Adamantinoma is a rare low-grade malignant bone tumor of uncertain histogenesis which occurs commonly in the diaphyses and metaphyses of the tibia. The term adamantinoma has been given to this tumor due to its histological resemblance to ameloblastoma of the jaws . Its histopathology shows biphasic patterns of epithelial cells and osteofibrous components. There are two types of adamantinoma: the classical and the differentiated type which resembles osteofibrous dysplasia . Despite advances in imaging techniques, the definitive diagnosis of adamantinoma is mainly established by histopathological examination.
The origin of adamantinoma is unknown. The most popular theory is that of displacement of basal epithelial cells of skin during embryological development . This theory is supported by the fact that the anterior tibia where enchondrally formed bone is closest to the skin surface, is predominantly involved by adamantinoma. Based on immunohistochemical and ultrastructural studies, there is a suggestion that adamantinoma may be of epithelial origin . The possible relationship between adamantinoma and osteofibrous dysplasia is still a matter of debate. The potential link between these two lesions has implications for the diagnosis, prognosis, and treatment .
Adamantinoma is a rare tumor accounting for approximately 0.4% of all primary malignant bone tumors. There is a slight male predominance with a sex-ratio of 5:4. Adamantinomas frequently occur in young to middle-aged adults (20 to 40 years of age) but rarely affect elderly individuals and children . The most common sites involved by adamantinoma are the anterior metaphysis or diaphysis of the tibia. Other sites include the fibula, ulna, femur, humerus, and radius .
Classic adamantinoma usually presents as a cortical, well-demarcated, yellowish-grey, lobulated tumor of a firm to bony consistency with peripheral sclerosis. It may be a single lesion or occasionally multifocal. Macroscopically detectable cystic spaces are commonly filled with straw-colored or blood-like fluid.
Classical adamantinomas are characterized by easily recognizable epithelial and osteofibrous components that may be mixed in various proportions and differentiation patterns. The four main differentiating patterns of classic adamantinoma are:
The first two patterns are most commonly encountered, but all patterns may be present. The spindle-cell component is more often observed in recurrences, lining cystic spaces, and in metastases. The osteofibrous component is composed of storiform-oriented spindle cells. Woven bone trabeculae are usually present in, or next to the center of the lesion prominently rimmed by osteoblasts, and with varying amounts of transformation to a lamellar bone at the periphery of the tumor. Foam cells or myxoid change may be present, and mast cells or multinucleated giant cells are occasionally detected. Mitotic activity is usually low. A fifth histological pattern, the so-called osteofibrous dysplasia-like variant, is characterized by a predominance of osteofibrous tissue, in which small groups of epithelial cells are only encountered by careful search or immunohistochemistry.
Extensive sampling of adamantinoma is significant especially in the differentiated form where the epithelial component is only focally encountered.
The fibrous tissue is positive for vimentin. The epithelial cells show coexpression of keratin, EMA, vimentin, p63, and podoplanin . Estrogen, progesterone, and N-cadherins are found in classic, but not in osteofibrous dysplasia-like adamantinoma . In classic adamantinomas, the epithelial component is surrounded by a continuous basement membrane consisting of collagen IV, laminin and galectin 3 , whereas less distinct epithelial islands show multiple interruptions or no surrounding basement membrane at all. EGF/EGFR expression is restricted to the epithelial component. FGF2/FGFR1 is present in both parts , while in culture, the cells express M-CSF and RANKL, which may contribute to the osteolysis observed. .
Clinically, adamantinoma often displays a protracted clinical behavior and gradually enlarges in size. The main complaint is a slow-growing swelling with or without pain. . Bone deformity and pathological fracture are other features which lead the patient to seek medical attention. The patient might also present with neurological deficits when the spine is involved .
On X-ray, the tumor is typically well-circumscribed, cortical, multi-lobulated and osteolytic. Intra-lesional opacities, septation, and peripheral sclerosis may also be seen. Multifocality within the same bone is regularly observed. The multifocal radiolucencies which are surrounded by ring-shaped densities produce the characteristic ''soap-bubble'' appearance . The lesion commonly remains intracortical and extends longitudinally, but may also destroy the cortex and invade the medullary cavity or surrounding periosteum and soft tissue. This situation is usually accompanied by a lamellar or solid periosteal reaction.
Computed tomography scan:
Computed tomography scan demonstrates the soft tissue extension and cortical involvement when they exist. However, it does not depict the intraosseous extension of adamantinomas. CT scan plays a role in the routine work-up of adamantinomas and is useful in detecting pulmonary metastases .
Magnetic resonance imaging:
MRI plays a crucial role in locoregional staging since it depicts distant cortical foci, intramedullary and soft tissue extension. MRI is also a useful tool for the determination of tumor-free margins as well as the strategy for reconstructive surgery 
Two morphological patterns of adamantinoma are described on MRI:
The most effective treatment of adamantinoma is wide excision with clear margins . After en block wide resection, reconstruction of the limb can be performed with distraction allografts, osteogenesis, non-vascularized autogenous bone grafts vascularized autografts and metallic segmental replacement . Amputation for adamantinoma does not improve survival rates compared to limb-preserving surgery . Because of the high rate of recurrence, curettage is not recommended . Radiotherapy and chemotherapy are not effective in the treatment of adamantinoma .
Several authors have pointed to the close relationship between differentiated adamantinoma (osteofibrous dysplasia-like adamantinoma) and osteofibrous dysplasia, which can cause differential diagnostic problems due to similar histological and radiological appearance and typical location in the tibia . Clinically, radiologically and histologically adamantinoma can resemble several bone tumors including bone cysts, giant cell tumor and malignant tumors (chondrosarcoma, angiosarcoma, and metastases) .
Adamantinoma is a locally aggressive neoplasm with the potential to metastasize. After inadequate surgery, recurrence of the tumor is frequent.
The risk factors for recurrent or metastatic disease are :
Adamantinoma metastasizes in about 15-30% of cases by a hematogenous or lymphatic route to other sites of the body, frequently to the lungs or lymph nodes, less frequently to the bones and abdominal viscera .
Patients and their families need to be educated on how to recognize the early signs and symptom of bone tumors. Patients with signs of bone pain, swelling of bones or joints, any palpable mass found on the bones, should seek early intervention.
Adamantinoma is ideally managed by a multidisciplinary team that consists of orthopedists, radiologists, surgical oncologists, oncologists, and pathologists. Correlation between gross, radiographic, and microscopic features of the lesion is crucial to establish the definitive diagnosis of adamantinoma. Despite its rarity, it is essential to recognize this bone tumor since adequate treatment in early stages result in a better prognosis. Postoperatively, patients require long term follow-up due to the possibility of tumor recurrence and distant metastases.
|Puchner SE,Varga R,Hobusch GM,Kasparek M,Panotopoulos J,Lang S,Windhager R,Funovics PT, Long-term outcome following treatment of Adamantinoma and Osteofibrous dysplasia of long bones. Orthopaedics [PubMed]|
|Jundt G,Remberger K,Roessner A,Schulz A,Bohndorf K, Adamantinoma of long bones. A histopathological and immunohistochemical study of 23 cases. Pathology, research and practice. 1995 Mar; [PubMed]|
|Qureshi AA,Shott S,Mallin BA,Gitelis S, Current trends in the management of adamantinoma of long bones. An international study. The Journal of bone and joint surgery. American volume. 2000 Aug; [PubMed]|
|Szendroi M,Antal I,Arató G, Adamantinoma of long bones: a long-term follow-up study of 11 cases. Pathology oncology research : POR. 2009 Jun; [PubMed]|
|Yoshida S,Murakami T,Suzuki K,Itou S,Watanuki M,Hosaka M,Hagiwara Y, Adamantinoma Arising in the Distal End of the Fibula. Rare tumors. 2017 Mar 24; [PubMed]|
|Keeney GL,Unni KK,Beabout JW,Pritchard DJ, Adamantinoma of long bones. A clinicopathologic study of 85 cases. Cancer. 1989 Aug 1; [PubMed]|
|Khémiri C,Mrabet D,Mizouni H,Abbes I,Mnif E,Sellami S,Essaddem H, Adamantinoma of the tibia and fibula with pulmonary metastasis: an unusual presentation. BMJ case reports. 2011 Oct 16; [PubMed]|
|Houdek MT,Sherman CE,Inwards CY,Wenger DE,Rose PS,Sim FH, Adamantinoma of bone: Long-term follow-up of 46 consecutive patients. Journal of surgical oncology. 2018 Dec; [PubMed]|
|Jain D,Jain VK,Vasishta RK,Ranjan P,Kumar Y, Adamantinoma: a clinicopathological review and update. Diagnostic pathology. 2008 Feb 15; [PubMed]|
|Dickson BC,Gortzak Y,Bell RS,Ferguson PC,Howarth DJ,Wunder JS,Kandel RA, p63 expression in adamantinoma. Virchows Archiv : an international journal of pathology. 2011 Jul; [PubMed]|
|Kashima TG,Dongre A,Flanagan AM,Hogendoorn PC,Taylor R,Athanasou NA, Podoplanin expression in adamantinoma of long bones and osteofibrous dysplasia. Virchows Archiv : an international journal of pathology. 2011 Jul; [PubMed]|
|Camp MD,Tompkins RK,Spanier SS,Bridge JA,Bush CH, Best cases from the AFIP: Adamantinoma of the tibia and fibula with cytogenetic analysis. Radiographics : a review publication of the Radiological Society of North America, Inc. 2008 Jul-Aug; [PubMed]|
|Kanamori M,Antonescu CR,Scott M,Bridge RS Jr,Neff JR,Spanier SS,Scarborough MT,Vergara G,Rosenthal HG,Bridge JA, Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma. The Journal of molecular diagnostics : JMD. 2001 Feb; [PubMed]|
|Van der Woude HJ,Hazelbag HM,Bloem JL,Taminiau AH,Hogendoorn PC, MRI of adamantinoma of long bones in correlation with histopathology. AJR. American journal of roentgenology. 2004 Dec; [PubMed]|
|Springfield DS,Rosenberg AE,Mankin HJ,Mindell ER, Relationship between osteofibrous dysplasia and adamantinoma. Clinical orthopaedics and related research. 1994 Dec; [PubMed]|
|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. Pediatric radiology. 2006 Oct; [PubMed]|
|Moon NF,Mori H, Adamantinoma of the appendicular skeleton--updated. Clinical orthopaedics and related research. 1986 Mar; [PubMed]|
|Zumárraga JP,Cartolano R,Kohara MT,Baptista AM,Dos Santos FG,de Camargo OP, TIBIAL ADAMANTINOMA: ANALYSIS OF SEVEN CONSECUTIVE CASES IN A SINGLE INSTITUTION. Acta ortopedica brasileira. 2018; [PubMed]|
|Maki M,Athanasou N, Osteofibrous dysplasia and adamantinoma: correlation of proto-oncogene product and matrix protein expression. Human pathology. 2004 Jan; [PubMed]|
|Bovée 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. The Journal of pathology. 1998 Jan; [PubMed]|
|Taylor RM,Kashima TG,Ferguson DJ,Szuhai K,Hogendoorn PC,Athanasou NA, Analysis of stromal cells in osteofibrous dysplasia and adamantinoma of long bones. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2012 Jan; [PubMed]|
|Satyanarayana S,Jawed KZ,Sirohi D,Sikdar J, Adamantinoma of Tibia. Medical journal, Armed Forces India. 2002 Oct; [PubMed]|
The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Surgery-Orthopaedic. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.
StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Surgery-Orthopaedic, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Surgery-Orthopaedic, you will already be prepared.
Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Surgery-Orthopaedic. When it is time for the Surgery-Orthopaedic board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Surgery-Orthopaedic.