Bone: Adamantinoma

2003-01-01   Hans Marten Hazelbag  , Pancras C.W. Hogendoorn  

1.Dept. of Pathology, Leiden University Medical Center, L1-Q, Leiden, the Netherlands

Summary

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.
Atlas Image
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).

Cytogenetics

Cytogenetics morphological

  • 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 Ewings sarcoma and adamantinoma, sometimes called atypical of Ewing-like adamantinoma. Ewings 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 Ewings 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 Ewings 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.

    • Article Bibliography

    Pubmed IDLast YearTitleAuthors
    20179241991Fibrous dysplasia vs adamantinoma of the tibia: differentiation based on discriminant analysis of clinical and plain film findings.Bloem JL et al
    95825231998Expression of growth factors and their receptors in adamantinoma of long bones and the implication for its histogenesis.Bovée JV et al
    81565031994Clonal chromosomal abnormalities in osteofibrous dysplasia. Implications for histopathogenesis and its relationship with adamantinoma.Bridge JA et al
    99898421999Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.Bridge JA et al
    100792501999Trisomies 8 and 20 characterize a subgroup of benign fibrous lesions arising in both soft tissue and bone.Bridge JA et al
    28049231989Morphologic diversity of long bone adamantinoma. The concept of differentiated (regressing) adamantinoma and its relationship to osteofibrous dysplasia.Czerniak B et al
    115921012001Adamantinoma-like Ewing's sarcoma and Ewing's-like adamantinoma. The t(11; 22), t(21; 22) status.Hauben E et al
    119109372001[Adamantinoma of the long bones: an anatomo-clinical review and its relationship with osteofibrous dysplasia].Hazelbag HM et al
    75676801995Adamantinoma of long bones. A histopathological and immunohistochemical study of 23 cases.Jundt G et al
    112270672001Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma.Kanamori M et al
    97124211998Osteofibrous dysplasia-like adamantinoma of bone: a report of five cases with immunohistochemical and ultrastructural studies.Kuruvilla G et al
    111070522000Expression 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 et al
    35140331986Adamantinoma of the appendicular skeleton--updated.Moon NF et al
    15990191992Cortical osteofibrous dysplasia of long bone and its relationship to adamantinoma. A clinicopathologic study of 30 cases.Sweet DE et al
    8528651977Adamantinoma of long bone. An analysis of nine new cases with emphasis on metastasizing lesions and fibrous dysplasia-like changes.Weiss SW et al

    Citation

    Hans Marten Hazelbag ; Pancras C.W. Hogendoorn

    Bone: Adamantinoma

    Atlas Genet Cytogenet Oncol Haematol. 2003-01-01

    Online version: http://atlasgeneticsoncology.org/solid-tumor/5154/bone-adamantinoma