Sarcom a (1997) 1 , 109 111

C ASE REPORT

D issem inating adam antinom a of the tibia

ALBERT N. VAN GEEL,1,2 HAN S M . HAZELBAG,3 ROB SLIN GERLAND 4 & M ARGIT I. VERM EULEN 1
D epartm ent of 1 Surgery and 4 Chest Disease, Zuider-ziekenhuis Rotterdam, 2 D epartment of Surgical O ncology, U niversity H ospital Rotterdam/D r D aniel den Hoed Cancer Center, Rotterdam & 3D epartm ent of O rthopaedic Surgery, Academic Hospital Leiden, The N etherlands

A bstract Patient. This report describes a patient with a primary long bone adamantinoma. The lesion was initially wrongly diagnosed as brous dysplasia and the patient was treated by curettage. At second local recurrence, the tumour had progressed from an osteo brous 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 years. The patient is currently alive without evidence of other metastatic disease. D iscussion. From the les of the Netherlands Comm ittee on Bone Tumors, another ve patients with lung metastases were 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 m odality. K ey w ords: tibia, adam antinom a, lung m etasta ses, treatm ent.

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 differentiation and com binations of these 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-

Correspondence to: A. N. van Geel, Department of Surgical Oncology, Dr Daniel den H oed Cancer Center, G roene Hilledijk 301, NL-3075 EA Rotterdam, The Netherlands. Tel: 1 31 10 4391506; Fax: 1 31 10 4864645; E-mail: geel@ chih.azr.nl 1357-714 X/97/020109 03 $9.00

1997 Carfax Publishing Ltd

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A. N . van Geel et al . 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 10 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 3 years, a new lung lesion was resected. T he patient is now 22 years after diagnosis of the prim ary tum our. D iscussion T he rate of distant m etastases in long bone adam antinom a is about 15 20% . 4,8 T his percentage m ay be higher because the indolent course of the adam antinom a necessitates long-term follow-up, and in the past, som e patients dying from m etastasizing adam antinom a m ay not have been diagnosed adequately. In their review in 1986, M oon and M ori found 14 m etastases in 109 cases. 4 D istant m etastases were m ainly found in patients with a history of local recurrence, m ostly due to inadequate initial treatment. Lungs are m ost frequently affected. Less frequently, m etastases are found in regional lym ph nodes, liver and bones. Pulm onary m etastases appear as solid tum ours of varying size and num ber in the lung parenchym a and the pleura. A very late app earance of the lung m etastases, after 10 years or m ore, is not unknown. 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 patients2 with a m ean duration of 10 years and 2 m onths, eight of these patients (29% ) developed m etastases, of which six were in the lungs. All of these patients had developed a local recurrence before the appearance of the lung m etastases and four patients had regional or other distant m etastases at the time of these lung m etastases. Four of the six patients with lung m etastases were treated by m etastasectomy. Apart from our current patient, all eight patients with metastases have died of disease.

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-

Disseminating adamantinom a T heir m ean survival after diagnosis of the rst m etastasis w as 4 years and 3 m onths; after diagnosis of the prim ary tum our, they survived 12 years and 8 m onths. The four deceased patients who underw ent a lung m etastasectomy had a mean survival of 4 years after m etastasectomy. Our patient is alive 4 years after rst m etastasectomy without current evidence of metastases. H owever, in contrast to three of the four patients who died of m etastatic disease, the lungs are the only location of detected dissem ination in our patient until now. 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 4 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

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