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.
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 metastasisse to bone, but also the fact that these are some of the most common tumours.
The majority of metastases to bone are asymptomatic. Symptoms can arise in a number of scenarios 1,3:
- local bone pain
- soft issue mass resulting in:
- direct compression of adjacent structures by extra-osseous soft tissue mass (e.g. cord compression)
- palpable mass
- 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.
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 disease.
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.
The distribution of skeletal metastases roughly mirrors the distribution of red-marrow, presumably reflecting increased blood flow in red-marrow compared to yellow-marrow. Thus, metastases are usually found in:
- especially posterior vertebral body, extending into pedicles (see: vertebral metastases)
- proximal femur
- proximal humerus
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:
Additionally, metastases can have different morphological characteristics:
- expansile (see: blow-out bone metastases)
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.
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 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.
Whole body MRI is not widely used, but is highly sensitive to replacement of normal bone marrow 2.
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.
A rule of thumb is that there is a high-risk of pathological fracture if the lesion is painful, >2.5 cm in size and involves >50% of the bone. There are more formal classification systems, although increasing cortical involvement is probably the most important factor 4,5:
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.
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
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
The differential diagnosis for bone tumours is dependent on the age of the patient, with a very different set of differentials for the paediatric patient.
- bone-forming tumours
- cartilage-forming tumours
- chondromyxoid fibroma
- fibrous bone lesions
- bone marrow tumours
- other bone tumours or tumour-like lesions
- aneurysmal bone cyst
- benign fibrous histiocytoma
- giant cell tumour of bone
- Gorham massive osteolysis
- haemophilic pseudotumour
- intradiploic epidermoid cyst
- intraosseous lipoma
- musculoskeletal angiosarcoma
- musculoskeletal haemangiopericytoma
- primary intraosseous haemangioma
- simple bone cyst
- impending fracture risk
- 1. Greenspan A, Jundt G, Remagen W. Differential diagnosis in orthopaedic oncology. Philadelphia : Lippincott Williams & Wilkins, c2007. (2006) ISBN:0781779308. Read it at Google Books - Find it at Amazon
- 2. Nakanishi K, Kobayashi M, Nakaguchi K et-al. Whole-body MRI for detecting metastatic bone tumor: diagnostic value of diffusion-weighted images. Magn Reson Med Sci. 2007;6 (3): 147-55. Magn Reson Med Sci (link) - Pubmed citation
- 3. Resnick D, Kransdorf MJ. Bone and joint imaging. W B Saunders Co. (2005) ISBN:0721602703. Read it at Google Books - Find it at Amazon
- 4. Rockwood CA, Bucholz RW, M.D. CC et-al. Rockwood and Green's Fractures in Adults. Lippincott Williams & Wilkins. (2010) ISBN:1605476773. Read it at Google Books - Find it at Amazon
- 5. Piccioli et al. Impending fracture: A difficult diagnosis. Injury (2014), http://dx.doi.org/10.1016/ j.injury.2014.10.038