(RadioGraphics. 2002;22:1191-1216.)
From the Archives of the AFIP
Radiologic Spectrum of Paget Disease of Bone and Its Complications with Pathologic Correlation1
Stacy E. Smith, MD,
Mark D. Murphey, MD,
Kambiz Motamedi, MD,
Michael E. Mulligan, MD,
Charles S. Resnik, MD and
Francis H. Gannon, MD
1 From the Department of Radiology, University of Maryland School of Medicine, Baltimore (S.E.S., M.D.M., M.E.M., C.S.R.); Departments of Radiologic Pathology (S.E.S., M.D.M., K.M.) and Orthopedic Pathology (F.H.G.), Armed Forces Institute of Pathology, 6825 16th St NW, Bldg 54, Rm M-127A, Washington, DC 20306; and Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (M.D.M.). Presented as an education exhibit at the 2000 RSNA scientific assembly. Received May 14, 2002; accepted May 24. Address correspondence to M.D.M. (e-mail: murphey@afip.osd.mil).
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Abstract
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Paget disease of bone is a common disorder affecting approximately 3%–4% of the population over 40 years of age. The pathologic abnormality in Paget disease is excessive and abnormal remodeling of bone. Three pathologic phases have been described: the lytic phase (incipient-active), in which osteoclasts predominate; the mixed phase (active), in which osteoblasts cause repair superimposed on the resorption; and the blastic phase (late-inactive) in which osteoblasts predominate. Radiographic appearance of Paget disease reflects these pathologic changes and is often characteristic. Initially, there is osteolysis, particularly affecting the skull (osteoporosis circumscripta) and subchondral long bones, with subsequent development of trabecular and cortical thickening and enlargement of bone in the mixed phase of the disease. Finally, areas of sclerosis may develop in the blastic phase. Frequent sites of involvement include the skull (25%–65% of cases), spine (30%–75%), pelvis (30%–75%), and proximal long bones (25%–30%). Bone scintigraphy typically demonstrates marked increased uptake of radionuclide in all phases of Paget disease. Computed tomography and magnetic resonance imaging often show changes similar to those seen radiographically in noncomplicated Paget disease with maintenance of yellow marrow. Complications of Paget disease include the effects of osseous weakening (deformity and fracture), arthritis, neurologic symptoms, and neoplastic involvement. Sarcomatous transformation is the most feared complication, occurring in approximately 1% of cases, and is seen on images as focal bone destruction extending through the cortex with an associated soft-tissue mass. Recognition of the radiologic spectrum of the appearances of Paget disease usually allows prospective diagnosis and differentiation of its associated complications, which helps guide therapy and improve patient management.
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LEARNING OBJECTIVES FOR TEST 6
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After reading this article and taking the test, the reader will be able to:
- Recognize the radiologic spectrum of Paget disease of bone and its complications.
- Describe the pathologic basis of the radiologic features of Paget disease of bone and its complications.
- Identify the radiologic manifestations that allow distinction of sarcomatous transformation in Paget disease of bone.
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Introduction
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Paget disease of bone, also known as osteitis deformans, was first described in a small group of patients in 1877 by Sir James Paget (1). These patients had an "odd overgrowth" of their heads and extremities, which often resulted in bowing of the long bones and increased propensity to develop subsequent fractures (1). Because Paget disease is extremely common, radiologists are frequently confronted with its many manifestations, both in asymptomatic (noncomplicated) and symptomatic (complicated) patients. In the asymptomatic patient in whom Paget disease was incidentally detected, it is important not to confuse its imaging appearance with those of other diseases. Complications of Paget disease include the effects of osseous weakening (deformity and fracture), arthritis, neurologic symptoms, and neoplastic transformation or involvement (2–8).
This article illustrates the spectrum of radiologic manifestations of Paget disease, both uncomplicated and complicated. Although we emphasize its radiographic appearance, a multimodality approach including bone scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging is used. The pathologic basis of these imaging manifestations is also emphasized.
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Demographics and Causes
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Demographic distribution of Paget disease is particularly high in Great Britain, site of the first reported cases (1–5,9). Interestingly, lands settled by the British such as Australia, New Zealand, and the United States share a common prevalence of Paget disease. The disease is also common in continental Europe but rare in Asia and Africa. Although there is variation among studies, there is an overall mild male predilection in Paget disease and age of onset is slightly younger in men. Paget disease is extraordinarily common, affecting 3%–4% of the population over 40 years of age and up to 10%–11% after 80 years of age (2–7). Although Paget disease is unusual in people younger than 40 years of age (only about 4% of patients with the disease are in this younger age group), its characteristic imaging features are maintained and thus allow an accurate diagnosis (4).
The cause of Paget disease remains uncertain. Although still controversial, a probable viral origin has been proposed because intranuclear inclusion bodies (resembling those of a paramyxovirus variety) are found in the osteoclasts in histologic specimens of Paget disease (8,10–12). Giant osteoclasts composed of numerous nuclei characterize the active phase of Paget disease (13). These osteoclasts contain organized groups of microcylinders in the nuclei and cytoplasm. Both findings help support the viral origin theory, because both enormous osteoclasts and inclusion bodies are also found in viral infections such as measles (caused by a paramyxovirus), an entity found in some patients with Paget disease.
A review of Paget disease cases in Japan noted that the disease was unknown among the population until the first case report in 1921 (14). Since that time, the number of cases in Japan has increased. This raises the question of whether it is a true increase in cases, secondary to a slow virus infection, or only an increase in detection, secondary to an increased number of imaging studies that reveal unsuspected disease in asymptomatic patients. Ashkenazi Jews have a higher prevalence of Paget disease, with an associated increased frequency of the serum marker HLA-DR2, a finding that suggests a possible genetic origin (3,4,15–17). Other purported causes include connective tissue disease, autoimmune disorder, vascular disease, metabolic disorder related to parathormone, or a true neoplastic process (4).
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Pathologic Characteristics
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Paget disease is characterized by excessive and abnormal remodeling of bone, with both active and quiescent phases (18,19). Three phases have classically been described as discrete and distinctive, although in reality they represent a continuum: the lytic phase (incipient-active), in which osteoclasts predominate (Fig 1a); the mixed phase (active), in which osteoblasts begin to appear superimposed on osteoclastic activity and eventually predominate; and finally, the blastic phase (late-inactive), in which osteoblastic activity gradually declines (Fig 1b).
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Figure 1a. Typical histologic appearance of Paget disease. (a) Lytic to mixed active phase. Photomicrograph (original magnification, x150; hematoxylin-eosin [H-E] stain) reveals multiple osteoclastic giant cells (black arrowheads) and osteoblasts (arrows) causing bone resorption (white arrowhead) and formation. The marrow cavity is replaced by fibrovascular tissue (*). (b) Blastic quiescent phase. Photomicrograph (original magnification x175; H-E stain) shows cement lines (arrows) and that the marrow cavity has returned to fatty tissue (*). (c) Mixed phase. Photomicrograph (original magnification x200; H-E stain under polarized light) shows multiple cement lines and the disorganized or mosaic pattern in cortical bone (arrows). (d) Photograph of an axially sectioned, whole-mounted tibia (H-E stain) shows thickening of the cortex with weak bone (pumice) lacking interconnection (between large straight arrows), compared with more normal underlying cortex (curved arrow).
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Figure 1b. Typical histologic appearance of Paget disease. (a) Lytic to mixed active phase. Photomicrograph (original magnification, x150; hematoxylin-eosin [H-E] stain) reveals multiple osteoclastic giant cells (black arrowheads) and osteoblasts (arrows) causing bone resorption (white arrowhead) and formation. The marrow cavity is replaced by fibrovascular tissue (*). (b) Blastic quiescent phase. Photomicrograph (original magnification x175; H-E stain) shows cement lines (arrows) and that the marrow cavity has returned to fatty tissue (*). (c) Mixed phase. Photomicrograph (original magnification x200; H-E stain under polarized light) shows multiple cement lines and the disorganized or mosaic pattern in cortical bone (arrows). (d) Photograph of an axially sectioned, whole-mounted tibia (H-E stain) shows thickening of the cortex with weak bone (pumice) lacking interconnection (between large straight arrows), compared with more normal underlying cortex (curved arrow).
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Figure 1c. Typical histologic appearance of Paget disease. (a) Lytic to mixed active phase. Photomicrograph (original magnification, x150; hematoxylin-eosin [H-E] stain) reveals multiple osteoclastic giant cells (black arrowheads) and osteoblasts (arrows) causing bone resorption (white arrowhead) and formation. The marrow cavity is replaced by fibrovascular tissue (*). (b) Blastic quiescent phase. Photomicrograph (original magnification x175; H-E stain) shows cement lines (arrows) and that the marrow cavity has returned to fatty tissue (*). (c) Mixed phase. Photomicrograph (original magnification x200; H-E stain under polarized light) shows multiple cement lines and the disorganized or mosaic pattern in cortical bone (arrows). (d) Photograph of an axially sectioned, whole-mounted tibia (H-E stain) shows thickening of the cortex with weak bone (pumice) lacking interconnection (between large straight arrows), compared with more normal underlying cortex (curved arrow).
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Figure 1d. Typical histologic appearance of Paget disease. (a) Lytic to mixed active phase. Photomicrograph (original magnification, x150; hematoxylin-eosin [H-E] stain) reveals multiple osteoclastic giant cells (black arrowheads) and osteoblasts (arrows) causing bone resorption (white arrowhead) and formation. The marrow cavity is replaced by fibrovascular tissue (*). (b) Blastic quiescent phase. Photomicrograph (original magnification x175; H-E stain) shows cement lines (arrows) and that the marrow cavity has returned to fatty tissue (*). (c) Mixed phase. Photomicrograph (original magnification x200; H-E stain under polarized light) shows multiple cement lines and the disorganized or mosaic pattern in cortical bone (arrows). (d) Photograph of an axially sectioned, whole-mounted tibia (H-E stain) shows thickening of the cortex with weak bone (pumice) lacking interconnection (between large straight arrows), compared with more normal underlying cortex (curved arrow).
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Because there is often widespread osseous involvement and because individual sites progress at variable rates, Paget disease of differing phases may be seen in the same patient. The end result is a thickened, disorganized trabecular pattern of bone, referred to as a "mosaic" or "jigsaw" pattern (1,4,19) (Fig 1c). Cement lines along the coarsened and enlarged trabeculae are characteristically seen; these lines represent osseous resorption and bone formation (Fig 1b, 1c). The trabecular areas of thickening usually lack the interconnection seen in normal bone and thus are weakened and often referred to as "pumice" bone (Fig 1d). The cortex is also thickened and is the area of most active bone turnover and repair. These areas of increased bone resorption and formation also reveal hypervascularity with small caliber vessels (20,21).
Bone marrow changes are noted throughout the disease process. Fibrovascular tissue replaces the normal yellow marrow in more active disease, particularly in the lytic phase and less extensively in the early mixed phase (Fig 1a). A return to diffuse yellow marrow gradually occurs in the late mixed phase (Fig 1b). This process often ultimately results in an actual increase in marrow fat deposition (compared with normal yellow marrow component), which we refer to as atrophic marrow, during the final inactive phase (4,22).
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Distribution of Disease
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Paget disease is predominantly located in the axial skeleton, with the most commonly affected sites being the pelvis (30%–75% of cases), spine (30%–75%), and skull (25%–65%) (3,4,6,23–30). Proximal long bones are also frequently involved, with the femur affected in 25%–35% of cases (2–5). Less commonly affected sites include the shoulder girdle and forearm (humerus, 31% of cases; scapula, 24%; and clavicle, 11%) (2–5). Involvement of other sites, including the ribs, fibula, bones of the hands and feet, calcaneus, patella, and tibial tubercle, is infrequent (2–5). Paget disease of the long bones typically begins in a subchondral location, with an advancing wedge of lucency estimated to progress at a rate of 1 mm per month (4).
Monostotic disease (10%–35% of cases) is more often seen in the axial skeleton, although any site can be the sole region of involvement (23–32). Polyostotic disease (65%–90%) is more frequent than monostotic disease, tends to have right-sided predominance, and usually involves lower extremities (3,4). Pelvic involvement is more often asymmetric than symmetric, and appendicular involvement is frequently unilateral (25).
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Clinical Findings
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Twenty percent of patients with Paget disease are asymptomatic initially (2–5,32). Skeletal symptoms include localized pain, tenderness, increased warmth (related to lesion hypervascularity), increased bone size, bowing deformities, kyphosis of the spine, and decreased range of motion. Neuromuscular symptoms can result from bone enlargement that encroaches on neural foramina or canals and leads to mechanical compression of neurogenic structures (particularly the cranialnerves), causing deafness, visual abnormalities, weakness, paralysis, and incontinence. Cardiovascular symptoms include high-output congestive heart failure, arterial calcification, and a rare report of Hashimoto thyroiditis (4,33). Recent studies have suggested a higher prevalence of aortic stenosis, heart block, and bundle branch block in severe cases of Paget disease (4,7).
Underlying osteoclastic and osteoblastic changes in bone are reflected in the patient’s serum and urine laboratory values (4,5). Patients often have an elevated serum level of alkaline phosphatase (related to increased rate of bone formation), particularly during more reparative disease phases (mixed and blastic). Increased serum and urine levels of hydroxyproline are seen in the lytic phase (related to increased rate of bone resorption) and are an accurate marker of resorptive activity, even in monostotic disease. Serum levels of calcium and phosphate are usually normal, but 10% of patients may develop secondary hyperparathyroidism owing to hypercalcemia related to the aggressive bone remodeling (3,4).
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Imaging of Noncomplicated Paget Disease
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Radiography
Radiography is the mainstay of diagnosis in noncomplicated Paget disease. Most pathognomonic findings are easily depicted on radiographs alone and reflect the pathologic abnormalities. \
Lytic Phase.—
The early phase of Paget disease is characterized by osteolysis on radiographs, an appearance that reflects the unopposed osteoclastic activity seen pathologically. In the skull, osteolysis is frequently seen as well-defined, often large areas of radiolucency most commonly affecting the frontal and occipital bones; these areas are referred to as osteoporosis circumscripta or osteolysis circumscripta (24,34) (Fig 2). Both inner and outer calvarial tables are involved, with the former usually more extensively affected. This pattern is in contradistinction to that of fibrous dysplasia, which usually affects the outer table more prominently (35). There is a notable absence of peripheral sclerosis surrounding the calvarial osteolysis secondary to the lack of significant osteoblastic activity. These areas of lysis are usually easily identified on radiographs, although it may be more difficult in patients with osteoporosis and correlative bone scans are helpful (Fig 2b, 2c).
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Figure 2a. Lytic phase of Paget disease of the skull in different patients with osteoporosis circumscripta. (a) Lateral radiograph of a 50-year-old man shows a well-defined area of lysis in the frontal and occipital regions (arrowheads). (b) Lateral radiograph of a 60-year-old woman with osteoporosis reveals frontal and occipital areas of osteolysis (*) that are more difficult to detect in this clinical setting. (c) Bone scan of the same patient as in b reveals intense uptake of radionuclide in the frontal and occipital areas, as well as in the face. (d) Axial CT scan of a 55-year-old man with mild expansion of the head reveals a lytic lesion with sharp borders (arrows) in the frontal bone. (e) Photograph of a whole-mounted, longitudinal section of the calvaria (H-E stain) shows calvarial expansion and extensive fibrovascular tissue in the diploic space (*).
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Figure 2b. Lytic phase of Paget disease of the skull in different patients with osteoporosis circumscripta. (a) Lateral radiograph of a 50-year-old man shows a well-defined area of lysis in the frontal and occipital regions (arrowheads). (b) Lateral radiograph of a 60-year-old woman with osteoporosis reveals frontal and occipital areas of osteolysis (*) that are more difficult to detect in this clinical setting. (c) Bone scan of the same patient as in b reveals intense uptake of radionuclide in the frontal and occipital areas, as well as in the face. (d) Axial CT scan of a 55-year-old man with mild expansion of the head reveals a lytic lesion with sharp borders (arrows) in the frontal bone. (e) Photograph of a whole-mounted, longitudinal section of the calvaria (H-E stain) shows calvarial expansion and extensive fibrovascular tissue in the diploic space (*).
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Figure 2c. Lytic phase of Paget disease of the skull in different patients with osteoporosis circumscripta. (a) Lateral radiograph of a 50-year-old man shows a well-defined area of lysis in the frontal and occipital regions (arrowheads). (b) Lateral radiograph of a 60-year-old woman with osteoporosis reveals frontal and occipital areas of osteolysis (*) that are more difficult to detect in this clinical setting. (c) Bone scan of the same patient as in b reveals intense uptake of radionuclide in the frontal and occipital areas, as well as in the face. (d) Axial CT scan of a 55-year-old man with mild expansion of the head reveals a lytic lesion with sharp borders (arrows) in the frontal bone. (e) Photograph of a whole-mounted, longitudinal section of the calvaria (H-E stain) shows calvarial expansion and extensive fibrovascular tissue in the diploic space (*).
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Figure 2d. Lytic phase of Paget disease of the skull in different patients with osteoporosis circumscripta. (a) Lateral radiograph of a 50-year-old man shows a well-defined area of lysis in the frontal and occipital regions (arrowheads). (b) Lateral radiograph of a 60-year-old woman with osteoporosis reveals frontal and occipital areas of osteolysis (*) that are more difficult to detect in this clinical setting. (c) Bone scan of the same patient as in b reveals intense uptake of radionuclide in the frontal and occipital areas, as well as in the face. (d) Axial CT scan of a 55-year-old man with mild expansion of the head reveals a lytic lesion with sharp borders (arrows) in the frontal bone. (e) Photograph of a whole-mounted, longitudinal section of the calvaria (H-E stain) shows calvarial expansion and extensive fibrovascular tissue in the diploic space (*).
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Figure 2e. Lytic phase of Paget disease of the skull in different patients with osteoporosis circumscripta. (a) Lateral radiograph of a 50-year-old man shows a well-defined area of lysis in the frontal and occipital regions (arrowheads). (b) Lateral radiograph of a 60-year-old woman with osteoporosis reveals frontal and occipital areas of osteolysis (*) that are more difficult to detect in this clinical setting. (c) Bone scan of the same patient as in b reveals intense uptake of radionuclide in the frontal and occipital areas, as well as in the face. (d) Axial CT scan of a 55-year-old man with mild expansion of the head reveals a lytic lesion with sharp borders (arrows) in the frontal bone. (e) Photograph of a whole-mounted, longitudinal section of the calvaria (H-E stain) shows calvarial expansion and extensive fibrovascular tissue in the diploic space (*).
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In the long bones, osteolysis begins as a subchondral area of lucency. The advancing wedge of osteolysis often demonstrates a characteristic sharp radiolucent margin without sclerosis likened to a blade of grass or flame (36) (Fig 3). In rare cases, the disease is isolated to the diaphysis, most commonly in the tibia, rather than subchondral bone, which can cause diagnostic confusion (29,37) (Fig 3b, 3c). However, in our experience, even these unusual cases often maintain the typical sharp margins that allow accurate diagnosis and differentiation from neoplastic disease (Fig 3b, 3c).
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Figure 3a. Lytic phase of Paget disease ("blade-of-grass" appearance) of the appendicular skeleton in different patients. (a) Anteroposterior radiograph of the knee in a 74-year-old man shows a large area of lysis beginning in subchondral bone with a sharp inferior margin (arrowheads). (b) Lateral radiograph of the upper tibia in a 41-year-old man shows a lytic lesion in the tibial tubercle, with blade-of-grass appearance superiorly and inferiorly (arrows). (c) Photograph of a sagittally sectioned, whole-mounted specimen (H-E stain) shows the intracortical, nonsubchondral location of the Paget disease (*) and the sharp superior margin (arrow).
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Figure 3b. Lytic phase of Paget disease ("blade-of-grass" appearance) of the appendicular skeleton in different patients. (a) Anteroposterior radiograph of the knee in a 74-year-old man shows a large area of lysis beginning in subchondral bone with a sharp inferior margin (arrowheads). (b) Lateral radiograph of the upper tibia in a 41-year-old man shows a lytic lesion in the tibial tubercle, with blade-of-grass appearance superiorly and inferiorly (arrows). (c) Photograph of a sagittally sectioned, whole-mounted specimen (H-E stain) shows the intracortical, nonsubchondral location of the Paget disease (*) and the sharp superior margin (arrow).
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Figure 3c. Lytic phase of Paget disease ("blade-of-grass" appearance) of the appendicular skeleton in different patients. (a) Anteroposterior radiograph of the knee in a 74-year-old man shows a large area of lysis beginning in subchondral bone with a sharp inferior margin (arrowheads). (b) Lateral radiograph of the upper tibia in a 41-year-old man shows a lytic lesion in the tibial tubercle, with blade-of-grass appearance superiorly and inferiorly (arrows). (c) Photograph of a sagittally sectioned, whole-mounted specimen (H-E stain) shows the intracortical, nonsubchondral location of the Paget disease (*) and the sharp superior margin (arrow).
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Early coarsening and prominence of the trabecular pattern of bone can be seen radiographically in the later stages of the incipient or active lytic phase, emphasizing the continuum with some overlap between phases.
Mixed Phase.—
The vast majority of cases of Paget disease seen by radiologists are in the mixed phase. The characteristic manifestations seen radiographically are coarsening and thickening of the trabecular pattern and cortex. These findings reflect the underlying pathologic changes of osteoblastic repair and are usually pathognomonic on radiographs, particularly in long bones of either the upper or lower extremities (Fig 4). The trabecular thickening occurs primarily along the lines of stress, although disorganized areas are also seen (Fig 4a).
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Figure 4a. Mixed phase of Paget disease of the pelvis in different patients. (a) Anteroposterior radiograph of an 81-year-old woman shows extensive involvement by Paget disease with areas of cortical (iliopectineal and ilioischial lines, arrows) and trabecular (arrowheads) thickening throughout the pelvis and coxa varus deformity in the right hip. (b) Photograph of a coronally sectioned, whole-mounted femoral specimen (H-E stain) shows cortical (arrows) and trabecular (arrowheads) thickening, fibrovascular marrow (*), and coxa varus deformity.
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Figure 4b. Mixed phase of Paget disease of the pelvis in different patients. (a) Anteroposterior radiograph of an 81-year-old woman shows extensive involvement by Paget disease with areas of cortical (iliopectineal and ilioischial lines, arrows) and trabecular (arrowheads) thickening throughout the pelvis and coxa varus deformity in the right hip. (b) Photograph of a coronally sectioned, whole-mounted femoral specimen (H-E stain) shows cortical (arrows) and trabecular (arrowheads) thickening, fibrovascular marrow (*), and coxa varus deformity.
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Paget disease of the pelvis usually manifests with cortical thickening and sclerosis of the iliopectineal and ischiopubic lines (5) (Fig 4). The iliac wing may also be involved. These findings are often asymmetric and more commonly seen on the right side. These manifestations are also often associated with enlargement of the pubic rami and ischium (2,3).
Paget disease of the spine frequently manifests with cortical thickening encasing the vertebral margins, which gives rise to the "picture frame" appearance on radiographs in mixed phase disease (4) (Fig 5). The osteoblastic activity is seen along all four margins of the vertebral body cortices, unlike the rugger jersey vertebrae in renal osteodystrophy, which only involves the superior and inferior endplates. Coarsening of the spinal trabeculae occurs, predominantly in a vertical direction. The vertical trabecular thickening pattern in Paget disease is coarser than the more delicate pattern seen in hemangiomas with which it can be confused. In addition, the condensation of trabeculae at the endplates coexisting with the picture frame appearance is not seen in spinal hemangiomas (Fig 5). Flattening or squaring of the normal concavity of the anterior margin of the vertebral body can be seen on the lateral spinal radiographs.
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Figure 5a. Paget disease of the spine in different patients. (a) Anteroposterior radiograph of the lumbar spine in a 45-year-old man shows subtle vertical trabecular thickening (white arrowheads) and early picture frame appearance with condensation of trabeculae about the superior and inferior endplates (black arrowheads). (b) Lateral radiograph of the lumbar spine in a 54-year-old woman shows cortical thickening (picture frame appearance) about the entire vertebral body at all levels (arrowheads). (c) Sagittal CT reformatted image in a 50-year-old man shows similar trabecular thickening (arrowheads) with extension into the posterior vertebral elements (*). (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical thickening encasing the vertebral body at two levels (arrows) as the cause of the radiologic findings as opposed to the diffuse bone formation at the most superior level (*), which could manifest as an ivory vertebral body (see Fig 7).
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Figure 5b. Paget disease of the spine in different patients. (a) Anteroposterior radiograph of the lumbar spine in a 45-year-old man shows subtle vertical trabecular thickening (white arrowheads) and early picture frame appearance with condensation of trabeculae about the superior and inferior endplates (black arrowheads). (b) Lateral radiograph of the lumbar spine in a 54-year-old woman shows cortical thickening (picture frame appearance) about the entire vertebral body at all levels (arrowheads). (c) Sagittal CT reformatted image in a 50-year-old man shows similar trabecular thickening (arrowheads) with extension into the posterior vertebral elements (*). (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical thickening encasing the vertebral body at two levels (arrows) as the cause of the radiologic findings as opposed to the diffuse bone formation at the most superior level (*), which could manifest as an ivory vertebral body (see Fig 7).
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Figure 5c. Paget disease of the spine in different patients. (a) Anteroposterior radiograph of the lumbar spine in a 45-year-old man shows subtle vertical trabecular thickening (white arrowheads) and early picture frame appearance with condensation of trabeculae about the superior and inferior endplates (black arrowheads). (b) Lateral radiograph of the lumbar spine in a 54-year-old woman shows cortical thickening (picture frame appearance) about the entire vertebral body at all levels (arrowheads). (c) Sagittal CT reformatted image in a 50-year-old man shows similar trabecular thickening (arrowheads) with extension into the posterior vertebral elements (*). (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical thickening encasing the vertebral body at two levels (arrows) as the cause of the radiologic findings as opposed to the diffuse bone formation at the most superior level (*), which could manifest as an ivory vertebral body (see Fig 7).
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Figure 5d. Paget disease of the spine in different patients. (a) Anteroposterior radiograph of the lumbar spine in a 45-year-old man shows subtle vertical trabecular thickening (white arrowheads) and early picture frame appearance with condensation of trabeculae about the superior and inferior endplates (black arrowheads). (b) Lateral radiograph of the lumbar spine in a 54-year-old woman shows cortical thickening (picture frame appearance) about the entire vertebral body at all levels (arrowheads). (c) Sagittal CT reformatted image in a 50-year-old man shows similar trabecular thickening (arrowheads) with extension into the posterior vertebral elements (*). (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical thickening encasing the vertebral body at two levels (arrows) as the cause of the radiologic findings as opposed to the diffuse bone formation at the most superior level (*), which could manifest as an ivory vertebral body (see Fig 7).
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Blastic Phase.—
Paget disease in the mixed phase may progress at a variable rate and extent to the blastic phase. In the long bones and pelvis, areas of sclerosis may develop and can be extensive, obliterating areas of previous trabecular thickening. Bone enlargement is particularly common in the blastic phase of Paget disease.
In the skull, the regions of sclerosis may become the predominant manifestation of Paget disease, with osteoblastic areas crossing sutures (Fig 6). This pattern may result in marked thickening of the diploic space, particularly the inner calvarial table, and has been referred to as a "tam-o’-shanter" skull, with resultant marked enlargement of the calvaria (Fig 6b). Initially, these areas of sclerosis may be circular and occur in previous areas of osteoporosis circumscripta (2–4). This pattern often creates focal areas of opacity that has been called the "cotton wool" appearance at radiography (2–4).
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Figure 6a. Blastic phase of Paget disease involving the calvaria. (a) Lateral radiograph of the skull in a 56-year-old man shows diffuse calvarial thickening including the calvaria and maxillary sinus region, with several areas of focal sclerosis ("cotton wool" appearance) (arrowheads). (b) Lateral radiograph of a skull specimen from an 85-year-old woman reveals diffuse sclerosis and calvarial thickening with platybasia. (c) Axial CT scan (same case as b) also reveals the posterior thickening and mixed lysis and sclerosis (area between arrows). (d) Photograph of the sectioned calvaria viewed from above at autopsy (same case as b and c) also shows widening of the diploic space (white *) and sclerosis anteriorly (black *).
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Figure 6b. Blastic phase of Paget disease involving the calvaria. (a) Lateral radiograph of the skull in a 56-year-old man shows diffuse calvarial thickening including the calvaria and maxillary sinus region, with several areas of focal sclerosis ("cotton wool" appearance) (arrowheads). (b) Lateral radiograph of a skull specimen from an 85-year-old woman reveals diffuse sclerosis and calvarial thickening with platybasia. (c) Axial CT scan (same case as b) also reveals the posterior thickening and mixed lysis and sclerosis (area between arrows). (d) Photograph of the sectioned calvaria viewed from above at autopsy (same case as b and c) also shows widening of the diploic space (white *) and sclerosis anteriorly (black *).
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Figure 6c. Blastic phase of Paget disease involving the calvaria. (a) Lateral radiograph of the skull in a 56-year-old man shows diffuse calvarial thickening including the calvaria and maxillary sinus region, with several areas of focal sclerosis ("cotton wool" appearance) (arrowheads). (b) Lateral radiograph of a skull specimen from an 85-year-old woman reveals diffuse sclerosis and calvarial thickening with platybasia. (c) Axial CT scan (same case as b) also reveals the posterior thickening and mixed lysis and sclerosis (area between arrows). (d) Photograph of the sectioned calvaria viewed from above at autopsy (same case as b and c) also shows widening of the diploic space (white *) and sclerosis anteriorly (black *).
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Figure 6d. Blastic phase of Paget disease involving the calvaria. (a) Lateral radiograph of the skull in a 56-year-old man shows diffuse calvarial thickening including the calvaria and maxillary sinus region, with several areas of focal sclerosis ("cotton wool" appearance) (arrowheads). (b) Lateral radiograph of a skull specimen from an 85-year-old woman reveals diffuse sclerosis and calvarial thickening with platybasia. (c) Axial CT scan (same case as b) also reveals the posterior thickening and mixed lysis and sclerosis (area between arrows). (d) Photograph of the sectioned calvaria viewed from above at autopsy (same case as b and c) also shows widening of the diploic space (white *) and sclerosis anteriorly (black *).
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The blastic phase may cause the vertebral body to become diffusely sclerotic, creating an ivory vertebral body (38) (Fig 7). The posterior vertebral elements may also be affected. Bone enlargement of either the vertebral body alone or including the posterior elements is common and often aids in distinguishing Paget disease from other diseases. Spinal involvement may affect only one vertebral level, multiple levels, or even all the vertebral segments.
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Figure 7a. Ivory vertebral body caused by Paget disease in a 50-year-old asymptomatic man. (a) Anteroposterior radiograph shows diffuse sclerosis in the T10 vertebral body. (b) Posterior bone scan reveals intense radionuclide uptake at the involved vertebral level (see Fig 5d for histologic specimen of an ivory vertebral body).
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Figure 7b. Ivory vertebral body caused by Paget disease in a 50-year-old asymptomatic man. (a) Anteroposterior radiograph shows diffuse sclerosis in the T10 vertebral body. (b) Posterior bone scan reveals intense radionuclide uptake at the involved vertebral level (see Fig 5d for histologic specimen of an ivory vertebral body).
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The differential diagnosis of local vertebral body sclerosis includes osteoblastic metastatic disease (particularly from breast and prostate carcinoma), lymphoma, chordoma, and in rare cases unusual infection such as tuberculosis. Diffuse vertebral sclerosis has an extensive differential diagnosis, including osteoblastic metastatic disease, sickle cell disease, myelofibrosis, fluorosis, mastocytosis, and renal osteodystrophy.
Bone Scintigraphy
Bone scintigraphy (including blood flow, blood pool, and static images) classically demonstrates increased radionuclide uptake in the region of abnormal bone in all three phases of Paget disease (39–45) (Figs 2c, 7b, 8). It is a sensitive but not specific examination for detection of hyperemia and osteoblastic activity seen in Paget disease (40,41). The area of abnormal radionuclide uptake is usually elongated, reflecting the distribution of Paget disease, rather than the characteristic circular abnormality identified with metastatic disease or myeloma (Fig 8). Because scintigraphy is more sensitive to changes in vascularity, the hypervascular nature of Paget disease is often demonstrated as marked increased radionuclide uptake, which may be detected even before the typical radiographic lucency is evident (3). Scintigraphy is most valuable in identifying the polyostotic distribution of the disease (42).
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Figure 8. Anterior bone scan of the pelvis and proximal femora shows intense elongated areas of increased radionuclide uptake in the left hemipelvis and right femur, areas affected by Paget disease. Lateral bowing of the affected femur is seen.
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In our experience, there is a broader spectrum of radionuclide uptake in abnormal pagetic bone than has been reported, since not all cases are as "hot" as has been classically described. This concept is supported in studies by Lavender et al (44) and Khairi et al (45). In these studies, results from both bone scans and radiographs were abnormal in 56%–86%, were abnormal only on bone scans in 2%–23%, and were abnormal only on radiographs in 11%–20% of sites of pagetic involvement. It is likely that more quiescent late phase disease may show normal radionuclide activity yet appear abnormal on radiographs. Indeed, in the study of Khairi et al, all the patients with normal-appearing bone scans and abnormal radiographic findings were asymptomatic, whereas 73% of those with abnormal bone scan results and normal-appearing radiographs were symptomatic representing more physiologically active disease (45). It is important to recognize this spectrum of scintigraphic and radiographic disparity that can occur in Paget disease so as not to cause diagnostic confusion. The various complications associated with Paget disease cannot typically be differentiated with bone scintigraphy.
CT and MR Imaging
Although Paget disease is usually apparent on radiographs, the disease may be discovered incidentally on CT or MR images obtained for other reasons (21,46–56). Familiarity with and the ability to recognize the typical appearance of this disease on CT or MR images is important so as to prevent misdiagnosis (particularly of metastatic disease in this age group of patients).
Findings at CT are largely identical to the radiographic findings of Paget disease previously discussed (49). Areas of lysis show loss of normal trabeculae (50). Cortical and trabecular thickening are also well demonstrated at CT (35) (Fig 9). The disorganized pattern of trabecular thickening seen pathologically is better demonstrated on CT scans than on radiographs. Areas of sclerosis may be seen in the blastic phase of the disease. The marrow space in Paget disease often reveals fat attenuation. Noncomplicated Paget disease shows no evidence of cortical destruction or any soft-tissue mass.
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Figure 9. Noncomplicated Paget disease found incidentally in an asymptomatic 58-year-old man. Axial CT scan of the pelvis (obtained for other reasons) shows cortical (large arrows) and trabecular (small arrows) thickening of the left iliac bone with maintained yellow marrow (*).
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Bone enlargement as well as trabecular and cortical thickening (which has low signal intensity with all MR pulse sequences) may be seen on CT and MR images; however, this pathognomonic appearance is easier to appreciate on radiographs. The MR imaging appearance of the remainder of the marrow in Paget disease is variable and depends on the disease phase and, more important, on the histologic composition of the marrow space as previously discussed (21). Three intrinsic patterns of the marrow space in noncomplicated Paget disease are noted on MR images. In the vast majority of these cases, the yellow marrow signal intensity is maintained regardless of pulse sequence, reflecting the fact that most disease is in the mixed phase and is relatively longstanding (51) (Figs 10, 11). In fact, in many cases, the marrow space of pagetic bone actually has more fat than found in the uninvolved bone, a finding that represents the atrophic marrow seen pathologically (Fig 10). The volume of the medullary canal can be decreased secondary to encroachment by cortical thickening.
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Figure 10a. Noncomplicated Paget disease of the calcaneus in a 58-year-old asymptomatic man. Sagittal T1-weighted (repetition time msec/echo time msec = 500/20) (a) and T2-weighted (2,000/80) (b) MR images show cortical and trabecular thickening (arrowheads) with maintained yellow marrow (*). In fact, there is more fat in the affected calcaneal marrow, compared with that in the noninvolved talus.
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Figure 10b. Noncomplicated Paget disease of the calcaneus in a 58-year-old asymptomatic man. Sagittal T1-weighted (repetition time msec/echo time msec = 500/20) (a) and T2-weighted (2,000/80) (b) MR images show cortical and trabecular thickening (arrowheads) with maintained yellow marrow (*). In fact, there is more fat in the affected calcaneal marrow, compared with that in the noninvolved talus.
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Figure 11a. Noncomplicated Paget disease of the distal femur in a 57-year-old woman. (a) Anteroposterior radiograph of the knee shows typical cortical and trabecular thickening of the entire distal femur to subchondral bone. (b) Coronal T1-weighted MR image (600/20) shows identical changes with maintained yellow marrow (*) between thickened trabeculae. (c) Coronal fat-suppressed short-inversion-time inversion-recovery MR image (2,000/30/100) reveals mild increased signal intensity in the marrow resulting from small fibrovascular elements. (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical and trabecular thickening (arrowheads) and yellow marrow centrally, with small components of fibrovascular tissue (*).
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Figure 11b. Noncomplicated Paget disease of the distal femur in a 57-year-old woman. (a) Anteroposterior radiograph of the knee shows typical cortical and trabecular thickening of the entire distal femur to subchondral bone. (b) Coronal T1-weighted MR image (600/20) shows identical changes with maintained yellow marrow (*) between thickened trabeculae. (c) Coronal fat-suppressed short-inversion-time inversion-recovery MR image (2,000/30/100) reveals mild increased signal intensity in the marrow resulting from small fibrovascular elements. (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical and trabecular thickening (arrowheads) and yellow marrow centrally, with small components of fibrovascular tissue (*).
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Figure 11c. Noncomplicated Paget disease of the distal femur in a 57-year-old woman. (a) Anteroposterior radiograph of the knee shows typical cortical and trabecular thickening of the entire distal femur to subchondral bone. (b) Coronal T1-weighted MR image (600/20) shows identical changes with maintained yellow marrow (*) between thickened trabeculae. (c) Coronal fat-suppressed short-inversion-time inversion-recovery MR image (2,000/30/100) reveals mild increased signal intensity in the marrow resulting from small fibrovascular elements. (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical and trabecular thickening (arrowheads) and yellow marrow centrally, with small components of fibrovascular tissue (*).
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Figure 11d. Noncomplicated Paget disease of the distal femur in a 57-year-old woman. (a) Anteroposterior radiograph of the knee shows typical cortical and trabecular thickening of the entire distal femur to subchondral bone. (b) Coronal T1-weighted MR image (600/20) shows identical changes with maintained yellow marrow (*) between thickened trabeculae. (c) Coronal fat-suppressed short-inversion-time inversion-recovery MR image (2,000/30/100) reveals mild increased signal intensity in the marrow resulting from small fibrovascular elements. (d) Photograph of a coronally sectioned, whole-mounted specimen (H-E stain) shows cortical and trabecular thickening (arrowheads) and yellow marrow centrally, with small components of fibrovascular tissue (*).
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The second MR imaging pattern is seen in the lytic to early mixed active phase, in which the marrow space has heterogeneous signal intensity with both T1- and T2-weighted sequences (Fig 12). On T1-weighted MR images, the marrow has decreased signal intensity, generally similar to that of muscle; however, it typically contains small to extensive foci of intermixed, normal and maintained yellow marrow. This feature is important because it excludes malignant transformation since no masslike marrow replacement is seen (48,55). On T2-weighted MR images, the marrow has heterogeneous high signal intensity, which is accentuated with water-sensitive pulse sequences (22,48,55). We believe this appearance corresponds to the fibrovascular marrow replacement seen pathologically in these more active phases of Paget disease. We refer to this pattern as the "speckled" appearance on MR images (Fig 12). Other investigators have suggested that dilated vascular channels in Paget disease may be responsible for the high-signal-intensity changes on T2-weighted images secondary to their slow flow state. In our experience, however, we have not recognized a serpentine appearance on MR images or large vascular structures pathologically. The final MR imaging pattern is seen in the late blastic inactive phase, in which the marrow space has low signal intensity representing sclerosis regardless of pulse sequence (Fig 13).
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Abstract
LEARNING OBJECTIVES FOR TEST...
