부산대학교 도서관

Previous studies showed that ALK is often positive in epithelioid fibrous histiocytoma (EFH). Two cases of EFH with ALKgene fusions have been recorded. Our objective was to study a series of EFH to present histopathological variations of EFH, identify novel ALKgene fusions, and determine whether there is a correlation between histopathological features and particular gene. We investigated 14 cases of EFH, all ALK immunopositive. The cases were assessed histopathologically as well as for ALKand TFE-3rearrangements using FISH and ALKgene fusions using next-generation sequencing. The analysis of the sequencing results was performed using the Archer Analysis software (v5; ArcherDX Inc). The study group consisted of 8 female and 6 male patients, ranging in age from 18 to 79 years (mean 42 years; median 37.5 years). All presented with a solitary lesion. Microscopically, most lesions were polypoid and composed of epithelioid cells with ample cytoplasm. In addition, a variable number of bi-, tri-, or multinucleated, spindled, multilobated, cells with eccentric nuclei, cells with nuclear pseudoinclusions, mucinous, and grooved cells were admixed. In 5 cases, the predominant epithelioid cell component consisted of rather small cells, whereas spindled cells dominated in 3 cases. Of these, 2 lesions were composed rather of pale eosinophilic to clear cells, occasioning a resemblance to PEComa or leiomyoma. Immunohistochemically, all cases expressed ALK and 11 were positive for TFE-3. The break apart test for ALKwas positive in 11 cases, whereas specimens from the remaining 3 cases were not analyzable. ALKgenes fusions were found in all but 3 cases and included SQSTM1-ALK(3), VCL-ALK(3), TMP3-ALK(2), PRKAR2A-ALK(1), MLPH-ALK(1), and EML4-ALK(1). No correlation between histological features and type of ALKfusion was found. TFE-3break apart test was negative. It is concluded that ALK-immunopositive EFH shows ALKgene fusions that involve various protein-coding genes, implicated in a variety of biological processes. Rare variants of EFH rather consist of spindled “non-epithelioid” cells.