Mesenchymal-epithelial differentiation of adamantinoma of long bones: an immunohistochemical and ultrastructural study.

Three cases of adamantinoma were studied by electron microscopy and immunohistochemistry. In the tubular pattern, well-differentiated epithelial cells and glandular structures were present, in addition to ill-defined glands. In the basaloid pattern, less differentiated epithelial cells with discohesion were seen in the central epithelial masses. This study established the epithelial nature of some tubular structures with slit-like lumina, easily misinterpreted as capillaries by light microscopy. Results also showed that the irregular spaces observed within the basaloid pattern probably result from cell discohesion. Moreover, this investigation demonstrates the epithelial nature of a subset of spindle cells within the stroma of adamantinoma and offers ultrastructural evidence for a probable mesenchymal-epithelial transformation as its histogenesis.

Analysis of stromal cells in osteofibrous dysplasia and adamantinoma of long bones.

Adamantinoma of long bones and osteofibrous dysplasia are rare, osteolytic primary bone tumours of uncertain origin containing areas of fibrous and fibro-osseous proliferation. We investigated the nature of the stromal cells in adamantinoma of long bones and osteofibrous dysplasia, and determined cellular and molecular mechanisms of osteolysis in these tumours. Cell culture, molecular (RT-PCR, western blot) and immunohistochemical studies on cases of adamantinoma of long bones and of osteofibrous dysplasia were undertaken to determine the expression of epithelial, osteoblast and osteoclast markers. Ultrastructural and immunophenotypic studies on cultured adamantinoma and osteofibrous dysplasia stromal cells showed that these cells were mainly fibroblast-like with few cells expressing epithelial markers. Osteofibrous dysplasia but not adamantinoma cells expressed alkaline phosphatase. Both osteofibrous dysplasia and adamantinoma cells expressed the ostoclastogenic factors M-CSF and RANKL. Adamantinoma and osteofibrous dysplasia cells also expressed messenger RNA for osteocalcin, osteonectin, osteopontin, osterix and collagen type 1. Adamantinoma and osteofibrous dysplasia cells cultured alone on dentine slices were not capable of lacunar resorption, but in co-cultures with monocytes induced formation of osteoclast-like cells was observered. Cultured osteofibrous dysplasia and adamantinoma stromal cells show similar ultrastructural and immunophenotypic characteristics, and differentially express osteoblast markers. Promotion of osteoclastogenesis by stromal cells may contribute to osteolysis in adamantinoma of long bones and osteofibrous dysplasia.

p63 expression in adamantinoma.

Adamantinoma is a rare primary bone neoplasm with epithelial differentiation that is frequently associated with a concomitant fibrous component. Clinical, cytogenetic and histomorphologic overlap has previously been described with osteofibrous dysplasia, thereby suggesting a relationship between these two lesions. We performed a retrospective review of our archives to characterize the clinical and pathologic aspects of adamantinoma and osteofibrous dysplasia diagnosed at our institution, and to compare the expression patterns of p63 and keratin. Nine cases of adamantinoma (six classical, three osteofibrous dysplasia-like) and 11 cases of osteofibrous dysplasia were identified. The epithelial component in adamantinoma was found to stain for p63. Rare cells expressing p63 were also identified in eight cases of osteofibrous dysplasia. Expression of p63 was not identified in any of the five cases of fibrous dysplasia controls. The presence of staining for p63, albeit rare, in osteofibrous dysplasia supports the notion of a possible relationship between osteofibrous dysplasia and adamantinoma. Furthermore, our results suggest that, in some situations, p63 may be useful in helping differentiate metastatic carcinoma from adamantinoma.

Podoplanin expression in adamantinoma of long bones and osteofibrous dysplasia.

Adamantinoma of long bones (ALB) and osteofibrous dysplasia (OFD) are rare osteolytic bone tumours that principally arise in the tibia. Both ALB and OFD contain epithelial and stromal elements, as well as areas of fibro-osseous proliferation. We assessed expression of podoplanin, a glycoprotein found in osteocytes, in OFD and ALB as well as in fibrous dysplasia and metastatic cancer. Forty-two cases of ALB and OFD, 20 cases of fibrous dysplasia and 20 cases of metastatic carcinoma to bone were stained by immunohistochemistry for expression of podoplanin, epithelial (cytokeratin, epithelial membrane antigen) and vascular (CD34, LYVE-1) markers. Podoplanin was expressed in epithelial cells and tumour glands in ALB as well as in scattered intertrabecular stromal cells in both ALB and OFD. Podoplanin was not expressed by intertrabecular stromal cells in fibrous dysplasia or in metastatic adenocarcinoma. Podoplanin was expressed by osteocytes but not osteoblasts of woven and lamellar bone trabeculae in ALB, OFD, fibrous dysplasia and skeletal metastases. The finding of a common osteocyte marker in OFD/ALB stromal cells is in keeping with a close histogenetic relationship between OFD and ALB; this may reflect the prominence of fibro-osseous proliferation in these tumours. The expression of podoplanin in an osteolytic tumour of the tibia may be useful as a diagnostic discriminant in distinguishing OFD from fibrous dysplasia and ALB from metastatic adenocarcinoma.

Dedifferentiated classic adamantinoma of the tibia: a report of a case with eventual complete revertant mesenchymal phenotype.

Adamantinomas of the long bones are low-grade malignant tumours. They seem to be related to osteofibrous dysplasia with a mesenchymal-to-epithelial transformation. We report a case of an adamantinoma with a revertant sarcomatoid transformation that showed a complete loss of epithelial differentiation. It corresponded to a 41-year-old male presented with an 8-cm multilobated lesion in the centre of the distal tibia. On the en bloc resection specimen, areas of classic adamantinoma were found but most of the tumor corresponded to a high-grade neoplasm with 2 histologic patterns: one made up by epithelial nests with a basaloid arrangement and positive for pankeratins and so-called glandular keratins, and a second sarcomatoid component, negative for these epithelial markers. Five months after surgery the patient had a massive relapse that consisted solely of the second sarcomatous component also negative for epithelial antibodies.Three cases of adamantinomas with sarcomatoid transformation of the epithelial component have been described but the tumours still preserved an epithelial immunophenotype. However, our case represents the extreme end of the sarcomatoid dedifferentiation of a classic adamantinoma with complete sarcomatoid transformation and total loss of epithelial markers. To our knowledge this has not been described previously.

Primary adamantinoma of the rib. Unusual presentation for a bone neoplasm of uncertain origin.

Adamantinomas are rare, low-grade malignant intra-osseous tumors composed of epithelial and mesenchymal elements, which show a marked predilection for the tibia and fibula of young adult male patients. Although cases of adamantinoma located to the axial skeleton have been reported either as recurrent or metastatic disease, only two cases of primary adamantinoma located to the thoracic wall have been previously described. In this study we present the clinical, radiological and histopathological features of a 24-year-old male with a slow growing, solid-cystic, painful mass, located to the right 11th rib, which was morphological and immunohistochemically diagnosed as a primary classic adamantinoma. Radiological studies showed a multiloculated lesion with a solid component. The patient underwent a whole surgical resection of the lesion. Histologically, multiple foci of epithelial cells with basaloid and squamous components were found intermixed within a fibrous stromal tissue. Immunohistochemical analysis demonstrated expression of cytokeratins, EMA, vimentin and other epithelial markers. Primary affection of the rib is an unusual feature of classic adamantinomas.

Treatment of osteofibrous dysplasia and associated lesions.

PURPOSE: To report long term treatment outcomes of osteofibrous dysplasia and association with adamantinoma. PATIENTS AND METHODS: From January 1984 to July 2001, 14 patients with osteofibrous dysplasia were followed for an average of 108 months (78 to 260 months). Our patient group consisted of 6 men and 8 women, with a mean age of 13.9 years (2 to 65 years). We reviewed the clinical and pathological features of all 14 patients. RESULTS: Thirteen patients had a lesion in the tibia, while one patient had lesions in both the tibia and the fibula. Initial treatments were observation after biopsy (6 patients), curettage with or without a bone graft (3 patients), resection followed by a free vascularized fibular bone graft (4 patients), or resection and regeneration with the Ilizarov external fixation (1 patient). Curettage was performed on 6 patients due to recurrence or progression after the initial treatment. Among these patients, one was diagnosed with AD from the biopsy of the recurrent lesion. This patient was further treated by segmental resection and pasteurization. After the initial pathology slides of the 13 patients were reviewed with immunohistochemical cytokeratin staining, one patient diagnosis was changed from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. CONCLUSION: Some patients with osteofibrous dysplasia require close observation because of the high association risk between osteofibrous dysplasia and adamantinoma, Immunohistochemical staining may be helpful in differentiating these two diagnoses.

Treatment of Osteofibrous Dysplasia and Associated Lesions

PURPOSE: To report long term treatment outcomes of osteofibrous dysplasia and association with adamantinoma. PATIENTS AND METHODS: From January 1984 to July 2001, 14 patients with osteofibrous dysplasia were followed for an average of 108 months (78 to 260 months). Our patient group consisted of 6 men and 8 women, with a mean age of 13.9 years (2 to 65 years). We reviewed the clinical and pathological features of all 14 patients. RESULTS: Thirteen patients had a lesion in the tibia, while one patient had lesions in both the tibia and the fibula. Initial treatments were observation after biopsy (6 patients), curettage with or without a bone graft (3 patients), resection followed by a free vascularized fibular bone graft (4 patients), or resection and regeneration with the Ilizarov external fixation (1 patient). Curettage was performed on 6 patients due to recurrence or progression after the initial treatment. Among these patients, one was diagnosed with AD from the biopsy of the recurrent lesion. This patient was further treated by segmental resection and pasteurization. After the initial pathology slides of the 13 patients were reviewed with immunohistochemical cytokeratin staining, one patient diagnosis was changed from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. CONCLUSION: Some patients with osteofibrous dysplasia require close observation because of the high association risk between osteofibrous dysplasia and adamantinoma, Immunohistochemical staining may be helpful in differentiating these two diagnoses.

Preliminary report of expression of bax in oral cavity pathologies.

Bax is considered one of major effectors of apoptosis--programmed cell death. Immunohistochemical analysis of in vitro patterns of bax expression was mostly investigated in mammalian cell lines and tissues. The present study is the first in vivo molecular analysis of bax expression in oral cavity pathologies. The study population consisted of 45 patients with hyperplasia, neoplasm in situ malignancy, and carcinoma. Biopsies were taken from incision line, tumour section, and healthy tissue. bax expression was investigated depending on the site of biopsy material sampling and final histopathology result. No statistically significant difference was demonstrated in bax expression between four hyperplasia subgroups. However, statistically significant differences in bax expression were found between the three basic study groups (P = 0.001). Statistically significant differences in bax expression were demonstrated depending on tissue collection site (P = 0.0002). We conclude that differences in bax expression may play a role in the pathogenesis of neoplastic disease.