASE PAGET’S DISEASE Is characterized by regions of “furious” bone resorption by osteoclasts, followed by a periods of irregular and disordered bone formation Is characterized by regions of “furious” bone resorption by osteoclasts, followed by a periods of irregular and disordered bone formation Chronic disease, divided into 1. osteolytic stage: 2. mixed osteoclastic- osteoblastic; 3. burnt-out osteosclerotic stage Chronic disease, divided into 1. osteolytic stage: 2. mixed osteoclastic- osteoblastic; 3. burnt-out osteosclerotic stage Pathogenesis – viral intranuclear inclusions in the nuclei of osteoclasts; bone marrow of the patients contains paramyxovirus nucleocapsid transcripts Pathogenesis – viral intranuclear inclusions in the nuclei of osteoclasts; bone marrow of the patients contains paramyxovirus nucleocapsid transcripts Axial skeleton and prox.femur involved in 80% of cases. Mostly polyostotic(pelvis,spine,scull), in 15% - monostotic (tibia, ilium,scull,femur,humerus) Axial skeleton and prox.femur involved in 80% of cases. Mostly polyostotic(pelvis,spine,scull), in 15% - monostotic (tibia, ilium,scull,femur,humerus)

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11 PAGET’S DISEASE - MICROSCOPY

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13 PAGET’S DISEASE - COURSE Pain Pain Bone deformations with various complications Bone deformations with various complications Fractures Fractures Hypervascularity may cause heart failure Hypervascularity may cause heart failure Benign tumors – giant cell tumor Benign tumors – giant cell tumor Sarcoma (5-10% of polyostotic PD) – osteosarcoma,chondrosarcoma,MFH Sarcoma (5-10% of polyostotic PD) – osteosarcoma,chondrosarcoma,MFH Most patients have mild symptoms,treated by calcitonin and diphosphonates Most patients have mild symptoms,treated by calcitonin and diphosphonates

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15 AVASCULAR NECROSIS OF BONE AVASCULAR NECROSIS OF BONE Infarction of bone and marrow – relatively common event Infarction of bone and marrow – relatively common event The cause is ischemia, the mechanisms are varied: mechanical rupture of blood vessels(fracture); thrombosis and embolism; vasculitis,radiation damage, increased intraosseous pressure due to steroid therapy and many others. The cause is ischemia, the mechanisms are varied: mechanical rupture of blood vessels(fracture); thrombosis and embolism; vasculitis,radiation damage, increased intraosseous pressure due to steroid therapy and many others.

16 AVASCULAR NECROSIS AVASCULAR NECROSIS In medullary necrosis cortical bone is preserved(collateral blood supply). Subchondral epiphyseal necrosis has triangular shape, cartilage is preserved, but will collapse later and will cause secondary osteoarthritis. In medullary necrosis cortical bone is preserved(collateral blood supply). Subchondral epiphyseal necrosis has triangular shape, cartilage is preserved, but will collapse later and will cause secondary osteoarthritis. Clinical picture depends on location and size, usually pain Clinical picture depends on location and size, usually pain About joint replacements annualy in US – due to complications of avascular necrosis About joint replacements annualy in US – due to complications of avascular necrosis

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21 BONE INFECTIONS - OSTEOMYELITIS Inflammation(infection) of bone and marrow Inflammation(infection) of bone and marrow Pyogenic Os – caused by bacteria: 80-90% Staph. Aureus; E.coli, Pseudomonas, Klebsiella – in genitourinary infections and IV drug users; H.influenzae and grour B streptococci – in neonates Pyogenic Os – caused by bacteria: 80-90% Staph. Aureus; E.coli, Pseudomonas, Klebsiella – in genitourinary infections and IV drug users; H.influenzae and grour B streptococci – in neonates Bacteria may reach the bone by (1) hematogenous spread (2) extension from contiguous site (3) direct implantation Bacteria may reach the bone by (1) hematogenous spread (2) extension from contiguous site (3) direct implantation Location – in children – metaphysis and epiphysis, in adults – epiphysis, vertebra Location – in children – metaphysis and epiphysis, in adults – epiphysis, vertebra

22 PATHOLOGY OF OSTEOMYELITIS Acute, subacute and chronic Acute, subacute and chronic Cause formation of necrotic bone area (“sequestrum”) Cause formation of necrotic bone area (“sequestrum”) Inflammation may reach the periost and rupture to the soft tissue with formation of draining sinus Inflammation may reach the periost and rupture to the soft tissue with formation of draining sinus In children (rarely in adults) inflammation can involve joints and produce septic arthritis In children (rarely in adults) inflammation can involve joints and produce septic arthritis In vertebra infection destroys the hyaline cartilage and involve intervertebral discs(“discitis-osteomyelitis”) In vertebra infection destroys the hyaline cartilage and involve intervertebral discs(“discitis-osteomyelitis”) Over time – resorbtion of bone,reactive bone formation and fibrosis Over time – resorbtion of bone,reactive bone formation and fibrosis New bone around sequestrum – “involucrum” New bone around sequestrum – “involucrum” Brodie abscess – small intraosseous (often – cortical) abscess Brodie abscess – small intraosseous (often – cortical) abscess Os of Garre – in the jaw with extensive new bone formation Os of Garre – in the jaw with extensive new bone formation

23 OSTEOMYELITIS – CLINICAL COURSE Acute systemic ilness with malaise,fever,leukocytosis,pain Acute systemic ilness with malaise,fever,leukocytosis,pain Symptoms may be mild (only pain,esp. infants) Symptoms may be mild (only pain,esp. infants) Culture is often negative due to antibiotic treatment Culture is often negative due to antibiotic treatment Chronicity may develop when: delay in diagnosis;ineffective treatment; large area of necrosis;weakened host defence Chronicity may develop when: delay in diagnosis;ineffective treatment; large area of necrosis;weakened host defence Complications of chronic Os: pathologic fracture, secondary amyloidosis,endocarditis,sepsis, squamous cell carcinoma in sinus tract, sarcoma of bone Complications of chronic Os: pathologic fracture, secondary amyloidosis,endocarditis,sepsis, squamous cell carcinoma in sinus tract, sarcoma of bone

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28 TUBERCULOUS OSTEOMYELITIS Increased incidence in western countries due to influx of immigrants and growing No of immunosupressed people Increased incidence in western countries due to influx of immigrants and growing No of immunosupressed people Usually blood borne infection Usually blood borne infection TB Os is more destructive and resistant to treatment than pyogenic Os TB Os is more destructive and resistant to treatment than pyogenic Os In the spine involves several vertebra and soft tissue(Pott’s disease), often with compression fractures and scoliotic or kiphotic deformations In the spine involves several vertebra and soft tissue(Pott’s disease), often with compression fractures and scoliotic or kiphotic deformations Complications - TB artrithis, sinus tract formation,amyloidosis Complications - TB artrithis, sinus tract formation,amyloidosis

29 BONE TUMORS

30 BONE TUMORS MAY BE PRIMARY OR SECONDARY.MOST COMMON MALIGNANCIES,PRODUCING BONE METASTASES: ADULTS. More than 75% of skeletal metastases originate from Ca of the prostate,breast,kidney, lung,thyroid and colon. DO NOT FORGET MELANOMA! CHILDREN. Neuroblastoma,rhabdomyosarcoma and retinoblastoma

31 RADIOGRAPHIC APPEARANCE OF METASTATIC TUMORS Purely lytic – kidney,lung,colon,melanoma Purely lytic – kidney,lung,colon,melanoma Purely blastic – prostate and breast Purely blastic – prostate and breast Mixed lytic and blastic (most common) Mixed lytic and blastic (most common)

32 PRIMARY BONE TUMORS More common in first 3 decades of life (skeletal growth activity) More common in first 3 decades of life (skeletal growth activity) The commonest sites for both benign and malignant – distal femur and proximal tibia – the bones with the highest growth rate The commonest sites for both benign and malignant – distal femur and proximal tibia – the bones with the highest growth rate Relatively specific radiologic presentation Relatively specific radiologic presentation Benign tumors are by far more common than malignant Benign tumors are by far more common than malignant Some are difficult to classify as benign or malignant(giant cell tumor) Some are difficult to classify as benign or malignant(giant cell tumor) Among malignant tumors osteosarcoma is most common,followed by chondrosarcoma and Ewing sarcoma Among malignant tumors osteosarcoma is most common,followed by chondrosarcoma and Ewing sarcoma

33 BONE TUMORS – RELEVANT CLINICAL INFORMATION Age – may be the most important clinical clue: primary osteoSa and Ewing Sa are tumors of children and young adults. After 40 – bone metastases and chondrosarcoma are most common. Age – may be the most important clinical clue: primary osteoSa and Ewing Sa are tumors of children and young adults. After 40 – bone metastases and chondrosarcoma are most common. Pain. Benign lesions tend to be asymptomatic.Pain may be symptom of a)growing lesion b)pathologic fracture c)significant local tissue reaction to the tumor. Pain can help in diagnosis of osteoid-osteoma and differential diagnosis between enchondroma and chondrosarcoma grade I Pain. Benign lesions tend to be asymptomatic.Pain may be symptom of a)growing lesion b)pathologic fracture c)significant local tissue reaction to the tumor. Pain can help in diagnosis of osteoid-osteoma and differential diagnosis between enchondroma and chondrosarcoma grade I

34 Radiological correlation Radiological correlation Plain radiograph – the first imaging technique for suspected bone lesion Plain radiograph – the first imaging technique for suspected bone lesion Computer tomography – method of choice when plain film is not sufficient. The best for assesment of mineralization, cortical detail, cystic and fatty lesions Computer tomography – method of choice when plain film is not sufficient. The best for assesment of mineralization, cortical detail, cystic and fatty lesions MRI is good for local staging – spread of tumor and its relation to critical neurovascular structures. MRI appearance of most bone tumors is non-specific MRI is good for local staging – spread of tumor and its relation to critical neurovascular structures. MRI appearance of most bone tumors is non-specific Bone scintigraphy – highly sensitive but relatively nonspecific method Bone scintigraphy – highly sensitive but relatively nonspecific method

35 RADIOLOGICAL EXAMINATION SHOULD ANSWER THE FOLLOWING QUESTIONS: The exact location of the lesion The exact location of the lesion Evidence of any underlying bone abnormality(bone infarct,Paget’s disease Evidence of any underlying bone abnormality(bone infarct,Paget’s disease Is the lesion multifocal? Is the lesion multifocal? Does the tumor have a well defined margin?The rim of sclerotic bone?(signs of benign lesions). Does the tumor have a well defined margin?The rim of sclerotic bone?(signs of benign lesions). Is there evidence of cortical destruction or expansion?(signs of aggressive behavior). Is there evidence of cortical destruction or expansion?(signs of aggressive behavior). Does the tumor produce mineralized matrix(osteoid or cartilage)? Does the tumor produce mineralized matrix(osteoid or cartilage)? Is there a soft tissue mass? Is there a soft tissue mass?

36 OTHER IMPORTANT DIAGNOSTIC FEATURES Skeletal location Skeletal location Site of long bone involvement Site of long bone involvement

37 BENIGN BONE TUMORS

38 OSTEOMA OSTEOMA Slowly growing tumors of low clinical significance Slowly growing tumors of low clinical significance Predominantly located in scull and facial bones Predominantly located in scull and facial bones Microscopically – coarse lamellar and trabecular bone Microscopically – coarse lamellar and trabecular bone Multiple osteomas are the part of Gardner syndrome(fibromatosis, familial intestinal polyposis) Multiple osteomas are the part of Gardner syndrome(fibromatosis, familial intestinal polyposis) Resected when cause cosmetic problems,impinge on the brain or eye etc. Resected when cause cosmetic problems,impinge on the brain or eye etc. Do not transform to osreosarcomas Do not transform to osreosarcomas

39 OSTEOID-OSTEOMA AND OSTEOBLASTOMA Have identical histological features; differs in size, sites of origin and symptoms. Have identical histological features; differs in size, sites of origin and symptoms. Osteoid-osteoma(OO): less than 2 cm in diameter. 75% of patients are younger than 25 years old. 50% involves femur and tibia(but every bone may be involved). Osteoid-osteoma(OO): less than 2 cm in diameter. 75% of patients are younger than 25 years old. 50% involves femur and tibia(but every bone may be involved). OO is painful lesion(excess production of prostaglandin E2). The pain is rather severe, nocturnal and relieved by aspirin OO is painful lesion(excess production of prostaglandin E2). The pain is rather severe, nocturnal and relieved by aspirin Osteoblastoma is larger than OO, the same age,more frequent in spine, the pain if present,is different –not so severe and not so responsive to salicilates Osteoblastoma is larger than OO, the same age,more frequent in spine, the pain if present,is different –not so severe and not so responsive to salicilates

40 OSTEOID-OSTEOMA OSTEOID-OSTEOMA

41 OSTEOBLASTOMA OSTEOBLASTOMA

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44 OSTEOID OSTEOMA AND OSTEOBLASTOMA TREATMENT AND PROGNOSIS Both are treated by conservative surgery Both are treated by conservative surgery Incomplete excision – may recur Incomplete excision – may recur Malignant transformation is very rare,usually after irradiation Malignant transformation is very rare,usually after irradiation

45 OSTEOGENIC SARCOMA (OSTEOSARCOMA)

46 OSTEOSARCOMA – MALIGNANT MESENCHYMAL TUMOR IN WHICH MALIGNANT CELLS PRODUCE BONE MATRIX Most common primary malignant tumor of bone(exc. myeloma and lymphoma) – 20% of primary bone cancers Most common primary malignant tumor of bone(exc. myeloma and lymphoma) – 20% of primary bone cancers About 75% of patients younger than 20 years old (primary OSa) About 75% of patients younger than 20 years old (primary OSa) In older patients – secondary OSa – in conditions associated with risk of OSa development – Paget’s disease,bone infarcts,prior irradiation In older patients – secondary OSa – in conditions associated with risk of OSa development – Paget’s disease,bone infarcts,prior irradiation Usual location – metaphysial region of bone, 60% about the knee: distal femur,proximal tibia,proximal humerus,proximal femur. Usual location – metaphysial region of bone, 60% about the knee: distal femur,proximal tibia,proximal humerus,proximal femur. Mutations are very important in development of OSa: Rb-gene (hereditary cases) and esp. p53 mutations in sporadic OSa Mutations are very important in development of OSa: Rb-gene (hereditary cases) and esp. p53 mutations in sporadic OSa

47 CLASSIFICATION OF OSTEOSARCOMA CLASSIFICATION OF OSTEOSARCOMA Acc. to anatomic origin: intramedullary,intracortical,surface Acc. to anatomic origin: intramedullary,intracortical,surface Grade of malignancy(low and high grade) Grade of malignancy(low and high grade) Primary or secondary Primary or secondary Histologic variants: osteoblastic,chondroblastic,fibroblastic,telangioectatic etc. Histologic variants: osteoblastic,chondroblastic,fibroblastic,telangioectatic etc. Most common type is intramedullary high grade primary OSa, which arises in metaphysis of the long bones in young patients Most common type is intramedullary high grade primary OSa, which arises in metaphysis of the long bones in young patients

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53 OSTEOSARCOMA – TREATMENT AND PROGNOSIS Appr. 20% of patients have lung metastases at the time of diagnosis Appr. 20% of patients have lung metastases at the time of diagnosis In the past with surgery alone(amputation) 5-years survival did not exceed 20%. In the past with surgery alone(amputation) 5-years survival did not exceed 20%. To-day – chemotherapy and limb-sparing surgery – up to 60% To-day – chemotherapy and limb-sparing surgery – up to 60% Resection of solitary lung metastases prolong survival Resection of solitary lung metastases prolong survival

54 CARTILAGE-PRODUCING TUMORS

55 SOLITARY CHONDROMA – ENCHONDROMA – IS A BENIGN INTRAOSSEOUS TUMOR COMPOSED OF WELL DIFFERENTIATED HYALINE CARTILAGE Most common location – metacarpals and phalanges of the hands and feet,may be in other tubular bones Most common location – metacarpals and phalanges of the hands and feet,may be in other tubular bones Radiologically – radiolucent,well delineated,with calcifications Radiologically – radiolucent,well delineated,with calcifications May be also on the surface of bone May be also on the surface of bone May be multiple (Ollier’s and Maffucci’ syndromes) May be multiple (Ollier’s and Maffucci’ syndromes) Treatment – curretage,rarely recur if incompletely excised Treatment – curretage,rarely recur if incompletely excised

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58 CHONDROSARCOMA – GROUP OF SARCOMAS,PRODUCING NEOPLASTIC CARTILAGE Second most frequent matrix producing sarcoma of bone(after OSa) Second most frequent matrix producing sarcoma of bone(after OSa) Commonly located in the central part of the skeleton – pelvis,shoulders,ribs Commonly located in the central part of the skeleton – pelvis,shoulders,ribs Patients usually are older than 30 years Patients usually are older than 30 years May arise in association with pre-exiting enchondroma May arise in association with pre-exiting enchondroma Radiologically – calcifications,destructive growth Radiologically – calcifications,destructive growth

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62 CHONDROSARCOMA - GRADING There is direct correlation between the grade and biologic behavior of the tumor There is direct correlation between the grade and biologic behavior of the tumor Five-year survival for grade I – 90%; grade II – 81%; grade III – 43% Five-year survival for grade I – 90%; grade II – 81%; grade III – 43% Most conventional chondrosarcomas are grade I-II and have relatively indolent course Most conventional chondrosarcomas are grade I-II and have relatively indolent course Tumor’s size is also significant prognostic feature – tumors >10cm behave more agressively, than those 10cm behave more agressively, than those <10cm

63 GRADE I GRADE II GRADE III GRADE I GRADE II GRADE III

64 Pathological differential diagnosis of chondrosarcoma – with enchondroma and chondroblastic osteosarcoma Microscopically enchondroma and chondrosarcoma may be practically indistinguishable Microscopically enchondroma and chondrosarcoma may be practically indistinguishable Diagnosis is based on clinical data – age,location,pain(in chondrosarcoma); radiological features are extremely important – the presence of destructive growth favor chondrosarcoma Diagnosis is based on clinical data – age,location,pain(in chondrosarcoma); radiological features are extremely important – the presence of destructive growth favor chondrosarcoma Chondroblastic osteosarcoma – younger patients,typical location(metaphysis of long bone), high microscopic grade,presence of osteoid Chondroblastic osteosarcoma – younger patients,typical location(metaphysis of long bone), high microscopic grade,presence of osteoid

65 Treatment of chondrosarcoma – surgery only(wide excision), resistant to chemotherapy!

66 GIANT CELL TUMOR OF BONE(GCT) GCT is relatively uncommon benign but locally aggressive neoplasm GCT is relatively uncommon benign but locally aggressive neoplasm The patients are usually in their ies The patients are usually in their ies Located in epiphysis and metaphysis,pred. around the knee,but every bone may be involved Located in epiphysis and metaphysis,pred. around the knee,but every bone may be involved Usually cause pain,arthritic symptoms or pathological fracture Usually cause pain,arthritic symptoms or pathological fracture The main cell of GCT is mononuclear cell of macrophage-monocyte lineage,the fusion(or incomplete division) of these cells produce giant cells The main cell of GCT is mononuclear cell of macrophage-monocyte lineage,the fusion(or incomplete division) of these cells produce giant cells

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69 TREATMENT AND PROGNOSIS GCT is biologically unpredictible GCT is biologically unpredictible Conservative surgery – up to 60% recurrence Conservative surgery – up to 60% recurrence 5-10% metastasize to the lungs 5-10% metastasize to the lungs Treatment usually – thorough curretage and grafting Treatment usually – thorough curretage and grafting In some cases “en block” resection or even amputation may be nesessary In some cases “en block” resection or even amputation may be nesessary


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