PMID- 32673681 OWN - NLM STAT- MEDLINE DCOM- 20210217 LR - 20210217 IS - 1532-8392 (Electronic) IS - 0046-8177 (Linking) VI - 103 DP - 2020 Sep TI - What is hiding behind S100 protein and SOX10 positive oncocytomas? Oncocytic pleomorphic adenoma and myoepithelioma with novel gene fusions in a subset of cases. PG - 52-62 LID - S0046-8177(20)30132-5 [pii] LID - 10.1016/j.humpath.2020.07.009 [doi] AB - Oncocytomas (OCs) in salivary glands are rare benign tumors composed of mitochondria-rich epithelial cells (oncocytes), mostly localized in the parotid gland. The treatment of choice is simple excision. Extensive oncocytic metaplasia of pleomorphic adenoma (PA) and myoepithelioma (ME) can be diagnostically challenging and may camouflage the correct diagnosis. These tumors should be treated more carefully compared with OC, given the risk of frequent recurrences and the possibility of malignant transformation. We have investigated 89 oncocytic lesions from our files, including OC (n = 74) and metaplastic oncocytic variant of PA/ME (n = 15). All OCs were stained for S100 protein and SOX10. The tumors with immunohistochemical expression of one or both markers were tested by next-generation sequencing (NGS). The NGS results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH). Ten cases originally diagnosed as OC, and 1 low-grade uncertain oncocytic tumor (11/74) revealed nuclear-cytoplasmic and/or nuclear positivity for S100 protein and/or SOX10, respectively. Fusion transcripts CHCHD7-PLAG1 and GEM-PLAG1 were found in 2 cases (1 fusion in each), and these were confirmed by RT-PCR and PLAG1 break-apart FISH probe, respectively. Another 5 cases were positive for PLAG1 rearrangement by FISH. In the control group of 15 oncocytic PA/ME, 4/15 tested tumors harbored gene fusions including NFT3-PLAG1, CHCHD7-PLAG1, FBXO32-PLAG1, and C1orf116-PLAG1 (1 fusion in each case) as detected by NGS. Two fusions were confirmed by RT-PCR, 1 case by FISH, and 1 case was not analyzable by FISH. We additionally tested 24 OCs negative for S100 protein and SOX10 by immunohistochemistry (IHC) and by FISH for rearrangement of PLAG1 gene, but none of them were positive. SOX10 and/or S100 protein immunopositivity in conjunction with rearrangement of the PLAG1 gene assisted in reclassification of a subset of oncocytomas as oncocytic variants of PA and ME. Therefore, we recommend to include S100 protein and SOX10 IHC when diagnosing tumors with predominantly oncocytoma-like differentiation. In addition, by NGS, 3 new gene fusions were detected in oncocytic ME, including NTF3-PLAG1, FBXO32-PLAG1, and GEM-PLAG1, and a new fusion C1orf116-PLAG1 was detected in oncocytic PA. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Baneckova, Martina AU - Baneckova M AD - Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, 30605, Czech Republic; Bioptic Laboratory Ltd, Plzen, 32600, Czech Republic. Electronic address: baneckova.martina@gmail.com. FAU - Uro-Coste, Emmanuelle AU - Uro-Coste E AD - Department of Pathology, Toulouse University Hospital, IUC-Oncopole, Toulouse, 31100, France; INSERM U1037, Cancer Research Center of Toulouse (CRCT), Toulouse, 31100, France. FAU - Ptakova, Nikola AU - Ptakova N AD - Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Plzen, 32600, Czech Republic. FAU - Steiner, Petr AU - Steiner P AD - Molecular and Genetic Laboratory, Bioptic Laboratory Ltd, Plzen, 32600, Czech Republic. FAU - Stanowska, Olga AU - Stanowska O AD - Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, 00 001, Poland. FAU - Benincasa, Giulio AU - Benincasa G AD - Department of Pathology, Clinic Pineta Grande, Castel Volturno (CE), 81030, Italy. FAU - Colella, Giuseppe AU - Colella G AD - Department of Maxillo-facial Surgery, University Della Campania "Luigi Vanvitelli", Policlinico Piazza Miraglia, Naples, 81100, Italy. FAU - Vondrak, Jan Jr AU - Vondrak J Jr AD - South Bohemian University, Ceske Budejovice, 37005, Czech Republic. FAU - Michal, Michal AU - Michal M AD - Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, 30605, Czech Republic; Bioptic Laboratory Ltd, Plzen, 32600, Czech Republic. FAU - Leivo, Ilmo AU - Leivo I AD - Institute of Biomedicine, Pathology, University of Turku, And Turku University Hospital, Turku, 20500, Finland. FAU - Skalova, Alena AU - Skalova A AD - Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, 30605, Czech Republic; Bioptic Laboratory Ltd, Plzen, 32600, Czech Republic. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200713 PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (Biomarkers, Tumor) RN - 0 (S100 Proteins) RN - 0 (SOX10 protein, human) RN - 0 (SOXE Transcription Factors) SB - IM MH - Adenoma, Oxyphilic/*diagnosis/genetics MH - Adenoma, Pleomorphic/*diagnosis/genetics MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*analysis MH - Female MH - Humans MH - Male MH - Middle Aged MH - Myoepithelioma/*diagnosis/genetics MH - Oncogene Fusion MH - Retrospective Studies MH - S100 Proteins/analysis/biosynthesis MH - SOXE Transcription Factors/analysis/biosynthesis MH - Salivary Gland Neoplasms/*diagnosis/genetics OTO - NOTNLM OT - Myoepithelioma OT - Oncocytoma OT - PLAG1 OT - Pleomorphic adenoma OT - S100 protein OT - SOX10 EDAT- 2020/07/17 06:00 MHDA- 2021/02/18 06:00 CRDT- 2020/07/17 06:00 PHST- 2020/06/02 00:00 [received] PHST- 2020/07/06 00:00 [revised] PHST- 2020/07/07 00:00 [accepted] PHST- 2020/07/17 06:00 [pubmed] PHST- 2021/02/18 06:00 [medline] PHST- 2020/07/17 06:00 [entrez] AID - S0046-8177(20)30132-5 [pii] AID - 10.1016/j.humpath.2020.07.009 [doi] PST - ppublish SO - Hum Pathol. 2020 Sep;103:52-62. doi: 10.1016/j.humpath.2020.07.009. Epub 2020 Jul 13.