PMID- 34906590 OWN - NLM STAT- MEDLINE DCOM- 20220509 LR - 20220531 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 120 DP - 2022 Feb TI - Pleomorphic adenoma: detection of PLAG1 rearrangement-positive tumor components using whole-slide fluorescence in situ hybridization. PG - 26-34 LID - S0046-8177(21)00198-2 [pii] LID - 10.1016/j.humpath.2021.11.010 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Murase, Takayuki AU - Murase T AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. FAU - Ishibashi, Kenichiro AU - Ishibashi K AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan; Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, 467-8601, Japan. FAU - Okumura, Yoshihide AU - Okumura Y AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan; Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, 467-8601, Japan. FAU - Ueda, Kaori AU - Ueda K AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan; Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, 467-8601, Japan. FAU - Nakano, Satsuki AU - Nakano S AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. FAU - Fujii, Keiichiro AU - Fujii K AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. FAU - Masaki, Ayako AU - Masaki A AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. FAU - Nagao, Toru AU - Nagao T AD - Department of Maxillofacial Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, 467-8601, Japan. FAU - Inagaki, Hiroshi AU - Inagaki H AD - Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan. Electronic address: hinagaki@med.nagoya-cu.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211211 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (DNA-Binding Proteins) RN - 0 (Lipids) RN - 0 (PLAG1 protein, human) RN - 0 (Transcription Factors) SB - IM MH - *Adenoma, Pleomorphic/diagnosis MH - Cell Transformation, Neoplastic/pathology MH - DNA-Binding Proteins/genetics MH - Endothelial Cells/pathology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lipids MH - *Salivary Gland Neoplasms/diagnosis MH - Transcription Factors/genetics OTO - NOTNLM OT - Fluorescence in situ hybridization OT - Immunohistochemistry OT - PLAG1 rearrangements OT - Pleomorphic adenoma OT - Tumor components OT - Whole-slide imaging EDAT- 2021/12/16 06:00 MHDA- 2022/05/10 06:00 CRDT- 2021/12/15 06:00 PHST- 2021/10/28 00:00 [received] PHST- 2021/11/28 00:00 [revised] PHST- 2021/11/29 00:00 [accepted] PHST- 2021/12/16 06:00 [pubmed] PHST- 2022/05/10 06:00 [medline] PHST- 2021/12/15 06:00 [entrez] AID - S0046-8177(21)00198-2 [pii] AID - 10.1016/j.humpath.2021.11.010 [doi] PST - ppublish SO - Hum Pathol. 2022 Feb;120:26-34. doi: 10.1016/j.humpath.2021.11.010. Epub 2021 Dec 11.