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Skeletal metastases

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 1,3:

  1. local bone pain
  2. soft issue mass resulting in:
    • 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
  • 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:

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 includes prostate cancer, some gastrointestinal malignancies, retinoblastoma and neuroblastoma 3.  

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:


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