Adamantinoma of Long Bones

Staging is according to bone sarcoma protocols (see TNM staging of tumors of bone).

Rare cases of OFD-like adamantinoma seem to arise from pre-existing OFD. OFD-like adamantinoma may also rarely progress into classic adamantinoma. Dedifferentiated adamantinoma arises in the setting of pre-existing classic adamantinoma.

A recurrent pattern of numerical abnormalities featuring extra copies of chromosomes 7, 8, 12, 19, and/or 21 has been detected in classic as well as OFD-like adamantinoma. Extra copies of one or more of these chromosomes (except for chromosome 19) have also been identified in OFD, supporting a related pathogenesis. In addition to trisomy 19, structural abnormalities including translocations and marker chromosomes have been reported in adamantinoma, but not in OFD. The progressive complexity of the karyotypic aberrations observed in OFD, OFD-like adamantinoma, and classic adamantinoma may be indicative of a multistep transformation process.

Trisomies 7, 8, and 12 have not been observed in osteoblasts or osteoclasts, suggesting that the osseous component is reactive and non-neoplastic, in contrast with the presence of these trisomies in the spindle cell stroma component of the same lesions. DNA index studies have shown that in aneuploid adamantinomas, the aneuploid population is always restricted to the epithelial component. TP53 aberrations are also restricted to the epithelial component.

Classic adamantinoma usually presents as a cortical, well-demarcated, lobulated, whitish-grey gritty tumor with peripheral sclerosis. It may be a single lesion or occasionally multifocal. Small lesions remain intracortical. Larger tumors may show intramedullary extension and cortical breakthrough, with soft tissue invasion in a minority of cases. Macroscopically detectable cystic spaces are common, filled with straw-coloured or blood-like fluid. The tumor varies in size from less than 1 cm to more than 10 cm.

The distinction between OFD-like and classic adamantinomas depends on the extent of the epithelial component. OFD-like adamantinoma contains a predominance of OFD-like areas with only small nests of epithelial cells; the epithelial nests may be difficult to see or to distinguish from endothelial cells by light microscopy. In classic adamantinoma, the epithelial component is prominent, with inconspicuous OFD-like areas. The epithelial component may be tubular, squamous, basaloid, or spindle-shaped. The basaloid cells usually have peripheral palisading and central stellate or spindle-shaped cells. By far the rarest subtype is dedifferentiated adamantinoma. In these tumors, areas of classic adamantinoma gradually merge with a diffuse growing proliferation in which the characteristic epithelial differentiation is lost and instead pleomorphic cells are present, with a high mitotic count. Chondroid differentiation, osteoid deposition, and clear cell changes can be seen.

Immunohistochemically
Immunohistochemically, the fibrous tissue is positive for vimentin. The epithelial cells show coexpression of keratin, EMA, vimentin, p63, and podoplanin. Chain-specific keratin expression reveals a predominantly basal epithelial cell differentiation, regardless of subtype, with widespread presence of basal epithelial cell keratins CK5, CK14, and CK19. CK1, CK13, and CK17 are also variably present. CK8 and CK18 are virtually absent.

Not clinically relevant.

Risk factors for recurrence are intralesional or marginal surgery and extracompartmental growth. In OFD-like adamantinoma, recurrence rates are about 20%. OFD-like adamantinomas may rarely metastasize after recurrence and subsequent progression to classic adamantinoma. In classic adamantinoma, the recurrence rate after non-radical surgery may be as high as 90%. Recurrence is associated with an increase in the ratio of epithelium to stroma and with more-aggressive behaviour. Additionally, male sex, female sex combined with young age, pain at presentation, short duration of symptoms, young age (less than 20 years), and lack of squamous differentiation of the tumor have been associated with increased rates of recurrence or metastasis. Classic adamantinomas metastasize in 12–29% of patients, with comparable mortality rates. The tumor spreads to regional lymph nodes and the lungs, and infrequently to the skeleton, liver, and brain. Dedifferentiated adamantinoma has an aggressive clinical course.

Not clinically relevant.

Essential: bone tumor with compatible imaging; primary biphasic fibro-osseous tumor of bone, almost exclusively of the tibia and/or fibula; always involves cortex; OFD-like adamantinoma: inconspicuous clusters of epithelial cells, embedded in the fibro-osseous stroma; classic adamantinoma: obvious epithelial elements embedded in fibro-osseous stroma; dedifferentiated adamantinoma: classic adamantinoma in which the epithelial component has progressed to high-grade sarcoma.