THE GIANT-CELL TUMOUR OF BONE

(With a report of six cases)

By V. S. HAR1HARAN, m.b., f.b.c.s. (Eng.) Surgeon, Ramakrishna Mission Hospital, Rangoon

Amongst all the controversies regarding the classification of osteogenic neoplasms, the giant- cell tumour, under one name or another, has always remained a distinct entity. In fact, the subject of contention in this connection has been the nomenclature of this distinct

variety of tumour formation in the bone which, though locally destructive, practically never

presents any of the general features of malig- nancy. It has been very widely known as the myeloma of bone, but to differentiate its

origin from the osteopoietic tissue of the bone as distinct- from the multiple myeloma arising from the hemopoietic tissue in the bone-marrow this term has been found to be rather unsatis-

factory. The appendage of sarcoma as in

myeloid sarcoma and giant-celled sarcoma is a misnomer and, besides leading to confusion, gives the tumour a serious prognostic outlook which is far from being correct. Osteoclastoma?the name recently suggested by M. J. Stewart?begs the question of the origin of the giant cells in the tumour, and, so long as this question as to whether they arise from the osteoclasts or the endothelial cell of the bone remains sub judicc, this nomenclature is rather unacceptable. The consensus of surgical opinion is that the term

giant-cell tumour suggested by the American

registry of bone sarcoma is satisfactory though not perfect, and among the other tumours of

the bone containing giant cell this remains a

distinct entity. The nomenclature is made more difficult

because of the lack of definite knowledge regard- ing its aetiology which is no exception to the

vexed question of the aetiology of tumours in

general. It occurs equally well in adult men

as well as women and is rarely known to occur in children. It has practically no causative

connection to trauma of any nature, though a

history of trauma is often obtainable. It is rather accidental than causative.

The giant-cell tumour may be periosteal arising from the periosteum of the upper or the lower jaw where it constitutes one variety of

epulis, or it may be medullary in type arising from the endosteum of the extremities of certain of the long bones such as the head of the tibia, lower end of femur, upper end of humerus, lower end of radius, upper end of fibula and occasion- ally at the sternal end of the clavicle. Rarely it is found to occur at the non-osseous sites such as the tendon sheaths, burssG and capsule of

joints. The endosteal form occurs in the dia-

physeal end of one of the long bones mentioned above, where the affected part is expanded to form a tumour of varying size. The tumour is somewhat rounded in shape, the bone appearing

152 THE INDIAN MEDICAL GAZETTE [March, 1937

to expand more or less equally in all directions or it may project more in one direction than the other. It is covered by periosteum and the bony shell underneath may be so thinned out that a sensation of egg-shell crackling is obtained on pressure with the finger. The cut surface usually exhibits a uniformly

dark-red appearance owing to its great vas-

cularity and the presence of blood clots. More

frequently it looks somewhat mottled like the cut surface of a pomegranate, the lighter areas indicating the sites of old and altered blood clots or of patches of degenerated necrotic tissue. With advancing degeneration, cysts containing a brownish fluid form inside the tumour. Round the periphery of the growth is a narrow zone

of more solid tissue, pinkish-white in colour, indicating a zone of more active tumour growth. This has a low local malignancy destroying the shell of overlying bone. New bone is formed from the osteogenic shells of the periosteum to form a new bony wall to the tumour. The bony shell of the tumour is thus re-formed from the

periosteum after destruction by the tumour

growth, or it is possible that it is the expanded remnant of what was once the wall of the normal

compact bone. The remains of the cancellous tissue may be represented by a few odd spicules of bone scattered irregularly in the pulp of the tumour. The periosteal variety grows from the alveolar

margin of the jaw in the form of a hard, more or less pedunculated growth covered by mucous membrane unless it is ulcerated.

Histologically, the tumour is made up of

spindle-shaped cells without hyperchromatic nuclei. But what catches the eye most is the

presence of large numbers of giant cells of different sizes, numerous in one part of the

microscopic field and scanty or absent in another. The giant cells possess numerous small oval nuclei situated towards the centre of the cells and not around the periphery as in tuberculosis. The cytoplasm is opaque, abundant, and baso- philic. These have the general characteristics of foreign-body giant cells and may be large osteoclasts or may be derived from the endo- thelial cells of the bone. No atypical forms are seen as in sarcomas. Numerous wide thin- walled blood vessels are seen with extravasated erythrocytes showing the tumour to be highly vascular. Some areas may reveal the remains of the osseous lamellse homogeneous in appear- ance and stained red by eosine, patches of myxomatous and fatty degeneration and areas

of necrosis with feebly-stained cells and degenerating nuclei.

Osteitis fibrosa cystica, first described by von Recklinghausen in 1891, seems to have a direct relationship to the giant-cell tumour of the bone. Cases have been described from time to time (like case 6 herein reported) where different portions of the same tumour present the typical appearances of the giant-cell tumour and of the

fibrocystic disease of the localized type. Cysts form in both conditions and typical giant cells, as in the giant-cell tumour, are often found in the walls of the cysts in the localized fibro-

cystic disease of bone. Typical giant-cell tumour is also known to arise from a previous case of localized fibrocystic disease, as is

probably the case in case 3 herein reported. Pathologically many American authorities, notably Ewing (1922), consider the giant-cell tumour as a separate variety derived from a

common condition?osteitis fibrosa cystica. Bloodgood (1910) and others consider the

fibrocystic disease to be essentially inflammatory in origin, i.e., a low-grade form of osteomyelitis. Or it may be one of the obscure disorders of calcium metabolism due to hyperactivity of the parathyroid glands. Phemister and Key (1933) suspect a low-grade infection and claim to have cultured the infective organisms from the cyst wall of some of their cases. The direct relationship between osteitis

fibrosa cystica and the giant-cell tumour, as

explained above, makes one agree with Barrie who considers the process in the giant-cell tumour to be inflammatory and not neoplastic, and to him it is a chronic hemorrhagic osteo- myelitis. Considerable evidence is also accumu- lating to show that the bone cysts and possibly the giant-cell tumours are due to the hyper- activity of the parathyroid glands. The condition is essentially chronic in nature.

The patient complains of slight fleeting pain, but never severe as in sarcoma, of a swelling in one of the usual sites of tumour, or he

may consult for a fracture of the bone due to some very trivial accident or violent muscular movement. Thus pain, swelling, or spontaneous fracture form the three essential symptoms of the condition. On examination, a tumour of varying size is

discovered in one of the usual sites of the

condition, towards the ends of the bones. It is more or less rounded in shape, situated more on the diaphyseal side of the end of the bone, though the epiphysial side may also be involved by the local destructive process. The articular

cartilage remains more or less intact and move- ments of the joint may be obtained but for the mechanical impediment due to the size of the tumour. The adjacent joint may contain slight fluid as a result of synovitis. The tumour may be hard, soft, or fluctuating giving an egg-shell crackling according to the extent of degenera- tive processes and bony destruction by the sub- jacent tumour growth. Blue telangiectatic veins may be present coursing over the sub- cutaneous surface of the tumour, caused by mechanical pressure of the tumour on the main venous channels, and rarely the tumour may be hot and pulsating due to the highly vascular nature of the tumour. More rarely still it may have ulcerated presenting a raw red fungating ulcer on the surface exuding a sanious fluid or

March, 1937] THE GIANT-CELL TUMOUR OF BONE : HARIHARAN 153

even blood and presenting a hemorrhagic appearance. The bone distal to the tumour is normal and there may be a fracture

at the site

the tumour. The distal portion of the limb is usually normal but may occasionally be

(edematous from venous obstruction. The

general condition of the patient is good except for any secondary infection from an ulcerated tumour. The urine is normal and does not

contain Bence-Jones protein, which is only found in cases of multiple myelomata and in some

cases of generalized fibrocystic disease.

A-ray shows the end of the bone expanded with the rest of the diaphysis normal and with no inflammatory periostitis round the tumour. rne expanded shell of bone may present varying grades of thickness with the lamell? of bone

traversing the matrix and dividing it up into

cysts of different size and number, giving the whole tumour a honeycombed appearance. The ower limit of the tumour appears rounded and cut off distinctly from the rest of the diaphysis. racture, if present, is detected by the discon- inuity in the length of the bone, and when the ?ny shell growth is notable, to keep up with

i, destructive process of tumour growth, the

siells of bone appear as islets of thinned out bone with discontinuity of bone surface. The diagnosis is rather difficult even with the

*elp of x-ray pictures. It has to be differ-

entiated from the other bone conditions of a

similar nature, such as the Brodie's abscess,

uberculosis, and gumma of the bone, the manv varieties of sarcoma, secondary carcinoma and he occasional hydatid cyst in the bones,

arely enough it may be mistaken for osteo- myelitis. A systematic examination together with x-ray will go a long way to help to arrive at the correct diagnosis of the condition. Diffi- culty arises in differentiating it from fibrocystic (Jsease because one may develop into the other 01 both may be associated together in the same condition. The treatment is essentially conservative in

nature. Local excision removes the growth, and

jn cases where portion of the compact bone can oe saved partial excision with thorough curet-

tage of the tumour tissue together with swab-

ojng the residual bony cavity with carbolic and alcohol or iodine will be sufficient to ensure a

permanent cure of the condition. Recurrences are rare or uncommon. Where the tumour occurs m single bones of the limb excision will leave ?e distal portion of the limb unsupported.

successful bone graft has saved ̂

many a limb in such cases. However this has o be considered more seriously in the case of le lower extremity where the question of

height-bearing has to be specially considered. u "en it is highly doubtful whether this will be

Possible, amputation of the limb will have to be resorted to, but in all cases amputation must oe regarded as a last resort. Even in cases of tne lower extremity conservative measures with

bone grafting, if necessary, may be given a trial in the first instance and amputation resorted to only if it proves a failure. The recuperative and compensatory processes of nature are well known to be far beyond the ken of human

judgment and it is always advisable to give the patient the benefit of the doubt. However

perfect an artificial limb may be it is hard to

compare it with nature's handicraft, not to

speak of the sentiments of the patients. How-

ever, in really hopeless cases there is no .use

stretching the argument to the extreme and

submitting the patient to the risks of operation twice. The surgeon's responsibility is thus enhanced in arriving at the correct decision in the matter of amputation. The following cases tend to throw some light

on some of the problems that present themselves to the surgeon when dealing with the varieties of this condition. Case 1.?Patient A., aged 18, male, was admitted into

the hospital in May 1933 with a tumour on the upper end of the left humerus. The duration of the disease was 13 months. He had slight pain, but not so severe as to interfere with his work. The tumour was large and rounded, of the size of a

tennis ball, occupying the whole of the upper end of the humerus including the epiphysial region. The surface veins were evident as blue lines coursing irregu- larly over the surface. There was slight pulsation on palpation as also egg-shell crackling. The rest of the humerus felt normal, as also the distal portion of the limb. There was slight limitation of movement at the shoulder only due to the size of the tumour. X-ray showed a typical giant-cell tumour of the

upper end of the humerus. The patient refused operation and absconded. Local

excision of the tumour with a bone graft from the tibia as in case 6, below, would have cured the disease and at the same time saved the limb. Case 2.?Patient B, aged about 36, female, was seen by

me in October 1933 on account of a fall she had and

consequent injury to her right knee. She had pain in the upper end of the tibia for about a year. She had consulted doctors who after proper examination and x-rays had diagnosed the condition as a giant-cell tumour of the upper end of the right tibia. On

examination the region of the knee joint was swollen and the skin discoloured. It was warm on palpation and there was distinct egg-shell crackling on the outer aspect of the upper end of the tibia in front of the head of the fibula. It was very tender and the knee joint was distended with fluid. There was rather free move- ment at the knee joint limited only by the synovitis and the tenderness due to the injury. There was slight cedema of the leg distal to the knee. X-ray showed a

typical giant-cell tumour on the upper end of the right tibia, with the shell of bone intact and with no fracture of the bone. The knee joint was aspirated and about two ounces

of thick blood-red fluid were removed. Lead lotion was

applied and the knee joint kept at rest. The inflamma- tion subsided gradually and the joint was kept at rest in a stiff knee cage and the patient not allowed to walk about. On further consultations the consensus of surgical

opinion was that amputation at the lower third of the thigh was the only safe treatment feasible because it was the tibia that was affected and that after any local excision there would not be proper support for the leg to bear any weight. The patient was averse to opera- tion of any sort and was much less willing for

amputation. However I advised a conservative operation in the

first instance and that the radical amputation could be

154 THE INDIAN MEDICAL GAZETTE [March, 1937

done if this were to prove a failure. After due consideration the patient consented to the operation and the further course of the case showed the wise move she had adopted. She was operated on in December 1933. The great

danger at the time of the operation is haemorrhage and the later danger is infection. The latter makes the healing process long and tedious and kills the bone graft, if any. All steps were taken to effectively prevent the advent of any secondary infection together with the no-touch-technique throughout the operation. A

tourniquet was applied to the middle of the thigh to control the haemorrhage and in fact at the end of the operation she had lost less than two drams of blood. Pure chloroform was used as the anaesthetic. Since the patient was very nervous there was no question of using local or spinal anaesthesia and since she had a

history of pleurisy and tuberculous glands in the neck ether as an anaesthetic was strictly avoided. An external linear incision four inches long was made

stretching downwards from the level of the knee joint. Particular care was taken not to open the joint. The bone was freely exposed and a shell of bone one and a half inches in diameter was punched out from the outer condyle of the tibia in front of the upper tibio- fibular articulation. The whole of the tumour-laden cavity was thus laid open. The tumour mass was

thoroughly scooped out until bare bone was felt in the

posterior medial and lower aspects. Towards the articular aspect the less hard articular cartilage was felt, and particular care was taken not to damage the

integrity and continuity of this. The whole cavity was then swabbed with phenol and then with rectified

spirit. A few chips of bone were chiselled out from the middle of the shin of the same tibia and these were

packed into the bony cavity left behind. A flap from the peroneal muscles was also separated distally and turned up into the cavity so as to fill in the same. The wound was sutured over in two layers with inter- rupted stitches and dressed. A back splint made of a plaster-of-paris slab was applied stretching from the middle of the thigh to the sole of the foot so that the knee and ankle joints were both immobilized. The tourniquet was then removed. The patient had an

uninterrupted recovery with a maximum temperature of only 99.5?F. for three or four days. The stitches were removed on the tenth day and the whole limb

put in plaster-of-paris casing from the middle of the thigh and including the foot.

Since it was rather uncomfortable the plaster casing was slit up two weeks later into two halves, upper and lower, and the limb still kept immobile. Two weeks later passive movements were started for the ankle joint and five days later for the knee joint also. In six weeks the patient was able to sit up in bed and move the joints herself, with the use of the back splint only at nights. In two months the splint was com-

pletely removed. The site of the tumour was hard to the touch and the outer condyle of the tibia felt hard and rounded. There was little or no pain. Medical diathermy and ultra-violet-ray exposures were given for about a week. She was allowed gradually to bear weight on the affected leg, first with the help of a

stick and later without it. Pathological examination of the growth removed at

the operation showed typical giant-cell tumour with no suspicion of malignancy at all. In June 1934 surface application of radium was made

so as to destroy by its radiations any more tumour tissue that might be present. X-rays have been taken every month or once in two months regularly and a

little honeycombing is found to persist on the outer

aspect. I am inclined to think that this is due probably to the muscle graft that has been put in. Deep x-ray therapy to the part will help a great deal to drive off

any more suspicion of recurrence of the tumour. Clinically, the upper end of the tibia is now hard

with no feeling of any cavity or thinned-out bone, and the movements of the knee joint are quite free. She is walking about now, climbs stairs by herself and is

just as strong on her leg as ever before.

Case 3.?Patient C., aged about 45, female, came to

the hospital in December 1933 with the history of her right leg giving way while climbing stairs and sprain- ing her thigh muscles. On examination there was a

fracture of the middle of the right femur and the

history was suggestive of a spontaneous fracture. X-ray confirmed the fracture with slight lateral displace- ment of the fragments. It further showed an area of rarefaction with cavities in the bone. There was no

primary malignant tumour anywhere and the patient was otherwise healthy. A tentative diagnosis of fibro- cystic disease was made and an operation advised. A local excision of the affected part of the bone on

both sides of the site of fracture was made and about three inches of bone thus removed. The ends of the bone were brought together and plated. The wound was closed in two layers and the limb put in plaster-of- paris casing including the hip and the foot. The patient had slight temperature of 100?F. for two or three days and had an uninterrupted recovery. In two months she was able to move the limb herself, with a shortening of three inches. The excised part of the bone showed five or six cysts

and the cysts wall showed on microscopic examination giant cells typical of giant-cell tumour. This i=

probably an instance where the condition started as a

fibrocystic disease and developed the tendencies of giant-cell tumour later on. The two are probably different appearances of the same pathological process and it is hard to know where one ends and the other begins. Further evidence is of course required for proot of this. She was walking about with the aid of crutches and

was advised to undergo another operation to shorten the femur of the opposite side. She refused however and was later lost sight of. Case 4.?Patient D., aged about 25, female, came to

the hospital in April 1934 with a haemorrhagic ulcer on the radial aspect of a swelling of the lower end of the right forearm. The duration of the disease was about six months. The tumour was pear-shaped and of the size of a small orange. It looked like a sarcoma of the lower end of the radius, but .r-ray showed an

expanded lower end of the radius with the rest of the diaphysis normal. There was discontinuity of the bony shell on the radial aspect where the ulcer was present. The ulna was normal in appearance. Her general con- dition was on the whole good. A tentative diagnosis of giant-cell tumour of the lower end of the radius was made. The ulcer was dressed with eusol for two or

three days and it was then clean. A week later a local excision of the tumour was done,

a bone graft four inches long from the right tibia was inserted and the limb put in a plaster-of-paris pad with the wrist dorsiflexed. The wound however got septic, the graft was dead and had to be removed. The septic wound healed in six weeks and the patient was

discharged with a deformed limb. No pathological examination of the specimen could be done. Two months later the patient came back again with

a sarcoma of the lower end of the ulna and the limb was then amputated at the lower third of the humerus. The initial tumour was a sarcoma to start with and

had probably affected the ulna also at the time; or the sarcoma of the ulna may be an independent process altogether. The lack of pathological evidence of the first specimen lgaves the whole thing in doubt. The bone graft should have been avoided at the time of the primary operation, because of the ulcerated condi- tion of the tumour and the impossibility of avoiding post-operative suppuration. Case 5.?Patient E., aged 18, male, was admitted into

the hospital in January 1934 with a swelling of the lower end of the left thigh and knee and with a sinus on the internal aspect of the knee exuding pus mixed with a sanious discharge. The history was as follows:?He had a feeling of

numbness in his leg for five months and there was also a swelling in the lower part of the thigh. One day he felt something breaking near the knee joint and was not able to move the joint after that. He went to a

March, 1937] CHICKEN-POX: WATS & DALAL 155

doctor who diagnosed the condition as an abscess probably due to osteomyelitis. He incised on the mnei aspect but could get only blood and no pus He dressed the case for a month and a half and sent him to the hospital. The sinus on the medial aspect was the result of the operation. He had also developed a bed sore over the posterior aspect of the sacrum. The whole part including the distal portion of the limb was hot, tender and oedematous and looked U cellulitis. He had a temperature of 103 F. on admission with a pulse of 130 per minute and his general condi- tion was very toxic. The swelling was of the size o a

big coco-nut, but the upper part of the femur was normal. Ihere was no pulsation of the tumour on palpation. 1 wenty cubic centimetres of blood-stained fluid wel(j aspirated from the knee joint. A large giant-celt tumour of the lower end of the femur with a Patho- logical fracture were seen on x-ray examination, Ine tumour had overgrown the limits of the bony se which only appeared as a few islets on the inner slde.

The condition of the patient was so precarious that the only idea was to save his life. The limb was

amputated at the middle of the femur and the flaps kept open. It was daily dressed with eusol, and anti- Sas-gangrene serum was freely administered to pi event spreading infection. The patient gradually came lound and on the 14th day after the operation the wound was closed with a side drain. He put on weight, the Wound and the bed sore healed and he was discharged nnnus his left leg seven weeks after his admission into the hospital. I have heard from him since and he is Quite well and has had no recurrence of the trouble. Case 6.?Patient F., aged 20, male, carpenter by

ino ' Was admitted into the hospital in October

ty34 complaining of pain and swelling in the upper thud oi the right arm. The history was rather interesting, seven years back he had a fracture of the upper third

the right humerus due to an injury. Three times alter that he had fractured the same bone at the same S"e due to a fall from a camel. This time he was trying l<-> throw a stick at a dog and felt his arm giving way at the same site.

. . '-'n examination there was a fusiform swelling in ths

J'pper third of right humerus extending to the head of the bone. There was also a distinct fracture at the site. ue shoulder joint was free. There was no temperature a.?d his general condition was quite good. It was istinctly a pathological fracture.

f. Tray showed a pathological fracture due to rare- action from a cystic condition of the bone. A tentative ?agnosia of fibrocystic disease of the humerus was made ana the patient advised operation.

, A local excision of the diseased portion of the

I one left only the head of the bone above and the

lower two-thirds of the humerus below with a gap of our inches in between. A bone graft four and a half Uches long was removed from the right shin and was put. into the medulla of the lower fragment below*

tv? mto a scooped out cavity on the distal surface of

^ upper fragment above. The wound was then sutured in three layers with interrupted stitches and dressed. The whole of the upper right extremity was , Rn put in plaster-of-paris casing with the limb in the ap ?l?^ane|' position. Pathologically the specimen removed showed distinct areas of giant-cell tumour and other areas of fibrocystic disease. The patient had a temperature of 101 ?F. for three days nu gradually came down to normal. He was able to

j and walk about in a week's time with the limb still n plaster. After six weeks the plaster was cut, the

sutures removed and the limb put up in the same posi- Jjon m a gutter-shaped plaster pad applied only to

6 Under aspect of the arm so as to support it, but the Patient was allowed to try to lift the limb up from the Pad once a day. Passive and active movements were started regularly a fortnight later. In another three j

eks the splint was left off and the patient instructed J? move the shoulder as much as possible with the nelP of the other hand, and to keep the arm to his

(Continued at jool of next column)

(Continued from -previous column) side while sleeping. X-rays were taken at regular intervals. The gralt was getting organized and the humerus becoming a solid whole. There was ankylosis at the shoulder joint and the movements of the head in the glenoid cavity of the scapula were getting restricted. However the scapular movements on the chest wall were making up for the loss of shoulder movements. He was discharged in May 1935 with no

pain and the movements fairly free, but for the limita- tions at the shoulder joint as explained above. He was able to lift things with the right hand and to do light work. He came back again three months later and showed that he was able to do more heavy work with that hand. He was looking forward to do his carpentry work.

Conclusions

1. The direct relationship between the giant- cell tumour and the localized fibrocystic disease is shown and both the pathological conditions

may be found in different parts of the same tumour.

2. The difficulty of differentiating the giant- cell tumour from an osteogenic sarcoma is

demonstrated, especially when the tumour has ulcerated on to the surface.

3. The appearance of sarcoma in the adja- cent bone after a tentative diagnosis and con-

sequent local excision of the giant-cell tumour in the other is described.

4. The possibility of saving the limb by means of a bone graft where otherwise the limb would have been amputated is proved.

5. The need for amputation still exists in

really hopeless cases.

N.B.?These cases were under my care when I was the Principal Medical Officer of Bikaner

State, Rajputana, India.

References

Bloodgood, J. C. (1910). Ann. Surg., Vol. LII, p. 145. Boyd, W. (1929). Surgical Pathology. W. B.

Saunders Co., Ltd., Philadelphia. Codman, E. A. (1926). Surg. Gyn. and Obstet.,

Vol. XLII, p. 381. Donaldson, R. (1931). Practical Morbid Histology.

William Heinemann, Ltd., London. Ewing, J. (1922). Arch. Surg., Vol. IV, p. 485. Key, J. A. (1933). Diseases of Bones and Joints.

Practitioners Library of Medicine, and Surgery. Vol. IV. D. Appleton and Co., New York. Kolodny, A. (1927). Surg. Gyn. and Obstet,

Vol. XLIV, p. 1. '

Love, R. J. M (1930). A Shorter Surgery. William Wood and Co., New York.

Ogilvie, W. H. (1929). Recent Advances in Surgery. J. and A. Churchill, London.