Adamantinoma of the long bones is a low-grade, slow-growing, primary malignant bone tumor composed of epithelial cells in a fibrous or osteofibrous stroma.1,2 It has a wide range of histological patterns.3-18 Despite the considerable range of each histologic pattern, most current studies have shown that long bone adamantinoma appears to be of an epithelial nature. The tibial lesions name comes from its somewhat similar histologic appearance to the more common odontogenic adamantinoma of the jaw bones.18,19 Despite the histological similarities there is no proof that these tumors have a similar histiogenetic origin.19
Long bone adamantinomas can be divided in two main groups with distinct histological and radiographic features. The firstclassic adamantinomais characterized by an abundance of tumor cells and a destructive growth pattern. The second, differentiated adamantinoma, is characterized histologically by a predominance of an osteofibrous dysplasia-like pattern with a small, inconspicuous component of epithelial tumor elements.12,18,19 Radiographically, classic adamantinomas are either intracortical or associated with complete cortical disruption, intramedullary involvement, and expansion beyond the periosteum into adjacent soft tissues, while differentiated adamantinomas are intracortical and often multicentric lesions.12,19,20
This article discusses the epidemiology, clinicopathological and imaging features, diagnosis, treatment, and prognosis of adamantinoma of the long bones.
Adamantinoma of the long bones is a rare tumor that accounts for 0.3%-1% of all malignant bone tumors.4-9,21 In 1986, Moon and Mori2 performed a meta-analysis of 200 cases. In 1996, Unni18 reported 36 cases in an analysis of 5641 primary malignant bone tumors from a single institution.
The literature suggests a slight male predominance.1,2,4-9,21 Adamantinomas usually are diagnosed after skeletal maturity. Although 75% of the cases occur between the second and third decades of life,18 adamantinomas have also been reported in older patients, as well as in children aged <14 years.18,22,23 Differentiated adamantinomas tend to occur in younger patients.18,19
More than 90% of adamantinomas appear in the tibia, with fibular involvement coexisting in 50% of the cases.12,18,19 The tumor usually is located in the diaphysis and, less frequently, the tibial metaphysis. Rare cases of adamantinomas of the olecranon, the ribs, the radius, the spine, the metatarsus, and the humerus also have been reported.24-31
| || |
| || |
Figure 1: AP (A) and lateral (B) plain radiographs show an expansile mixed lytic and sclerotic lesion of the mid-portion of the right tibia.
A history of previous trauma or fracture occurring months or years prior to the onset of symptoms is reported in approximately 60% of patients. The most common presentation is of a gradually evolving mass associated with dull, insidious, aching pain. Bowing deformity of the tibia and pathologic fractures may occur. Advanced or recurrent lesions may be associated with soft-tissue involvement.12,18,21 Severe paraneoplastic, humorally mediated hypercalcaemia, hypercalcaemic coma, and pancreatitis have been reported.32-35
Radiographically, adamantinoma usually appears as a mixed lytic and sclerotic central lesion or multiple, sharply circumscribed lucencies with sclerosis of the intervening bone (Figure 1). This slowly growing, expansile tumor eventually causes endosteal scalloping and thinning, interruption, or destruction of the cortex without periosteal reaction. Moderate to severe anterior bowing deformity is common.19,20 Classical adamantinoma usually is intracortical with evidence of complete cortical disruption and intramedullary and soft-tissue involvement. Involvement of the anterolateral cortex of the tibia with multiple lucencies and sclerotic foci characterizes differentiated adamantinoma. These imaging features may be similar to those observed in osteofibrous dysplasia.12,18,20
Technetium pyrophosphate bone scan shows intense increased uptake tracer accumulation, corresponding closely to the extent of the lesion.18,21,36 In addition, bone scan may show a coexisting fibular involvement.
Computed tomography reveals an osteolytic lesion with expansion and destruction of the cortex (Figure 2), and probable extension to the surrounding soft tissues.21,37 Magnetic resonance imaging (MRI) is useful in providing information concerning the intramedullary and soft-tissue extent of the tumor.9,20,36-38 On T1-weighted MRI, the lesion has a low intensity signal, whereas on T2-weighted MRI the signal is much brighter and does not diminish with the fat suppression technique.
In a study of 22 patients, two morphologic patterns were distinguished in MRI: a solitary, lobulated focus versus a pattern of multiple small modules in one or more foci; however, these characteristics were not related to the histologic subtype.38
Figure 2: CT scan of the right leg shows a lytic expansile lesion within the tibia. There is intramedullary involvement with some calcifications and thinning of the cortex, particularly posteriorly.
Histologically, adamantinoma is composed of epithelial islands in a spindle cell stroma. The relative amounts of the two components can vary considerably (Figure 3). Several histologic variants have been described corresponding to a variety of different epithelial cell patterns that can be found. Therefore, this range of morphologic patterns can mimic many primary or metastatic bone lesions.21,39 A number of immunohistochemical and electron microscopic studies have shown adamantinoma to be of epithelial derivation.1,9-11,36,40-44 In some tumors the stromal component has a fibrous dysplsia-like appearance with or without scattered spicules of woven bone.18,19
| || |
Figure 3: Histological appearance of adamantinoma. Low-power view (A) shows islands of epithelial cells surrounded by fibrous tissue and high-power view (B) of the cluster of epithelial cells within the fibrous stroma.
Because of its rarity and differing histological patterns, adamantinoma histologically may resemble epithelial metastasis, hemangioendothelioma, hemangiosarcoma, fibrous and osteofibrous dysplasia, nonossifying fibromas, and chondromyxoid fibromas.18,19,44-47 Clinical information such as patient age and history, as well as the location in the tibial diaphysis, may aid in diagnosis.
It is important to differentiate adamantinoma from osteofibrous dysplasia.20 Adamantinoma generally is painful, is observed during adulthood, has different radiographic features, is progressive during adult age, and may expand into the soft tissues. However, osteofibrous dysplasia seldom progresses during childhood, and any progression of the lesion stops after puberty. Exceptional cases have been reported of adamantinoma that began during childhood and have radiographic features similar to osteofibrous dysplasia.45-47
Adamantinoma must be suspected if a tibial lesion becomes painful or if it grows after puberty. In such cases, extensive biopsy from the most radiolucent areas is recommended. However, given the heterogeneity of the histology within different areas of adamantinomas, sampling errors are possible with limited biopsy specimens. These errors have led to reclassification of these tumors from osteofibrous dysplasia to adamantinoma after repeat biopsy with adequate tissue.45-47
| || |
| || |
Figure 4: AP (A) and lateral (B) plain radiographs after wide resection of the tumor and reconstruction using a 13 cm intercalary tibial allograft fixed using a DCP plate and screws and autologous iliac bone grafting at the host bone allograft junction.
Treatment and Prognosis
Owing to the rarity of adamantinomas, data is insufficient concerning the safest and most effective treatment modality. These tumors are of low-grade malignancy and highly radioresistant.48,49 Thus surgery is the treatment of choice. Although limited experience with them has been reported, chemotherapy and radiation therapy have not been shown to be effective.8
Operative treatment includes either surgical resection with wide margins and reconstruction of the segmental defect,4,5,8,9,12,18,21,50-52 or amputation.1,2,5,9 Limb reconstruction options include the use of allografts (intercalary, osteoarticular, or morselized), vascularized and nonvascularized fibular autografts, metallic segmental implants, and distraction osteogenesis.9,21,51,53 Intercalary reconstruction appears to be the most successful method (Figure 4). Qureshi et al9 reported a limb salvage rate of 84%. They used allografts in 61% of the reconstructions after resection of adamantinomas of long bones. The majority were intercalary reconstructions. No differences in the efficacy of different fixation techniques were noted. Complications related to the reconstruction were unacceptably high (48% of patients), including nonunion (24%) and fracture of the allograft (23%). Vascularized fibular grafts have been considered the best type of graft for large segmental bone defects after bone tumor resections.54,55
Local recurrence is common in inadequately treated patients.12,21,56,57 Wide operative margins are associated with a lower rate of local recurrence than marginal or intralesional margins.8,9,24 However, a 18.6% rate of local recurrence at 10 years has been reported after wide-margin surgical excision of adamantinomas.9 Local recurrences usually occur 5 to 15 years after primary excision of the tumor. Late local recurrences have been reported at 24 and 36 years after diagnosis.21,56 No statistically significant difference between local recurrence rate and tumor stage, duration of symptoms, patient gender and age, type of biopsy, and type of grafting has been documented.9,12 Wide resection is also indicated for recurrent tumors.56
The near-benign biology and slow-growing nature of adamantinoma are reflected in the good survival rates even after local recurrences and lung or regional lymph node metastases.21,39,51 Late metastases may occur in 10%-30% of patients with adamantinomas, most frequently in the lungs, the regional lymph nodes, or the bones.19,21,24,32-35 After wide margin surgical excision of the tumor or amputation, overall 10-year survival rates vary from 82% to 87%.1,2,8,12
Adamantinoma of the long bones is a rare, primary, low-grade, slow-growing malignant bone tumor. It is expressed with a wide range of histological patterns. Histologically, the tumor is composed of an epithelial component surrounded by a fibrous stroma that may or may not contain spicules of woven bone. In the majority of cases, adamantinomas are located in the tibial diaphysis. Limb salvage with wide surgical resection and reconstruction or amputation is the most effective treatment. Local recurrence is associated with incomplete resection. Survival rates range from 82% to 87%. Late metastases, mainly to the lungs, may occur.
- Hauben E, van den Broek LC, Van Marck E, Hogendoorn PC. Adamantinoma-like Ewings sarcoma and Ewings-like adamantinoma. The t(11; 22), t(21; 22) status. J Pathol. 2001; 195:218-221.
- Moon NF, Mori H. Adamantinoma of the appendicular skeletonupdated. Clin Orthop Relat Res. 1986; 204:215-237.
- Schajowicz F, Ackerman LV, Sissons HA. Histological Typing of Bone Tumors. International Histological Classification of Tumors No. 6., Geneva, Switzerland: World Health Organization; 1972.
- Unni KK, Dahlin DC, Beabout JW, Ivins JC. Adamantinomas of long bones. Cancer. 1974; 34:1796-1805.
- Huvos AG, Marcove RC. Adamantinoma of long bones. A clinicopathological study of fourteen cases with vascular origin suggested. J Bone Joint Surg Am. 1975; 57:148-154.
- Czerniak B, Rojas-Corona RR, Dorfman HD. Morphologic diversity of long bone adamantinoma. The concept of differentiated (regressing) adamantinoma and its relationship to osteofibrous dysplasia. Cancer. 1989; 64:2319-2334.
- Campanacci M. Adamantinoma of the long bones. In: Bone and Soft Tissue Tumors. New York, NY: Springer; 1990:629-638.
- Hazelbag HM, Taminiau AHM, Fleuren GJ, Hogendoorn PC. Adamantinoma of the long bones. A clinicopathological study of thirty-two patients with emphasis on histological subtype, precursor lesion, and biological behavior. J Bone Joint Surg Am. 1994; 76:1482-1499.
- 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; 82:1122-1131
- Rosai J, Pinkus GS. Immunohistochemical demonstration of epithelial differentiation in adamantinoma of the tibia. Am J Surg Pathol. 1982; 6:427-434.
- Hazelbag HM, Fleuren GJ, van den Broek LJ, Taminiau AH, Hogendoorn PC. Adamantinoma of the long bones: keratin subclass immunoreactivity pattern with reference to its histogenesis. Am J Surg Pathol. 1993; 17:1225-1233.
- Keeney GL, Unni KK, Beabout JW, Pritchard DJ. Adamantinoma of long bones. A clinicopathologic study of 85 cases. Cancer. 1989; 64:730-737.
- Knapp RH, Wick MR, Scheithauer BW, Unni KK. Adamantinoma of bone. An electron microscopic and immunohistochemical study. Virchows Archive. A, Pathological Anatomy and Histopathology. 1982; 398:75-86.
- Mori H, Yamamoto S, Hiramatsu K, Miura T, Moon NF. Adamantinoma of the tibia. Ultrastructural and immunohistochemic study with reference to histogenesis. Clin Orthop Relat Res. 1984; 190:299-310.
- Elliott GB. Malignant angioblastoma of long bone. So-called tibial adamantinoma. J Bone Joint Surg Br. 1962; 44:25-33.
- Llombart-Bosch A, Ortuno-Pacheco G. Ultrastructural findings supporting the angioblastic nature of the so-called adamantinoma of the tibia. Histopathology. 1978; 2:189-200.
- Lederer H, Sinclair AJ. Malignant synovioma simulating adamantinoma of the tibia. J Pathol Bacteriol. 1954; 67:163-168.
- Unni KK. Dahlins Bone Tumors: General Aspects and Data on 11,087 Cases. 5th ed. Philadelphia, Pa: Lippincott-Raven; 1996:333-342.
- Dorfman HD, Czerniak B. Bone Tumors. St Louis, Mo: Mosby; 1998:949-973.
- Kahn LB. Adamantinoma, osteofibrous dysplasia, and differentiated adamantinoma. Skeletal Radiol. 2003; 32:245-258.
- 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; 49:75-77.
- van Rijn R, Bras J, Schaap G, van den Berg H, Maas M. Adamantinoma in childhood: report of six cases and review of the literature. Pediatr Radiol. 2006; 36:1068-1074.
- Kumar D, Mulligan ME, Levine AM, Dorfman HD. Classic adamantinoma in a 3-year-old. Skeletal Radiol. 1998; 27:406-409.
- Soucacos PN, Hartofilakidis GK, Touliatos AS, Theodorou V. Adamantinoma of the olecranon. A report of a case with serial metastasizing lesions. Clin Orthop Relat Res. 1995; 310:194-199.
- van Haelst UJ, de Haas van Dorsser AH. A perplexing malignant bone tumor. Highly malignant so-called adamantinoma or non-typical Ewings sarcoma. Virchows Archive. A, Pathological Anatomy and Histopathology. 1975; 365:63-74.
- Beppu H, Yamaguchi H, Yoshimura N, Atarashi K, Tsukimoto K, Nagashima Y. Adamantinoma of the rib metastasizing to the liver. Intern Med. 1994; 33:441-445.
- Bourne MH, Wood MB, Shives TC: Adamantinoma of the radius: a case report. Orthopedics. 1988; 11:1565-1566.
- Dimi LI, Mendonca R, Adamy CA, Saraiva GA. Adamantinoma of the spine: case report. Neurosurgery. 2006; S9:E426.
- Clarke RP, Leonard JR, von Kuster L, Wesseler TA. Adamantinoma of the humerus with early metastases and death: a case report with autopsy findings. Orthopedics. 1989; 12:1121-1125.
- Mohler DG, Cunningham DC. Adamantinoma arising in the distal fibula treated with distal fibulectomy: a case report and review of the literature. Foot Ankle Int. 1997; 18:746-751.
- Henneking K, Rehm KE, Schulz A. Adamantinoma of the long tubular bones. Case report of a fibular tumor. Chirurg. 1984 ; 55:407-410.
- Van Schoor JX, Vallaeys JH, Joos GF, Roels HJ, Pauwels RA, Van Der Straeten ME. Adamantinoma of the tibia with pulmonary metastases and hypercalcemia. Chest. 1991; 100:279-281.
- Enneking WF. The staging system for benign and malignant tumors of muskoloskeletal system (Appendix A). In: Clinical Muskoloskeletal Pathology. Gainesville, Fla: University Press of Florida; 1990:451-466.
- Plump D, Haponik EF, Katz RS, Tipton-Donovan A. Primary adamantinoma of rib: thoracic manifestations of a rare bone tumor. South Med J. 1986; 79:352-355.
- Altmannsberger M, Poppe H, Schauer A. An unusual case of adamantinoma of long bones. J Cancer Res Clin Oncol. 1982; 104:315-320.
- Brain EC, Raymond E, Goldwasser F, Extra JM, Marty M. Adamantinoma of the proximal end of the tibia. A case. Presse Med. 1994; 23:1522-1526.
- Garces P, Romano CC, Vellet AD, Alakija P, Schachar NS. Adamantinoma of the tibia: plain-film, computed tomography and magnetic resonance imaging appearance. Can Assoc Radiol J. 1994; 45:314-317.
- Van der Woude HJ, Hazelbag HM, Bloem JL, Taminiau AH, Hogendoorn PC. MRI of adamantinoma of long bones in correlation with histopathology. AJR Am J Roentgenol. 2004; 183:1737-1744.
- Johnson LC. Congenital pseudoarthrosis, adamantinoma of long bone, and intracortical fibrous dysplasia of the tibia. J Bone Joint Surg Am. 1972; 54:1355.
- Hazelbag HM, Fleuren GJ, Cornelisse CJ, van den Broek LJ, Taminiau AH, Hogendoorn PC. DNA aberrations in the epithelial cell component of adamantinoma of long bones. Am J Pathol. 1995; 147:1770-1779.
- Jundt G, Remberger K, Roessner A, Schulz A, Bohndorf K. Adamantinoma of long bones. A histopathological and immunohistochemical study of 23 cases. Pathol Res Pract. 1995; 191:112-120.
- Bovee JV, van den Broek LJ, de Boer WI, Hogendoorn PC. Expression of growth factors and their receptors in adamantinoma of long bones and the implication for its histogenesis. J Pathol. 1998; 184:24-30.
- Kanamori M, Antonescu CR, Scott M, et al. Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma. J Mol Diagn. 2001; 3:16-21.
- Hazelbag HM, Wessels JW, Mollevangers P, van den Berg E, Molenaar WM, Hogendoorn PC. Cytogenetic analysis of adamantinoma of long bones: further indications for a common histogenesis with osteofibrous dysplasia. Cancer Genet Cytogenet. 1997; 97:5-11.
- Campanacci M, Laus M. Osteofibrous dysplasia of the tibia and fibula. J Bone Joint Surg Am. 1981; 63:367-75.
- 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; 25:71-76.
- Campanacci M. Bone and Soft Tissue Tumors: Clinical Features, Imaging, Pathology and Treatment. Wien, Austria: Springer; 1999.
- Lokich J. Metastatic adamantinoma of bone to lung? A case report of the natural history and the use of chemotherapy and radiation therapy. Am J Clin Oncol. 1994; 17:157-159.
- Weiss SW, Dorfman HD. Adamantinoma of long bones. An analysis of nine new cases with emphasis on metastasizing lesions and fibrous dysplasia-like changes. Human Pathol. 1977; 8:141-153.
- Campanacci M, Giunti A, Bertoni F, Laus M, Gitelis S. Adamantinoma of the long bones: The experience at the Instituto Ortopedico Rizzoli. Am J Surg Pathol. 1981; 5:533-542.
- 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; 69:1177-1188.
- Rock MG, Beabout JW, Unni KK, Sim FH. Adamantinoma. Orthopedics. 1983; 6:472.
- Wang JW, Shih CH, Hsu WW, Chen WJ. Treatment of recurrent adamantinoma of the tibia by wide resection: report of three cases. J Formos Med Assoc. 1993; 92:274-277.
- Taylor GI. The current status of free vascularized bone grafts. Clin Plast Surg. 1983; 10:185-209.
- Weiland AJ, Moore JR, Daniel RK. Vascularized bone autografts. Experience with 41 cases. Clin Orthop Relat Res. 1983; 174:87-95.
- Szendroi M, Renyi-Vamos A, Marschalko P, Minik K, Kiss AL. Behavior of adamantinoma of the long bones based on long-term follow up studies. Magyar Traumatologia Ortopedia Kezsebeszet Plasztikai Sebeszet. 1994; 37:37-44.
- De Keyser F, Vansteenkiste J, Van Den Brande P, Demedts M, Van de Woestijne KP. Pulmonary metastases of a tibia adamantinoma. Case report and review of the literature. Acta Clin Belg. 1990; 45:31-33.
Drs Papagelopoulos and Mavrogenis are from the First Department of Orthopedic Surgery, Athens University Medical School, Athens, Greece, Dr Galanis is from the Division of Medical Oncology, Mayo College of Medicine, Rochester, Minn, Dr Savvidou is from the Department of Orthopedics, Thriasion General Hospital, Elefsis, Hellas-Greece, Ms Inwards is from the Division of Anatomic Pathology, Mayo College of Medicine, Rochester, Minn, and Dr Sim is from the Department of Orthopedic Surgery, Mayo College of Medicine, Rochester, Minn.
Drs Papagelopoulos, Mavrogenis, Galanis, Savvidou, and Sim and Ms Inwards have no industry relationship to declare.
The material presented at or in any Vindico Medical Education continuing education activity does not necessarily reflect the views and opinions of Vindico Medical Education or Orthopedics. Neither Vindico Medical Education or Orthopedics, nor the faculty endorse or recommend any techniques, commercial products, or manufacturers. The faculty/authors may discuss the use of materials and/or products that have not yet been approved by the US Food and Drug Administration. All readers and continuing education participants should verify all information before treating patients or utilizing any product.
Correspondence should be addressed to: Panayiotis J. Papagelopoulos, MD, DSc, Athens University Medical School, 4 Christovassili Street, Neo Psychikon, 15451, Athens, Greece.