Giant-cell lesions of bone. Osteoclastoma and giant-cell tumour variants. Survey of a radiotherapeutic series

GIANT-CELL LESIONS OF BONE. OSTEOCLASTOMA AND GIANTCELL TUMOUR VARIANTS. SURVEY OF A RADIOTHERAPEUTIC SERIES*

J. WALTER, M.A., B.M., M.R.C.P., F.F.R., D.M.R.E. SheffieM National Centre for Radiotherapy, Sheffield, 10 " Let us n o t lightly cast aside things t h a t belong to the past, for only with the past c a n we weave the fabric o f t h e future." --Anatole France.

This paper records the experience at one centre, from 1936 to 1957, of cases referred for treatment bearing the label " Osteoclastoma." The modern clarification of the concept of giant-cell turnout of bone as a distinct pathological entity dates from the paper of Jaffe, Lichtenstein and Portis (1940). It has been a subject of perennial interest ever since. A recent discussion dealt chiefly with the standpoints of the surgeon (Eyre-Brook 1956) and the pathologist (Thomson 1956; Sissons 1956); both of these are highly relevant to, but not identical with, the standpoint of the radiotherapist, and it should be of interest to supplement the picture from the radiotherapist's angle. The material will also be found to throw some light on the diagnostic and therapeutic aspects of some of the many " giant-cell variants." These have been a fruitful source of confusion in the past--and continue still to be so--to surgeon, pathologist, and radiotherapist, as well as to the diagnostic radiologist. G I A N T - C E L L LESIONS The number of lesions in which giant-cells may be a more or less prominent feature is now considerable. To distinguish between them may be difficult, and it is easy to appreciate why the subject has been bedevilled by uncertainty. They include the following :-Osteoclastoma. Fibroma (medullary fibroma, osteofibroma, nonosteogenic fibroma, chondromyxoid fibroma). Giant osteoid osteoma (benign osteoblastoma). Chondroma. Benign chondroblastoma. Simple bone cyst. Aneurysmal bone cyst. " Brown tumours " of hyperparathyroidism. Fibrous dysplasia (osteitis fibrosa). Epulis (reparative granuloma). Osteogenic sarcoma.

Differential diagnosis rests on a combination of clinical, radiological and histological considerations. Biopsy is usually advisable, and in no field is the close collaboration of radiologist, surgeon, radiotherapist and ioathologist of greater importance than in the assessment of the high proportion of doubtful lesions of this type. T H E P R E S E N T SERIES All the cases of this series were originally referred as "osteoclastoma." Diagnosis was based on either radiological or histological evidence. The following break-down of the material is largely retrospective, made either on the later history or on a recent re-assessment of the pathological material. For this I am mainly indebted to Professor D. H. Collins.* Since the recognition and separation of several of these various lesions are of recent origin, and since there are still many details of pathogenesis, etc., that are obscure and debatable, it is not surprising that a retrospective survey should lead to drastic modifications of diagnosis. The same would presumably hold good for a comparable series elsewhere that went back as far as the present one, and our experience may therefore be of value to others in obtaining a sharper focus on a picture that has been so blurred. The final analysis gave the following diagnostic list.

No. of Cases Osteoclastoma 15 Simple cyst 3 Fibrous dysplasia 3 Giant-cell epulis 3 Aneurysmal bone cyst 2 Hyperparathyroidism 2 Benign osteoblastoma 2 Osteochrondoma 1 Osteogenic sarcoma 1 Grand total 32

* The pathological material was reviewed by Professor Collins in a separate c o n t r i b u t i o n to the s y m p o s i u m

(unpublished).

*Based on part o f a p a p e r r e a d at a Meeting of the Faculty o f Radiologists in Sheffield, October 1958. 114

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Thus, out of a total of thirty-two, barely half were finally accepted as true osteoclastoma. Some of these categories will now be surveyed in more detail. OSTEOCLASTOMA Table 1 gives details of the seven cases confirmed histologically, and Table 2 details of the eight cases where the diagnosis rests on radiological and clinical grounds only. The cases of Table 2 are therefore inevitably less valuable in a scientific assessment, though accepted here after careful review. Unfortunately, there is no " typical " radiological appearance. The classical " soap bubble " picture is far less c o m m o n than was formerly believed, and may be produced by other lesions (chondroma, fibrous dysplasia, fibroma, angioma, etc.). The site of the tumour, and changes in the cortex are probably of greater diagnostic value. Age is also important, and a diagnosis o f osteoclastoma in a patient much younger than eighteen to twenty must always be suspect. Dahlin (1957) states that when giant-cell variants are excluded, 90 per cent occur beyond the age of nineteen, and most of those in the second decade are nearly twenty. Lichtenstein (1959) concludes that genuine osteoelastoma is not often seen at under twenty

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years, and " the odds are very much against anyone who ventures a diagnosis o f giant-cell tumour in a child or an adolescent, published data to the contrary notwithstanding." It is always desirable to obtain a biopsy if possible, preferably by open operation. Needle or drill biopsies may sometimes be satisfactory, but many pathologists dislike them. This is especially so in bone lesions where it is usually desirable to study a larger section than can be obtained with a needle, particularly if it is desired to use a histological grading based on the stromal cells (Lichtenstein 1959). This type of biopsy can occasionally be seriously misleading, as shown in Case 2, where a drill biopsy soon after the conclusion of radiation treatment was reported as showing sarcoma, but this was not confirmed after amputation. Table 3 summarises the combined results.

Surgery or radiotherapy ? The relative merits of surgery and radiation are still controversial. Surgical resection has the advantage of greater speed and certainty, and where it does not involve disability or injury to a joint (e.g., fibula) it is probably the best treatment. Unfortunately the great majority of cases, like all of the present series, are unsuitable for primary excision.

T~LE1 OSTEOCLASTOMA--HISTOLOGICALLY CONFIRMED

No.

Sex

Age

Site

Histology

Dosage (DXR)

Result

1

F

28

Upper tibia

Positive on amputation

3,000 r in 3 weeks

Radiological improvement at 1 year, then deterioration with soft tissue invasion suspicious of malignancy. Amputation at 18 months; active growth and pathological fractures found. Well at 13 years.

2

F

34

Lower radius

Positive on amputation

2,400 r in 3 weeks

Drill biopsy just before DXR, reported sarcoma; therefore amputation at 1 month. Well at 8 years.

3

M

49

Ilium

Positive on amputation

4,350 r in 7 weeks (2,100 by DXR, 2,250 by cobalt beam)

Some improvement, but progress unsatisfactory to surgeon, therefore amputation at 6 months. Active growth found, locally invasive only. Well at 4 years.

4

M

34

Upper humerus

openP°Sitive'biopsy 3,000Afterr 14inmonths2 weeks 2,500 r in 2 weeks

Clinically well at 3~ years. Radiological improvement slow, still considerable cavitation (Fig. 3).

~ -

M

26

Lower femur

Positive, open biopsy

5,100 r in 4 weeks (cobalt beam)

Hardly any sclerosis radiologically (Fig. 2). Functionally satisfactory, limited flexion. Well at 2½ years.

6

F

48

Metatarsal

Positive~ open biopsy

3,000 r in 3 weeks (cobalt beam)

Clinically satisfactory. Radiologically, very little sclerosis (Fig. 4). Well at 2 years.

F

16

Skull--petrous, mastoid, occiput

Positive, open biopsy

3,100 to 3,700 r in 4 weeks. (Supervoltage--2 MeV).

Previous surgical removal of accessible part of growth, leaving considerable residue. Well at 2 years.

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RADIOLOGY TABLE 2

OSTEOCLASTOMA--NoT HISTOLOGICALLY CONFIRMED

No.

Sex

Age

Site

Dosage (DXR)

.I

Result

8

F

27

L o w e r radius

3,500 r in 3 weeks

9

F

37

L o w e r femur

10

F

52

Sacrum

A b o u t 2,500 r in 2 weeks

Well at 11 y e a i s

11

F

24

L o w e r femur

2,600 r in 2 weeks

Well at 10 years (Fig. 1)

12

M

61

Ilium

2,000 r in 3 weeks

Sclerosis with considerable residual trabeculation. Well at 6 years (then died of nephritis)

13

F

67

Ischium

3,500 r in 3 weeks

Well at 4 years

14

F

! 17

L o w e r femur

4,000 r in 3} weeks

Well at 4 years

15

M

i 35

L o w e r radius

4,000 r in 3~ weeks

Well at 2 years

~ R a d i o l o g i c a l c o n s o l i d a t i o n b e g a n at 3 months, excellent at .i 2 years. Well at 20 years.

2,300 r in 2k weeks; I Sclerosi s very slow therefore second course of radiation, after after 9 m o n t h s which sclerosis i m p r o v e d . Well at 13 years. 2,000 r in 2} weeks

I

TABLE 3 C O M B I N E D R E S U L T S - - C A S E S OF T A B L E S 1 A N D 2 TOTAL CASES--15

Histology ---No

Total

Clinically and radiologically satisfactory at two to twenty years Clinically satisfactory, but radiological progress uncertain

1

3

.

3

-

Operation after (failure of) r a d i a t i o n .

3 t

Curettage, combined with chemical cauterisation of the walls of the cavity, or packing with bone chips, is the most generally applicable of the surgical methods. It may be followed by radiation, though this combination has often been considered undesirable and liable to promote recurrence or increased aggressiveness. The evidence for this, however, is dubious, and the recent small series of Tudway (1959) shows good results in five out of six such cases. Criteria of progress after radiotherapy.--It is well recognised now that in the first few weeks following radiation treatment there may be apparent radiological deterioration due to decalcification, but this is normally followed by gradual healing with reossification. When good consolidation is achieved, one has no hesitation in accepting a cure. But there may be appreciable cystic residues with satisfactory clinical results, as exemplified in

Figure 1. It would be interesting to see the histological picture of such a residue, ten years after radiation--would there be any residual giant-cell tissue, and if there were, what significance should be attached to it? (Lichtenstein (1959, page 141) illustrates a lesion after radiation, with sclerosis and cavitation, where biopsy after seven years showed giant-cell tissue regarded as viable.) H o w long should one wait before pronouncing judgement as to the success or failure of treatment ? Cade (1955) states " The full benefit of radiation is achieved in about eighteen months." Whether this refers to the clinical or radiological picture, or both, is not specified, but there are such wide variations that it is sometimes very difficult to assess the degree of progress. This difficulty can obviously be of great significance to the clinician weighing the need for further treatment. Figures 2a and 2b show a lesion before and two and a half years after heavy radiation to 5,100 r (Case No. 5). Recalcification has here been minimal. Such cases, with little or no expansion of bone, are known to be apt to respond much more slowly and less satisfactorily than the expansive trabeculated type of lesion. But how long can one afford to wait? Further radiation would clearly be unwise; should the surgeon use a surgical approach, or should he be satisfied to observe ? - - a n d what are the risks of sarcomatous change ? Figure 3 shows another case (No. 4) where radiological improvement is very slow, though the clinical state is satisfactory. Figure 4 shows yet another lesion (Case No. 6) in a metatarsal, where the radiological picture at two

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L E S I O N S OF B O N E

117

FIG. 1A Osteoclastoma (Case No. 11 of Table 2).

Before treatment.

Fie. 1B Osteoclastoma (Case No. 11 of Table 2). Ten years after treatment; cystic residue.

Fro. 2A Osteoclastoma (Case No. 5 of Table 1).

Before treatment.

FIG. 2B Osteoclastoma (Case No. 5 of Table I). Two and a half year8 after treatment; cystic residue and slight sclerosis,

D(4)

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RADIOLOGY

FIG. 3A Osteoclastoma (Case No. 4 of Table 1). Before treatment (separate fracture b e l o w ) .

FIG. 3B Osteoclastoma (Case No. 4 of Table 1). Three and three quarter years after treatment; cystic residue with some sclerosis.

FIG. 4A Osteoclastoma (Case No. 6 of Table 1).

FIG. 4B Osteoclastoma (Case No. 6 of Table 1). Two years after treatment; cystic residue and poor sclerosis.

Before treatment.

GIANT-CELL

LESIONS

years is bound to cause some anxiety; should another course of radiation be advised? One hopes that the cases illustrated in Figures 2, 3 and 4 will be as well after ten years as that shown in Figure 1. Only a prolonged follow-up will provide the answers. It is in such cases that one can echo the sentiment of Coley (1949) : - - " There are few situations in the entire field of bone tumours which afford greater anxiety or which tax the judgement and intuition of the professional adviser more sorely than those cases of giant-cell tumour which fail to yield to radiation therapy." The problem of deciding whether a lesion has failed to yield to radiation therapy is clearly not always a simple one. Dosage.--Dosage varied between 2,000 r in three weeks and 4,000 r in four weeks by D.X.R. ; the cobalt beam was used for the whole treatment in two cases (Nos. 5 and 6)--5,100 r in four weeks and 3,000 r in three weeks; supervoltage (2 mV) was used in one case (No. 7)--3,100 to 3,700 r in four weeks. These doses are comparable with those in use at other centres, but there is a tendency to use higher doses than formerly, e.g., 3,000 to 4,000 r rather than 2,000 to 3,000 r, and also to prefer single to repeated courses. There can be little doubt that supervoltage or gamma-ray beams are preferable to deep x-rays at 200 to 300 kV, and are likely to be used wherever available. The difference in the energy absorption between soft and bony tissue is very considerable with the softer ray; the calcified parts m a y receive double the dose to the soft parts under D.X.R., but this difference is only about 10 per cent with supervoltage. Tudway (1959) recommends 4,500 r (supervoltage) in one course of four weeks. There have been no cases of malignant degeneration observed so far. Results.--Table 3 summarises the results to date. Radiotherapy was followed by surgery in three cases : No. 1 (Table 1).--Amputation was deemed advisable on suspicion of malignancy, and because the chances of a useful limb appeared remote in any event. Whether a second course of radiation, or a higher dose at first, would have made any difference, can be a matter only of speculation. No. 2 . - - A m p u t a t i o n would not have been performed so soon but for the misleading information from the drill biopsy. Radiation here did not therefore have the chance to show its effect. No. 3.--This was a large tumour, treated by 2 0 × 2 0 cm. fields, front and back, by D.X.R. at first, then by cobalt beam owing to the pigmentary D*(16)

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skin reaction. Possibly a shorter overall time might have had a greater biological effect. Cases No. 4, 5 and 6 are clinically well but radiological healing is very slow and uncertain so far (Figs. 2, 3 and 4). Summarising the effect of radiation, we may omit Case No. 2 and say that out of fourteen treated cases nine have made satisfactory clinical and radiological progress for two to twenty years, three have made good clinical but uncertain radiological progress at two to two and three-quarter years, while two have failed and come to amputation. S I M P L E B O N E CYSTS AND FIBROUS DYSPLASIA These may be considered together, as they are pathologically related. One of the monostotic types of fibrous dysplasia is probably an adult form of simple bone cyst that has come to be in the diaphysis as a result of growth of normal bone (Coley 1949). Many of these lesions are clinically

A Fibrous dysplasia.

FIG. 5 A - - B e f o r e treatment, after treatment.

B B - - F o u r t e e n years

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CLINICAL R A D I O L O G Y

silent. W h e r e active t r e a t m e n t is indicated, some f o r m o f surgery is the s t a n d a r d m e t h o d . R a d i a t i o n t r e a t m e n t has h a d its advocates in the past, b u t there are obvious objections to t r e a t i n g a nonm a l i g n a n t lesion, especially in a child, where d a m a g e m a y be done to an epiphysis, n o t to m e n t i o n the real, if remote, risk o f late sarcoma. T h e relative merits o f r a d i a t i o n a n d surgery in localised fibrocystic disease o f b o n e are discussed by A l l d r e d g e (1942); in fifteen cases treated b y r a d i a t i o n alone, there were no c o m p l e t e l y satisf a c t o r y results; p a i n was nearly always relieved, b u t even if the f u n c t i o n a l result was g o o d , there was usually residual cavitation, a n d some f o r m o f surgery b e c a m e i n d i c a t e d later in m a n y cases. There w o u l d p r o b a b l y be few n o w a d a y s to press the claims o f r a d i o t h e r a p y here, b u t there can be n o d o u b t t h a t m a n y cases have in the p a s t been treated b y r a d i a t i o n , u n d e r a m i s t a k e n histological o r r a d i o l o g i c a l diagnosis o f o s t e o c l a s t o m a . The case illustrated as o s t e o c l a s t o m a in C a d e (1952, pages 234 a n d 239), in a b o y t r e a t e d b y t e l e r a d i u m in 1937 at the age o f e i g h t - - t o o y o u n g to be a c c e p t a b l e n o w as o s t e o c l a s t o m a - - w o u l d a p p e a r to be o f this nature. A n illustrative case o f o u r o w n is as follows : Female, age thirty-seven. Painful lesion in right arm (Fig. 5a), 1943. It was explored, and a large cyst was found, filled with gelatinous fluid; the lining was curetted. Section

A Aneurysmal bone cyst.

A--Before treatment.

was r e p o r t e d as s h o w i n g c e l l u l a r growth, consisting chiefly

of spindle cells, with numerous giant-cells scattered throughout; a diagnosis of osteoclastoma was made. Progress was not satisfactory, and three months later D.X.R. was given-2,000 r by parallel opposed fields in two weeks. Re-calcification set in within four months, and the clinical result was-and still is--satisfactory. Figure 5b shows the state of the bone in 1957, i.e., fourteen years after treatment. Recent review of the section has established the diagnosis as fibrous dysplasia. In any event, a cystic lesion in the middle of a long bone would nowadays hardly be acceptable as osteoclastoma. O f the other five cases in o u r series, one received no t r e a t m e n t at all a n d r e m a i n s satisfactory to d a t e (fourteen years); o n e received D . X . R . (3,000 r) with no obvious r a d i o l o g i c a l change b u t has been clinically well for sixteen years. T w o received D . X . R . followed b y early surgery; one received 2,400 r to the h e a d o f the tibia, b u t progress was u n s a t i s f a c t o r y a n d a m p u t a t i o n was p e r f o r m e d . T a k i n g all six cases, therefore, we m a y say t h a t r a d i a t i o n t r e a t m e n t was used in five, b r o u g h t a b o u t a g o o d r a d i o l o g i c a l a n d clinical result in one patient, no definite benefit in two o t h e r patients, while its value p r e - o p e r a t i v e l y in two others was a l m o s t certainly negligible. GIANT-CELL EPULIS This lesion o f the j a w b o n e s is p r o b a b l y a reactive or r e p a r a t i v e g r a n u l o m a rather t h a n a n e o p l a s m ,

B F16. 6 B - - F o u r months after treatment.

c C - - F o u r years after treatment.

GIANT-CELL

L E S I O N S OF B O N E

but, owing to the frequency of giant-cells in the histological picture, has often been labelled " osteoclastoma," as in the present series. Surgical treatment is normally preferable, but radiation may be effective, as shown by two of our cases. One of these was a cystic lesion expanding the mandible in a woman aged fifty-five; D.X.R. was applied, to 2,000 r in eighteen days, and led to good sclerosis. The second case was in the maxilla of a girl aged fifteen; D.X.R. to 2,500 r in twentysix days proved satisfactory. The third case, in the maxilla of a girl aged twelve, was treated surgically. Radiation would probably not have been used if the true nature of the lesions had been recognised at the start. However, in the first of the above cases, surgery would have been relatively difficult and on retrospect radiation seems to have been a reasonable alternative. A N E U R Y S M A L B O N E CYST This is a lesion first described as a separate entity by Jaffe and Lichtenstein (1942) and has been gradually gaining increasing recognition since then. Its exact nature is uncertain; it may be due to a local circulatory disturbance with increased venous pressure causing engorgement and dilatation of the vascular bed, or it may be a type of cavernous haemangioma. It is worth noting that most cases occur at under twenty years of age, in contrast to true osteoclastoma. A recent discussion, reporting fifty cases, is by Lichtenstein (1957). It is perhaps not surprising that the lesion is not as widely known among radiotherapists as it deserves to be, and many cases must have been treated in the past as osteoclastoma, like the two in this series. The first case has already been reported with illustrations by Taylor (1956). It involved the spinous process of the atlas in a girl aged four. Treatment was by D.X.R. with a single posterior field, 6 cm. diameter and an incident dose of 2,000 r in thirty-three days. The size of the cyst increased following this, then recalcification set in; eight years later, the spinous process was larger than normal but well consolidated. The second case is as follows : Baby girl aged one year eight months. Painful elbow following a fall. Films showed a cystic lesion, ? osteoclastoma. A t operation, a cystic t u m o u r was found, containing blood; this was evacuated and the cyst swabbed out. Progress was not satisfactory, the lesion extended rapidly and after six weeks was referred for radiotherapy (Fig. 6a). Treatment was by D.X.R., opposed fields 8 × 6 cm., to a tumour dose o f 2,100 r in eighteen days. Clinical improvement was early. Figure 6b shows the lesion four months after radiation. Disability rapidly disappeared. Figure 6c shows the appearance after four years.

121

Radiation is clearly of great value in surgically awkward situations, as in the first case, or in the unusual event of surgical failure, as in the second. Only moderate dosage is needed; Lichtenstein (1957) suggests 1,400 r, with 2,000 r as the upper limit owing to the danger of late sarcoma. HYPERPARATHYROIDISM This syndrome is now well recognised, with its typical biochemical changes (raised serum calcium, lowered phosphorus, raised alkaline phosphatase, etc.). However, in the early stages, with attention focused on one region, biopsy may be misleading, as instanced by our own two cases; the histological picture may simulate that of osteoelastoma very closely indeed, and mislead even an experienced pathologist. The first patient, a woman aged forty, had an aspiration biopsy f r o m a lesion in the head of the humerus, which was reported as showing the typical structure of a giant-cell tumour of bone. X-ray therapy was considered, but multiple bony lesions were rapidly discovered, leading to the true

FIG. 7 Section of bone turnout from clavicle in hyperparathyroidism. Numerous prominent giant-cells. The picture is strikingly similar to that of osteoclastoma. ( × 136.)

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RADIOLOGY

A Fro. 8 A--Benign osteoblastoma (giant osteoid osteoma) arising from lumbar vertebra.

diagnosis. three, had which was (Fig. 7). A by D.X.R. ment. In appeared.

The other patient, a woman aged fiftyhad a clavicle excised for a tumour also reported as typical osteoclastoma lesion in the skull next year was treated (1,500 r) with symptomatic improvethe following year, multiple lesions

BENIGN OSTEOBLASTOMA Alternative names for this rare tumour are osteogenic fibroma and giant osteoid osteoma (Dahlin 1957; Lichtenstein 1959). It is a source of confusion especially as many of its features, clinical, radiological and histological, merge into ordinary osteoid osteoma and aneurysmal bone cyst (in addition to osteoclastoma and osteogenic sarcoma). It occurs typically in the first three decades of life, with a high incidence in the vertebral column (eight out of seventeen cases in the series of Dahlin (1957)).

B

B--Seven years after treatment.

Radiological appearances in the early stages are those of bone destruction, that may be well circumscribed, and may expand the periosteum to give a picture resembling that of aneurysmal bone cyst. In later stages, ossification gives an appearance as of osteoma, as in the first of our cases. Histological appearances are very variable and confusing, and it is not surprising that cases in the past have been considered to be osteoclastoma (giant-cells), osteogenic fibroma (actively proliferating connective tissue), osteoid osteoma, osteoma, osteogenic sarcoma, angioma (numerous dilated blood vessels), and aneurysmal bone cyst. Dahlin (1957) raises the speculation w h e t h e r " both of these two rather poorly understood processes (giant osteoid osteoma and aneurysmal bone cyst) are related, a possibility that is enhanced by the similar age and skeletal distribution and their similar response to therapy." Treatment should be conservative, as the lesion is benign. Surgical removal or curettage may be

GIANT-CELL

L E S I O N S OF B O N E

FIG. 9 Section of turnout arising in lumbar vertebra--benign osteoblastoma (giant osteoid osteoma). Note the cellularity, osteoid tissue and giant-cells. ( × 78.)

123

Fm. 10 Section of tumour from mandible--benign osteoblastoma (giant osteoid osteoma). Cellularity, osteoid tissue and giant-cells resembling picture of Figure 9. ( x 194.)

appropriate, and even incomplete removal may be followed by cure. Lesions involving the spinal column may raise special problems. It is difficult to evaluate the usefulness of radiotherapy. Dahlin (1957) considers that there is no good evidence that it is helpful. In our own two cases, radiation was used, though the true pathology was not recognised at t h e time, and the results have been satisfactory so far. CASE REPORTS Case 1 . - - A girl aged thirteen complained o f low back pain for a year. A swelling was noted in the angle between lumbar spine and pelvis. X-ray films (not n o w available) are said to have shown a destructive lesion in the transverse process of L.5. A biopsy was taken, a n d " giant-cell t u m o u r " reported. D . X . R . was given, with two opposing fields, to a t u m o u r dose o f 1,250 r in three weeks, and a further course three m o n t h s later, to 1,800 r. The turnout became progressively calcified and Figure 8 shows the appearance seven years later. A t this time the patient m a r r i e d and although there were fears of sterility a child was born. Figure 9 shows the microscopic picture. Case 2 . - - A boy aged ten presented with a rapidly enlarging t u m o u r of the ascending ramus of the mandible. A biopsy was taken and a histological diagnosis was made of " o s t e o g e n i c sarcoma with a b u n d a n t o s t e o c l a s t s " (Fig. 10). Treatment was by D.X.R., to a t u m o u r dose o f 3,000 r in three weeks. Regression followed a n d the clinical result is

FIG. 11 Benign osteoblastoma (giant osteoid osteoma) in ramus of mandible. Two years after treatment.

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satisfactory seventeen years later. Figure 11 shows the radiographic picture two years after treatment. SUMMARY A series o f t h i r t y - t w o cases is r e v i e w e d , all originally considered to be osteoclastoma. Fifteen a r e a c c e p t e d as g e n u i n e o s t e o c l a s t o m a , t h e r e s t assigned to various categories of " giant-cell tumour variant." Some problems in the radiation treatment of osteoclastoma are discussed, and detailed results of the cases given. The following " variants " are also discussed, with special reference to their radiation treatment :--simple cyst and fibrous dysplasia, g i a n t - c e l l epulis, a n e u r y s m a l b o n e cyst, t u r n o u t s i n h y p e r p a r a thyroidism, benign osteoblastoma (giant osteoid osteoma).

Acknowledgements.--My grateful thanks for help on the pathological side are due to Professor D. H. Collins and on the radiological side to Dr L. L. Ralph (Chesterfield) who contributed the radio-diagnostic part of the symposium. I would also thank M r L. R. Reeves, F.I.M.L.T., for the microphotographs, Mr N. S. Morton, M.S.R., C.T., for the

radiographs and Mrs Ruth Martin for secretarial assistance. I acknowledge also the kind help of the University Departments of Pathology of Edinburgh and Leeds, by the loan of sections. REFERENCES ALLOREDGE, R. H. (1942). J. Bone Jr. Surg. 24, 795. CADE, S. (1952). Malignant Disease and its Treatment by Radium, 4 vols., 2nd ed. Bristol: Wright. CAPE, S. (1955). In British Practice in Radiotherapy. Ed. CARLING,Sir Ernest Rock, WINDEYER, B. W., & SMITHERS, D . W . London: Butterworth. COLEY, B. L. (1949). Neoplasms o f Bone and Related Conditions. New York: Hoeber. DAHLIN, D. C. (1957). Bone Tumors. Springfield: Thomas. EYRE-BROOn, A. L. (1956). Proe. roy. Soe. Med. 49, 409. JAFFE, H. L., & LICHTENSTEIN,L. (1942). Arch. Surg. 44, 1004. JAFFE, H. L., LICHTENSTEIN, L., & PORTIS, R. B. (1940). Arch. Path. 30, 993. LICHTENSTE1N, L. (1957). J. Bone ,It. Surg. 39A, 873. LICHTENSTEIN, L. (1959). Bone Tumours, 2nd ed. St Louis: Mosby. SlSSONS, H. A. (1956). Proc. roy. Soe. Med. 49, 416. TAYLOR, F. W. (1956). J. Bone .It. Surg. 38B, 293. THOMSON, A. D. (1956). Proe. roy. Soc. Med. 49, 414. TUDWAY, R. C. (1959). Brit. J. RadioL 32, 315.

BOOK REVIEW Radioisotope Techniques in Clinical Research and Diagnosis. By N. VEALL and H. VeTTER. (1958.) Pp. 417. London: Butterworth & Co. Ltd. 50s. A great many books covering the diagnostic uses of radioisotopes are now available. It is questionable whether there is any need for a new publication, but this addition to an overcrowded list is fully justified for one reason alone. It is without doubt the most outstanding publication on the subject at present available for the clinical worker. Even a book of such high quality is liable to have weak points and the following criticisms are emphasised in the hope that the second edition will surpass the high standard set by the first. The authors have clearly intended to cover all the important investigative aspects of radioisotopes. This is indicated by the title, and suggested in the foreword by D r Seligman. In this they have succeeded admirably. They refer in the General Introduction to " The brief chapter on isotope t h e r a p y . . , written on the assumption that this is a specialised field of medical practice, which in any case is adequately covered elsewhere." This assumption is correct, and it is useless to try to cover the subject in ten pages. The limitations imposed by such a lack of space can lead to dangerous over-simplification, and to the appearance of false generalisations. For example, when referring to the treatment of thyroid cancer, it is stated that patients should be kept myxoedematous until a radio-iodine uptake can be demonstrated. If the turnout is poorly differentiated this procedure is a complete waste of time, and the patient will be unnecessarily distressed by the symptoms of hypothyroidism. If the tumour is well differentiated, this may be dangerous, encouraging the development of a rapidly growing, highly malignant cancer. This chapter should be omitted. In the space of twenty chapters, the authors cover all the important aspects of their subject. The first half of the book

deals with the general problems behind all radioisotope investigations, and these chapters are remarkably clear. Physical and physiological principles which could easily have been confusing, are completely comprehensible. N o t all the chapters make good light reading but none of them appear so formidable when compared with similar chapters in other books. Excellent line drawings are used to illustrate " Radiation detectors " and the diagrams in " Some simple dynamic systems" cannot fail to make intelligible the physiological facts underlying these techniques. The last chapters are devoted to the investigation of specific groups of problems. They are all good, and some are outstanding. The latter i n c l u d e " Body composition and electrolyte studies" (seventy-six references), " T h y r o i d function and localisation studies " (eighty references), and " Circulation studies." A failing common to all books of this type is that little or no attempt is made to compare diagnostic isotopic procedures with the various routine tests that have become established over the years in hospital laboratories. This is particularly so in the " Localisation and differential diagnosis of malignant tumours." The microscopic diagnosis of malignant melanoma is occasionally difficult, but the errors are very much smaller than those encountered when attempting to make the diagnosis with radioisotopes. A negative p32 test will give little comfort at a later date to the patient dying with widespread bony metastases, and more emphasis should be laid on the relative value of these investigations. The authors are to be congratulated on producing such an easily understood, comprehensive and compact volume. The references are excellent. The production is first class and the price reasonable. To all those interested in this particular subject, it can be recommended unreservedly as an outstanding book.--A. M. JELLIFFE.