Adamantinoma is a rare tumor with an indolent course that occurs most commonly in the tibia. It is locally aggressive, and local recurrences are described after resection. Pain is the most common symptom. Since the lesion is typically slow growing, the pain can be present for many years before the patient seeks medical attention. Microscopically, adamantinoma consists of islands of epithelial cells in a fibrous stroma. Nuclear atypia is minimal, and mitotic figures are rare. The most common radiographic appearance is that of multiple sharply demarcated radiolucent lesions surrounded by areas of dense, sclerotic bone. This tumor most often affects the tibial diaphysis and produces lytic lesions that can cause fractures.
A 31-year-old man presented with a rapidly growing lytic lesion of the distal tibia. On histological examination, many areas of epithelial cells in a fibrous stroma were identified. Diagnosis of adamantinoma was performed. The lesion was treated with en bloc resection and reconstruction with distal tibia allograft and ankle arthrodesis with retrograde nail. At 2-year follow-up, there were no clinical or radiological signs of recurrence of disease.
Adamantinoma is a low-grade malignant tumor with a peculiar epithelial-like component sometimes reminiscent of the ameloblastoma of the jaw bones.1,2 It is rare, slightly prevails in men, and affects any age, although it is more common between 20 and 40 years. Adamantinoma has an indolent course and diagnosis can be retarded. The interval between first symptoms and surgical treatment may be as long as 20 years. The most common radiographic appearance is that of multiple sharply demarcated radiolucent lesions separated by areas of dense, sclerotic bone. This tumor most often affects the tibial diaphysis and produces lytic lesions that can cause fractures.
A 31-year-old man presented with limping, local pain, and swelling in the right ankle of 6 months duration. The patient reported a previous trauma 1 year prior. On physical examination, a tender, tough, immobile mass placed in the distal tibia was identified. No other swellings were present in the extremities, and there was no clinical evidence of lymphadenopathy. Active and passive range of motion testing of the ankle and neurovascular examination were normal. Laboratory tests were negative for infection or tumor.
A previous radiograph of the ankle showed an irregularly expanded osteolytic lesion in the distal metaphysis of the tibia (Figure 1). Radiographs 2 months later revealed a rapid growth with extension to the epiphysis, destruction of the cortical bone, and involvement of surrounding soft tissues (Figure 2).
Bone scanning showed an increased uptake with a cold central area in the distal tibia (Figure 3). Computed tomography (CT) demonstrated a solid vascularized tissue that blew up the distal tibia with large cortical destruction and extension to the subcutaneous tissue. A multilobulated lesion extending for 7.7 cm along the distal tibial meta-ephysis was evident on magnetic resonance imaging (MRI). T1-weighted spin echo images demonstrated an intermediate-to-low signal intensity, while T2-weighted images demonstrated a high signal intensity. Cystic components with fluid-fluid levels were not identified (Figure 4). No secondary pulmonary lesions were revealed on chest CT. The result of a core needle biopsy of the tibial lesion was adamantinoma of bone.
Figure 3: Bone scan showing a solitary lesion in the distal tibia with increased uptake and a cold central area.
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Figure 4: MRI demonstrating a multilobulated lesion with cortical disruption and soft tissue extension. T1-weighted image shows an intermediate-to-low signal intensity (A) while T2-weighted image shows a high signal intensity (B).
The patient underwent an en bloc resection and reconstruction with distal tibia allograft and ankle artrodesis with retrograde nail. Macroscopic examination of the neoplasm revealed a solid whitish to pale yellow lesion with hemorrhagic and cystic areas. On histological examination, many epithelial cells in a fibrous stroma were identified. The epithelial cells appeared arranged in islands, cords, or nests. Nuclear atypias were present like mitotic figures (Figure 5). In the available specimen, the study of the margins confirmed a wide margin of healthy tissue.
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Figure 5: Macroscopically, the neoplasm appears as a solid lesion with hemorrhagic and cystic areas (A). Histological examination shows islands and cords of basaloid epithelial cells in a fibrous stroma (B, C). Nuclear atipias and mitotic figures are present.
Weight bearing was not allowed for 2 months and then was progressively allowed, with the patient reaching full weight bearing at 6 months. At that time, antithromboembolic prophylaxis with fondaparinux sodium was given. At 2-year follow-up, there were no clinical or radiological signs of recurrence of disease (Figure 6). Neurovascular examination was normal and the patient was pain free.
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Figure 6: AP (A) and lateral (B) radiographs of the right ankle 2 years after en bloc resection and reconstruction with distal tibia allograft and ankle artrodesis with retrograde nail.
Adamantinoma is a rare neoplasm, representing <1% of all primary malignancies of bone. The tumor was first described by Maier1 in 1900 and subsequently by Fischer2 in 1913; both authors noted the histologic similarities to an odontogenic tumor known as ameloblastoma or adamantinoma. Additional cases were reported by Ryrie3 in 1932, Dockerty and Myerding4 in 1942, and Baker et al5 in 1954, but it was Campanacci et al6,7 who named the tumor, described it in detail, and reviewed its biology. They distinguished it from a similar but benign disease principally occurring in children, which they named osteofibrous dysplasia.7,8
Osteofibrous dysplasia and adamantinoma have similar clinical presentations and histological appearances; therefore, some authors propose a relationship between the 2 lesions. Osteofibrous dysplasia could represent the benign differentiation of adamantinoma7,9,10 or the histological substratum from that adamantinoma may arise.11 There were reported cases in the literature of osteofibrous dysplasia in childhood progressing to conventional adamantinoma in an adult patient.12
Adamantinoma has a wide age distribution, but most patients are in the second or third decade at the time of diagnosis. It has a peculiar predilection for occurring in the tibia (approximately 85%).
Pain is the most common symptom. Since the lesion is typically slow growing, the pain can be present for many years before the patient seeks medical attention. Approximately 20% of patients have a pathological fracture.
Radiological appearance consists of an eccentric osteolysis, mostly involving the anterior cortex of the tibial diaphysis, with frequent cancellation of the cortex and no or minimal periosteal reaction. It frequently appears with sclerotic borders and soft tissue mass. The lesion is typically oriented longitudinally along the anterior tibial diaphysis, and a large portion or even the entire tibia can be involved. Radiolucent lesions with moth-eaten borders separated by areas of dense, sclerotic bone are present.
Computed tomography and MRI indicate a multilobulated lesion consisting of solid fibrous tissue (low T1-weighted and high T2-weighted signal). Sometimes (mainly in younger patients) the osteolyses are multifocal, extended in the diaphysis, and associated with anterior bowing of the tibia, so that the imaging is, at least initially, identical to that of osteofibrous dysplasia.
Radiographic features of our case primarily directed our opinion toward the diagnosis of teleangiectatic osteosarcoma due to the purely osteolitic lesion with ill-defined limits, the extended cortical destruction, and the rapid growth of the lesion with unusual localization in the meta-epyphisis. Only the biopsy allowed us to rule out teleangiectatic osteosarcoma. Another possible diagnosis based on imaging could be aneurysmal bone cyst characterized by subperiosteal involvement and poorly defined osteolysis that inflates the periosteum and progressively erodes the cortex. In aneurysmal bone cyst, bone scans commonly reveal an increased uptake with a cold central area. Computed tomography and MRI did not show the presence of fluid levels in our case.
Adamantinoma may also be mistaken for fibrous dysplasia, vascular neoplasm, myoepithelial tumor, malignant mixed tumor of the bone, and metastatic carcinoma.7,8,13-15 Metastasis usually affects older patients, and the tibia does not represent a common site of metastatic involvement. Moreover, on standard radiographs metastasis show a more destructive pattern predominantly involving the medullary canal.
Microscopically, adamantinoma consists of islands of epithelial cells in a fibrous stroma. A zonal architecture may be evident, in which the diagnostic epithelial cells are gathered in the center of the lesion and the fibroblastic tissues occupies the periphery. Nuclear atypia is usually minimal, and mitotic figures are rare. Immunohistochemical staining is usually positive for cytokeratins and vimentin.13 Electron microscopic findings of adamantinoma are typical of epithelial cells with the presence of desmosomes, tonofilaments, and microfilaments.16 In our case, several basaloid epithelial cells grouped in islands and cords were noted. These nests were surrounded by highly vascularized fibrous stroma.
Our case confirms the possibility that adamantinoma can involve the meta-epiphyseal region of the tibia. Correct presurgical staging is mandatory; radiological appearance and clinical and histological features are basic for a clear diagnosis of adamantinoma.
Chemotherapy and radiation therapy are not effective modalities of treatment.17
Some studies reported the long-term outcome of adamantinoma.6,18-20 Male sex, pain, symptoms of <5 years duration, and initial treatment by biopsy, curettage, excision or resection are risk factors for recurrent or metastatic disease.18 Metastasis and late local recurrences can occur as late as 24 years after diagnosis and surgical therapy of the primary lesion.19 The most common site for metastasis is the lung, with an incidence of approximately 15%, while the incidence of recurrence is approximately 30%.21 The tumor can also metastasize to the lymph nodes. Szendroi et al20 published a long-term follow-up study of 11 cases of adamantinoma of long bones. The authors reported 6 recurrences in 4 patients 20 and 16 years after initial treatment. One patient died of pulmonary metastases 9 years after diagnosis of the tumor. Although adamantinoma is a low-grade, slow-growing malignant bone tumor, a lifelong follow-up of the patient is necessary due to the possibility of recurrences or metastases, even decades after recognition of the primary tumor.
Adamantinomas are usually treated by excision with wide surgical resection of the tumor and insertion of a segment of intercalary bone allograft or osteoarticular segment.15,22,23 In our case, the graft was fixed with a retrograde nail, resulting in an ankle artrodesis.
Amputation is the treatment of choice in patients presenting with local recurrences, wide soft tissue components, metastases, or failure of reconstruction.23
Other options for reconstruction are described in the literature: distraction osteogenesis, vascularized and nonvascularized fibular autografts, and metallic segmental implants.15,24-26
Distraction osteogenesis requires a long treatment time, and moreover, pin tract infection, joint stiffness, and nonunion can represent other possible complications of the technique.
Vascularized fibular autografts have a lower infection rate and a higher rate of union than traditional allograft reconstruction. The need to wait for remodelization of the graft after union and the need to achieve large segments of autograft from the patient are the main disadvantages. Chen et al26 recommended the use of microvascular fibula transfer in reconstructing large, complex long bone defects after tumor extirpation.
Filippou et al19 reported a surgical procedure including wide resection of adamantinoma of tibia and reconstruction with combined osteosynthesis (screw and acrylic cement in a unique body) to assure stability and thus early remobilization.
The unusual radiographic appearance (purely osteolitic lesion with extended cortical destruction) and the rapid growth of the lesion in our case primarily directed our opinion toward the diagnosis of teleangiectatic osteosarcoma. For this reason, we consider core or open biopsy as essential procedures prior to any treatment intervention, whatever the radiographic appearance may be.
- Maier C. Ein primäres myelogenes PlatenepithelCarcinom der Ulna. Bruns Beitr Klin Chir. 1900; (26):553-566.
- Fischer B. Über ein primäres Adamantinoma der Tibia. Frankfurt Z Pathol. 1913; (12):422-441.
- Ryrie BJ. Adamantinoma of the tibia: etiology and pathogenesis. Br Med J. 1932; (2):1000-1003.
- Dockerty MB, Myerding HW. Adamantinoma of the tibia: report of two new cases. JAMA. 1942; (119):932-937.
- Baker PL, Dockerty MB, Coventry MB. Adamantinoma (so-called) of the long bones; review of the literature and report of three new cases. J Bone Joint Surg Am. 1954; 36(4):704-720.
- Campanacci M, Giunti A, Bertoni F, Laus M, Gitelis S. Adamantinoma of the long bones. The experience at the Istituto Ortopedico Rizzoli. Am J Surg Pathol. 1981; 5(6):533-542.
- Campanacci M, Laus M. Osteofibrous dysplasia of the tibia and fibula. J Bone Joint Surg Am. 1981; 63(3):367-375.
- Campanacci M. Bone and Soft Tissue Tumors: Clinical Features, Imaging, Pathology and Treatment. Wien, Austria: Springer; 1999.
- Markel SF. Ossifying fibroma of long bone: its distinction from fibrous dysplasia and its association with adamantinoma of long bone. Am J Clin Pathol. 1978; 69(1):91-97.
- Boriani S. Osteofibrous dysplasia of the long bones [in Italian]. Chir Organi Mov. 1978; 64(6):625-628.
- Ishida T, Iijima T, Kikuchi F, et al. A clinicopathological and immunohistochemical study of osteofibrous dysplasia, differentiated adamantinoma, and adamantinoma of long bones. Skeletal Radiol. 1992; 21(8):493-502.
- Unni KK, Dahlin DC, Beabout JW, Ivins JC. Adamantinomas of long bones. Cancer. 1974; 34(5):1796-1805.
- Benassi MS, Campanacci L, Gamberi G, et al. Cytokeratin expression and distribution in adamantinoma of the long bones and osteofibrous dysplasia of tibia and fibula. An immunohistochemical study correlated to histogenesis. Histopathology. 1994; 25(1):71-76.
- Unni KK. Dahlins Bone Tumors: General Aspects and Data on 11,087 Cases. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1996.
- Papagelopoulos PJ, Mavrogenis AF, Galanis EC, Savvidou OD, Inwards CY, Sim FH. Clinicopathological features, diagnosis, and treatment of adamantinoma of the long bones. Orthopedics. 2007; 30(3):211-215.
- Perez-Atayde AR, Kozakewich HP, Vawter GF. Adamantinoma of the tibia. An ultrastructural and immunohistochemical study. Cancer. 1985; 55(5):1015-1023.
- Kahn LB. Adamantinoma, osteofibrous dysplasia and differentiated adamantinoma. Skeletal Radiol. 2003; 32(5):245-258.
- Keeney GL, Unni KK, Beabout JW, Pritchard DJ. Adamantinoma of long bones. A clinicopathologic study of 85 cases. Cancer. 1989; 64(3):730-737.
- Filippou DK, Papadopoulos V, Kiparidou E, Demertzis NT. Adamantinoma of tibia: a case of late local recurrence along with lung metastases. J Postgrad Med. 2003; 49(1):75-77.
- Szendroi M, Antal I, Arató G. Adamantinoma of long bones: a long-term follow-up study of 11 cases. Pathol Oncol Res. 2009; 15(2):209-216.
- Damjanov I, Linder J. Andersons Pathology: Primary Bone Tumours. 10th ed. St Louis, MO: Mosby; 1996.
- Qureshi AA, Shott S, Mallin BA, Gitelis S. Current trends in the management of adamantinoma of long bones. An international study. J Bone Joint Surg Am. 2000; 82(8):1122-1131.
- Gebhardt MC, Lord FC, Rosenberg AE, Mankin HJ. The treatment of adamantinoma of the tibia by wide resection and allograft bone transplantation. J Bone Joint Surg Am. 1987; 69(8):1177-1188.
- Kiral A, Pehlivan O, Cilli F, Akmaz I, Rodop O, Solakoglu C. Reconstruction of intercalary gap after wide surgical resection of adamantinoma of the tibia. Orthopedics. 2008; 31(11):1143.
- Kitsoulis P, Mantellos G, Xenakis T. Adamantinoma of the tibia: local resection and distraction osteogenesis. Acta Chir Belg. 2009; 109(1):126-129.
- Chen CM, Disa JJ, Lee HY, et al. Reconstruction of extremity long bone defects after sarcoma resection with vascularized fibula flaps: a 10-year review. Plast Reconstr Surg. 2007; 119(3): 915-924.
Drs Cappuccio and Bosco are from the Department of Orthopedics and Traumatology Spine Surgery, Ospedale Maggiore, and Dr Montalti is from the Department of Musculoskeletal Oncology and Drs Gasbarrini and Boriani are from the Department of Oncologic and Degenerative Spine Surgery, Rizzoli Institute, Bologna, Italy.
Drs Cappuccio, Montalti, Bosco, Gasbarrini, and Boriani have no relevant financial relationships to disclose.
Correspondence should be addressed to: Michele Cappuccio, MD, Department of Orthopedics and Traumatology Spine Surgery, Ospedale Maggiore C.A. Pizzardi, Largo Nigrisoli, 2-40100 Bologna, Italy (firstname.lastname@example.org).