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The Journal of Bone and Joint Surgery 79:1545-51 (1997)
© 1997 The Journal of Bone and Joint Surgery, Inc.

Case Report

Dedifferentiated Chondrosarcoma in Albright Syndrome. A Case Report and Review of the Literature*

TOSHIFUMI OZAKI, M.D.{dagger}, NORBERT LINDNER, M.D.{ddagger} and SEBASTIAN BLASIUS, M.D.{ddagger}, MÜNSTER, GERMANY

Investigation performed at the Department of Orthopaedics, University of Münster, Münster


   Introduction
Top
 Introduction
Case Report
 Discussion
 References
 
Fibrous dysplasia is a developmental condition in which the skeleton fails to mature normally. Albright syndrome, which was first reported in 1937 by McCune and Bruch23 and by Albright1, is characterized by polyostotic fibrous dysplasia, endocrine disorders, and brown patches on the skin (café-au-lait spots)3,17,25. It is seen more often in female than in male patients35. Malignant transformation in fibrous dysplasia was noted, in 1945, by Coley and Stewart5, and since then it has been reported in more than 100 patients12,19,33,43. The most common secondary malignant lesion in fibrous dysplasia is osteosarcoma, followed by fibrosarcoma and chondrosarcoma6,9,15,18,33,42. The prevalence of malignant transformation in fibrous dysplasia is only 0.4 per cent (six of 1517 patients)36. However, the prevalence of malignant transformation in Albright syndrome is 4 per cent (four of 100 patients36), which is higher than that in other forms of fibrous dysplasia36. To our knowledge, we are the first to report the case of a patient who had a dedifferentiated chondrosarcoma secondary to Albright syndrome.


   Case Report
Top
 Introduction
 Case Report
Discussion
 References
 
A fifty-two-year-old man who had had polyostotic fibrous dysplasia and many café-au-lait spots since he was an infant was seen at our hospital because of mild pain and increased swelling of the left knee. There was no family history of bone tumors, skin pigmentation, or precocious puberty. During childhood, he had sustained multiple fractures of the long bones of the lower limbs. When he was five years old, acne, growth of pubic hair, and an increase in the size of the penis and testes were observed. During adolescence and adulthood, more fractures of the lower limbs occurred. Neither the lower limbs nor the pituitary gland had been treated with radiation therapy. Since the age of fifty years, he had been confined to a wheelchair because of the marked deformities and risk of fractures of the lower extremities.

On admission to our hospital, six months after he was first seen, the patient reported constant pain in the proximal aspect of the left tibia and marked tenderness was noted. The findings of laboratory tests were normal except for the level of serum alkaline phosphatase, which was 420 international units per liter (normal, 0 to 170 international units per liter).

Radiographs of both femora revealed lesions with characteristics ranging from lytic to a ground-glass appearance to sclerotic. Both hips had severe varus deformity (shepherd's crook deformity), which is typical of fibrous dysplasia. In the proximal aspect of the left tibia, several large osteolytic lesions and areas of osseous destruction were noted (Fig. 1). A bone scan showed increased uptake of isotope in the skull, maxillae, mandible, humeri, shoulders, ribs, forearms, hands, vertebrae, pelvis, femora, tibiae, and feet (Fig. 2). Computed tomography revealed disruption of the posterior cortex of the left tibia and an extraskeletal tumor mass (Fig. 3). T1-weighted magnetic resonance imaging after injection of gadolinium-diethylenetriamine penta-acetic acid showed a heterogeneous bone tumor with a soft-tissue component as well as areas of low and high signal intensity. On the basis of these clinical and radiographic findings, malignant transformation of the polyostotic fibrous dysplasia was suspected. Radiographs and computed tomography scans of the chest revealed no evidence of pulmonary metastases.



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  		Fig. 1 Anteroposterior and lateral radiographs showing multifocal radiolucent areas, several osteolytic lesions (arrowheads indicate the largest lesion), ballooning, and deformity of the tibia.

 


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  		Fig. 2 Whole-body bone scan revealing polyostotic lesions and osseous deformity.

 


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  		Fig. 3 Computed tomography scan showing an osseous lesion, disruption of the tibial cortex, and an extraskeletal tumor mass (arrowheads).

 
Incisional biopsies were performed on the left tibia, and core biopsy specimens were taken from different sites of tumor involvement in the right tibia and in both femora to exclude the diagnosis of polyostotic malignant transformation and to decide on a safe level of amputation. The histological findings revealed a malignant tumor only in the left tibia, and a through-the-knee amputation was performed. The initiation of chemotherapy was delayed at the request of the patient, and adjuvant chemotherapy was started two months after the operation according to the COSS-86 (Cooperative Osteosarcoma Study) protocol41. Pulmonary metastases developed fourteen months after the operation. At the time of writing, fifteen months after the initial operation, the patient was alive with disease.

Pathological Findings
The sectioned surfaces of the amputated specimen revealed multiple grayish-white granular lesions in the tarsus, first metatarsal, and phalanges. The proximal aspect of the tibia had a glossy blue-white cartilaginous tumor, measuring twelve by six centimeters, extending from the epiphysis into the diaphysis (Fig. 4). A white soft-tissue mass was seen in the posterior region of the proximal metaphysis and diaphysis, and a cystic lesion that measured four by five centimeters was found in the anteromedial region of the proximal part of the diaphysis. The distal part of the diaphysis had a lobulated area of firm cartilaginous tissue.



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  		Fig. 4 Resected specimen of the proximal and diaphyseal region of the tibia, showing mainly cartilaginous tumor tissue in the proximal aspect of the tibia. There is complete destruction of the cortex by hemorrhagic tumor tissue with extraosseous extension of the tumor into the soft tissue on the medial side (arrowheads).

 
On histological examination, the tissue taken from the tarsus, metatarsals, and phalanges had the characteristic morphology of fibrous dysplasia with islands of woven bone in a fibrous stroma. Examination of the tibia revealed fibrous dysplasia as a pre-existing lesion in all areas that were not infiltrated by the tumor. Enchondroma-like nodules with a diameter of about two centimeters were found in the distal diaphyseal region, indicating a chondroid differentiation in fibrous dysplasia (Fig. 5)20. These observations suggested that our patient had fibrocartilaginous dysplasia rather than typical fibrous dysplasia. The main lesion in the proximal aspect of the tibia was composed of cartilaginous tumor with low-to-moderate cellularity. At the periphery of the cartilaginous tumor, a destructive growth pattern was evident as the tissue had infiltrated cortical bone and the pre-existing fibrous dysplasia. In addition to the infiltrating growth pattern of the cartilaginous tumor, the findings included mild-to-moderate nuclear atypia, double nuclei, and some mitotic figures, which are features of a grade-1 or grade-2 chondrosarcoma (Fig. 6-A). The white soft-tissue area that was located posteriorly in the cartilaginous lesion in the proximal part of the diaphysis showed osteosarcomatous differentiation (Fig. 6-B), and the lytic lesion located anteromedially was a high-grade anaplastic sarcoma. These areas of high-grade sarcoma were immediately adjacent to the low-grade chondrosarcoma (Figs. 7-A and 7-B). This growth pattern led to the diagnosis of dedifferentiated chondrosarcoma with anaplastic osteosarcomatous components.



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  		Fig. 5 Photomicrograph of a specimen taken from an area of fibrocartilaginous dysplasia, showing highly differentiated cartilaginous tissue with marginal ossification, consistent with enchondroma-like nodules (x 64).

 


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  		Fig. 6-A: Photomicrograph showing low-grade (highly differentiated) chondrosarcoma (x 400).

 


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  		Fig. 6-B: Photomicrograph showing an area of osteosarcoma with osteoid production (x 400).

 


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  		Fig. 7-A Photomicrograph showing the sharp transition between low-grade chondrosarcoma and high-grade sarcoma, which is a characteristic feature of dedifferentiated chondrosarcoma (x 100).

 


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  		Fig. 7-B High-magnification photomicrograph of the area of transition (x 200).

 


   Discussion
Top
 Introduction
 Case Report
 Discussion
References
 
The dedifferentiated chondrosarcoma in our patient developed in an area of pre-existing fibrocartilaginous dysplasia. In rare cases of fibrous dysplasia, the cartilage elements may be large and reach several centimeters in diameter20,39. The fibro-osseous lesion adjacent to the cartilage islands is the most important diagnostic criterion for fibrocartilaginous dysplasia39,40. Most dysplasias of this type involve the proximal part of the femoral shaft40. The main part of the tumor in our patient consisted of a low-grade chondrosarcoma juxtaposed with a high-grade anaplastic sarcoma or osteosarcoma. These histopathological features meet the definition of dedifferentiated chondrosarcoma as initially described, in 1971, by Dahlin and Beabout7.

The main problem in the case of our patient was the differential diagnosis between dedifferentiated chondrosarcoma and chondroblastic osteosarcoma. The lesion first was regarded as chondrosarcoma because of the cytological findings of a low-to-moderate grade of malignancy, including double nuclei, and then because of the permeative growth pattern at the tumor margins. Chondroblastic osteosarcoma was unlikely because there were mostly areas of low-grade chondrosarcoma. In chondroblastic osteosarcoma, irregular neoplastic osteoid usually is intermixed with high-grade chondrosarcoma that has no grossly separated malignant elements14. The sharp transition between high-grade sarcoma and low-grade chondrosarcoma seen in our patient is typical of dedifferentiated chondrosarcoma.

It is probable that the dedifferentiated chondrosarcoma originated from fibrocartilaginous dysplasia with enchondroma-like nodules25, which developed into chondrosarcoma and finally resulted in dedifferentiated chondrosarcoma. The interpretation that the enchondroma-like nodules transformed into chondrosarcoma is supported by the presence of enchondroma-like nodules in the distal part of the tibia, in which there was no tumor. To our knowledge, there have been only eight reported cases of malignant cartilaginous components in a sarcoma (usually an osteosarcoma26,28,31,33,43 but also a chondrosarcoma42) secondary to fibrous dysplasia.

The prevalence of malignant transformation in fibrous dysplasia has been reported to be 0.4 per cent (six of 1517 patients)36, and most of the patients were more than thirty years old when a sarcoma developed. Yabut et al.42 analyzed the cases of eighty-three patients who had malignant transformation of fibrous dysplasia. Of the seventy-three patients for whom the histological diagnosis was described, forty had osteosarcoma; twenty-two, fibrosarcoma; and eleven, chondrosarcoma. The mean period of survival for the eighty-three patients was thirty-six months42. Ruggieri et al.33 reported that, in twenty-eight patients who had malignant transformation of fibrous dysplasia, the secondary sarcoma was osteosarcoma (nineteen patients), fibrosarcoma (five), chondrosarcoma (three), or malignant fibrous histiocytoma (one). The most frequent sites of secondary sarcomas in these two reports were the craniofacial bone followed by the femur.

As far as we know, there have been only eleven reports, including our report, of malignant degeneration in a patient who had Albright syndrome (Table I)2,11,16,21,27,29,30,32,34,38. All of the patients had Albright syndrome according to the reports, but the triad of the syndrome (polyostotic fibrous dysplasia, areas of pigmented skin, and precocious puberty) was noted in only two patients (Cases 10 and 11). Eight of the patients had secondary osteosarcoma; one, fibrosarcoma; and one (our patient), dedifferentiated chondrosarcoma. The type of sarcoma was not known for the eleventh patient. Two patients (Cases 2 and 4) had sarcoma in a previously irradiated area.


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  		TABLE I REVIEW OF THE LITERATURE

 
Early recognition of malignant transformation in fibrous dysplasia depends mainly on an accurate clinical history of symptoms such as pain and swelling33. As lesions of fibrous dysplasia show a high uptake of isotope10,13, a bone scan has limited value for revealing malignant transformation. Unless a malignant change occurs22,25,37,42, fibrous dysplasia usually remains contained within the bone21. Radiographically, the most constant feature of malignant transformation of fibrous dysplasia is infiltration of the tumor into the surrounding soft tissues33. If extraskeletal tumor growth is identified on computerized tomography or magnetic resonance imaging, malignant transformation should be strongly suspected.

The prognosis for patients who have a malignant lesion secondary to fibrous dysplasia is virtually the same as that for patients who have the corresponding primary tumor33. Dedifferentiated chondrosarcoma is likely to be followed by pulmonary metastasis, and the prognosis is poor4,8,24. After operative resection, our patient received chemotherapy with methotrexate, cisplatin, Adriamycin (doxorubicin), and ifosfamide and had no sign of recurrent disease or metastases for thirteen months. However, pulmonary metastases developed fourteen months after the operation. The prognosis may be improved by early diagnosis and adequate treatment.


   Footnotes
 
*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study.

{dagger}Department of Orthopaedic Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700, Japan.

{ddagger}Departments of Orthopaedics (N. L.) and Pathology (S. B.), Westfälische Wilhelms-University, 48129 Münster, Germany.


   References
Top
 Introduction
 Case Report
 Discussion
 References
 

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