Original articlesGenetic Characterization of Angiomatoid Fibrous Histiocytoma Identifies Fusion of the FUS and ATF-1 Genes Induced by a Chromosomal Translocation Involving Bands 12q13 and 16p11
Introduction
Descriptions of angiomatoid fibrous histiocytoma (AFH) have appeared in the medical literature for the last 20 years, beginning with the widely cited monograph by Franz Enzinger [1]. Typically, this tumor forms solid, lobulated sheets of plump to spindled cells having histiocytic features adjacent to areas of hemorrhage. When the classic cyst-like spaces, the peripheral fibrosis, and chronic inflammatory infiltrate are not seen, these lesions may be misdiagnosed as cellular or sclerosing hemangiomas, hemangiopericytoma, hemangioendothelioma, nodular synovitis, or malignant fibrous histiocytoma.
The multiplicity of antigen expression and ultrastructural features of AFH spur continued interest in its histogenesis. Most studies document histiocytic differentiation with frequent, but not universal, positivity for lysozyme, chymotrypsin, alpha-1-antichymotrypsin, alpha-1-antitrypsin, and CD 68 2, 3, 4, 5, 6. Myxoid differentiation has been described in six cases [7]. Ultrastructural morphology supports histiocytic, vascular, smooth, and striated muscle differentiation 2, 8, 9, 10. Thus, one may conclude that AFH arises from a pluripotent mesenchymal cell.
There are currently no reliable indicators of behavior. The majority of patients are cured upon initial excision but recurrences are documented. Using variable lengths of follow-up, recurrences develop in about 19% of patients 1, 2, 3, 4, 5, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17. Of the 33 patients with recurrences, 7 died of tumor 1, 4, 7, 15, 17.
Investigators hoped that flow cytometry might aid in prognostication; however, 26 cases of AFH were found to be all diploid 5, 18. Five of those patients had recurrences and 1 died of metastases. To add to the scant knowledge of the chromosomal make-up of these tumors, we present karyotypic, fluorescence in situ hybridization (FISH), flow cytometric, and molecular data of another AFH that arose and recurred in a 5.5-year-old girl. In addition, we show that the FUS and ATF-1 genes are fused as a result of chromosomal translocation involving bands 12q13 and 16p11.
Section snippets
Case report
A 5.5-year-old girl presented to her pediatrician with a firm mass in her left forearm. The mass had enlarged over the preceding 7 months. Physical examination revealed a healthy child with a slightly mobile, firm, nontender mass in the left forearm covered with normal, nonerythematous skin. Magnetic resonance imaging located the mass deep to the subcutaneous tissue. Upon surgical excision, the mass was noted to be infiltrating the adjacent fascia. It was completely removed without
Materials and methods
Fresh tumor tissue from the first excision was minced and grown in AmnioMAX (GIBCO/BRL). Cells were harvested after 4 days, then examined following trypsin-Giemsa banding. Fluorescence in situ hybridization (FISH) using Vysis WCP Chromosome Paint DNA FISH probes for chromosomes 2, 12, 16, and 17 facilitated further elucidation of the rearranged chromosomes. The FISH methods were performed according to the manufacturer's instructions. DNA flow cytometry was conducted on both lesions using a
Results
Of the 20 cells examined, 1 had a normal female karyotype. The remaining 19 cells displayed complex rearrangements involving chromosomes 2, 12, 16, and 17. The derivative 17 appears to have a pericentric inversion. There was also a terminal deletion of the long arm of chromosome 11 (Fig. 3). The FISH of the cultured cells, as described above, confirmed a karyotype as follows: 46,XX,der(2),t(2;17;12;16)(2pter→2q13::2q33→2qter), del(11) (q24),der(12),t(2;17;12;16)(12pter→12q13::12q24.1→12qter),
Discussion
Other histiocytic lesions have shown equally complicated, but disparate karyotypic abnormalities. Two reports of plexiform fibrohistiocytic tumor documented karyotypes 46,XY,−6,−8,del(4)(q25q31),del(20)(q11.2),+der(8)t(8;?)(p22;?),+mar and 46,XY,t(4;15)(q21;q15) 21, 22. A case of malignant histiocytosis in a 12-year-old boy proved to have the karyotype of 45,Xp+,−Y,9p+,18q− [23]. A malignant fibrous histiocytoma arising in the brain of a 6-year-old girl had a very complex karyotype with
Acknowledgements
The authors wish to thank Margareth Isaksson for her excellent technical assistance and Drs. Cheryl Coffin and Kumarasen Cooper for their help in reaching the correct diagnosis. This study was supported, in part, by grants from the Swedish Cancer Society, the Children's Cancer Fund of Sweden, and the Medical Faculty of Lund University.
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