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Bone: Adamantinoma

Written2003-01Hans Marten Hazelbag, Pancras C.W. Hogendoorn
Dept. of Pathology, Leiden University Medical Center, L1-Q, Leiden, the Netherlands

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ICD-Topo C400-C403,C408-C414,C418-C419 BONES & JOINTS
ICD-Morpho 9261/3 Adamantinoma of long bones
Atlas_Id 5154
Phylum Bones::Adamantinoma
WHO/OMS Classification Bones
Note Adamantinoma of long bones is a low-grade, malignant biphasic tumor, characterized by a variety of morphological patterns, most commonly epithelial cells, surrounded by a relatively bland spindle-cell osteo-fibrous component.

Clinics and Pathology

Etiology Cumulating evidence indicates that classic adamantinomas derive from their osteofibrous dysplasia (OFD)-like counterparts.OFD and adamantinoma show common cytogenetic abnormalities (see below), and by immunohistochemistry, it has been shown that the epithelial component of adamantinoma is directly derived from the fibrous tissue. However, clinical aggressiveness among OFD, OFD-like adamantinoma and classic adamantinoma varies considerably, and many OFD-like lesions may never progress to classic adamantinoma.
Epidemiology Adamantinomas are rare, they comprise 0.1-0.5% of primary bone tumors. The peak incidence is in the second and third decade. The youngest age group (up to 15 years) mainly includes patients with osteofibrous dysplasia (OFD)-like adamantinoma, whereas in older patients classic adamantinomas are predominant.
Clinics At conventional radiography, typically a well-circumscribed, central or eccentric, (multi-)lobulated osteolytic lesion is seen. Multifocality in the tibia as well as ipsilateral fibula is regularly observed. MRI is essential for pre-operative staging of the tumor and planning surgical margins. The treatment for most cases wide en-bloc resection.
Adamantinomas may display a protracted clinical behavior. Some tumors have radiologically proven to be present 30 years prior to histological diagnosis, whereas metastases may occur decades after local treatment. Recurrence rate after irradical surgery may be as high as 90%, whereas up to 25% of these patients may develop metastases.
Pathology Two main subtypes of adamantinoma are recognized: OFD-like adamantinomas lack a clear histological epithelial component, and mainly consist of osteofibrous tissue, in which woven bone trabeculae are rimmed by osteoblasts. Keratin immunohistochemistry highlights individual or small aggregates of positive cells. Classic adamantinomas have abundant epithelium, which may be arranged in basaloid, tubular, squamoid, spindle-cell, of mixed differentiation. Recently, sarcomatous dedifferentiation of the epithelial component has been described.
Figure 1: Classic adamantinoma, hematoxylin and eosin, x 100. Strings of epithelial cells embedded in fibrous tissue.
Figure 2: OFD-like adamantinoma, HE x 100. No epithelial cells are distinguishable in osteofibrous tissue.
Figure 3: OFD-like adamantinoma, immunohistochemistry for pankeratin, x 100. Individual keratin-positive cells (same case as figure 2).


  • With DNA flow and image cytometry it was shown that about 40% (6 of 15) of adamantinomas were aneuploid, all of them classic adamantinomas, and most of them near diploid. The aneuploid population was always restricted to the epithelial component.
  • p53-Protein accumulation was shown by immunohistochemistry (IHC) in 48% (12 of 25) adamantinomas, all classic subtype. LOH at the p53 locus was confirmed in DNA-sorted nuclei of epithelial cells in an IHC-positive tumor.
  • Cytogenetic analysis by GTG-banding is restricted to 15 cases of adamantinoma (n=11) and OFD (n=4) in literature. OFD and the fibrous and epithelial component of adamantinoma show comparable numerical chromosomal abnormalities, mainly involving trisomies of chromosomes 7, 8, 12, 19 and 21. These findings further substantiate the clonal origin of OFD and the common histogenesis of OFD and adamantinoma. The finding of translocations, deletions, and inversions is common but not structural, and only present in adamantinomas. This suggests that expansion of an abnormal clone to include structural changes may parallel progression from OFD to adamantinoma. One young patient with classic adamantinoma had a constitutional t(7;13)(q32;q14), also present in his father.
  • In literature some cases have been described with histological features of both Ewing's sarcoma and adamantinoma, sometimes called 'atypical' of 'Ewing-like' adamantinoma. Ewing's sarcoma is characterized by a t(11;22)(q24;q12). In one study on 3 archival cases with epithelial features, originally described as adamantinoma or non-typical Ewing's sarcoma (of which two were not located in the tibia), it was shown by FISH and RT-PCR that all had the typical t(11;22). They were therefore named 'adamantinoma-like' Ewing's sarcoma. Additionally, using RT-PCR on archival tissue, a t(11;22) or t(21;22) was not found in any of 12 informative adamantinomas. These data indicate that tumors showing overlapping morphological and immunohistochemical features can be readily distinguished with these techniques.
  • Bibliography

    Fibrous dysplasia vs adamantinoma of the tibia: differentiation based on discriminant analysis of clinical and plain film findings.
    Bloem JL, van der Heul RO, Schuttevaer HM, Kuipers D
    AJR. American journal of roentgenology. 1991 ; 156 (5) : 1017-1023.
    PMID 2017924
    Expression of growth factors and their receptors in adamantinoma of long bones and the implication for its histogenesis.
    Bovée JV, van den Broek LJ, de Boer WI, Hogendoorn PC
    The Journal of pathology. 1998 ; 184 (1) : 24-30.
    PMID 9582523
    Clonal chromosomal abnormalities in osteofibrous dysplasia. Implications for histopathogenesis and its relationship with adamantinoma.
    Bridge JA, Dembinski A, DeBoer J, Travis J, Neff JR
    Cancer. 1994 ; 73 (6) : 1746-1752.
    PMID 8156503
    Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.
    Bridge JA, Fidler ME, Neff JR, Degenhardt J, Wang M, Walker C, Dorfman HD, Baker KS, Seemayer TA
    The American journal of surgical pathology. 1999 ; 23 (2) : 159-165.
    PMID 9989842
    Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in both soft tissue and bone.
    Bridge JA, Swarts SJ, Buresh C, Nelson M, Degenhardt JM, Spanier S, Maale G, Meloni A, Lynch JC, Neff JR
    The American journal of pathology. 1999 ; 154 (3) : 729-733.
    PMID 10079250
    Morphologic diversity of long bone adamantinoma. The concept of differentiated (regressing) adamantinoma and its relationship to osteofibrous dysplasia.
    Czerniak B, Rojas-Corona RR, Dorfman HD
    Cancer. 1989 ; 64 (11) : 2319-2334.
    PMID 2804923
    Adamantinoma-like Ewing's sarcoma and Ewing's-like adamantinoma. The t(11; 22), t(21; 22) status.
    Hauben E, van den Broek LC, Van Marck E, Hogendoorn PC
    The Journal of pathology. 2001 ; 195 (2) : 218-221.
    PMID 11592101
    [Adamantinoma of the long bones: an anatomo-clinical review and its relationship with osteofibrous dysplasia]
    Hazelbag HM, Hogendoorn PC
    Annales de pathologie. 2001 ; 21 (6) : 499-511.
    PMID 11910937
    Adamantinoma. In: Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone.
    Hogendoorn PCW, Hashimoto H
    Lyon. : page I.
    Adamantinoma of long bones. A histopathological and immunohistochemical study of 23 cases.
    Jundt G, Remberger K, Roessner A, Schulz A, Bohndorf K
    Pathology, research and practice. 1995 ; 191 (2) : 112-120.
    PMID 7567680
    Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma.
    Kanamori M, Antonescu CR, Scott M, Bridge RS Jr, Neff JR, Spanier SS, Scarborough MT, Vergara G, Rosenthal HG, Bridge JA
    The Journal of molecular diagnostics : JMD. 2001 ; 3 (1) : 16-21.
    PMID 11227067
    Osteofibrous dysplasia-like adamantinoma of bone: a report of five cases with immunohistochemical and ultrastructural studies.
    Kuruvilla G, Steiner GC
    Human pathology. 1998 ; 29 (8) : 809-814.
    PMID 9712421
    Expression of cytokeratin 1, 5, 14, 19 and transforming growth factors-beta1, beta2, beta3 in osteofibrous dysplasia and adamantinoma: A possible association of transforming growth factor-beta with basal cell phenotype promotion.
    Maki M, Saitoh K, Kaneko Y, Fukayama M, Morohoshi T
    Pathology international. 2000 ; 50 (10) : 801-807.
    PMID 11107052
    Adamantinoma of the appendicular skeleton--updated.
    Moon NF, Mori H
    Clinical orthopaedics and related research. 1986 : 215-237.
    PMID 3514033
    Cortical osteofibrous dysplasia of long bone and its relationship to adamantinoma. A clinicopathologic study of 30 cases.
    Sweet DE, Vinh TN, Devaney K
    The American journal of surgical pathology. 1992 ; 16 (3) : 282-290.
    PMID 1599019
    Adamantinoma of long bone. An analysis of nine new cases with emphasis on metastasizing lesions and fibrous dysplasia-like changes.
    Weiss SW, Dorfman HD
    Human pathology. 1977 ; 8 (2) : 141-153.
    PMID 852865


    This paper should be referenced as such :
    Hazelbag, HM ; Hogendoorn, PCW
    Bone: Adamantinoma
    Atlas Genet Cytogenet Oncol Haematol. 2003;7(2):122-124.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

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