Paget's disease of the bone - Imaging the appendicular skeleton

Transcription

1 Paget's disease of the bone - Imaging the appendicular skeleton Poster No.: C-1765 Congress: ECR 2016 Type: Educational Exhibit Authors: G. Galea, C. Cannataci, C. Azzopardi, A. Mizzi, K. Cortis ; BZN1427/MT, Msida/MT, Birkirkara/MT, ATTARD/MT, 5 Bromley, Kent/UK Keywords: Diagnostic procedure, MR, Digital radiography, CT, Musculoskeletal bone, Extremities, Bones, Metabolic disorders DOI: /ecr2016/C-1765 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 52

2 Learning objectives 1. To describe the epidemiology, clinical features & pathology of Paget's disease of bone 2. To outline the radiological features of Paget's disease in the appendicular skeleton on various imaging modalities 3. To illustrate complications of Paget's disease in the appendicular skeleton Background 2.1 A BRIEF HISTORY In 1877, Sir James Paget (Fig 1), a prominent British surgeon and pathologist described 'osteitis deformans' in five middle-aged men. Although several reports of middle-aged men whose hats no longer fit had already been published in the literature, by the end of the century, the affliction would become widely known as Paget's disease of bone. Page 2 of 52

3 Fig. 1: Sir James Paget ( ) by John Everett Millais. References: Page 3 of 52

4 Paget described the disease as a rare, slowly progressive inflammatory disorder which did not affect the individual's overall general health, but resulted in change in body shape, size and deformity of affected bones. 2.2 PAGET'S IN CLINICAL PRACTICE Paget's disease demonstrates certain geographical and racial characteristics: it is more common in Great Britain, France, Germany, Italy and migrants from these countries while it is particularly rare in Ireland, sub-saharan Africa, the far East and Scandinavia. Overall incidence of the disease is on a steep decline. Prevalence increases with age - those over 85 years of age are 5 times more likely to be affected than those under the age of 60. A slight male predominance is also seen with a 3:2 male-to-female ratio reported in the literatute. This non-inflammatory, metabolic disorder may affect single or multiple bones in a synchronous or metachronous fashion; polyostotic disease is more often seen. Patients are frequently asymptomatic and cases are usually discovered incidentally on imaging carried out for other reasons. The most common manifestation of this disease, if any, is pain of the involved bone and adjacent joints. Bone turnover markers, including bone specific alkaline phosphatase, reflect the level of osteoblast activation, and may be used to monitor the level of activity and therapeutic efficacy. Paget's disease shows a predilection for the axial skeleton with the skull and vertebral column being the most commonly affected sites. The pelvis is the most commonly affected part of the appendicular skeleton (Fig 2). Page 4 of 52

5 Fig. 2: AP radiograph of the lumbar spine showing polyostotic Paget's disease involving both femora, ilii, T12-L2 and L5 vertebrae References: Mater Dei Hospital - Msida/MT Page 5 of 52

6 2.3 PATHOLOGY OF PAGET'S DISEASE In the initial osteolytic phase, focal excessive osteoclastic action causes bone resorption. In the later (though still relatively early) mixed osteolytic/osteoblastic phase, excessive osteoclastic activity continues but is accompanied by simultaneous disorganised activation of osteoblasts and fibroblasts resulting in new bone formation. In time, osteoblastic activity predominates, with random deposition of dense but disorganized and structurally weak new bone. This translates into increasing bone density and thickening of the remaining trabeculae, giving a classic histological "mosaic pattern" of woven and lamellar bone, which replaces the organised parallel Haversian systems that characterize normal bone. Replacement of bone marrow with vascular and fibrous tissue is also seen in this stage. In the late osteosclerotic "burnt-out" phase, osteoclastic activity declines and bone turnover may return to an almost normal level. The thickened trabeculated bone and prominent mosaic pattern persist, and there is restoration of the marrow. Histopathological appearances of Paget's disease closely mirror radiological features; imaging studies can be used to stage Paget's disease as well as monitor disease activity. Images for this section: Page 6 of 52

7 Fig. 1: Sir James Paget ( ) by John Everett Millais. Page 7 of 52

8 Fig. 2: AP radiograph of the lumbar spine showing polyostotic Paget's disease involving both femora, ilii, T12-L2 and L5 vertebrae Mater Dei Hospital - Msida/MT Page 8 of 52

9 Findings and procedure details 3.1 RADIOLOGIC PHASES OF UNCOMPLICATED PAGET'S DISEASE OSTEOLYTIC PHASE The incipient osteolytic phase is characterized by well-defined osteolysis with a leading edge of resorption. In long bones, this sharply-demarcated, wedge-shaped advancing edge of osteolysis is seen to advance from the subarticular or metaphyseal region into the diaphysis and is typically referred to as a 'cutting-cone', 'blade of grass', or 'candle flame sign' (Fig 3). Fig. 3: Multimodality imaging of the lytic phase of Paget's disease of the right distal femur. The 'blade of grass' leading edge of osteolysis is clearly demonstrated on this frontal radiograph of the right knee. Oblique craniocaudal reconstructed CT image and sagittal T1-weighted MR image from the same patient outline the same appearance. References: Mater Dei Hospital - Msida/MT MIXED OSTEOLYTIC/OSTEOSCLEROTIC PHASE Page 9 of 52

10 The intermediate mixed lytic/sclerotic phase is the stage at which Paget's disease of bone is most commonly diagnosed. It is characterized by thickening of the cortex, expansion and deformity of bone, loss of corticomedullary differentiation (due to endosteal new bone formation obliterating the medullary cavity) and accentuated coarse trabecular markings. The advancing wedge of resorption described above may be also seen. Similar to the initial osteolytic phase, sclerosis and expansion in the appendicular skeleton are usually first seen in a subarticular or metaphyseal location, at the site of initial osteolysis. At this stage, it is sometimes possible to discern the two phases within the same bone: the early osteolytic front seen to have advanced further into the diaphysis with bone showing signs of the later mixed lytic/sclerotic phase following a few centimetres behind (Fig 4-6). Page 10 of 52

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12 Fig. 4: Lateral radiograph of the right knee shows mixed osteolytic/osteosclerotic disease of the right fibula as evidenced by cortical thickening with encroachment of the medullary cavity, prominent coarse trabecular markings, osseous expansion and illdefined lucent zones. References: Mater Dei Hospital - Msida/MT Fig. 5: Anteroposterior radiograph of the pelvis shows mixed disease of the right femur as well as iliac and pubic bones bilaterally. Axial CT scan on bone window at the level of the SI joints demonstrates the two phases within the same bone: the posterior medial end of the right iliac bone is lucent whereas there is expansion and sclerosis of the more anterior right iliac wing. References: Mater Dei Hospital - Msida/MT Page 12 of 52

13 Fig. 6: Paget's disease affecting the hands is rare, with hand involvement reported in less than 1% of patients affected by the disease. Anteroposterior radiograph of the right Page 13 of 52

14 hand shows expansion of the proximal phalanx of the middle finger with thickened bony cortex, loss of corticomedullary differentiation and well-defined lucent areas in keeping with mixed lytic/sclerotic disease. References: Mater Dei Hospital - Msida/MT LATE OSTEOSCLEROTIC PHASE In the late sclerotic or 'burnt-out' form of Paget's disease, considerable new bone formation is evident as a diffuse increase in density, medullary sclerosis, and markedly increased bone size. Bone deformity is often present at this stage as random deposition of new bone matrix leads to structurally weak bone that is easily bent by otherwise normally innocuous forces (Fig 7-10). Page 14 of 52

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16 Fig. 7: Lateral radiograph of the right calcaneum showing burnt-out Paget's disease. Coarse trabeculation, marked irregular sclerosis and deformity of the calcaneum are noted. Bohler's angle is at the lower limit of normal suggesting loss of calcaneal height, likely secondary to bone softening. References: Mater Dei Hospital - Msida/MT Page 16 of 52

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18 Fig. 8: Anteroposterior radiograph of the right foot showing monostotic osteosclerotic phase Paget's disease of the right 5th metatarsal bone. References: Mater Dei Hospital - Msida/MT Fig. 9: Anteroposterior (top) and lateral (bottom) radiographs of the right forearm show dense sclerosis and marked deformity of the right radius in keeping with late osteosclerotic phase Paget's disease. Bone deformity is not exclusive to the weightbearing limbs and may be particularly disabling in the upper limbs. References: Mater Dei Hospital - Msida/MT Page 18 of 52

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20 Fig. 10: Paget's disease of the right scapula and proximal humerus on anteroposterior radiograph of the chest (top) and on bone window on axial CT (bottom). The disease is predominantly in the burnt out phase as demonstrated by the thickened, sclerotic right scapula in stark contrast to the normal left scapula. References: Mater Dei Hospital - Msida/MT 3.2 COMPLICATIONS OF PAGET'S DISEASE Complications of Paget's disease of bone depend on the affected bone as well as disease activity and duration. Incremental stress fractures ('banana fractures', 'pseudofractures' or 'Looser's zones') may be seen in the long bones. These stress fractures are incomplete transverse fractures of the convex surface of the bone, typically lying at right angles to the long axis of the affected bone. They are more common with increasing deformity of the affected bone due to the increasingly abnormal transmission of forces: typical sites include the lateral aspect of a laterally bowed femur or anteriorly along an anteriorly bowed tibia (Fig 11). Fig. 11: Anteroposterior radiographs of the distal right femur and the pelvis (left and middle) demonstrate marked deformity of the right femur on a background of mixed osteolytic/osteosclerotic Paget's disease of the right femur. Serial, parallel, horizontal Page 20 of 52

21 lucencies are seen in the lateral cortex of the femoral diaphysis in keeping with multiple incremental stress fractures. Whole body bone scintigraphy (right) shows the marked deformity of the right lower limb, typical uptake of Paget's disease as well as foci of increased uptake along the lateral border of the right femur in keeping with previously described 'pseudofractures'. References: Mater Dei Hospital - Msida/MT Pagetic bone is also more prone to complete fracture following minor or no trauma. Such pathological fractures are typically transverse and show poor healing with a high rate of non-union (Fig 12). Fig. 12: Anteroposterior radiographs of the left femur (left) and left humerus (right) show transverse fractures through the respective bones, both of which are affected by mixed lytic/sclerotic phase disease. These pathological fractures usually necessitate open reduction and internal fixation, however long-term outcome remains poor. References: Mater Dei Hospital - Msida/MT Page 21 of 52

22 Paget's disease of bone adjacent to weight bearing joints is thought to cause accelerated osteoarthritis of the affected joint. This is likely due to altered mechanics of transmission of force through the joint due to the deformity of the Pagetic bones forming the joint. Nonweight bearing joints adjacent to diseased bones also show accelerated degenerative change; the reasons for this are poorly understood (Fig 13-15). Fig. 13: There is marked expansion of the right hemi-pelvis and right femur and the right iliopectineal line is thickened. Multiple well defined foci of lucency and sclerosis are seen in keeping with mixed lytic/sclerotic Paget's disease of the right hemi-pelvis and femur. Complete loss of joint space together with subchondral sclerosis are noted at the right hip joint in keeping with advanced degenerative change. The left hip joint, unaffected by Paget's disease, is comparatively unremarkable. Total arthroplasty in hip joints affected by Paget's disease is technically more difficult and outcomes are typically worse than 'normal' joints. References: Mater Dei Hospital - Msida/MT Page 22 of 52

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24 Fig. 14: Protrusio acetabuli secondary to Paget's disease of the left hip is seen on bone window on axial CT scan (top) and on anteroposterior radiograph (bottom). This condition is defined as intrapelvic displacement of the acetabulum and femoral head, so that the femoral head projects medial to the ischioilial line. It may be primary in origin, however in cases of Paget's disease it is secondary to weakening of bone. References: Mater Dei Hospital - Msida/MT Fig. 15: Burnt-out Paget's disease of the left third metacarpal is seen. Adjacent carpometacarpal degenerative changes are noted. Degenerative change may be particularly disabling when around the wrist and 1st carpometacarpal joints. References: Mater Dei Hospital - Msida/MT Page 24 of 52

25 Malignant sarcomatous transformation is a well-recognized complication of Paget's disease though its incidence is on the decline. The most common form of sarcomatous transformation is into osteosarcoma, usually of the osteogenic type. It carries a poor prognosis. Fibrosarcoma, chondrosarcoma, and malignant fibrous histiocytoma may also be rarely seen in the context of Paget's (Fig 16-18). Page 25 of 52

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27 Fig. 16: Anteroposterior (right) and lateral (left) radiographs of the right tibia and fibula of a 75-year-old male were performed after he complained of increasing shin pain. Radiographs demonstrated burnt-out Paget's disease with a well-defined medullary based lucency in the middle third of the tibia causing thinning of the overlying cortex. A pathological fracture (black arrow) at this location was suspected and was further evaluated by cross-sectional imaging. References: Mater Dei Hospital - Msida/MT Fig. 17: Sagittal unenhanced CT scan (left) confirms a lesion of soft tissue attenuation in the mid shaft of the right tibia with destruction of overlying cortex. Sagittal and axial (middle and top right) MR images show a T1-intermediate signal and T2-high signal lesion arising from the medulla of a Pagetic right tibia with oedema in the surrounding Page 27 of 52

28 soft tissues. The lesion enhanced avidly after the administration of intravenous gadolinium (bottom right). References: Mater Dei Hospital - Msida/MT Page 28 of 52

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30 Fig. 18: FDG-PET CT (A & B) confirmed the lesion to be highly glucose avid. CTguided biopsy (C) and histopathological analysis revealed a pleomorphic osteosarcoma on a background of Paget's disease of bone. PET-CT (D-G) also demonstrated lung metastases from the same lesion. References: Mater Dei Hospital - Msida/MT Images for this section: Fig. 3: Multimodality imaging of the lytic phase of Paget's disease of the right distal femur. The 'blade of grass' leading edge of osteolysis is clearly demonstrated on this frontal radiograph of the right knee. Oblique craniocaudal reconstructed CT image and sagittal T1-weighted MR image from the same patient outline the same appearance. Mater Dei Hospital - Msida/MT Page 30 of 52

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32 Fig. 4: Lateral radiograph of the right knee shows mixed osteolytic/osteosclerotic disease of the right fibula as evidenced by cortical thickening with encroachment of the medullary cavity, prominent coarse trabecular markings, osseous expansion and ill-defined lucent zones. Mater Dei Hospital - Msida/MT Fig. 5: Anteroposterior radiograph of the pelvis shows mixed disease of the right femur as well as iliac and pubic bones bilaterally. Axial CT scan on bone window at the level of the SI joints demonstrates the two phases within the same bone: the posterior medial end of the right iliac bone is lucent whereas there is expansion and sclerosis of the more anterior right iliac wing. Mater Dei Hospital - Msida/MT Page 32 of 52

33 Fig. 6: Paget's disease affecting the hands is rare, with hand involvement reported in less than 1% of patients affected by the disease. Anteroposterior radiograph of the right Page 33 of 52

34 hand shows expansion of the proximal phalanx of the middle finger with thickened bony cortex, loss of corticomedullary differentiation and well-defined lucent areas in keeping with mixed lytic/sclerotic disease. Mater Dei Hospital - Msida/MT Page 34 of 52

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36 Fig. 7: Lateral radiograph of the right calcaneum showing burnt-out Paget's disease. Coarse trabeculation, marked irregular sclerosis and deformity of the calcaneum are noted. Bohler's angle is at the lower limit of normal suggesting loss of calcaneal height, likely secondary to bone softening. Mater Dei Hospital - Msida/MT Page 36 of 52

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38 Fig. 8: Anteroposterior radiograph of the right foot showing monostotic osteosclerotic phase Paget's disease of the right 5th metatarsal bone. Mater Dei Hospital - Msida/MT Fig. 9: Anteroposterior (top) and lateral (bottom) radiographs of the right forearm show dense sclerosis and marked deformity of the right radius in keeping with late osteosclerotic phase Paget's disease. Bone deformity is not exclusive to the weightbearing limbs and may be particularly disabling in the upper limbs. Mater Dei Hospital - Msida/MT Page 38 of 52

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40 Fig. 10: Paget's disease of the right scapula and proximal humerus on anteroposterior radiograph of the chest (top) and on bone window on axial CT (bottom). The disease is predominantly in the burnt out phase as demonstrated by the thickened, sclerotic right scapula in stark contrast to the normal left scapula. Mater Dei Hospital - Msida/MT Fig. 11: Anteroposterior radiographs of the distal right femur and the pelvis (left and middle) demonstrate marked deformity of the right femur on a background of mixed osteolytic/osteosclerotic Paget's disease of the right femur. Serial, parallel, horizontal lucencies are seen in the lateral cortex of the femoral diaphysis in keeping with multiple incremental stress fractures. Whole body bone scintigraphy (right) shows the marked deformity of the right lower limb, typical uptake of Paget's disease as well as foci of increased uptake along the lateral border of the right femur in keeping with previously described 'pseudofractures'. Mater Dei Hospital - Msida/MT Page 40 of 52

41 Fig. 12: Anteroposterior radiographs of the left femur (left) and left humerus (right) show transverse fractures through the respective bones, both of which are affected by mixed lytic/sclerotic phase disease. These pathological fractures usually necessitate open reduction and internal fixation, however long-term outcome remains poor. Mater Dei Hospital - Msida/MT Page 41 of 52

42 Fig. 13: There is marked expansion of the right hemi-pelvis and right femur and the right iliopectineal line is thickened. Multiple well defined foci of lucency and sclerosis are seen in keeping with mixed lytic/sclerotic Paget's disease of the right hemi-pelvis and femur. Complete loss of joint space together with subchondral sclerosis are noted at the right hip joint in keeping with advanced degenerative change. The left hip joint, unaffected by Paget's disease, is comparatively unremarkable. Total arthroplasty in hip joints affected by Paget's disease is technically more difficult and outcomes are typically worse than 'normal' joints. Mater Dei Hospital - Msida/MT Page 42 of 52

43 Fig. 14: Protrusio acetabuli secondary to Paget's disease of the left hip is seen on bone window on axial CT scan (top) and on anteroposterior radiograph (bottom). This condition Page 43 of 52

44 is defined as intrapelvic displacement of the acetabulum and femoral head, so that the femoral head projects medial to the ischioilial line. It may be primary in origin, however in cases of Paget's disease it is secondary to weakening of bone. Mater Dei Hospital - Msida/MT Fig. 15: Burnt-out Paget's disease of the left third metacarpal is seen. Adjacent carpometacarpal degenerative changes are noted. Degenerative change may be particularly disabling when around the wrist and 1st carpometacarpal joints. Mater Dei Hospital - Msida/MT Page 44 of 52

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46 Fig. 16: Anteroposterior (right) and lateral (left) radiographs of the right tibia and fibula of a 75-year-old male were performed after he complained of increasing shin pain. Radiographs demonstrated burnt-out Paget's disease with a well-defined medullary based lucency in the middle third of the tibia causing thinning of the overlying cortex. A pathological fracture (black arrow) at this location was suspected and was further evaluated by cross-sectional imaging. Mater Dei Hospital - Msida/MT Fig. 17: Sagittal unenhanced CT scan (left) confirms a lesion of soft tissue attenuation in the mid shaft of the right tibia with destruction of overlying cortex. Sagittal and axial (middle and top right) MR images show a T1-intermediate signal and T2-high signal lesion arising from the medulla of a Pagetic right tibia with oedema in the surrounding soft Page 46 of 52

47 tissues. The lesion enhanced avidly after the administration of intravenous gadolinium (bottom right). Mater Dei Hospital - Msida/MT Page 47 of 52

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49 Fig. 18: FDG-PET CT (A & B) confirmed the lesion to be highly glucose avid. CTguided biopsy (C) and histopathological analysis revealed a pleomorphic osteosarcoma on a background of Paget's disease of bone. PET-CT (D-G) also demonstrated lung metastases from the same lesion. Mater Dei Hospital - Msida/MT Page 49 of 52

50 Conclusion Paget's disease of the bone demonstrates a plethora of imaging patterns. The variable appearances which are closely linked to the pathological stage of the disease should enable the radiologist to make an early diagnosis of the condition. In spite of the fact that the incidence of this disease is on the decline, it continues to afflict many individuals whose lives are severely affected by it. Its pathology is well-understood however its treatment remains limited to that of its many musculoskeltal complications. Recognition of the main imaging findings may allow early diagnosis and help to guide therapy and improve patient management. Personal information Dr. Gabriel Galea Basic specialist trainee Medical Imaging Department Mater Dei Hospital gabriel.galea@gov.mt Dr. Christine Cannataci Basic specialist trainee Medical Imaging Department Mater Dei Hospital christine.cannataci@gov.mt Dr. Christine Azzopardi Higher specialist trainee Medical Imaging Department Mater Dei Hospital christine.azzopardi@gov.mt Page 50 of 52

51 Dr. Adrian Mizzi Consultant interventional radiologist Medical Imaging Department Mater Dei Hospital Dr. Kelvin Cortis Resident specialist Medical Imaging Department Mater Dei Hospital References The Ugly Duchess by Quinten Massys. The National Gallery website. (Accessed: 16th December 2015) Portrait of Sir James Paget by John Everett Millais. The BBC website, arts section. (Accessed: 16th December 2015) Paget J. On a form of chronic inflammation of bones (osteitis deformans). Med Chir Trans 1877;60:37e64. Cortis K, Micallef K, Mizzi A. Imaging Paget's disease of bone from head to toe. Clinical Radiology 66 (2011) 662e672 Altman RD. Epidemiology of Paget's disease of bone. Clin Rev Bone Mineral Metab 2002;1:99e102. Ralston SH. Pathogenesis of Paget's disease of Bone. Bone 2008;43(5): Hosking DJ. Paget's disease of bone. Br Med J 1981;283:686e8. Ivars VB, Marques AO, Holgado S, et al. Paget's Hand. Rheumatol Clin 2011;7:343-5 Page 51 of 52

52 9. Smith SE, Murphey MD, Motamedi K, et al. From the archives of the AFIP. Radiologic spectrum of Paget disease of bone and its complications with pathologic correlation. RadioGraphics 2002;22:1191e Mirra JM, Brien EW, Tehranzadeh J. Paget's disease of bone: review with emphasis on radiologic features, part I. Skeletal Radiol 1995;24:163e Guyen O, Vaz G, Vallese P, et al. Total Hip Arthroplasty and Paget's Bone Disease. J Bone Joint Surg Br 2005 vol. 87-B no. SUPP II 134 Page 52 of 52