Dedifferentiated adamantinoma with revertant mesenchymal phenotype

In adamantinoma of long bones, an osteofibrous dysplasia-like form with scattered epithelial elements and a classic form with abundant epithelium are distinguished. Osteofibrous dysplasia-like adamantinomas occur in children and adolescents and behave relatively benign, whereas classic adamantinomas predominate in adults and have a more aggressive clinical course. Because some osteofibrous dysplasia-like tumors have progressed to classic adamantinomas, it is hypothesized that the former is a potential precursor of the latter, showing mesenchymal-to-epithelial transformation. We report a new morphologic variant of adamantinoma in three patients with sarcomatoid transformation of the epithelial component: one in a primary tumor and two in local recurrences. One patient died of metastatic disease. Histologically, the tumors showed loss of the original characteristic epithelial differentiation with transition to fields of highly pleomorphic cells without epithelial features, high mitotic count, and deposition of osteoid and chondroid matrix. These dedifferentiated areas showed pankeratin positivity as well, although there were some changes in keratin subclass profile compared with other classic adamantinomas. This peculiar variant of long bone adamantinoma shows that in addition to mesenchymal-to-epithelial transformation in the early stage of development, progression to an aggressive subtype may be associated with epithelial-to-mesenchymal transition ("sarcomatoid dedifferentiation"), in which the epithelial immunophenotype is conserved. Thereby it may serve as an example of the plasticity of the mesenchymal phenotype. When confronted with a biopsy of a cortical tumor of the tibia showing sarcomatoid morphology and keratin positivity, adamantinoma should be included in the differential diagnosis, as its distinction has important implications for treatment and prognosis.