Clear Cell Chondrosarcoma of Bone

Purpose. Clear cell chondrosarcoma is a rare variant of chondrosarcoma. Six cases are herein reported. Subjects. We have treated six patients with clear cell chondrosarcoma in the past 28 years, representing 1.6% of all chondrosarcomas seen in this time period. Results and Discussion. Half the patients had been initially underdiagnosed and inappropriately treated. Conclusions. Our results and our review of the literature highlight the fact that inadequate initial treatment leads to a high rate of both local recurrence and metastasis whilst wide initial excision is usually curative.


Introduction
Clear cell chondrosarcom a is a very rare m alignant bone tum our. It was initially described by U nni et al. in 1976, 1 and was called`C lear-cell Variant of Chondrosarcom a' . U p to that time, the tum our had usually been m istaken for a benign tumour. Because of it's rarity this lesion is still being confused with benign or m ore m alignant bone tum ours, both radiologically and histologically. We have reviewed our experience in treating clear cell chondrosarcom a at the Royal O r th o p a ed ic H o sp ital, B ir m in gh a m , w ith th e advantage of m odern m ethods of diagnostic im aging and lim b-salva ge surgical techniques.

Patients and m ethods
We have undertaken a retrospective review of all patients with clear cell chondrosarcom a treated by the Royal O rthopaedic H ospital Oncology Service, Birm ingham , UK . D ata has been retrieved from the depar tmental com puterised database supplem ented by reviews of the case notes, and histological and radiological studies. Since 1970, six such cases have been treated, representing 1.6% of the 370 cases of chondrosarcom a registered at our centre in the last 28 years. F ive patients were m ale, and one was fem ale. Their age ranged from 15 to 45 years. T he predom inant clinical presentation of the tum our was local pain in the affected bone of variable duration. Further clinical details are m entioned in Table 1.

Radiog raphic features
Initial radiographs were available for review in four of the six patients (Table 1). All the tum ours were situated in the epiphyseo-m etaphyseal area of the long bones.T he most com mon radiographic features were; an expansile radiolucent bony lesion, absence of any periosteal reaction and absence of soft tissue m ass (Fig. 1). M agnetic resonance im ag ing (M RI) was obtained for two patients. O n T1-weighted im ages, the lesion showed relatively hom ogeneous low to interm ediate signal intensity, and heterogeneous high signal intensity on T2-weighted im ages (Fig. 2).

Pathological features
O n gross histolo gical exam ination , the tu m ou rs showed a lobulated m ixed soft and solid lesio n, com posed of glassy tissue. O n microscopic exam inatio n , fain t m icro lo bu lar a n d o steo b la st om a-lik e features predom inated on low -p ower exam ination (Fig. 3). The constant feature was the presence of large tumour cells, round-to-oval in shape with distinct borders, abundant clear cytoplasm and a centrally located round nucleus (Clear Cell Chondrocytes). 2 M itotic features were rare, and occasionally these cells showed eosinophilia. The other predom inant feature was woven bone trabeculae within the m icrolobules or scattered between sheets of tum our cells. M ultinucleated giant cells were seen in all tum ours. T here w as variable car tilage m atr ix prod u ction . Alive with disease Imm unohistochem ical analysis revealed the tum our cells were strongly positive to S-100.

Treatm ent and results
T he clinical follow-up ranged from 12 m onths to 20 years (Table 1). T hree patients in our study were given`inappro priate' treatm ent at the referring institutions due to a m istaken provisional diagnosis of a benign car tilaginous tum our. O ne of these three patients had curettage of a tum our in her ilium for what was thought a chondroblastom a. She developed local recurrence after 34 m onths which was treated by further curettage. W ithin 4 m onths, she developed a rap id-g row ing local re cu rren ce o f th e tum our spreading to the whole hem i-pelvis. Further biopsies then revealed the diagnosis of clear cell chondrosarcom a. T he patien t w as offered radical su rgical treatm ent (am putation ) w hich she d eclined in o rder to keep her leg. S he u nderwent a fu r ther two-stag e curettage of her tum our and bone cem ent im planted in the defect. F ive years later, an other recu rrence was treated by hind quarter am putation . E ight years afte r the am pu tation, she is still alive and free of disease. T he second patient was diagnosed initially as a case of chondrom yxoid ® brom a of the distal fem ur which was treated by curettage. After 63 m onths he developed a local recurrence treated by above-knee am putation following revision of the diagnosis to clear cell ch o nd ro sarcom a. S ix m on th s fo llow in g the amputation he developed lung m etastases and died shortly after that.  T he other three patients all had the correct initial diagnosis of clear cell chondrosarcom a m ad e on presentation. All had prim ary wide resection of the tum our with satisfactory outcom es (Table 1). O ne of these three patients had a prim ary resection and endoprosthetic replacement of his proximal femur in 1977. In 1996 he had revision surgery for aseptic loosening of the acetabular com ponent of his prosthesis, and the histological study of the`curettage' taken from the ac etabu lum showed n o m align an cy. In early 1997, the patient star ted to show evid ence of local recurrence of the tum ou r in the ipsilateral iliu m . H e und erwen t en -blo ck excision of the iliu m w ith a w id e m ar g in an d reco n str u ctive p ro ced u re fo r h i s h em i-p e lv i s. T h e h is to lo g y r e p o r t o f t h e resected spe cim en con ® r m ed the diagno sis of clear cell chon dro sarc om a, recurrin g 19 years follow in g the in itial treatm ent. H e re m ains d isease -fre e two ye ars later.
In summ ary, six patients were included in this study. Three patients had m is-diagnosis of the tum our and treated with intra-lesional procedures. This resulted in two local recurrences, and one death due to lung metastasis. T he other three patients in this study had correct diagnosis and app ropriate treatment initially for the tum our resulting in good outcom es.

D iscussion
C lear cell chondrosarcom a was described by U nni et al. in 1976 w hen they published a series on 16 patients. 1 It is a ver y rare m alignant bone tum our, comprising 1.6± 5.4% of all chondrosarcom a, 3± 5 0.2% of biopsy-an alysed prim ar y bone tum ours. 2 Various suppositions have been m ade regarding the source of this tum our. Som e considered that the m ost likely source of this rare chondrosarcom a variant is the sam e group of cells that give rise to chondroblastom a. 2 O thers suggested that it m ay represent the m alignant counterpart of chondroblastom a. 6 The age at initial presentation ranges from 13 to 85, although m ost patients will be in their third to ® fth decades. T here is a m ale pre dom in an ce o f 1.6± 2.6:1.
3,4 Clear cell chondrosarcom a involves the proxim al end of the long bone in 75% of the cases (60% fem ur, 15% hum erus), 15% around the knee (distal fem ur and proxim al tibia). In about 10% , the lesion has been noted in the skull, spine, ribs, pelvis, ulna or phalanges. 3 There have been case reports of clear cell chond rosarcom a involving m ore than on e bo n e. 1 C lin ically, th e m ost co m m on pre se n ting sym ptom is local pain of lon g du ration . Bjor nsso n et al. m en tion ed in his series of 47 cases, the larg est ser ies pu blished, th at 55% o f the p atien ts had sym ptom s lastin g for m ore than 1 year be fore their presentation . 3 O the r frequ ent form s o f pre sentation were swellin g, various disabilities affe ctin g the adjacen t joint and patholo gical fra ctures (from 2% 2 to 37% 1 ). Som e of the other s were asym ptom atic and the lesion d iscovered as an incid ental ® n din g on plain x-ray.
Radiographically, when the tum our affects the long bone, the lesion is alm ost alw ays located in the The`Average' is obtained by dividing the sum of patients who had the speci® c complication (e.g. local recurrence) reported in those series by the total number of patients in either of the m ain groups (i.e. adequate or inadequate treatment group), multiplied by 100.
epihyseal area with or without extension to the m etaphysis. Ver y few cases are repor ted w ith tum our extending to or located entirely in the diaphysis. 3,7 T he m ost com m on radiographic features on plain X-ray, as described in this study and the previous literature, 1± 4,7 are; radiolucency (83% ), expansion of the bone (75% ), densi® cation/calci® cation (45% ), a border between tumour and host bone with or without sclerotic rim (49% ), cortical involvem ent, often in the form of thinning (71%), the cortex was intact in the m ajor ity of cases and periosteal reaction (3% ). Soft tissue m asses are ver y rare (less than 10% ). O n com puted tomography (CT ), the appearances are sim ilar to those seen on plain X -ray but CT is m ore sensitive at detecting calci® cation and cortical involvem ent. 8,9 The m agnetic resonance im ag ing (M RI) of th is tu m o u r ten d s to sh ow a w ell d em a rcated geograph ic lesion with interm ediate signal intensity on T 1-weighted im ages, and a higher signal intensity on T2-weighted im ages. 10± 12 All these features are n o n sp eci® c. D iff eren tia l d ia gn o ses freq u en tly reported include chondroblastom a, giant cell tumour, chondrom a, chondromyxoid ® brom a and cysts. If the tumour showed any m alignant features, the differential diagnoses include osteosarcom a, m alignant ® brous histiocytom a and ® brosarcom a. T he slow-g row ing nature of clear cell chondrosarcom a and the app arently benign radiographic and histological appearances in the m ajority of cases often results in difficulty in diagnosing the tum our at an early stage, with subsequent provision of conservative treatment. Various treatment m odalities were used with fairly consistent outcom es throughout m any publish ed series. Intra-lesional surgical rem oval of the tumour (e.g. curettage, incomplete excision) yields an u n accep tab ly h igh lo ca l recu r ren ce o f approxim ately 83 1 to 86% , 3 and death rate from 29 3 to 50% . 1 In contrast, com plete surgical rem oval of the tum our with a wide m arg in of disease-free tissue (e.g. en-bloc resection, primary am putation) has given a lower local recurrence rate of less than 15% , 3 and m u ch lo w er d eath r ate. 1,3,5 R ad io th erap y w as employed as an initial treatm ent with som e claim ed local control but poor outcom e. 1,3 Am putation was u sed in a few patien ts, u su ally w hen the in itial diagnosis was incorrect and hence am putation was a salvage procedure. 1,3 From our experience in this study and from the larger published studies, 1,3± 5 we con® rm that inadequate treatment (e.g. curettage, incom plete excision, radiotherapy and chem otherapy as a prim ary treatment) certainly yields a poorer result compared with the adequate treatment (en-block excision of the tumour as a prim ary treatment) summarised in Table 2. O nly patients with adequate follow-up information are considered in this table for comparison.

Conclusion
Clear cell chondrosarcom a is a low -grade and slowgrowing tum our. C ure can be achieved by wide local excision in the m ajor ity of cases. Awareness of the condition and the diagnostic pitfalls will help im prove both detection and survival.