Volhme 69 August 1976

Joint Meeting No. 4

543

Section of Oncology
President E Cotchin MRCVS
President W Alexander Law OBE FRCS
2

.;;&

with Section of Orthop 'Cs

,.,

and Section of Radiology

President Margaret Snelling FRCS

Meeting 4 November 1975

Osteosarcoma
Dr Philip Jacobs (The General Hospital, Steelhouse Lane, Birmingham, B4 6NH; and the Royal Orthopaedic Hospital, Birmingham, B15 JAT)
matory lesions are associated with clear-cut paravertebral abscesses. (2) An osteosarcoma, by definition, produces osteoid or bone. Moreover, the reaction of any bone to an irritant, be it inflammatory or neoplastic, is either osteolytic or osteoblastic; often both responses are present at the same time. Such factors are responsible for a very early radiographic sign of osteosarcoma - localized, illdefined clouds of increased density within the medulla (Fig 2).

Radiological Diagnosis of Osteosarcoma

Osteosarcomata affect mainly children and young adults. The tumour is rarely seen in subjects under the age of 10 years or in middle or later life. Paget's disease accounts for many of the uncommon cases in older people. Most osteosarcomata occur in the metaphyses: the lower end of the femur, the upper end of the tibia and the upper end of the humerus are sites of election, However, the lesion may attack any bone and it may arise in the diaphysis. Rarely is an osteosarcoma primarily epiphyseal in site and it seldom spreads from the metaphysis across the epiphyseal line.

Unfortunately for the patient osteosarcomata are late presenters. Radiographic signs are always present when the patient first attends for examination.
Basic Radiological Signs (1) Well demarcated soft tissue swelling (Fig 1) is a very important sign and should always be sought; if necessary, by obtaining oblique, tangential and under-penetrated radiographs. Neoplastic soft tissue masses displace tissue planes though, of course, they also infiltrate them. The masses are well defined in contradistinction to osteomyelitis, where the swelling is caused by general cedema of the soft tissues infiltrating all planes. Exceptions may occur; for example, the rule does not apply to the spine, where inflam-

Fig 1 Early sarcoma lower end offemur. Note well demarcated soft tissue mass (arrows). Periosteal spicules at right angles to the shaft are seen posteriorly

544 Proc. roy. Soc. Med. Volume 69 August 1976

(3) Periosteal changes: all types of periosteal reaction may be found in osteosarcoma but, alas, none is specific. Spicules at right angles to the shaft (Fig 1), palisades or the sun-ray appearance are found occasionally but they may also be seen in benign lesions, e.g. angiomata. Coarse fibrelike spicules are more frequent (Fig 3). The lamellar type of response may be found (Fig 4); the classical onion-peel effect is more common in Ewing's tumour but, again, it may be seen in nonneoplastic lesions. Codman's cuffs (Fig 3) were once regarded as being specific for neoplasm but they, too, may be seen in simple lesions. The Codman cuff is merely a reflection of the loss of periosteum in the middle of a lesion caused by its rapid progression. Aneurysmal bone cyst is a good example of a nonmalignant condition associated with Codman's cuffs.

dense areas are seen within the shaft of the bone. Some linear periosteal reaction is shown. A soft tissue mass anterior to the lower end of the femur was visible on the original radiograph

Fig 2 Early

osteosarcoma lower

end offemur. Cloudy,

Fig 4 The lamellarperiosteal reaction is ofa type usually seen in benign lesions. Nevertheless, this lesion
was an osteosarcoma

Fig 3 Skip

areas

of sclerosis. In the

upper medial part

of the lesion a Codman's cuff and coarse periosteal fibres are seen

In general one might say that periosteal reaction in osteosarcoma tends to be irregular and interrupted' and that different types may be found at the same time. (4) Bone destruction: the response may, as noted above, be osteolytic and there is no need to emphasize the huge areas of destruction that may be found with accompanying breach of cortex. Calcification in surrounding soft tissues may be seen at the same time. (5) Osteosclerosis: lesions may appear to be entirely osteoblastic. Sometimes well demarcated disseminated skip areas may be seen (Fig 3). These are of therapeutic implication and are more usually seen in the osteosclerotic reaction; one assumes that they occur in the osteolyte forms also but are less well visualized radio-

graphically.

Section ofOuicology with Section of Orthopwdics anid Sectioni ofRadiology 545

14...

Fig 5A, earl)' central lesion characterized by a translucence in the anterosuperior part of the femoral head and neck. No periosteal reaction or soft tissue swelling wasfJound. Histological examination revealed an osteosarconma

(6) Localized expansion of bone may be caused in some osteosarcomata, but this sign is not a prominent feature. It is seen more often in Ewing's tumours. (7) Pathological fracture is a not uncommon feature of osteosarcoma and may be its first presentation. (8) Lesions that start centrally may cause diagnostic difficulties (Fig 5A, B). The radiographic abnormality will be merely a central translucent

Fig 5B, large central cavity. No breach of cortex, soft tissue swelling or periosteal reaction was fouind. This lesion was an osteosarcoma

zone that will probably be indistinguishable from the appearances presented by some benign lesions. Not until the cortex is attacked will the true state of affairs be seen. Such central lesions are not very common but they have accounted for practically all the errors in the author's series. (9) Htematological spread: metastases may be present in the lungs at the time of the first radiographic examination. Pulmonary metastases from osteosarcoma often have some distinctive characteristics: (a) They tend to cavitate. (b) If subpleural, a spontaneous pneumothorax may result (Fig 6). (c) The deposits may calcify or become frankly ossific. The question of lung tomography at first examination may be raised. Suffice it to say that tomography may reveal some lesions that are invisible on plain radiographs. One's practice will depend upon treatment protocols. (10) Some osteosarcomata complicate underlying benign lesions such as old osteomyelitis, fractures, Paget's disease, benign tumours, &c. In such cases the radiograph will give a lead to the underlying lesion.

Fig 6 Large metastatic masses. A pneumothorax is

present on each side

Angiography Angiography is of limited use in the diagnosis of sarcoma of bone though it does have some worthy champions. Against angiography are the following facts: (a) The vascular bed of normal

546 Proc. roy. Soc. Med. Volume 69 Aulgust 1976 bone is not visualized. (b) The cortex has to be breached before angiographic changes are visible in osteosarcomata. (c) Hypervascularity may be found in both benign and malignant lesions. Champions of angiography point out that: (a) Angiography will define the extent of a lesion - radiologists may be regarded as cartographers for the surgeon. This knowledge is hardly likely to be of practical significance because it is well known that bone tumours are always more extensive than shown by radiography and surgical treatment is planned accordingly. (b) Angiography may help to show the best site for the surgeon to take a biopsy sample. However, the most malignant part of the tumour may be avascular, in which case angiographic appearances are not helpful.
the incisor teeth. It is not known whether local trauma or blood supply or some other factor is responsible for this local development. After intra-arterial injection into the external iliac artery tumours develop in the femur and tibia and smaller bones of the injected limb. Tissue culture cells have also been successfully grown in Nude mice, producing tumours of histological appearance similar to tumour transplants in dogs (Oughton &Owen 1974).

Dr L N Owen

(Departmenit of Clinlical Veteriniary Medicinle, Uniiversity of Cambridge,

Madingley Road, Cambridge, CB3 OES)
Osteosarcoma in the Dog The main clinical, radiological and pathological features of spontaneous canine osteosarcoma have been previously described and the dog is undoubtedly the best model for osteosarcoma in man (Owen 1 969a, b). The condition is found more often in the giant breeds such as Wolfhound and Great Dane, with lung metastasis being the major cause of death, as in man.

Transplanitatioti
Canine osteosarcoma transplantation has been successfully performed by injecting fetuses in itero, at the 6th or 7th week of gestation, with osteosarcoma cells (Owen 1 969a, b). Tumours usually develop within a few weeks of birth. Another successful method of transplantation is by injecting osteosarcoma cells into neonatal dogs which have been immunosuppressed with antilymphocyte serum.
Many tumours have been grown successfully in tissue culture for several passages and two cell lines have been established (Bostock & Owen 1970). These cells produce sarcomas when injected into fetuses or immunosuppressed dogs but with little or no osteoid or new bone formation. Following intravenous injection, however, tumours appear to grow preferentially in bone in some dogs. Another interesting observation has been that, in some dogs injected intravenously with osteosarcoma cells at birth, tumours develop at about 3 weeks of age at the site of eruption of

Propliylacdtic X-irradiation of the Luntigs X-irradiation of one lung in young dogs previously injected intravenously with osteosarcoma cells led to less tumour development in the Xirradiated lung compared with the normal lung. This result, however, was not found when prophylactic X-irradiation was used in spontaneous cases. In 22 spontaneous cases the primary tumour was treated by amputation of the affected limb, or by X-irradiation to a total dose of 4000-5000 rad. One lung was X-irradiated with 600 rad on two occasions with a one-week interval using a 15 MeV Mullard linear accelerator (Owen & Bostock 1973). This dose was chosen as one not likely to produce severe pneumonitis and is equivalent in biological terms to slightly more than 14 x 150 rad (relevant to normal connective tissue), a dose which has been used in bilateral prophylactic lung X-irradiation in children. At post-mortem examination 4-11 months later differences between X-irradiated and nonirradiated lungs in 20 dogs were nil or small, and in 2 dogs where the primary tumour had been X-irradiated but left in sitit more tumour grew in the X-irradiated lung. The reason for this highly undesirable effect has not been finally determined but studies on 51Cr-labelled osteosarcoma cells injected intravenously into experimental dogs have shown that tumour cells initially localize in the X-irradiated lung and in the normal lung in equal numbers, so that the mechanism is not due to 'trapping' of cells. The results of Newton (1975, personal communication) on bilateral prophylactic lung X-irradiation for osteosarcoma in man have also shown that over a five-year period there is no therapeutic benefit.

Chemothercpy
Treatment of primary tumours using ethoglucid administered intravenously, intra-arterially or by limb perfusion has produced only temporary regression. In vitro studies on osteosarcoma cells treated with many different drugs or hormones have shown that most cytopathic effects were produced by actinomycin D, ethoglucid, vincristine, vinblastine and mycophenolic acid. If the vinca alkaloids are classified together, the four drugs all act by different mechanisms. No results of trials are yet available on chemo-