Skeletal metastases

Dr Yuranga Weerakkody and Dr Frank Gaillard et al.

Skeletal metastases are common, and result in significant morbidity in patients with metastatic disease.
Although the diagnosis is often straightforward, especially as in many cases there is well documented
history of metastatic malignancy, sometimes they may mimic benign disease or other primary
malignancies.

Epidemiology
Skeletal metastases account for 70% of all malignant bone tumours, and are seen in a vast number of
primary cancers, although lung cancer, breast cancer, renal cell carcinoma and prostate cancer account
for approximately 80% of all skeletal metastases 1. This is due to not only the propensity of these tumours
to metastasize to bone, but also the fact that these are some of the most common tumours.

Clinical presentation
The majority of metastases to bone are asymptomatic. Symptoms can arise in a number of scenarios
1.

local bone pain

2.

soft issue mass resulting in:

1,3

direct compression of adjacent structures by extra-osseous soft tissue mass (e.g. cord
compression)

palpable mass

deformity

3.
pathological fracture(s)
In most cases the diagnosis of metastatic disease is already known. If no known primary exists, or there
is uncertainty regarding the diagnosis (e.g. no known metastases; unusual imaging appearances) then a
bone biopsy can allow usually definitive diagnosis.
Laboratory investigations are of limited value, but will often demonstrate increased serum calcium and
alkaline phosphatase 1,3. Increase in hydroxyproline excretion may also be present 3.

Pathology
The major route of spread of tumour to bone is hematogenous, although lymphatic spread is also seen
(e.g. in pelvic tumours spreading to para-aortic nodes, and then directly into bone c.f the more common
hematogenous spread from the same tumours)3. Although direct extension of tumours in bone is also not
infrequently seen (e.g. oral cavity tumours into mandible, or Pancoast tumours into first rib or upper
thoracic vertebrae) this is not usually what is considered metastatic.
Regardless of the route of spread, metastases lead to both bone loss and bone formation, in varying
amounts. The former is most likely due to direct enzymatic destruction and osteoclast activation. The
latter can be due to stromal bone formation (formation of bone within tumour substrate; the case in
prostate cancer metastases) or reactive new bone formation which represents the normal adjacent bone's
response to the presence of tumour and is similar to callus formation 3.

Distribution
The distribution of skeletal metastases roughly mirrors the distribution of red-marrow, presumably
reflecting increased blood flow in red-marrow compared to yellow-marrow. Metastases are thus usually
found in:

vertebrae

especially posterior vertebral body, extending into pedicles

(see vertebral metastases)

pelvis

proximal femur

proximal humerus

skull
Metastases distal to the elbow and knee are distinctly uncommon (see distal appendicular skeletal
metastases).

Radiographic features
Skeletal metastases invariably incite a mixture of bone resorption and bone formation and can thus take
on one of three patterns, depending on the dominant process:
1.
lytic metastases
2.
sclerotic metastases
3.
mixed lytic and sclerotic metastases
Additionally, metastases can have different morphological characteristics:

diffuse

focal

expansile (see blow-out bone metastases)

Plain film
As is the case with other other bone lesions, skeletal metastases can be difficult to identify on plain films
on account of extensive (30-50%) bone mineral loss is required before the density loss is visible 1. When
visible skeletal metastases
In many other cases the lesion is visible due to destruction of cortex, or the presence of visible sclerosis.
It is important to note that unlike primary bone tumours, in general metastases incite no or only limited
periosteal reaction. The occasional exception to this general rule includesprostate cancer, some
gastrointestinal malignancies, retinoblastoma and neuroblastoma3.

CT
CT does not have a role in primary assessment for the presence of metastases (except for difficult areas
to image such as the spine) but is excellent at defining the extent of bony involvement and in helping
assess the risk of pathological fracture.

MRI
Whole body MRI is not widely used, but is highly sensitive to replacement of normal bone marrow 2.

Nuclear medicine
Bone scans are the most sensitive routine imaging modality to try and identify both sclerotic and lytic
lesions 1. In most cases they demonstrate increased uptake (hot spot) although occasionally (in very
aggressive purely lytic lesions) a photopaenic defect (cold spot) may be visible. A superscan is also a
possible pattern where extensive diffuse metastatic disease results in uniform increase in uptake 3.

Treatment and prognosis

In general treatment can be thought of as systemic (e.g. chemotherapy or hormonal therapy) or local (e.g.
radiotherapy or surgery). Pain management is also often an important part of managing patients with
skeletal metastases.
When metastases involve the majority of the cross section of a bone, especially is structurally critical
bones such as the femur, prophylactic pinning may be required to prevent a pathological fracture.
No single statement can be made in regards to the prognosis of patients with skeletal metastases as this
will vary greatly depending on the primary tumour.

Differential diagnosis
There are, unfortunately, no specific features of metastases, although often the diagnosis is straight
forward in the setting of known advanced malignancy and multiple lesions.
When no history of malignancy is present, but lesions are multiple in an elderly patient, the main
differential is multiple myeloma.
When no helpful features are present (in other words a solitary lesion in an otherwise supposedly well
patient) one needs to consider numerous entities:

benign and malignant tumour

infection

trauma

osteonecrosis
The differential can be narrowed according to specific appearances and locations:

lytic bone metastases

sclerotic bone metastases
mixed lytic and sclerotic bone metastases
expansile bony lesion

solitary lesions

o
o
o

solitary sclerotic bone lesion

solitary lucent bone lesion: FOG MACHINES is a good place to start
solitary lucent skull lesion

Metastatic Disease to Bone

Metastases are most common malignant bone tumors

Most involve axial skeleton
o Skull, spine and pelvis
o Rarely do mets occur distal to elbows or knees
Spread hematogenously
o Most frequently occur where red bone marrow is found
o Mets to spine frequently destroy posterior vertebral body including pedicle
first=pedicle-sign
90% of skeletal mets are multiple
Primary carcinomas that frequently metastasize to bone
o The next four lesions comprise 80% of all metastases to bone
Breast (70% of bone mets in women)
Lung
Prostate (60% of all bone mets in men)
Kidney
o Also
Thyroid
Stomach and intestines
Clinical
o Most lesions are asymptomatic
When symptomatic, pain is major symptom
o Fractures of the lesser trochanter in adults should be considered pathologic until
proven otherwise
Imaging Findings
o In general, mets have little or no soft tissue mass associated with them
o Usually no periosteal reaction
o May appear as moth-eaten, permeative or geographic lesions
Indistinct zones of transition
No sclerotic margins
May be expansile
Soap-bubbly (septated)
May be sharply circumscribed or have indistinct borders
o Metastases that are typically purely lytic
Kidney
Thyroid
o Metastases that are usually mixed lytic and sclerotic
Lung
Breast
o Metastases that are usually purely blastic
Prostate
Medulloblastoma

Bronchial carcinoid
No matter what the primary, skull metastases are usually lytic in appearance

Most Common Tumors to Metastasize to Bone (80% of bone mets)

Tumor
Appearance
Prostate
Blastic
Breast
Mixed
Lung
Predominantly lytic
Renal Cell Ca
Predominantly Lytic
Imaging findings suggestive of a particular primary tumor
Lesions distal to elbows and knees
50% are from lung and breast
Expansile and lytic (soap-bubbly)
Renal cell
Diffuse skeletal sclerosis or multiple round, well-circumscribed sclerotic
lesions
Prostate
Breast

Multiple osteoblastic metastases to the pelvis and lumbar vertebral bodies from carcinoma of the
prostate
Note discrete rounded sclerotic lesions in right ilium and "ivory vertebra" involving

L4 and S1.

Cookie-bite lesions of the cortices of long bones

Lung
o Radioscintographic studies
Bone scans are extremely sensitive but not very specific
10-40% of lesions will not be visible on plain film but will be positive on
bone scans
CT or MRI can be used to show findings in patients with negative
conventional radiographs and positive bone scans
Complications of metastases to bone
o Pathologic fractures
Destruction of 50% or more of bone suggests impending pathologic
fracture
o Spinal cord compression
o Treated lytic mets may become sclerotic with treatment

References:
Orthopedic Radiology: A Practical Approach, Greenspan, Adam; Lippincott, 2000
Diagnosis of Bone and Joint Disorders, Resnick, Donald, W. B. Saunders
Musculoskeletal Imaging: The Requisites, Manaster, BJ et al; Mosby, 2002

Overview
Metastases from carcinoma are by far the most common malignant tumors involving the skeleton.
Imaging has an important role in the detection, diagnosis, prognostication, treatment planning, and followup monitoring of bone metastases. In patients with proven nonskeletal tumors, imaging is useful for
screening the skeleton to assess metastatic disease and, if it is present, to determine its extent. [1, 2, 3]
In a patient without a known malignancy, a possible diagnosis of bone metastases may be made by
recognizing radiographic and other imaging findings. If bone metastases are present or suspected, further
imaging or imaging-guided techniques may be required to confirm the diagnosis, to establish the extent of
the disease, and to find the primary tumor.
Bone metastases are often multiple at the time of diagnosis. In adults, the lesions generally occur in the
axial skeleton and other sites with residual red marrow, although the lesions may be found anywhere in
the skeletal system. Common sites for metastases are the vertebrae, pelvis, proximal parts of the femur,
ribs, proximal part of the humerus, and skull. More than 90% of metastases are found in this distribution.
Certain carcinomas may have a predilection for particular skeletal sites. For example, metastases to the
bones of the hands and feet are rare, but 50% of hand metastases originate from lung neoplasms (see
the image below). Primary tumors arising from the pelvis have a predilection for spread to the
lumbosacral spine.

Bone metastases to the finger. Radiograph shows a destructive expanded osteolytic lesion in
the metacarpal of the thumb in a 55-year-old man with lung carcinoma.

Occasionally, patients with bone metastases may present with a pathologic fracture; therefore, checking
the state of underlying bone for disease is important if such a fracture is suspected (see the first image
below).[4] In addition, patients may present with complications of bone metastases, such as neurologic
impairment due to spinal epidural compression (see the second image below).

Pathologic fracture. Radiograph shows a displaced fracture through an osteolytic lesion in the

distal femur of a 53-year-old woman with lung carcinoma.

Spinal epidural compression in a 70year-old man with leg weakness. Lateral lumbar myelogram shows a complete epidural block due to a destructive osteolytic
lesion of the L3 vertebral body. Lumbar puncture was performed at the L2-3 level.

Pathophysiology
A basic knowledge of the processes by which metastases involve bone helps in understanding radiologic
findings.

Bone involvement in metastases occurs by means of 3 main mechanisms: (1) direct extension, (2)
retrograde venous flow, and (3) seeding with tumor emboli via the blood circulation. Seeding occurs
initially in the red marrow; this process accounts for the predominant distribution of metastatic lesions in
the red marrowcontaining areas in adults. In contrast, bone metastases are usually widespread in
children. Retrograde venous embolism is probably the major mechanism when spread from intraabdominal cancer involves the vertebrae. Increased intra-abdominal pressure causes blood to be diverted
from the systemic caval system to the valveless vertebral venous plexus of Batson; this diversion allows
the caudal and cranial flow of blood.
As a metastatic lesion grows in the medullary cavity, the surrounding bone is remodeled by means of
either osteoclastic or osteoblastic processes. The relative degree of resultant bone resorption or
deposition is highly variable and depends on the type and location of the tumor. The relationship between
the osteoclastic and osteoblastic remodeling processes determines whether a predominant lytic, sclerotic,
or mixed pattern is seen on radiographs.[5, 6]

Differential diagnosis and other problems to be considered

When evaluating for bone metastases, also consider bone islands, eosinophilic granuloma of the
skeleton, bone lymphoma, osteomalacia and renal osteodystrophy, chronic
osteomyelitis, Paget disease, pelvic insufficiency fractures, stress fractures, tuberous
sclerosis, and secondary osteoarthritis.

Preferred examination
Technetium-99m (99m Tc) bone scintiscanning (ie, radionuclide bone scanning) is widely regarded as the
most cost-effective and available whole-body screening test for the assessment of bone metastases.
Conventional radiography is the best modality for characterizing lesions that are depicted on bone
scintiscans. Combined analysis and reporting of findings on radiographs and 99m Tc bone scintiscans
improve the diagnostic accuracy in detecting bone metastases and assessing the response to therapy.[7, 8,
9]

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are useful in evaluating
suspicious bone scintiscan findings that appear equivocal on radiographs. [10, 11, 12, 13] MRI can also help in
detecting metastatic lesions before changes in bone metabolism make the lesions detectable on bone
scintiscans.[14, 15, 16] CT scanning is useful in guiding needle biopsy, particularly in vertebral lesions. MRI is
helpful in determining the extent of local disease in planning surgery or radiation therapy.
The first screening test used for the detection of bone metastases depends on the relative availability of
MRI and99m Tc bone scintiscanning. The selection will become less of an issue when more MRI units are
established and when its cost decreases. Factors such as cost and relatively long imaging times, as well
as considerations of patient throughput, are important. MRI is estimated to cost 2-3 times as much
as99m Tc bone scintigraphy[17, 18] ; fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning
costs 8 times as much.[19, 20, 21, 22, 23]

Limitations of techniques
Radiographs are relatively insensitive in the detection of early or small metastatic lesions. Although CT
scans are superior to radiographs, CT scanning is also relatively insensitive in showing small
intramedullary lesions, and it has the disadvantage of limited skeletal coverage. Bone scintiscan findings
are sensitive but nonspecific. Whole-body MRI and FDG-PET scanning are accurate techniques that are
currently limited by their high cost.[24, 25, 26, 27, 28]

Radiography
Radiography remains the best method for characterizing bone metastases.
Bone metastases may be osteolytic, sclerotic, or mixed on radiographs (see the first image
below). Lesions usually appear in the medullary cavity, spread to destroy the medullary bone,
and then involve the cortex. Osteolytic metastases are encountered most frequently, especially in
breast and lung carcinomas (see the second image below).[29, 30, 31, 32] The specific appearance of
bone metastases is often useful in suggesting the nature of the underlying primary malignancy.

Lateral radiograph shows mixed osteolytic-sclerotic bone metastases in

the skull vault.

Radiograph shows osteolytic metastasis in the distal femur of a 51year-old woman with breast carcinoma.

Metastases from certain primary sites (eg, renal cell or thyroid carcinomas) are almost always
osteolytic, whereas those from other sites (eg, prostatic carcinoma) are predominantly sclerotic
(see the image below).[33] Other malignancies associated with sclerotic metastases include breast
carcinoma, colonic carcinoma, melanoma, bladder carcinoma, and soft-tissue sarcoma. The
findings of sclerotic metastases virtually exclude an untreated renal tumor or hepatocellular
carcinoma.[34]

Lateral radiograph shows sclerotic metastasis of the L2 vertebra in a 54-year-old

man with prostatic carcinoma.

In vertebrae, clues to metastatic involvement include pedicular destruction, an associated softtissue mass, and an angular or irregular deformity of the vertebral endplates.
The response to therapy can be evaluated by using radiographs and by correlating the
radiographic changes with bone scintiscan findings and clinical and laboratory data. The initial
manifestation of healing in an osteolytic metastatic lesion is a sclerotic rim of reactive bone.
With progressive healing, sclerosis increases and advances from periphery of the lesion to its
center: The lesion shrinks and eventually resolves. For a mixed osteolytic-sclerotic lesion, a
healing response to therapy is demonstrated as uniform lesional sclerosis, whereas increasing
osteolysis indicates disease progression.
Purely sclerotic lesions are more difficult to assess. A sclerotic lesion that shrinks or completely
disappears after therapy signifies disease regression, whereas one that grows and causes
destruction implies progression. The comparison of current images with previous radiographs is
essential, particularly in the detection of subtle lesional changes.

Degree of confidence
Compared with other imaging techniques, radiography is relatively insensitive in detecting bone
metastases, especially subtle lesions. As a general rule, only lesions 2 cm or larger are
radiographically apparent. Metastases to bone become apparent on radiographs only after the
loss of more than 50% of the bone mineral content at the site of disease.

False positives/negatives
On radiographs, advanced destructive lesions of the cancellous bone may not be visible,
particularly in the absence of reactive new bone or cortical involvement. This problem is more
apparent in elderly patients with osteopenic bones than in others.
Osteolytic metastases can mimic osteoarthritis both clinically and radiographically; for example,
they can mimic subchondral cysts and Schmorl nodes in the spine. Osteolytic foci may resemble
amyloidosis, cystic angiomatosis, and infiltrative bone marrow lesions. Sclerotic metastases may
be difficult to distinguish from other sclerotic bone lesions such as bone islands, tuberous
sclerosis, mastocytosis, and osteopoikilosis.
In assessing the response to therapy, an increasing number of sclerotic bone metastases may be
difficult to distinguish from the healing of sclerotic lesions that were not previously identified.

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