ALK Gene Fusions in Epithelioid Fibrous Histiocytoma: A Study of 14 Cases, With New Histopathological Findings. (November 2018)

• Record Type: Journal Article
• Authors: Kazakov, Dmitry V.; Kyrpychova, Liubov; Martinek, Petr; Grossmann, Petr; Steiner, Petr; Vanecek, Tomas; Pavlovsky, Michal; Bencik, Vladimir; Michal, Michael; Michal, Michal
• Is Part Of: American journal of dermatopathology. Volume 40:Number 11(2018)
• Publication Date: 2018-11
• Subjects: epithelioid fibrous histiocytoma -- ALK -- TFE-3 -- gene fusions -- Spitz nevus; Skin -- Diseases -- Periodicals; Histology, Pathological -- Periodicals; 616.50705
• DOI: 10.1097/DAD.0000000000001085
• Languages: English
• ISSNs: 0193-1091

Abstract

Abstract : Abstract: Previous studies showed that ALK is often positive in epithelioid fibrous histiocytoma (EFH). Two cases of EFH with ALK gene fusions have been recorded. Our objective was to study a series of EFH to present histopathological variations of EFH, identify novel ALK gene 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 ALK and TFE-3 rearrangements using FISH and ALK gene 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 ALK was positive in 11 cases, whereas specimens from the remaining 3 cases were not analyzable. ALK genes 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 ALK fusion was found. TFE-3 break apart test was negative. It is concluded that ALK-immunopositive EFH shows ALK gene 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.