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H M Hazelbag

Publications and source records attributed to H M Hazelbag.

8 recordsLinked to original sources

[Adamantinoma of the long bones: an anatomo-clinical review and its relationship with osteofibrous dysplasia].

Adamantinoma of long bones is a perplexing tumor for its histology as well as for its histogenesis. Recent progress has been made with ultrastructural and immunohistochemical works. The possible relationship with osteofibrous dysplasia is the subject of conflicting discussions and the potential link has implications for the diagnosis, prognosis, and treatment. Clinical aspects of adamantinomas are described: location, age, gender, symptoms, imaging, diagnosis, treatment, clinical course, prognosis. Histopathology is extensively covered for usual and peculiar forms. Immunohistochemical results are described and discussed. Data of electron microscopy, cytological findings, and DNA flow cytometry are also reported. The putative association with osteofibrous dysplasia is the subject of an extensive development with the report of the personal experience and works of the authors, and arguments for viewing osteofibrous dysplasia and "osteofibrous dysplasia-like" adamantinomas as precursor lesions of classic adamantinomas are favoured.

Bone Neoplasms↗

Distribution of extracellular matrix components in adamantinoma of long bones suggests fibrous-to-epithelial transformation.

Adamantinoma of long bones is a rare skeletal tumor of unknown origin with epithelial and fibrous elements. The ill-defined distinction between the two components in some cases earlier led to the assumption that these might be derived from the same (mesenchymal) stem cell. In this study, we investigated the distribution of extracellular matrix components in 21 adamantinomas by immunohistochemistry, to gain information on the interaction between the epithelial and fibrous parts of the tumor. Collagens I and III, and fibronectin were generally present in the (osteo-)fibrous tissue of adamantinoma but lacked in the epithelial aggregates. There was a clear relation between the identification of the epithelial and fibrous components at the histological level, and the staining for basement membrane proteins collagen IV and laminin. Prominent areas with cohesive epithelial growth were surrounded by continuous basement membranes, whereas less distinct epithelial islands contained membrane interruptions or had no surrounding basement membrane at all. Tenascin stained intensely surrounding demarcated epithelial aggregates, but weakly or absent more distantly. Osteofibrous dysplasia (OFD)-like tumors displayed local spicular density or pericellular staining of basement membrane factors in fields of isolated keratin-positive cells. These findings suggest that in adamantinoma individual epithelial cells transform from the osteofibrous tissue and thereafter form clusters of epithelium, as can be recognized in classic adamantinoma. This is in analogy to the development of the glandular component of biphasic synovial sarcoma. The fibrous part of adamantinoma is, however, believed to be of benign nature. These results further substantiate the hypothesis of osteofibrous dysplasia being a potential precursor lesion of adamantinoma.

Ameloblastoma↗

Cytogenetic analysis of adamantinoma of long bones: further indications for a common histogenesis with osteofibrous dysplasia.

Five adamantinomas of long bones were cytogenetically characterized to investigate the role of chromosomal aberrations in their histogenesis, as well as a putative relationship between adamantinoma and osteofibrous dysplasia (OFD). Three tumors had a classic histologic subtype, with abundant epithelium. Two of them revealed trisomies 7, 8, 12, and 19, combined with a balanced translocation, t(10;12), with centromere breakpoints in one tumor. The third showed a karyotype 51,XY, +X, +7, +12, +19, +21. The fourth tumor, of OFD-like subtype, showed trisomies 7, 8, and a small marker chromosome in a low percentage of cells. The fifth tumor, also of OFD-like subtype, displayed only a few keratin-positive cells from the multiple tissue blocks investigated. This latter tumor revealed a clonal abnormality with a karyotype 46,XX,t(2;11)(p23;q14)inv(11)(p14q14), which was confirmed with fluorescence in situ hybridization (FISH), using chromosome-specific library probes and chromosome 11 locus-specific probes. The trisomies 7, 8, and 12 also were described in OFD, which suggests a common histogenesis of OFD and adamantinoma. Our findings further support the probability of clonal origin of OFD. The OFD-like component may be an integral element of adamantinoma, rather than a tissue reaction to epithelial tumor cells.

Adolescent↗

Immunostaining of chain-specific keratins on formalin-fixed, paraffin-embedded tissues: a comparison of various antigen retrieval systems using microwave heating and proteolytic pre-treatments.

The use of chain-specific monoclonal antibodies (MAbs) against keratins in pathology is hampered by their limited staining on formalin-fixed, paraffin-embedded tissue. In the present study, various treatments before immunohistochemistry on paraffin sections were compared, including proteolytic enzymes and microwave antigen retrieval in various solutions. Sections of normal cervical and skin tissue were stained in a three-step immunoperoxidase method, employing a broad panel of MAbs against chain-specific keratins 4, 5, 7, 8, 10, 13, 14, 17, 18, 19 and pankeratin. Using microwave heating, Target Unmasking Fluid (TUF), Antigen Retrieval Solution (ARS), a simple detergent solution (DET), PBS, and distilled water (MiQ) were compared. Microwave heating in PBS or MiQ strongly improved staining results. Moreover, microwave pre-treatment in TUF or DET gave excellent and specific staining with the majority of MAbs tested, comparable with or even better than staining obtained on frozen sections. Using microwave antigen retrieval, tissue morphology remained optimal, and only in a very limited number of MAbs did immunoreactivity on paraffin sections fail to be restored. Proteolytic pre-treatment with trypsin, pepsin, or pronase gave moderate to strong staining with some of the MAbs. Other MAbs, for which microwave pre-treatment was able to restore the loss of immunoreactivity, failed to give appropriate staining with proteolytic pre-treatment. Our results show that microwave heating in either TUF or a simple detergent solution before immunohistochemistry is a reliable method for antigen retrieval of chain-specific keratins in formalin-fixed, paraffin-embedded tissues.

Antibodies, Monoclonal↗

DNA aberrations in the epithelial cell component of adamantinoma of long bones.

Adamantinoma of long bones is a rare malignant tumor composed of cells with epithelial characteristics in various differentiation patterns surrounded by fibrous cells. Evidence as to whether this neoplasm should be designated as an epithelial bone tumor or a biphasic sarcoma with both epithelial and mesenchymal features is lacking. In this study the nature of the mesenchymal and epithelial components of adamantinoma was investigated by DNA flow cytometry, DNA image cytometry, p53 immunohistochemistry, and polymerase chain reaction-based loss of heterozygosity detection at the p53 locus. Specimens from 6 of 15 patients (40%) analyzed by flow cytometry had an aneuploid DNA index. Image cytometry analysis of Feulgen-stained paraffin sections of 6 aneuploid and 2 diploid tumors revealed that aneuploid nuclei were detected in cells with an epithelial phenotype only, whereas all fibrous cells were diploid. Immunohistochemistry for p53 on specimens from 25 patients revealed moderate or strong immunoreactivity in 12 tumors (48%) restricted to the epithelial cells. Loss of heterozygosity at the p53 locus could be confirmed in the epithelial component of an immunohistochemically p53-positive tumor. Additionally, sections of 7 lung metastases were studied histologically. Only keratin-positive epithelial cells, predominantly in the spindle cell pattern, were present in these metastases, whereas the osteofibrous tissue present in the primary tumors was not detected. These results suggest that either adamantinoma consists of a malignant epithelial part with a reactive osteofibrous stroma or that the malignant epithelial cells develop next to a proliferating benign fibrous component. Additional analysis of common genetic abnormalities in the fibrous and epithelial cells of adamantinoma is therefore indicated.

Adolescent↗

Adamantinoma of the long bones. A clinicopathological study of thirty-two patients with emphasis on histological subtype, precursor lesion, and biological behavior.

The records of thirty-two patients who had had an adamantinoma of the long bones were examined to investigate the relationship between the clinical presentation, the histological subtype, and the method of treatment, and the clinical result. All histological patterns of differentiation that are characteristic of adamantinoma were observed, including the basaloid, spindle-cell, tubular, squamous, and osteofibrous dysplasia-like subtypes. Follow-up data were available for twenty-eight (88 per cent) of the thirty-two patients. These patients were followed for a mean duration of 122 months (range, eleven months to twenty-nine years and two months). Nine patients (32 per cent), all of whom had been managed with an intralesional or marginal procedure, had a local recurrence of the tumor after a mean disease developed in three of the nine patients. In five other patients, metastasis developed without having been preceded by a local recurrence. Thus, the over-all rate of metastasis was 29 per cent (eight patients). The mean duration of survival for the patients who had metastasis was twelve years and eight months. Statistical analysis of various clinicopathological variables revealed intralesional or marginal excision to be the most significant risk factor for a local recurrence or metastasis (p < 0.001). Two patients who had had a presumed osteofibrous dysplasia-like adamantinoma, which contained few isolated keratin-positive epithelial cells within the stroma at the time of presentation, had a full-blown adamantinoma at the time of the local recurrence. Although the clinical course that was observed may be the result of a sampling error, it poses questions as to the regressive nature of osteofibrous dysplasia-like adamantinoma. On the basis of our findings and the data in the literature, we believe that an osteofibrous dysplasia-like adamantinoma may be a precursor lesion of the classic type of adamantinoma.

Adolescent↗

Adamantinoma of the long bones: keratin subclass immunoreactivity pattern with reference to its histogenesis.

To gain more insight into the differentiation characteristics of the epithelial cells of the adamantinoma of the long bones, we studied the specific keratin immunoreactivity pattern using monoclonal antibodies on 34 primary, recurrent, or metastatic specimens of 22 patients. The results revealed the widespread presence of keratins 14 and 19 in all specimens studied; 74% showed immunoreactivity of keratin 5, and focal staining of keratin 17 was detected in 50%. Keratins 7 and 13 were found in three adamantinoma specimens. This keratin immunoreactivity pattern was independent of histologic subtype, despite marked variety in differentiation pattern, suggesting a common histogenesis for all subtypes of adamantinoma. Furthermore, the pattern was conserved both in local recurrences and in metastasis. The major pattern found in our study differs significantly from other bone and soft tissue tumors with known epithelial characteristics, e.g., synovial sarcomas, chordomas, and epithelioid sarcomas, in that it lacks immunoreactivity of keratins 8 and 18. Our results suggest a basal epithelial cell-like differentiation of adamantinomas.

Adolescent↗