Imaging findings

A systematic approach utilizing various imaging modalities for visualizing both Paget’s disease and bone metastases enhances the diagnostic confidence. Indications and disadvantages of the different imaging techniques are summarized in Table 1. 

Table 1: Indications and limitations of the different imaging techniques to study Paget’s disease and bone metastases.

1. Plain Radiography and CT

Paget’s Disease

• Bone Enlargement: bones appear enlarged, a hallmark of Paget’s disease due to accelerated and disorganized bone remodeling.
• Cortical Thickening: the cortices are thickened, indicative of compensatory new bone formation.
• Coarsened Trabeculae: the trabecular structure appears disorganized, reflecting the chaotic remodeling process.
• Distribution: pelvis, skull, vertebrae, and long bones are frequently affected.

Bone Metastases

• Lesion Types:

Lytic Lesions: represent bone destruction, visible as lucent areas.

Sclerotic Lesions: reflect abnormal bone deposition, visible as opaque areas.

• Cortical Destruction: refers to the disruption and erosion of the cortical bone layer, often caused by aggressive tumor infiltration, resulting in structural weakening and potential pathological fractures.
• Distribution: typically multifocal and asymmetric, commonly involving the axial skeleton, pelvis, and ribs.

A summary of the main radiographic differences is provided in Table 2. 

Table 2: Radiographic differences between Paget's disease and bone metastases.

    2. Magnetic Resonance Imaging (MRI)

Paget’s Disease

• Mixed Signal Intensities: reflects mixed osseous and fibrous tissues.

T1-Weighted: retains regions of marrow fat (high signal intensity)

T2-Weighted: displays a combination of hyper- and hypo-intense regions.

• Preservation of marrow fat: suggests bone remodeling without total marrow replacement.
• Bone expansion: evident and correlates with imaging from radiography or CT.

Bone Metastases

• Marrow replacement: tumor infiltration replaces marrow, appearing hypointense on T1 and hyperintense on T2.
• Cortical and soft tissue invasion: disruption of cortical bone with soft tissue extension is often observed.
• Uniform signal changes: signals are consistent with extensive marrow involvement.

Key MRI Differences

• Paget’s disease retains marrow fat and shows heterogeneous signals, while metastases exhibit uniform marrow replacement and more extensive cortical invasion.

    3. Bone Scintigraphy

Paget’s Disease

• Intense radiotracer uptake: intense accumulation of radiopharmaceutical throughout the affected part with uniform distribution.
• Single or limited bone involvement: typically affects one or a few bones in a polyostotic pattern.
• Patterned uptake: specific and rare pattern such as the “Mickey Mouse (an upside-down triangle consisting of three foci of intense radiopharmaceutical uptake, and corresponding to the involvement of the pedicles and spinous process)

Bone Metastases

• Focal uptake: localized areas of increased tracer accumulation, often scattered throughout the skeleton without any characteristic patterns.
• Multiple focal hot spots: scattered areas of intense uptake corresponding to metastatic sites.
• Asymmetric Distribution: multiple sites may be involved, depending on the primary cancer.

Diagnostic Tips and Tricks

We provide characteristic images highlighting the radiological differences between Paget's disease and metastases. Additionally, we present various clinical scenarios and imaging patterns to enhance awareness of potential diagnostic challenges.

1. Cotton wool appearance: sclerotic lesions in the skull during the sclerotic phase of Paget’s disease vs Geographic lesions in bone metastases: well-defined but destructive areas, often without bone expansion. (Fig.1,2) 

Fig 1: AP (A) and Lateral (B) views of the skull in a patient with Paget's disease show marked calvarial thickening, widened diploic space, and mixed sclerotic and lucent areas ("cotton wool appearance"). No platybasia, basilar invagination, or overriding frontal bone is observed.

Fig 2: AP (A) and Lateral (B) views of the skull in a patient with lung cancer metastases reveal multiple rounded osteolytic lesions without calvarial thickening.

2. Blade of grass sign in Paget's disease: a wedge-shaped, radiolucent lesion with sharp, well-defined borders in the osteolytic phase, vs metastatic lesion: a destructive, irregular lesion often associated with cortical breaches and soft-tissue extension. (Fig. 3,4)

Fig 3: Lateral (A) and frontal (B) and lateral views of the right tibia in progressed Paget's disease (mixed phase) reveal cortical thickening, irregular trabecular patterns, areas of sclerosis and lucency, and deformity with bowing, reflecting active bone remodeling.

Fig 4: Lateral X-ray of the tibia shows a radiolucent, wedge-shaped osteolytic lesion with sharp, well-defined borders, characteristic of the "blade of grass" sign, a hallmark of the osteolytic phase of Paget's disease.

Note: While progressed images are characteristic of Paget’s disease, the "blade of grass" sign can mimic metastases; radiologists must search for malignancy indicators, such as cortical destruction or soft-tissue extension. (Fig.5)

Fig 5: Axial CT of the femurs in soft-tissue window shows an aggressive, irregular metastatic lesion in the left femur, characterized by bone destruction and an associated soft-tissue mass (arrow). These features are indicative of malignancy.

3. Can Paget’s disease and metastases coexist? (Fig.6, Fig. 7)

Fig 6: A patient with known gastric cancer. Bone scintigraphy using Tc-99M labeled MDP shows high osteoblastic activity in the ribs, some vertebrae, and the pelvis, with increased activity in a lower thoracic vertebra. The involvement of anterior and posterior elements creates a characteristic "Mickey Mouse" appearance (blue circle), a specific finding for Paget's disease.

4. Decoding the overlap (Fig.7)

Fig 7: (A) Axial CT scan of the L3 vertebra demonstrates thickened trabeculae, and slight enlargement compared to other vertebrae. (B) Axial CT of the pelvis (bone window) shows coarse trabeculation predominantly on the right side (green arrow) of the pelvic bones, mixed with patchy osteoblastic lesions more prominent in the left hemipelvis and sacrum (blue arrow)

Possible pitfall: misinterpreting the irregular sclerotic or osteolytic lesions of metastases as the organized trabecular thickening and cortical expansion seen in Paget’s disease.

5. Can metastases mimic Paget's disease?  (Fig.8,9)

Fig 8: (A) Axial CT (bone window) at the level of the sacrum shows a large osteolytic lesion (blue arrow) in a patient with lung cancer. (B) Axial CT images of the same patient reveal cortical thickening and trabecular coarsening in both acetabuli, mimicking the radiologic appearance of Paget's disease.

Note: The bilateral changes in the acetabuli, including cortical thickening and trabecular coarsening, make metastatic disease more likely than Paget's disease, which typically presents with unilateral involvement.

Fig 9: (A) CT scan (axial view, bone window) in a patient with prostate cancer shows mixed diffuse osteoblastic metastases involving the pelvis and sacrum, with well-defined lytic lesions causing cortical destruction and associated bone enlargement on the right side. (B) CT scan (axial view, bone window) demonstrates osteosclerotic changes in the left acetabulum (unilateral) and an osteosclerotic rounded lesion in the head of the humerus.

Note: Unilateral changes, such as those observed in the left acetabulum or humeral head, should not lead to premature exclusion of metastases, especially in cancer patients.

6. MRI insights (Fig. 10,11)

Fig 10: MRI of the left humerus shows marrow replacement due to tumor infiltration, where normal marrow is replaced by pathological tissue. This results in the marrow appearing hypointense on T1-weighted images (T1WI) and hyperintense on T2-weighted images (T2WI), reflecting the altered composition and water content typical of tumor involvement.

Fig 11: An abnormal lesion is seen in the head, neck, and proximal metaphysis of the right femur, showing low (hypointense) signal on T1WI, along with thickening of the cortex and expansion of the bone. There is also a reduction in both the size and signal of the medullary cavity.