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Pleomorphic adenoma: detection of PLAG1 rearrangement–positive tumor components using whole-slide fluorescence in situ hybridization

肌上皮细胞 病理 多形性腺瘤 荧光原位杂交 免疫组织化学 间充质干细胞 生物 原位杂交 唾液腺 医学 基因表达 染色体 生物化学 基因
作者
Takayuki Murase,Kenichiro Ishibashi,Yoshihide Okumura,Kaori Ueda,Satsuki Nakano,Keiichiro Fujii,Masaki Awata,Toru Nagao,Hiroshi Inagaki
出处
期刊:Human Pathology [Elsevier]
卷期号:120: 26-34
标识
DOI:10.1016/j.humpath.2021.11.010
摘要

Pleomorphic adenoma (PA) consists of heterogeneous histological architecture mixed with epithelioid and mesenchymal forms. Various types of epithelial or myoepithelial malignancies arise from PA, but sarcomas are extremely rare. A human androgen receptor gene (HUMARA) clonality assay has suggested that PA is clonal in nature. However, clonality of various tumor components of PA would be difficult to determine with this assay. In addition, the results obtained should be carefully interpreted. PLAG1 rearrangements are considered a good molecular marker for neoplasticity in PA. We aimed to clarify the neoplasticity of the various tumor components present in PA using whole-slide fluorescence in situ hybridization (FISH). Five PA cases positive for PLAG1 rearrangements were examined. Using an immunohistochemistry panel, cell components in PA were classified into eight cell types. To precisely localize PLAG1 rearrangement-positive cell components at the cellular level, sequential retrieval of whole-slide imaging (WSI) data of HE histology and FISH for PLAG1 rearrangement was carried out. PLAG1 rearrangements were detected in ductal cells, myoepithelial spindle cells, myoepithelial oncocytic cells, myoepithelial plasmacytoid cells, and mesenchymal chondroid cells, but not in mesenchymal lipid cells, mesenchymal fibrous cells, or vascular endothelial cells. Immunohistochemical PLAG1 expression was restricted to cell components harboring PLAG1 rearrangements.The results of the present study indicate that ductal and myoepithelial, chondroid cells are neoplastic but lipid, fibrous, and endothelial cells are not. PLAG1 immunohistochemistry is useful in discriminating neoplastic from non-neoplastic cell components. These findings may be important for elucidating tumorigenesis and the process of malignant transformation in PA.
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