The diagnosis of a bone tumour usually starts with identification of a bony swelling (Figure 1) often associated with considerable discomfort, and then demonstrating that the lesion is radiographically “aggressive”. In dogs, the principal radiographic features of an aggressive bone lesion are osteolysis (particularly permeative osteolysis), an irregular periosteal reaction and a long transition zone from the “healthy” bone surrounding (Figure 2). In cats, there are no well-characterised radiographic features of aggressive bone lesions and sometimes “aggressive” bone lesions can look extremely non-aggressive (Figure 3); in the feline patient diagnosis of a bone lesion often relies heavily on cytology or histopathology.
Why is a preoperative diagnosis needed after diagnosing an aggressive bone lesion?
In UK-based dogs, the majority of aggressive bone lesions will be malignant tumours; however, bacterial osteomyelitis or rarely systemic mycoses and other granulomatous diseases should be considered (particularly in dogs who have travelled). Providing that the stability of the bone has not been significantly undermined, such diseases may be successfully treated medically. Similarly, some of the less common bone tumours are part of systemic disease processes (for example metastatic tumours, lymphoma or plasma cell tumours); these systemic diseases are also treated medically, and amputation need only be considered as a salvage procedure in cases with intractable pain or where the stability of the bone cortex has been undermined.
It is true, however, that amputation will be an appropriate first step for the majority of cases, since osteosarcoma represents at least 85 percent of canine bone tumours. Despite the prevalence of osteosarcoma, many other bone tumour histologies are recognised. While many other sarcomas (for example chondrosarcoma, fibrosarcoma and haemangiosarcoma) will necessitate amputation, histiocytic sarcoma is an important exception, where hypofractionated radiation therapy is a highly effective limb-sparing treatment, returning most cases to full weight-bearing in a rapid time frame.
Finally, we should not underestimate the value of prognostic information. Many clients will be unsure whether they want to pursue amputation without more certainty about their pet’s prognosis. Knowing whether a dog’s lesion is an osteosarcoma (for which chemotherapy will be required after amputation and average survival is in the order of 10 to 14 months from diagnosis) or a chondrosarcoma (where the benefit of chemotherapy is unclear and survival is in the order of several years with amputation alone) may provide valuable information to an owner, even if the first step in the treatment journey will remain the same.
In cats, an aggressive bone lesion has fewer differential diagnoses. Osteosarcoma is the most important bone cancer, but care should be taken to differentiate this from the benign osteochondroma or multiple cartilaginous exostoses. Infectious differential diagnoses are also an important consideration, and in the UK mycobacterial disease should always be considered. The clinician should be well aware of the health and safety connotations of sampling such a lesion.
How do I sample an aggressive bone lesion?
All tumours should be sampled in their centre. A common mistake is to try to sample the tumour from the side, including normal tissue as well as the tumour (as you would sample a skin lesion), but this technique risks seeding of some tumours, the formation of a haematoma and crucially, obtaining reactive tissue instead of a diagnostic sample. The sampling site should be selected carefully after evaluating orthogonal radiographs of the lesion – sampling deep into the centre of the lesion is desired, so the biopsy or aspirate should be aimed through the area of maximum osteolysis. Sampling the lesion at the periphery will often yield reactive bone only. Similarly, care should be taken to avoid the path of nerves or blood vessels.
The best-established method of sampling an aggressive bone lesion involves using a Jamshidi needle (approximately 8 to 11 gauge for most dogs, 12 to 14 gauge for small dogs and cats). This is a reliable and easy technique that poses a small risk of pathological fracture providing correct technique is used. A 3 to 4mm skin incision is made in the carefully selected location in the centre of the tumour and then the Jamshidi needle is used to procure a cylinder of tissue, taking care to avoid penetration of the far cortex of the bone. The biopsy can be repeated several times through the same skin incision, until solid pieces of tissue are obtained. Such biopsies should be at least 0.5 to 1cm in length and sink in formalin. If an infectious process is considered as an important differential diagnosis, tissue should also be procured for fresh tissue culture and a small segment should be frozen in case PCR tests are required at a later date.
Fine needle aspiration (FNA) cytology has also been shown to be a highly accurate means of diagnosis of an aggressive bone lesion, and this carries an even lower risk of pathological fracture. In many cases this is the author’s first choice; cytology samples can easily be checked in real time using the practice microscope, and if the sample is considered of poor diagnostic quality, a Jamshidi biopsy can then be procured. FNA cytology is an effective way of demonstrating sarcoma cells (Figure 4) and use of the ALP stain on the cytology sample has been shown to be a highly sensitive and specific test for identification of an osteosarcoma compared to other sarcomas. Histiocytic sarcoma often has a characteristic cytological appearance and, along with an often characteristic signalment (retriever breeds and Bernese Mountain Dogs), further tests are rarely needed for this diagnosis.
To get a good cell harvest with an FNA of a bone, you need a very different aspirate technique to that for a lymph node. The author would recommend the following:
- Use a long 21g needle with 10ml syringe attached
- Insert into the middle of the lesion and apply 5 to 10ml negative pressure
- Move the needle back and fore / re-angle it several times, keeping negative pressure applied
- Release negative pressure immediately before withdrawal of the needle
- You will get a lot of blood with this method, but also a decent yield of neoplastic cells, so make at least 10 slides, and stain one or two in-house and check to make sure you have caught cells other than blood and inflammation before sending them off
Do I really need to X-ray the chest?
Although fulminant metastasis at the time of bone tumour diagnosis is uncommon, it is certainly possible, and if it has occurred it will have a very significant effect on the animal’s prognosis. For example, fewer than 20 percent of dogs with osteosarcoma will present with radiographically discernible pulmonary metastasis, but the presence of these pulmonary metastases will diminish the expected survival from approximately one year to approximately three months (with treatment). Most Flat-coated Retrievers with appendicular histiocytic sarcoma will have the localised form of the disease, where a survival time between 10 and 18 months is reported (after radiation therapy/amputation and then chemotherapy). If histiocytic sarcoma lesions are found in the thorax or abdomen, however, the histiocytic sarcoma would be classified as “disseminated” and survival time is typically measured in months. The client may find this staging information useful in deciding whether to proceed with surgery and chemotherapy.
It is also worth considering that a number of bone tumours are in fact metastatic lesions (eg urogenital carcinomas) or part of a systemic disease process (eg multiple myeloma, haemangiosarcoma or lymphoma). Knowing the distribution of these lesions can help direct therapy; for example, radiation therapy on a number of osseous sites can provide effective palliative analgesia in urogenital carcinomas. In the case of some systemic cancers such as lymphoma or multiple myeloma, the presence of multiple lesions is expected and should not have a strong effect on prognosis in most cases. Imaging the dog in these cases will help to increase suspicion about a systemic disease and may demonstrate a lesion which is easier to sample than the bone tumour.
Before amputation should the dog have an orthopaedic assessment?
In most cases of dogs with appendicular bone tumours, the dog will have effectively been three-legged for some time due to non-weight-bearing lameness, so the ability to cope on three legs will have already been demonstrated. However, it is always prudent to consider the orthopaedic function of the remaining limbs before an irreversible amputation surgery and in these increasingly litigious times we should document that we have done this. Particularly where chronic orthopaedic disease exists or is suspected, orthopaedic examination by another veterinary surgeon or even assessment by a specialist orthopaedic surgeon can be very helpful.
Is limb-sparing surgery any good?
Numerous techniques of removing a bone tumour (principally canine osteosarcoma) while avoiding amputation of the limb have been described. The most common limb-sparing surgeries involve the creation of a bespoke endoprosthesis for the dog. Discussion with specialist orthopaedic surgeons is recommended when a clinician has a potential candidate for such a procedure. These “limb-sparing” techniques have their place, but they’re not appropriate for most cases. Currently, limb-sparing procedures are only suitable for distal radial tumours, with a small tumour size and minimal involvement of soft tissues. Sadly, many bone tumours are diagnosed at other locations or at a more advanced stage. The majority of dogs receiving limb-sparing operations (regardless of technique) have complications, for example implant infection or implant failure, and many of these need to proceed to amputation later. For some of the less common anatomic locations of bone tumours, however, easier options for limb-sparing exist. For example, dogs with scapular tumours or ulnar tumours can regain adequate mechanical function of their limbs with just a scapulectomy or ulnectomy.
“I’d go for surgery, but I wouldn’t put him through chemo…”
This attitude is understandably held by a number of clients, but their perception is ill-founded! Chemotherapy in dogs (in particular carboplatin therapy for osteosarcoma) will be associated with a normal quality of life throughout treatment; side effects will be either absent, or mild and self-limiting. Therefore, we need to educate our clients that side effects of chemotherapy will be no more likely or no more severe than treatment for many other chronic medical conditions. The use of post-operative chemotherapy is often “putting him through” much less than amputation surgery, and in the case of canine appendicular osteosarcoma, it can transform the expected survival time from five months (amputation only) to 10 to 14 months (amputation and chemotherapy).
What does the post-operative chemotherapy consist of?
For a canine osteosarcoma, the standard-of-care adjuvant (post-operative) chemotherapy treatments would either be intravenous carboplatin (every three weeks) or doxorubicin (every two to three weeks), for a total of four to six doses. Neither drug has been found to be superior, and an alternating protocol has shown no benefit. Since carboplatin is cheaper and has fewer potential side effects, this drug is most commonly used as single-agent. For canine chondrosarcoma or fibrosarcoma then the benefit of chemotherapy has yet to be established and for many non-metastatic cases with relatively unconcerning histopathology the use of chemotherapy may not be considered justified. For canine haemangiosarcoma the standard treatment would be a doxorubicin-based protocol (sometimes involving cyclophosphamide and vincristine as well), and for a histiocytic sarcoma, treatment is typically single-agent lomustine. The use of chemotherapy requires further knowledge of adverse effects, dosing and monitoring which are beyond the scope of this article. Discussion with a clinical oncologist is also recommended before such treatments are used for the first time.
The client refuses surgery. Is there any benefit of just medical treatment?
This situation is always a concern. Osteolytic lesions are extremely painful, and care has to be taken to preserve the dog’s welfare. The stoic nature of many dogs may lead clients to erroneously believe that their pets are not as painful as they actually are. If the client opts for palliative treatment, palliative-intent radiation therapy (for example one fraction of radiation, once weekly for three to four weeks) is the most analgesic treatment we can consider and all radiation therapy centres will be happy to provide this. Osteoclast inhibitors (for example pamidronate or zoledronate, given by intravenous infusion every four to six weeks) are also very analgesic and can be used with or without radiation therapy (the author would advocate using both together). Systemic analgesics should be used in all cases but even a combination of a non-steroidal drug, tramadol and gabapentin are unlikely to be adequate on their own. If radiation therapy is used as part of the palliative care, the average survival time can be as high as five to six months. The cause of death is often euthanasia after pathological fracture or intractable bone pain, rather than metastatic disease.
How do bone tumours in cats differ?
Primary bone tumours in cats are rare, and consequently we have a much smaller evidence base from which to treat them. Approximately 70 to 80 percent of the malignant lesions are osteosarcomas, with fibrosarcoma, chondrosarcoma and haemangiosarcoma making up the bulk of the remainder. Osteosarcomas in cats are much less aggressive than those in dogs, with fewer than 10 percent being reported to metastasise, so osteosarcomas of the appendicular skeleton are often cured with limb amputation. Adjunctive chemotherapy in cats is not indicated after adequate surgical control. The author would recommend awareness of the possibility of mycobacterial disease when sampling a feline bone tumour, and routinely taking tissue for culture and PCR tests as well as observing appropriate safety precautions.