Kazakov Dmitry V, Kyrpychova Liubov, Martinek Petr, Grossmann Petr, Steiner Petr, Vanecek Tomas, Pavlovsky Michal, Bencik Vladimir, Michal Michael, Michal Michal
Sikl's Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic.
Bioptical Laboratory, Pilsen, Czech Republic.
Am J Dermatopathol. 2018 Nov;40(11):805-814. doi: 10.1097/DAD.0000000000001085.
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.
以往研究表明，间变性淋巴瘤激酶（ALK）在上皮样纤维组织细胞瘤（EFH）中常呈阳性。已记录了2例伴有ALK基因融合的EFH。我们的目的是研究一系列EFH，以呈现EFH的组织病理学变异，鉴定新的ALK基因融合，并确定组织病理学特征与特定基因之间是否存在相关性。我们调查了14例EFH，所有病例ALK免疫阳性。对这些病例进行了组织病理学评估，并使用荧光原位杂交（FISH）检测ALK和TFE-3重排，使用下一代测序检测ALK基因融合。测序结果分析使用Archer Analysis软件（v5；ArcherDX公司）。研究组包括8名女性和6名男性患者，年龄在18至79岁之间（平均42岁；中位数37.5岁）。所有患者均表现为孤立性病变。显微镜下，大多数病变为息肉样，由具有丰富细胞质的上皮样细胞组成。此外，还混合有数量不等的双核、三核或多核、梭形、多叶状、核偏心的细胞、有核假包涵体的细胞、黏液样细胞和有沟细胞。5例中，主要的上皮样细胞成分由相当小的细胞组成，而3例中梭形细胞占主导。其中，2个病变主要由淡嗜酸性至透明细胞组成，类似血管周上皮样细胞瘤（PEComa）或平滑肌瘤。免疫组化方面，所有病例均表达ALK，11例TFE-3阳性。11例ALK的分离试验呈阳性，而其余3例标本无法分析。除3例病例外，其余病例均发现ALK基因融合，包括SQSTM1-ALK（3例）、VCL-ALK（3例）、TMP3-ALK（2例）、PRKAR2A-ALK（1例）、MLPH-ALK（1例）和EML4-ALK（1例）。未发现组织学特征与ALK融合类型之间存在相关性。TFE-3分离试验为阴性。结论是，ALK免疫阳性的EFH显示ALK基因融合，涉及各种蛋白质编码基因，参与多种生物学过程。EFH的罕见变异型主要由梭形“非上皮样”细胞组成。
