Disseminating Adamantinoma of the Tibia

Patient. This report describes a patient with a primary long bone adamantinoma. The lesion was initially wrongly diagnosed as fibrous dysplasia and the patient was treated by curettage. At second local recurrence, the tumour had progressed from an osteofibrous dysplasia-like to a full-blown classic adamantinoma, with metastatic potential to the lungs 19 years after the initial treatment. Lung metastasectomy by sternotomy was carried out twice in a period of over 3.5 years. The patient is currently alive without evidence of other metastatic disease. Discussion. From the files of the Netherlands Committee on Bone Tumors, another five patients with lung metastaseswere studied. All types of adamantinoma should be treated by complete en bloc resection. For patients with metastatic spread to the lungs, close radiological follow-up and excision of tumour nodules seems to be the only logic treatment modality.


Introduction
Adam antinom a of the long bones was ® rst described by F ischer in 1913. 1 It was given its name because of the histological resem blance to the adam antinom a of the jaw (nowadays called am eloblastom a), but is regarded as a distinct clinicopathological entity.
Adam antinom as are rare skeletal neoplasm s w hich account for about 0.3± 0.5% of all m alignant bone tumours. About 300 cases w ere reported up to 1994. 2± 4 T here is a slight predom inance in males. T he peak age incidence lies between 11 and 30 years, fem ales being slightly younger than males. T he de® nite site of predilection is the tibia, in which over 85% of adamantinom as occur. W ithin this bone, the tumour is usually found in the diaphysis, but it m ay also extend to the m etaphysis. O ccasionally, a m ulti-focal occurrence is present, in which tibia and ® bula m ay both be affected. Rarely, a pretibial soft tissue location has been reported. 5,6 The radiographic appearance varies from a sm all to extensive m ulti-lobulated radiolucent lesion in an area of bone destruction involving the anterior diaphysis. T he cortex is m ostly thinned and the periosteum m ay be elevated with a lam ellar or solid periosteal reaction. 7± 9 The radiological differential diagnosis includes ® brous dysplasia, (non-)ossifyin g ® brom a or osteo® brous dysplasia (O FD ), m etastatic carcinom a and vascular sarcom a.
Histologically, the tumour consists of epitheliallike cells in strands or nests, embedded in a ® brous or osteo® brous tissue. Two main subtypes of adam antinom a are recognized: the so-called`classic' adam antinom a w ith a predom inance of epithelial tum our cells, and the`OFD -like' or`differentiated' adam antinom a in which the osteo® brous component dom inates the lesion and inconspicuous epithelial elements can only be recognized after use of im m unohistochem istry. F our basic patterns of epithelial differentiationÐ and com binations of theseÐ m ay be encountered in classic adam antinom a: a basaloid pattern consisting of cell nests w ith peripheral pallisading, resembling basal cell carcinoma; a squamous pattern characterized by squam ous cells with keratinization, keratohyalin granules and intercellular bridges, resem bling squam ous cell carcinom a; a spindle cell pattern w ith large areas of spindle cells, resem bling ® brosarcom a; and a tubular pattern characterized by form ation of channels, occasionally ® lled w ith erythrocytes and lined by cuboidal or¯attened cells, resem bling vascular tu- m ours. Regardless of its histological variety, the epithelial nature of the tumour cells has been con® rm ed by im m unohistochem istry and electron m icroscopy. 10± 13 The recom m ended treatm ent is w ide en bloc resection. Am putation m ay not be avoidable when lesions contain a large soft tissue com ponent or w hen local recurrences occur. T he recurrence rate of patients treated just with biopsy or curettage is considerably higher.
O f particular interest are recent indications of a close relationship between adam antinom a and O FD , a benign lesion with sim ilar clinicopathological characteristics. O pposite theories propose that adam antinom a m ay arise from OF D , or that O FD m ay result from reactive tissue overgrowing m aturing neoplastic epithelial cells. 2,14± 17 O FD -like adam antinom as in particular are som etimes dif® cult to distinguish from O FD , considering their clinical and histopathological features. T his case report, w hich has previously been described in part (case 13) 2 shows the rarely reported progression of a prim ary OF D -like adam antinom a to a spindle cell classic adam antinom a at local recurrence, with eventual dissem ination to the lungs.

C ase history
In 1974, a 13-year-o ld girl was seen because of a painful sw elling of 1 m onth duration at the m edial aspect of the diaph ysis of the right tibia. At the age of six, she had twice sustained a fracture at this site. C onventional radiographs revealed a well-de® ned, m ulti-lobulated osteolytic lesion with intralesional opaci® cations and sclerotic m argins in the anterior cortex. The lesion m easured 8 3 3 3 2.5 cm . T he tum our was extensively curetted, leaving no m acroscopic evidence of residual tum our; the site was then rinsed w ith carbolic acid and w as ® lled with cancellous-b one chips. T he histopathological diagnosis w as ® brous dysplasia. T wo-and-a-half years later the patient was treated in the sam e w ay for a recurrence. T he pathological diagnosis w as then changed to non-ossifying ® brom a.
For a second recurrence with progressive sym ptom s, an en bloc resection was perform ed 5 years later. Routine pathological evaluation of the resected specimen revealed a large cyst bordered by num erous spindle-shaped cells. At the periphery of the tum our, strands of tum our cells in® ltrated the cortex and the periosteum . Areas of loose ® brous tissue resem bling the lesions identi® ed in 1974 and 1977 were observed as well. Electron microscopic exam ination show ed that the spindle-shaped cells contained m icrolum ina, m icrovilli and m itochondria. There were several desm osom es between the spindle-shap ed cells, a ® nding clearly characteristic of epithelial cells. O n the outer site, the cell nests w ere bordered by basal lam ina. T hus, the resection specimen contained an adam antinom a of the spin-dle cell subtype. Review of the original slides as well as im m unohistochemical analysis of the prim ary tum our showed isolated and sm all aggregates of keratin-p ositive epithelial cells.
In 1993, m ore than 10Ã years after the last resection, two lung metastases were detected. There were no signs of other system ic spread and the tw o lesions were excised by sternotomy. T he diagnosis of m etastases of the adam antinom a, of the sam e spindle cell subtype, was con® rmed by histology and im m unohistochem istry. After 3Ã years, a new lung lesion was resected. T he patient is now 22 years after diagnosis of the prim ary tum our.  18,19 The histology of m etastases of an adam antinom a show s the predom inance of a spindle cell differentiation of the epithelial com ponent, as in our patient. The osteo® brous com ponent, which is of benign nature, is always absent. Because of the resem blance of this epithelial subtype to som e spindle cell sarcom as like ® brosarcom a, the epithelial nature of the tumour cells can often only be con® rm ed after im munohistochem istry for keratins (the cytoskeletal proteins present in epithelial cells).
From the ® les of the registry of the N etherlands C om m ittee on Bone T um ors containing approxim ately 10 500 patients registered between 1953 and 1996, 37 patients (0,35% ) with an adam antinom a of long bone have been reported. 2,20,21 All of these cases were reviewed and the histopathological diagnosis was con® rm ed. In a follow-up study of 28 of these patients 2  M etastasectom y is the ® rst-line treatment for pulm onary recurrences. In the D utch series, radiotherapy and chem otherapy neither reduced the tum our volum e nor im proved survival. 2 T o our knowledge, only one patient had at least stable disease for 4Ã years after treatment with several courses of various chemotherapeutical regim es and ® nally by radiotherapy (30 G y/15 fractions). 22 W ith som e selection based on prognostic factors such as disease-free interval, num ber of m etastases and radical resection, a 5-year survival after m etastasectomy of 36% is reported for a group of 5206 patients with a variety of m alignant tum ours and a 10-year survival of 26% . 23 Prognosis of m etastases of an adam antinoma is probably better but data availab le in the literature are scarce. A rough approximation of the 5-year survival rate of dissem inated adam antinom a app ears to be in the range of 50± 60%. 2,4,8