- Email: [email protected]
Giant cell tumour of bone and its variants
GIANT
CELL
TUMOUR
OF BONE
AND
ITS
VARIANTS
LESLIE L. RALPH, M.B., CH.B., F.F.R.
Chesterfield Royal Hospital, Chesterfield OSTEOCLASTOMA, or giant cell tumour of bone, is a comparatively rare but well known tumour which usually presents no great diagnostic difficulties. A few are sufficiently atypical to make the diagnosis doubtful and the recent trend has been towards more critical analysis of these atypical tumours. Undue emphasis on the giant cell was partly responsible for the accumulation o f diverse lesions masquerading as osteoclastoma, but in a classic paper Jaffe, Lichtenstein and Portis (1940) laid down more stringent diagnostic criteria which are now generally accepted. Attention was thereby turned to the imitative lesions and over the last twenty years there have been a number of reports of newly recognised turnouts which superficially resemble osteoclastoma, radiologically or histologically, and are conveniently and collectively known as *' giant cell tumour variants." Opinions still differ concerning the validity and interrelationships of these variants, but they must now be considered in the differential diagnosis of osteoclastoma along with the better known alternatives. Although even more uncommon than osteoclastoma there are at least two reasons why they should be seriously considered. First, they are generally benign tumours which may be unnecessarily drastically treated. Secondly, the pathologist's difficulties in making up his mind about an odd-looking tumour of doubtful malignancy may be resolved by the intelligent cooperation of the radiologist. An attempt has been made to collect turnouts diagnosed as osteoclastoma from the Sheffield region. Preliminary sorting showed that many have been treated without pathological confirmation, and while most of them undoubtedly were true osteoclastoma there were others which were atypical. Review of the remainder where the histology was available, discovered a few which were " variants "leaving twelve histologically acceptable osteoclastoma, and one which remains doubtful.
any doubt that the bone is abnormal, and in the long bones the correct diagnosis is usually not difficult. In arriving at this diagnosis the simple considerations of the patient's age and site of the tumour are of the highest importance. At least 90 per cent occur between the ages of twenty and thirty-five, and it is particularly rare below the age of twenty. Conversely many of the lesions which simulate osteoclastoma commonly occur in younger people and it follows that one should not diagnose osteoclastoma under the age of twenty without full investigation, certainly never on radiological evidence alone. One of our series occurred in a girl of sixteen who complained of an increasing lump behind the mastoid for at least one year, and she had had an episode of diplopia at the age of thirteen. There proved to be a large tumour o f the petrous temporal and occipital bones which could not be completely removed and was treated by radiotherapy. Review of the histology has shown no reason to question the original diagnosis of osteoclastoma in spite of the early age and unusual site. The radiographs showed only the
RADIOLOGICAL DIAGNOSIS OF O S T E O C L A S T O M A FIG, 1 It is generally agreed that true osteoclastoma is a Osteoclastoma spreading into neck of femur well beyond limits bone destroying tumour which is almost always of of the epiphysis. Successfullytreated by curettageand cancellous considerable size when first seen. There is rarely grafts. 269
270
CLINICAL
RADIOLOGY
extent of bone destruction and were in no way diagnostic. The position of the tumours in the long bones is remarkably constant. They occur almost invariably at the ends reaching to the articular surface which may fracture, but the tumour rarely " bursts " through it. This position is sometimes described as " epiphyseal," usually to make the point of distinction from the bone cyst which arises in the metaphysis and " grows dowI1 the bone." Unfortunately it tends to suggest that it usually begins at an age when the epiphysis is a separate entity which is untrue, nor is the average osteoclastoma confined to the epiphyseal region in the adult. (Fig 1). Where in fact does an osteoclastoma begin in those rare cases discovered in adolescence ? Willis (1949) states that they begin in the metaphysis and only spread later to the epiphysis, a view which is upheld in an editorial in the same issue of the Journal of Bone and Joint Surgery by Cade (1949), and also later by Stewart and Richardson (1952). A second editorial in the same issue (Platt
1949) states the opposite view, emphasising this distinct diagnostic difference from bone cyst. There is no doubt that tumours said to be osteo. clastoma have been reported in the epiphysis or in the metaphysis, and the dispute revolves around the histological interpretation. Unless orte accepts the second view it is obvious that it is not so easy to distinguish the common bone cyst (in the metaphysis) from the rare juver~ile osteodastoma (possibly also in the metaphysis). One of our cases illustrates this. She was a gM of fourteen who presented with a tumour slightly expanding the metaphysis of the lower fibula (Fig. 2). The original biopsy diagnosis was osteoclastoma, growing actively and possibly not innocent. After responding by marginal sclerosis to radiotherapy, it recurred two years later in a very aggressive manner by destroying the surrounding sclerotic bone and cortex to form a soft tissue swelling (Fig. 3). A second biopsy now indicated sarcoma and the fibula and tumour were excised. The real nature of this tumour is unknown. Pugh
FIG. 2 Lesion in metaphysis of fibula originally treated as osteoclastoma by radiotherapy. Age fourteen.
FIG. 3 Same patient two years later, showing much more malignant appearance after initial response to radiotherapy.
GIANT
CELL TUMOUR
OF B O N E A N D I T S V A R I A N T S
(1951) illustrates a similar case which he describes as a " giant cell variant of bone cyst," a term introduced by Geschickter and Copland to cover certain rapidly growing cysts containing numerous giant cells. Professor Collins, who reviewed our cases, is inclined to doubt the original biopsy diagnosis since it was atypical. There is also the possibility that the radiotherapy may have caused the malignant change, yet in spite of this she remains perfectly well six years after excision. To the radiologist it looked and behaved exactly as many proved osteoclastoma do except for the unusual age and site. The aggressive growth and even the histological appearance of sarcoma with long survival was seen in other cases. Osteoclastoma sometimes occurs in bones which have no epiphysis, such as the skull. In the short tubular bones they usually follow the rule, by being at the epiphyseal end (Jaffe 1958), but the only one in a metatarsal in the present series was at the base. In spite of all this the simple fact remains that most osteoclastomata occur in long bones, and the overwhelming majority are then at the end and are found in patients over twenty years of age. This characteristic position is so important that when one is confronted by a tumour not in a long bone, the radiological diagnosis of osteoclastoma is much less reliable. Jaffe (1958) estimates that 15 to 20 per cent of cases occur elsewhere than in the long tubular bones. This agrees with Dahlin's (1957) findings in a large series of 109 cases containing nineteen not in long bones, of which five were in the pelvis, and eleven in the sacrum. Perhaps the most important points to be taken from the differing opinions on the distribution of these rarer tumours is that the spine is very rarely involved (contrary to earlier opinion) but the pelvis, including sacrum, is a more common site. The present series of twelve cases contained five which were not in the long bones (two in scapula, and one each in pelvis, metatarsal and skull). This high proportion probably reflects the exclusion of the more typical turnouts by selecting only those which were histologically examined. Although the margin of the benign osteoclastoma is always easily defined it is not a limiting line of bone sclerosis because there is no bone reaction to make it so. Any untreated tumour with a definite margin of dense bone between it and adjacent cancellous bone is therefore most unlikely to be an osteoclastoma. This is sometimes a useful point of differentiation from the variants. Other characteristics are less diagnostically useful. Trabeculation is fairly common but has
271
FIG. 4 Trabeculated (" soap bubble ") form of osteoclastoma.
sometimes been over-emphasised by describing a typical " soap bubble " appearance (Fig. 4). This is certainly not the usual form taken and as a descriptive term could be equally or better applied to some of the variants. When trabeculation does occur it seems to be related to degree of activity in that rapid growth destroys pre-existing trabeculae in the active region, but the tumour which is completely without trabeculation does not necessarily progress faster than one which is trabeculated. Eccentricity is sometimes described as a feature of osteoclastoma. In the common sites around the knee it does tend to grow into one or other condyle, but in other long bones eccentricity is doubtful and of little diagnostic value. Most of the variants are much more definitely eccentric than osteoclastoma. MALIGNANT OSTEOCLASTOMA It is generally believed that about 10 per cent are malignant. Malignancy of an osteoclastoma is not easy to define. They are all " locally aggressive " in varying degree, and some become frankly sarcomatous and metastasise as such, or with traces of their ancestry detectable in the metastases. Some pathologists argue that it is wrong to speak of malignant change and that these tumours are malignant from the start and that they should be classified as sarcoma. On the other hand, a few
272
CLINICAL
which metastasise have a " benign " histological appearance in both primary and secondary. When the ordinary benign osteoclastoma reaches the cortex it usually first expands the bone, maintaining a thin shell around it. Later it m a y " burst" through into soft tissue and at this late stage may cause a little periosteal reaction. The more aggressive tumours will break through the cortex earlier and more completely with less expansion, closely resembling a malignant tumour. This violent growth is not necessarily an indication of malignancy in the sense that metastases and death will shortly follow (Russell 1949). Figure 5 shows an osteoclastoma of this kind, a biopsy from which suggested malignancy. The hand was practically useless and the arm was amputated, but the patient has remained completely well for seven years. One other patient with a similar osteoclastoma has now survived for ten years without recurrence, and the girl of fourteen described previously remains well eight years after the lesion was first discovered. Still another osteoclastoma with this radiological appearance recurred three times, being successively treated by evacuation and cancellous chip grafts, radiotherapy, and total excision of the affected lower end radius with replacement by grafting in the lower fibula. The final recurrence in 1957 occurred in the soft tissue but since this was curetted the patient has remained well.
A
B FIG. 5 Rapidly growing osteoclastoma resembling a sarcoma.
RADIOLOGY
It cannot be denied that rapid soft tissue extension is very alarming and may necessitate drastic surgical excision, but these patients seem to have had very much better results than are expected from primary bone sarcoma. It is also well known to radiologists that an initial period of alarmingly rapid growth is not uncommon as a response to radiotherapy and this underlines the importance of a full knowledge of the clinical history. None of the present series have metastasised. Dahlin (1957) reporting eleven malignant osteoclastoma, stated that in eight the sarcomatous tissue had completely replaced the osteoclastoma known to exist previously and only in three was it possible to find any trace of the original benign tumour, and the radiographs did not differ from typical osteolytic sarcoma. If it is true that soft tissue extension fails to determine potentially metastasising tumours, the early diagnosis of malignant " change " seems to rest upon the difficult task of recognising loss of the normally well defined boundary against cancellous bone and mottled destruction spreading into the bone beyond. GIANT CELL T U M O U R VARIANTS Benign ehondroblastoma (Fig 6) is the name given by Jaffe and Lichtenstein in 1942 to the tumour previously regarded as a cartilaginous type of osteoclastoma. Among others, Codman had described some in the shoulder (which was his particular sphere of interest) as "epiphyseal
FIG. 6 Benign chondroblastoma in the epiphysis of the humeruS. Age twelve.
GIANT
CELL TUMOUR
OF B O N E A N D i T S V A R I A N T $
chondromatous giant cell tumours." While some still hold this view (Willis 1953) others follow the new interpretation as a distinctive tumour of the cartilage series. The basic tumour cell somewhat resembles those of the osteoclastoma but there are areas of chondroid material which tends to calcify. They are almost always in an epiphysis, and about 80 per cent occur under twenty years. Small in size as a rule, they occasionally grow to expand the cortex or spread to the metaphysis. A thin sclerotic margin surrounds the translucent centre which may appear faintly granular or show recognisable calcification. Malignant change has never yet been seen, and most are cured by simple curettage, but the primitive cartilage it contains may lead to an erroneous diagnosis of chondrosarcoma. A similar and possibly related tumour is the chondromyxoid fibroma which contains chondroid tissue but with myxoid and fibrous areas as well. Most occur before the age of thirty, thus overlapping the common age range of osteoclastoma, but tend like the simple cyst to occur in the metaphysis or further into the shaft instead of the extreme end of the bone. It presents as an ovoid eccentric " c y s t " either expanding the bone over the surface as a thin shell, or if this shell is absent, as a well defined " bite " out of the bone. The inner margin is sclerotic and usually scalloped. Illustrations of previously reported cases suggest that there is often a characteristic picture which should be recognisable. Figure 7 shows such a tumour discovered in a man of forty-five. Histology of the resccted specimen was originally said to be myxochondrosarcoma but on review after the patient had remained symptom free for nine years it was recognised as a chondromyxoid fibroma. Both these tumours contain cells which may lead the pathologist to suggest that they are chondrosarcoma or malignant osteoclastoma. This is a potentially serious error, since the benign chondroblastoma has never been known to become malignant (except after radiotherapy) and only once has it ever been suggested that a chondromyxoid fibroma became malignant (Iwata and Coley 1958). Many have been cured by curettage, but some recur, and local resection is preferable. A more common lesion is the small cyst-like area in the cortex around the knee of young children, the so-called metaphyseal fibrous defect. These are minor developmental defects which usually move away from the bone end as growth proceeds and ultimately disappear in the remodelling process. Occasionally they may persist or grow larger, and Lichtenstein (1959) and Jaffe (1958) still believe that these larger lesions discovered in older children C(16)
273
FIG. 7 Chondromyxoid fibroma. Visible punctate calcification in the tumour, but this is unusual. Age forty-five.
and young adults are true bone tumours which they jointly described in 1942 under the name of nonosteogenic fibroma of bone. Whatever may be the true nature of these related lesions, both have the same histological characteristics being composed mainly of spindle cell fibroblastic tissue or more mature connective tissue with some giant cells and occasional foam cells containing lipid. They are therefore sometimes mistaken for xanthomatous deposits or have been labelled " healing " or "xanthic giant cell tumours." These tumours have recently been fully reviewed in this journal by Purcell and Mulcahy (1960). Briefly the larger tumours, the " non-osteogenic fibroma," appear on the radiograph near, but not at, the bone ends, and are distinctly eccentric, lying in the cortex or subcortex tending to bulge the overlying bone. Considerable reactive sclerosis characteristically forms the inner margin and there is often a rather coarse bony trabeculation. The aneurysmal bone cyst may occur in any bone, but like most variants tends to occur before the age of twenty and to involve the metaphysis of a long bone. It also has a marked predeliction for the spine, a rare site for osteoclastoma. The cyst markedly expands the bone, pushing out a thin bony shell before it, in an eceerttric position almost
274
CLINICAL
on. the surface of the bone. The superficial, thinwalled cyst often looks like a large bubble on the bone. It contains large cavernous spaces from
Fro. 8 Aneurysmal bone cyst in metaphysis of humerus. twenty months.
Age
RADIOLOGY
which blood oozes at operation. There is little solid tissue and it may appear to be only a bloodfilled cyst from which material for biopsy is difficult to obtain. Sometimes thin bony strands form in the fine septa between the cavernous spaces causing a fine trabeculation on the radiograph. They are always benign and often cured by even an incomplete curettage, nevertheless early and adequate treatment is desirable because they can grow fast, causing considerable bone destruction if neglected. In the spine this may lead to neurological complications. Of the four cases known to us, three have been reported in detail by Taylor (1956). Two were in spinous processes, one in lower humerus, and the fourth (Fig. 8) was also in the lower humerus of a baby of twenty months. Discovered after a fall, it was opened to disclose a cyst containing blood, and was successfully treated by radiotherapy. Figure 9 shows another kind of spinal lesion originally diagnosed in 1947 as an osteoclastoma, although she was only thirteen. Beginning by expanding and then destroying a transverse process it was diagnosed as an osteoclastoma after biopsy, although the pathologist was rather doubtful and made special comment on the amount of osteoid tissue. It responded rapidly to radiotherapy by calcifying until it resembled a chondroma, most unlike the response expected from an osteoclastoma (Fig. 10). On review it is
Fm. 9 FIG. 10 Fro. 9--Osteogenic fibroma destroying transverse processes of lumbar spine. A few small bony nodules in the large soft tissue mass. Age thirteen. FIG. 10--Same tumour after treatment by radiotherapy, showing dense ossification.
G I A N T CELL T U M O U R OF BONE AND ITS V A R I A N T S
now realised that this is an osteogenic fibroma (benign osteoblastoma) a benign tumour characterised by its osteoblastic tissue, but which has been mistaken for osteogenic sarcoma or, as in this case, for osteoclastoma because of the stromal cells and giant cells it contains. These are rare tumours which have no characteristic radiological appearance. They destroy bone but sometimes distend it first, and the opacity of the tumour area depends on the degree of calcification or ossification of the osteoid tissue. Again it occurs in young people particularly aged ten to thirty, but unlike nearly all other turnouts it is most common in the spine where, like the aneurysmal bone cyst, it may cause neurological complications. The tendency to a spinal location of these two tumours is most striking in contrast to the osteoclastoma for which they may be mistaken. All these variants can be diagnosed provided they are considered at all, sometimes with considerable accuracy by the radiologist alone, but the radiologist and pathologist on occasion may find their interpretations at variance. Neither are infallible and in this field as in all others, close personal co-operation with a knowledge of their individual powers and limitations is necessary to achieve success and avoid potentially serious failure. SUMMARY The radiology of the osteoclastoma is reviewed, and attention is drawn to the " giant cell tumour variants." The purpose and possibility of differential diagnosis is discussed with illustrative examples
275
taken from a review of bone tumours collected from the Sheffield region. Aeknowledgements.--The material for this paper was collected in association with Dr J. Walter from many different places in the Sheffield region and I am indebted to very many people for offering it. Most of the cases come from the larger cemres, from Dr Wilkie and Dr Lodge (United Sheffield Hospitals), Dr Abbott (City General Hospital, Sheffield), Dr Mouat (Nottingham), Dr Forbes Lawson (Leicester) and Dr Miller (Doncaster). Beyond them one is indebted to all their associated clinicians and pathologists. The histology of the reported case of osteogenic fibroma was reviewed by Dr Dawson of Edinburgh University Pathology Department, the remainder by Professor Collins, Sheffield University, who took part in the symposium on which this paper is based.
REFERENCES CADE, S. (1949). or. Bone ,It. Surg. 31B, 158. DAHLIN, D. C. (1957). Bone Tumours. Oxford: Blackwell. IWATA, S., & COLEY, B. L. (1958). Surg. Gynec. Obstet. 107, 571. JAFFE, H. L., LICHTENSTEIN, L., & PORTIS R. B. (1940). Arch. Pathol. 30, 993. JAFFE, H. L. (1958). Tumours and Tumorous Conditions of Bones and Joints. London: Kimpton. LICHTENSTEIN,L. (1959). Bone Tumours. London: Kimpton. PLATT, H. (1949). or. Bone Jt. Surg. 31B, 157. PUGH, D. G. (1951). Roentgenologic Diagnosis of Diseases of Bones. Baltimore: Williams & Wilkins. PURCELL,W. M., & MULCAHY,F. (1960). Clinical Radiology, 11, 51. RUSSELL, D. S. (1949). or. Bone ,It. Surg. 31B, 281. STEWART, M. J., & RICHARDSON,T. R. (1952). J. Bone ,It. Surg. 34A, 372. TAYLOR, F. W. (1956). or. Bone Jr. Surg. 38B, 293. WILLIS, R. A. (1949). J. Bone .It. Surg. 31B, 236. WILLIS, R. A. (1953). Pathology of Tumours. London: Butterworth.
CELL
TUMOUR
OF BONE
AND
ITS
VARIANTS
LESLIE L. RALPH, M.B., CH.B., F.F.R.
Chesterfield Royal Hospital, Chesterfield OSTEOCLASTOMA, or giant cell tumour of bone, is a comparatively rare but well known tumour which usually presents no great diagnostic difficulties. A few are sufficiently atypical to make the diagnosis doubtful and the recent trend has been towards more critical analysis of these atypical tumours. Undue emphasis on the giant cell was partly responsible for the accumulation o f diverse lesions masquerading as osteoclastoma, but in a classic paper Jaffe, Lichtenstein and Portis (1940) laid down more stringent diagnostic criteria which are now generally accepted. Attention was thereby turned to the imitative lesions and over the last twenty years there have been a number of reports of newly recognised turnouts which superficially resemble osteoclastoma, radiologically or histologically, and are conveniently and collectively known as *' giant cell tumour variants." Opinions still differ concerning the validity and interrelationships of these variants, but they must now be considered in the differential diagnosis of osteoclastoma along with the better known alternatives. Although even more uncommon than osteoclastoma there are at least two reasons why they should be seriously considered. First, they are generally benign tumours which may be unnecessarily drastically treated. Secondly, the pathologist's difficulties in making up his mind about an odd-looking tumour of doubtful malignancy may be resolved by the intelligent cooperation of the radiologist. An attempt has been made to collect turnouts diagnosed as osteoclastoma from the Sheffield region. Preliminary sorting showed that many have been treated without pathological confirmation, and while most of them undoubtedly were true osteoclastoma there were others which were atypical. Review of the remainder where the histology was available, discovered a few which were " variants "leaving twelve histologically acceptable osteoclastoma, and one which remains doubtful.
any doubt that the bone is abnormal, and in the long bones the correct diagnosis is usually not difficult. In arriving at this diagnosis the simple considerations of the patient's age and site of the tumour are of the highest importance. At least 90 per cent occur between the ages of twenty and thirty-five, and it is particularly rare below the age of twenty. Conversely many of the lesions which simulate osteoclastoma commonly occur in younger people and it follows that one should not diagnose osteoclastoma under the age of twenty without full investigation, certainly never on radiological evidence alone. One of our series occurred in a girl of sixteen who complained of an increasing lump behind the mastoid for at least one year, and she had had an episode of diplopia at the age of thirteen. There proved to be a large tumour o f the petrous temporal and occipital bones which could not be completely removed and was treated by radiotherapy. Review of the histology has shown no reason to question the original diagnosis of osteoclastoma in spite of the early age and unusual site. The radiographs showed only the
RADIOLOGICAL DIAGNOSIS OF O S T E O C L A S T O M A FIG, 1 It is generally agreed that true osteoclastoma is a Osteoclastoma spreading into neck of femur well beyond limits bone destroying tumour which is almost always of of the epiphysis. Successfullytreated by curettageand cancellous considerable size when first seen. There is rarely grafts. 269
270
CLINICAL
RADIOLOGY
extent of bone destruction and were in no way diagnostic. The position of the tumours in the long bones is remarkably constant. They occur almost invariably at the ends reaching to the articular surface which may fracture, but the tumour rarely " bursts " through it. This position is sometimes described as " epiphyseal," usually to make the point of distinction from the bone cyst which arises in the metaphysis and " grows dowI1 the bone." Unfortunately it tends to suggest that it usually begins at an age when the epiphysis is a separate entity which is untrue, nor is the average osteoclastoma confined to the epiphyseal region in the adult. (Fig 1). Where in fact does an osteoclastoma begin in those rare cases discovered in adolescence ? Willis (1949) states that they begin in the metaphysis and only spread later to the epiphysis, a view which is upheld in an editorial in the same issue of the Journal of Bone and Joint Surgery by Cade (1949), and also later by Stewart and Richardson (1952). A second editorial in the same issue (Platt
1949) states the opposite view, emphasising this distinct diagnostic difference from bone cyst. There is no doubt that tumours said to be osteo. clastoma have been reported in the epiphysis or in the metaphysis, and the dispute revolves around the histological interpretation. Unless orte accepts the second view it is obvious that it is not so easy to distinguish the common bone cyst (in the metaphysis) from the rare juver~ile osteodastoma (possibly also in the metaphysis). One of our cases illustrates this. She was a gM of fourteen who presented with a tumour slightly expanding the metaphysis of the lower fibula (Fig. 2). The original biopsy diagnosis was osteoclastoma, growing actively and possibly not innocent. After responding by marginal sclerosis to radiotherapy, it recurred two years later in a very aggressive manner by destroying the surrounding sclerotic bone and cortex to form a soft tissue swelling (Fig. 3). A second biopsy now indicated sarcoma and the fibula and tumour were excised. The real nature of this tumour is unknown. Pugh
FIG. 2 Lesion in metaphysis of fibula originally treated as osteoclastoma by radiotherapy. Age fourteen.
FIG. 3 Same patient two years later, showing much more malignant appearance after initial response to radiotherapy.
GIANT
CELL TUMOUR
OF B O N E A N D I T S V A R I A N T S
(1951) illustrates a similar case which he describes as a " giant cell variant of bone cyst," a term introduced by Geschickter and Copland to cover certain rapidly growing cysts containing numerous giant cells. Professor Collins, who reviewed our cases, is inclined to doubt the original biopsy diagnosis since it was atypical. There is also the possibility that the radiotherapy may have caused the malignant change, yet in spite of this she remains perfectly well six years after excision. To the radiologist it looked and behaved exactly as many proved osteoclastoma do except for the unusual age and site. The aggressive growth and even the histological appearance of sarcoma with long survival was seen in other cases. Osteoclastoma sometimes occurs in bones which have no epiphysis, such as the skull. In the short tubular bones they usually follow the rule, by being at the epiphyseal end (Jaffe 1958), but the only one in a metatarsal in the present series was at the base. In spite of all this the simple fact remains that most osteoclastomata occur in long bones, and the overwhelming majority are then at the end and are found in patients over twenty years of age. This characteristic position is so important that when one is confronted by a tumour not in a long bone, the radiological diagnosis of osteoclastoma is much less reliable. Jaffe (1958) estimates that 15 to 20 per cent of cases occur elsewhere than in the long tubular bones. This agrees with Dahlin's (1957) findings in a large series of 109 cases containing nineteen not in long bones, of which five were in the pelvis, and eleven in the sacrum. Perhaps the most important points to be taken from the differing opinions on the distribution of these rarer tumours is that the spine is very rarely involved (contrary to earlier opinion) but the pelvis, including sacrum, is a more common site. The present series of twelve cases contained five which were not in the long bones (two in scapula, and one each in pelvis, metatarsal and skull). This high proportion probably reflects the exclusion of the more typical turnouts by selecting only those which were histologically examined. Although the margin of the benign osteoclastoma is always easily defined it is not a limiting line of bone sclerosis because there is no bone reaction to make it so. Any untreated tumour with a definite margin of dense bone between it and adjacent cancellous bone is therefore most unlikely to be an osteoclastoma. This is sometimes a useful point of differentiation from the variants. Other characteristics are less diagnostically useful. Trabeculation is fairly common but has
271
FIG. 4 Trabeculated (" soap bubble ") form of osteoclastoma.
sometimes been over-emphasised by describing a typical " soap bubble " appearance (Fig. 4). This is certainly not the usual form taken and as a descriptive term could be equally or better applied to some of the variants. When trabeculation does occur it seems to be related to degree of activity in that rapid growth destroys pre-existing trabeculae in the active region, but the tumour which is completely without trabeculation does not necessarily progress faster than one which is trabeculated. Eccentricity is sometimes described as a feature of osteoclastoma. In the common sites around the knee it does tend to grow into one or other condyle, but in other long bones eccentricity is doubtful and of little diagnostic value. Most of the variants are much more definitely eccentric than osteoclastoma. MALIGNANT OSTEOCLASTOMA It is generally believed that about 10 per cent are malignant. Malignancy of an osteoclastoma is not easy to define. They are all " locally aggressive " in varying degree, and some become frankly sarcomatous and metastasise as such, or with traces of their ancestry detectable in the metastases. Some pathologists argue that it is wrong to speak of malignant change and that these tumours are malignant from the start and that they should be classified as sarcoma. On the other hand, a few
272
CLINICAL
which metastasise have a " benign " histological appearance in both primary and secondary. When the ordinary benign osteoclastoma reaches the cortex it usually first expands the bone, maintaining a thin shell around it. Later it m a y " burst" through into soft tissue and at this late stage may cause a little periosteal reaction. The more aggressive tumours will break through the cortex earlier and more completely with less expansion, closely resembling a malignant tumour. This violent growth is not necessarily an indication of malignancy in the sense that metastases and death will shortly follow (Russell 1949). Figure 5 shows an osteoclastoma of this kind, a biopsy from which suggested malignancy. The hand was practically useless and the arm was amputated, but the patient has remained completely well for seven years. One other patient with a similar osteoclastoma has now survived for ten years without recurrence, and the girl of fourteen described previously remains well eight years after the lesion was first discovered. Still another osteoclastoma with this radiological appearance recurred three times, being successively treated by evacuation and cancellous chip grafts, radiotherapy, and total excision of the affected lower end radius with replacement by grafting in the lower fibula. The final recurrence in 1957 occurred in the soft tissue but since this was curetted the patient has remained well.
A
B FIG. 5 Rapidly growing osteoclastoma resembling a sarcoma.
RADIOLOGY
It cannot be denied that rapid soft tissue extension is very alarming and may necessitate drastic surgical excision, but these patients seem to have had very much better results than are expected from primary bone sarcoma. It is also well known to radiologists that an initial period of alarmingly rapid growth is not uncommon as a response to radiotherapy and this underlines the importance of a full knowledge of the clinical history. None of the present series have metastasised. Dahlin (1957) reporting eleven malignant osteoclastoma, stated that in eight the sarcomatous tissue had completely replaced the osteoclastoma known to exist previously and only in three was it possible to find any trace of the original benign tumour, and the radiographs did not differ from typical osteolytic sarcoma. If it is true that soft tissue extension fails to determine potentially metastasising tumours, the early diagnosis of malignant " change " seems to rest upon the difficult task of recognising loss of the normally well defined boundary against cancellous bone and mottled destruction spreading into the bone beyond. GIANT CELL T U M O U R VARIANTS Benign ehondroblastoma (Fig 6) is the name given by Jaffe and Lichtenstein in 1942 to the tumour previously regarded as a cartilaginous type of osteoclastoma. Among others, Codman had described some in the shoulder (which was his particular sphere of interest) as "epiphyseal
FIG. 6 Benign chondroblastoma in the epiphysis of the humeruS. Age twelve.
GIANT
CELL TUMOUR
OF B O N E A N D i T S V A R I A N T $
chondromatous giant cell tumours." While some still hold this view (Willis 1953) others follow the new interpretation as a distinctive tumour of the cartilage series. The basic tumour cell somewhat resembles those of the osteoclastoma but there are areas of chondroid material which tends to calcify. They are almost always in an epiphysis, and about 80 per cent occur under twenty years. Small in size as a rule, they occasionally grow to expand the cortex or spread to the metaphysis. A thin sclerotic margin surrounds the translucent centre which may appear faintly granular or show recognisable calcification. Malignant change has never yet been seen, and most are cured by simple curettage, but the primitive cartilage it contains may lead to an erroneous diagnosis of chondrosarcoma. A similar and possibly related tumour is the chondromyxoid fibroma which contains chondroid tissue but with myxoid and fibrous areas as well. Most occur before the age of thirty, thus overlapping the common age range of osteoclastoma, but tend like the simple cyst to occur in the metaphysis or further into the shaft instead of the extreme end of the bone. It presents as an ovoid eccentric " c y s t " either expanding the bone over the surface as a thin shell, or if this shell is absent, as a well defined " bite " out of the bone. The inner margin is sclerotic and usually scalloped. Illustrations of previously reported cases suggest that there is often a characteristic picture which should be recognisable. Figure 7 shows such a tumour discovered in a man of forty-five. Histology of the resccted specimen was originally said to be myxochondrosarcoma but on review after the patient had remained symptom free for nine years it was recognised as a chondromyxoid fibroma. Both these tumours contain cells which may lead the pathologist to suggest that they are chondrosarcoma or malignant osteoclastoma. This is a potentially serious error, since the benign chondroblastoma has never been known to become malignant (except after radiotherapy) and only once has it ever been suggested that a chondromyxoid fibroma became malignant (Iwata and Coley 1958). Many have been cured by curettage, but some recur, and local resection is preferable. A more common lesion is the small cyst-like area in the cortex around the knee of young children, the so-called metaphyseal fibrous defect. These are minor developmental defects which usually move away from the bone end as growth proceeds and ultimately disappear in the remodelling process. Occasionally they may persist or grow larger, and Lichtenstein (1959) and Jaffe (1958) still believe that these larger lesions discovered in older children C(16)
273
FIG. 7 Chondromyxoid fibroma. Visible punctate calcification in the tumour, but this is unusual. Age forty-five.
and young adults are true bone tumours which they jointly described in 1942 under the name of nonosteogenic fibroma of bone. Whatever may be the true nature of these related lesions, both have the same histological characteristics being composed mainly of spindle cell fibroblastic tissue or more mature connective tissue with some giant cells and occasional foam cells containing lipid. They are therefore sometimes mistaken for xanthomatous deposits or have been labelled " healing " or "xanthic giant cell tumours." These tumours have recently been fully reviewed in this journal by Purcell and Mulcahy (1960). Briefly the larger tumours, the " non-osteogenic fibroma," appear on the radiograph near, but not at, the bone ends, and are distinctly eccentric, lying in the cortex or subcortex tending to bulge the overlying bone. Considerable reactive sclerosis characteristically forms the inner margin and there is often a rather coarse bony trabeculation. The aneurysmal bone cyst may occur in any bone, but like most variants tends to occur before the age of twenty and to involve the metaphysis of a long bone. It also has a marked predeliction for the spine, a rare site for osteoclastoma. The cyst markedly expands the bone, pushing out a thin bony shell before it, in an eceerttric position almost
274
CLINICAL
on. the surface of the bone. The superficial, thinwalled cyst often looks like a large bubble on the bone. It contains large cavernous spaces from
Fro. 8 Aneurysmal bone cyst in metaphysis of humerus. twenty months.
Age
RADIOLOGY
which blood oozes at operation. There is little solid tissue and it may appear to be only a bloodfilled cyst from which material for biopsy is difficult to obtain. Sometimes thin bony strands form in the fine septa between the cavernous spaces causing a fine trabeculation on the radiograph. They are always benign and often cured by even an incomplete curettage, nevertheless early and adequate treatment is desirable because they can grow fast, causing considerable bone destruction if neglected. In the spine this may lead to neurological complications. Of the four cases known to us, three have been reported in detail by Taylor (1956). Two were in spinous processes, one in lower humerus, and the fourth (Fig. 8) was also in the lower humerus of a baby of twenty months. Discovered after a fall, it was opened to disclose a cyst containing blood, and was successfully treated by radiotherapy. Figure 9 shows another kind of spinal lesion originally diagnosed in 1947 as an osteoclastoma, although she was only thirteen. Beginning by expanding and then destroying a transverse process it was diagnosed as an osteoclastoma after biopsy, although the pathologist was rather doubtful and made special comment on the amount of osteoid tissue. It responded rapidly to radiotherapy by calcifying until it resembled a chondroma, most unlike the response expected from an osteoclastoma (Fig. 10). On review it is
Fm. 9 FIG. 10 Fro. 9--Osteogenic fibroma destroying transverse processes of lumbar spine. A few small bony nodules in the large soft tissue mass. Age thirteen. FIG. 10--Same tumour after treatment by radiotherapy, showing dense ossification.
G I A N T CELL T U M O U R OF BONE AND ITS V A R I A N T S
now realised that this is an osteogenic fibroma (benign osteoblastoma) a benign tumour characterised by its osteoblastic tissue, but which has been mistaken for osteogenic sarcoma or, as in this case, for osteoclastoma because of the stromal cells and giant cells it contains. These are rare tumours which have no characteristic radiological appearance. They destroy bone but sometimes distend it first, and the opacity of the tumour area depends on the degree of calcification or ossification of the osteoid tissue. Again it occurs in young people particularly aged ten to thirty, but unlike nearly all other turnouts it is most common in the spine where, like the aneurysmal bone cyst, it may cause neurological complications. The tendency to a spinal location of these two tumours is most striking in contrast to the osteoclastoma for which they may be mistaken. All these variants can be diagnosed provided they are considered at all, sometimes with considerable accuracy by the radiologist alone, but the radiologist and pathologist on occasion may find their interpretations at variance. Neither are infallible and in this field as in all others, close personal co-operation with a knowledge of their individual powers and limitations is necessary to achieve success and avoid potentially serious failure. SUMMARY The radiology of the osteoclastoma is reviewed, and attention is drawn to the " giant cell tumour variants." The purpose and possibility of differential diagnosis is discussed with illustrative examples
275
taken from a review of bone tumours collected from the Sheffield region. Aeknowledgements.--The material for this paper was collected in association with Dr J. Walter from many different places in the Sheffield region and I am indebted to very many people for offering it. Most of the cases come from the larger cemres, from Dr Wilkie and Dr Lodge (United Sheffield Hospitals), Dr Abbott (City General Hospital, Sheffield), Dr Mouat (Nottingham), Dr Forbes Lawson (Leicester) and Dr Miller (Doncaster). Beyond them one is indebted to all their associated clinicians and pathologists. The histology of the reported case of osteogenic fibroma was reviewed by Dr Dawson of Edinburgh University Pathology Department, the remainder by Professor Collins, Sheffield University, who took part in the symposium on which this paper is based.
REFERENCES CADE, S. (1949). or. Bone ,It. Surg. 31B, 158. DAHLIN, D. C. (1957). Bone Tumours. Oxford: Blackwell. IWATA, S., & COLEY, B. L. (1958). Surg. Gynec. Obstet. 107, 571. JAFFE, H. L., LICHTENSTEIN, L., & PORTIS R. B. (1940). Arch. Pathol. 30, 993. JAFFE, H. L. (1958). Tumours and Tumorous Conditions of Bones and Joints. London: Kimpton. LICHTENSTEIN,L. (1959). Bone Tumours. London: Kimpton. PLATT, H. (1949). or. Bone Jt. Surg. 31B, 157. PUGH, D. G. (1951). Roentgenologic Diagnosis of Diseases of Bones. Baltimore: Williams & Wilkins. PURCELL,W. M., & MULCAHY,F. (1960). Clinical Radiology, 11, 51. RUSSELL, D. S. (1949). or. Bone ,It. Surg. 31B, 281. STEWART, M. J., & RICHARDSON,T. R. (1952). J. Bone ,It. Surg. 34A, 372. TAYLOR, F. W. (1956). or. Bone Jr. Surg. 38B, 293. WILLIS, R. A. (1949). J. Bone .It. Surg. 31B, 236. WILLIS, R. A. (1953). Pathology of Tumours. London: Butterworth.