Tumours of bone joints

Question 1

Where do the most common bone tumours arise?

Answer 1

Mesenchymal precursors of osseus and cartilaginous tissues

But any of the different cell types that are found in bones can potentially become neoplastic.

Question 2

Classification of tumours affecting the skeleton

Answer 2

1. Primary tumours of bone that make bone.
   e.g.: osteoma, osteosarcoma.
2. Other primary tumours that do not make bone.
   e.g.: myeloma, lymphoma, chondrosarcoma
3. Tumours which locally invade bone.
   e.g.: squamous cell carcinoma (eg: digit), malignant melanoma (eg: digit).
4. Tumours which metastasise to bone.
   e.g.: carcinomas.

Question 3

Benign tumour originating from osteoblasts and osteoclasts - make bone

Answer 3

Osteoma

Question 4

Malignant tumour originating from osteoblasts and osteoclasts - make bone

Answer 4

Osteosarcoma

Question 5

Benign tumour originating from chondrocytes - make chondroid matrix

Answer 5

Chondroma

Question 6

Malignant tumour originating from chondrocytes - make chondrid matrix

Answer 6

Chondrosarcoma

Question 7

Benign tumour originating from pluripotent periosteal cells

Answer 7

Monostotic and polyostotic osteochondroma

Question 8

Malignant tumour originating from pluripotent periosteal cells

Answer 8

Periosteal osteosarcoma, fibrosarcoma, etc.

Question 9

Benign tumour originating from endothelial cells - make vasculature

Answer 9

Haemangioma

Question 10

Malignant tumour originating from endothelial cells - make vasculature

Answer 10

Haemangiosarcoma

Question 11

Benign tumour originating from fibroblasts- make collagenous stroma

Answer 11

Fibroma

Question 12

Malignant tumour originating from fibroblasts - make collagenous stroma

Answer 12

Fibrosarcoma

Question 13

Malignant tumour originating from haematopoietic tissue - make cellular components of blood

Answer 13

Myeloma
Lymphoma
Histiocytic sarcoma

Question 14

Benign tumour originating from adipocytes

Answer 14

Lipoma

Question 15

Malignant tumour originating from adipocytes

Answer 15

Liposarcoma

Question 16

Malignant tumour originating from unknown tissue

Answer 16

Anaplastic sarcoma

Question 17

Most important benign primary bone tumours

Answer 17

Osteoma
Osteochondroma
Multilobular tumour of bone
Chondroma
Ossifying fibroma

Benign primary bone tumours are uncommon in all domestic species.

Question 18

Osteoma

Answer 18

Most commonly found on the head.

Single, dense mass, projects from the surface.

Well organised, mature trabecular (cancellous) bone.

Radiodense, well circumscribed.

Treatment: local resection.

Question 19

Osteochondroma

Answer 19

Any bone that forms by endochondral ossification.

Cap of cartilage, overlying cancellous bone.

Monostotic (single) and polyostotic (multiple) forms.

Monostotic form:
○ Expansile lesions that develop at growth plates of long bones or suture lines of flat bones - generally young animals that usually stop growing when the growth plates/suture lines close.
○ Usually they become fully ossified and remodel when the animal stops growing so if not a mechanical problem, then they don’t need treating.

Polyostotic form (syn. osteochondromatosis, multiple cartilaginous exostosis)
○ In cats, multiple lesions can occur - osteochondromatosis (associated with FeLV, FSV infection), and can progress to osteosarcomas.
○ In dogs and horses it is an autosomal dominant inherited disease. In dogs it can undergo malignant transformation, and the lesions do not cease to grow when skeletally mature.

Question 20

Multilobular tumour of bone

Answer 20

Usually develops on flat bones of the skull.

Proliferations of mesenchymal cells with central cores of cartilage that undergo osseus metaplasia to bone.

Vast majority are benign, with occasional reports of metastasis.

Question 21

Chondroma

Answer 21

Benign neoplasm of hyaline cartilage.

Most commonly develop on the flat bones or ribs.

Multilobulated, blue-white cut surface.

Can undergo ossification to form bone within the mass.

Microscopically, multiple lobules of well differentiated cartilage.

Question 22

Ossifying chondroma

Answer 22

A benign tumour that contains bone, but is of uncertain cell origin.

Mostly seen in young horses (equine juvenile mandibular ossifying fibroma).

Affects mainly the rostral mandible in horses.

Usually roughly spherical firm/hard, radiodense mass, arising from the periosteum of the underlying bone.

Can destroy adjacent bony structures, displace teeth, etc.

Histology: well differentiated fibrous connective tissue with spicules of woven bone covered by osteoblasts.

Question 23

Most common malignant bone tumours

Answer 23

Osteosarcoma
Chondrosarcoma

Malignant bone tumours are uncommon in most domestic species with the exception of the dog, where they account for about 5% of all tumours.

Question 24

Osteosarcoma

Answer 24

Most common tumour of the long bones of dogs, accounting for 90% of primary bone neoplasms.

It is a tumour of osteoblasts and hence production of osteoid (bone matrix) by the neoplastic cells is a pre-requisite to make the diagnosis.

It affects:
· Middle-aged and older dogs.
· Large and giant breed dogs.
· Males > females.

They arise most commonly on the metaphyses (distal radius, distal tibia, proximal humerus). Or ribs, vertebrae, bone of the head, etc.

Histologically, the tumour is very variable and there are many different subtypes (poorly differentiated, osteoblastic, chondroblastic, fibroblastic, telangiectatic and giant cell types).

Osteosarcomas cause early haematogenous pulmonary metastasis and aggressive local invasion.

Its aetiology is not fully understood.

Bone stress due to weight bearing, resulting in microfractures, rapid bone growth during early development and genetic predisposition are implicated.

Familial incidence has been reported in rottweilers, St Bernards and Scottish deerhounds.

Tumours may occasionally develop at the sites of old fractures (especially those with a history of delayed healing), at sites of metallic implants and in irradiated bone.

Question 25

Chondrosarcoma

Answer 25

Neoplasms of chondrocytes from the medullary cavity or the periosteum in which the neoplastic cells produce cartilaginous matrix but not osteoid or bone tissue.

It is the most common bone tumour in sheep.

In dogs is most common in mature patients of the large breeds. Most common location is the flat bones of dogs, nasal bones, ribs and pelvis.

Chondrosarcomas are usually locally aggressive, destroying the bone around them and extending into the adjacent soft tissues. They tend to be slow to metastasise, with this occurring only late in the disease process.

Microscopically: well differentiated, myxosarcoma-like, anaplastic.

Question 26

Predilection sites of osteosarcoma

Answer 26

metaphyseal regions of long bones:
- proximal humerus
- distal radius
- distal femur
- proximal tibia

Question 27

Clinical signs of canine bone tumours

Answer 27

Affected animals usually present with progressive lameness (gradual or quite acute onset) with or without painful swelling of the affected area of the limb or joint.

Question 28

Radiography of osteosarcoma

Answer 28

Destruction - osteolysis
Irregular, haphazard new bone production

Question 29

Clinical behaviour of the primary bone tumour of osteosarcoma

Answer 29

Osteosarcoma is an invasive and destructive tumour.

Its presence within the bone causes pain and the destruction of normal structural bone leads to weakening of the bone, predisposing to pathological fracture.

The tumour tends to spread along the medullary cavity and may invade through the periosteum and deep fascia to involve adjacent soft tissues.

OSA does not cross joints.

Question 30

Behaviour of the metastases of an osteosarcoma

Answer 30

Osteosarcoma (of long bones) is a highly malignant tumour which metastasises early in the course of the disease.

Metastasis is haematogenous and the lungs are the most common site for the development of secondary tumours.

Other sites of distant metastases include kidney, liver spleen and the skeleton itself.

(Note osteosarcoma which arises in the axial skeleton, for example in the skull, is less aggressive in terms of the risk and the rate of metastasis)

Question 31

Diagnostic work up of an osteosarcoma

Answer 31

History and clinical presentation are usually suggestive of diagnosis of primary bone tumour.

Radiography of primary site usually shows characteristic features of osteolysis, irregular new bone & Codman’s triangle, BUT NOTE THAT a radiographic diagnosis does not equal an histological diagnosis.

Radiographically one can say that these features are consistent with a “Primary Malignant Bone tumour” but not that this is an “Osteosarcoma”.

Histological diagnosis requires biopsy of lesion, various techniques available e.g. bone biopsy needles (Jamshidi) or open techniques.

Question 32

Bone biopsies

Answer 32

Obtaining representative tissue can be problematic, samples often take time to process because of need for decalcification.

In particular co-existing/pathological fracture sites can exhibit many of the cytological features and histological features of a malignant bony tumour (e.g.: highly activated osteoblasts, osteoclasts, fibroblasts and endothelial cells) and therefore biopsy of fracture sites should be avoided.

Due to extensive periosteal (and endosteal) new bone formation at the site of many bony lesions (eg: secondary to trauma, inflammation, infection, infarction, tumour, etc), it is very important to take a representative, and deep biopsy samples from the bony lesion.

Radiography prior to, and following biopsy is recommended to confirm that the sample has been obtained from the correct place.

Question 33

Staging of an osteosarcoma

Answer 33

Right and left lateral thoracic radiographs essential but will not detect micrometastases. There is significantly lower risk/rate of metastasis in the cat.

CT (if available) is more sensitive for detection of pulmonary metastasis

Question 34

Tumour associated complications

Answer 34

Mainly pain/fracture

Clinical pathology
○ Calcium
○ Alkaline phosphatase (bone isoenzyme)

Question 35

Prognosis for osteosarcoma

Answer 35

The prognosis for osteosarcoma of long bone in dogs is universally poor.

In most cases micrometastatic disease is present at the time of presentation / diagnosis of the primary tumour.

Whatever course of treatment is selected almost all patients are eventually euthanased as a result of metastatic disease.

Question 36

Options for management of osteosarcoma

Answer 36

Euthanasia: Dogs with osteosarcoma are lame because they are in pain. If this pain cannot be relieved through treatment of the primary tumour then euthanasia should be carried out on humane grounds.

Analgesia: NSAID’s can be used for short term relief of pain to allow the owners time to come to terms with the imminent loss of their pet.

Amputation: Probably treatment of choice for pain relief, but post-amputation survival times are alarmingly short and adjunctive chemotherapy should be considered (cisplatin, carboplatin, doxorubicin).

Limb salvage: Techniques have been described which allow surgical resection of the affected segment of bone and its replacement by a cortical allograft, thus allowing the salvage of the limb. Impressive but in whose interest? Plus problem of metastasis remains.

Radiotherapy: May be of short term value as a palliative for pain relief in a small proportion of cases but should not be viewed as a treatment of the tumour.

Other ?? Bisphosphonates (Zolendronate or Alendronate) for palliation

Question 37

Tumours of joints and associated structures

Answer 37

Tumours affecting the joints and the adjacent tissues are rare in both the cat and the dog.

Large (but not giant) breed dogs appear to be predisposed, and the average age at presentation is 8 years with a range of 1 – 12 years.

Question 38

Most common primary joint tumour

Answer 38

Synovial sarcoma

Question 39

Two types of synovial cells

Answer 39

A cells originate in bone marrow and migrate to joints (phagocytic),

B cells have characteristics of fibroblasts (produce synovial fluid and extracellular matrix of the synovium).

Question 40

Synovial sarcoma

Answer 40

A malignant tumour that is thought to arise from undifferentiated mesenchymal cells in the deep connective tissue associated with synovial joints, which differentiate into synovioblasts.

Histologically this tumour is composed of two cellular elements:
· Fibroblastic component.
· Synovioblastic or epithelioid component.

Question 41

Behaviour of synovial sarcomas

Answer 41

Locally aggressive tumours which invade into the subchondral bone at the articular margins, causing osteolysis of the periarticular bone and destruction of the joint.

They tend not to affect articular cartilage directly.

The reported metastatic rate for canine synovial sarcoma varies from 25 - 40 %.

The pattern of metastasis is to regional lymph nodes, lungs and other organs.

However a recent study showed that when immunohistochemistry was used to distinguish histiocytic sarcoma from synovial sarcoma, it was found that dogs with synovial sarcoma could expect long term survival post amputation, whereas dogs with histiocytic sarcoma experienced poor survival with widespread metastasis

Question 42

Soft tissue sarcomas arising from the periarticular soft tissues

Answer 42

Histiocytic sarcoma

can be difficult to distinguish clinically or radiologically from true synovial sarcoma.

Immunohistochemistry with CD18 and more recently Iba1 has been used to distinguish histiocytic sarcoma (CD18+) from synovial sarcoma and this has been shown to be important with respect to prognosis.

Question 43

Synovial ‘cysts’

Answer 43

reported in both cats and dogs and a number of proliferative conditions of the synovium may also present with nodular or hyperplastic tumour-like lesions

Question 44

Presentation/signs of tumours of joints

Answer 44

Progressive lameness of the affected limb with a mild to pronounced peri-articular soft tissue swelling.

The stifle is the joint most frequently affected followed by the elbow and the hock.

Radiography of the affected joint will generally show:
· A quite well-defined periarticular soft tissue swelling,
· Permeative or punctate osteolysis of the metaphyses and epiphyses adjacent to the joint
· Multiple bone involvement. I.e. all bones contributing to joint
· Irregular, spiculated periosteal new bone is a feature in some cases.

Radiography of the thorax would be required for clinical staging, although most cases do not have demonstrable metastases at the time of first presentation.

Question 45

Diagnosis of synovial tumours

Answer 45

Fine needle aspirate cytology is of limited value in the diagnosis of synovial tumours, a biopsy of the lesion is required to reach a histological diagnosis and an incisional biopsy is probably the preferred technique.

Immunohistochemistry may be required to distinguish synovial sarcoma from histiocytic sarcoma.

Question 46

Treatment of synovial tumours

Answer 46

Surgical resection is the treatment of choice for synovial sarcoma and other sarcomas involving the joints, however, because of the close proximity of these tumours to the joint and the invasion of bone, surgical resection usually requires an amputation of the affected limb.

Radiotherapy may be of short term value as a palliative for pain relief in a small proportion of cases but there is no clinical evidence to support the use of radiotherapy as an effective treatment for synovial sarcoma.

Chemotherapy is unlikely to be of benefit in treatment of the primary tumour, although the use of doxorubicin alone or in combination has been reported to delay the progression of the disease in cases where amputation is not deemed acceptable.

Question 47

Prognosis of synovial tumours

Answer 47

Most dogs with synovial sarcoma treated by amputation have disease-free survival times in excess of 36 months / 3 years.

The prognosis with amputation is therefore quite good.

In contrast the prognosis for histiocytic sarcoma is poor.