PMID- 25581728 OWN - NLM STAT- MEDLINE DCOM- 20150409 LR - 20171116 IS - 1532-0979 (Electronic) IS - 0147-5185 (Linking) VI - 39 IP - 3 DP - 2015 Mar TI - Clear cell myoepithelial carcinoma of salivary glands showing EWSR1 rearrangement: molecular analysis of 94 salivary gland carcinomas with prominent clear cell component. PG - 338-48 LID - 10.1097/PAS.0000000000000364 [doi] AB - This study examines the presence of the EWSR1 rearrangement in a variety of clear cell salivary gland carcinomas with myoepithelial differentiation. A total of 94 salivary gland carcinomas with a prominent clear cell component included 51 cases of clear cell myoepithelial carcinomas de novo (CCMC), 21 cases of CCMCs ex pleomorphic adenoma (CCMCexPA), 11 cases of epithelial-myoepithelial carcinoma (EMC), 6 cases of EMC with solid clear cell overgrowth, and 5 cases of hyalinizing clear cell carcinoma of minor salivary glands. In addition, 10 cases of myoepithelial carcinomas devoid of clear cell change and 12 cases of benign myoepithelioma were included as well. All the tumors in this spectrum were reviewed, reclassified, and tested by fluorescence in situ hybridization (FISH) for the EWSR1 rearrangement using the Probe Vysis EWSR1 Break Apart FISH Probe Kit. The EWSR1 rearrangement was detected in 20 of 51 (39%) cases of CCMC, in 5 of 21 (24%) cases of CCMCexPA, in 1 of 11 (9%) cases of EMC, and in 4 of 5 (80%) cases of hyalinizing clear cell carcinoma. The 25 EWSR1-rearranged CCMCs and CCMCexPAs shared similar histomorphology. They were arranged in nodules composed of compact nests of large polyhedral cells with abundant clear cytoplasm. Necrosis, areas of squamous metaplasia, and hyalinization were frequent features. Immunohistochemically, the tumors expressed p63 (96%), cytokeratin CK14 (96%), and S100 protein (88%). MIB1 index varied from 10% to 100%, with most cases in the 20% to 40% range. Clinical follow-up information was available in 21 cases (84%) and ranged from 3 months to 15 years (mean 5.2 y); 4 patients were lost to follow-up. Ten patients are alive with no evidence of recurrent or metastatic disease in the follow-up period from 3 months to 15 years (mean 5 y), 3 patients are alive with recurrent and metastatic disease, and 8 died of disseminated cancer 9 months to 16 years after diagnosis (mean 6 y). Lymph node metastasis appeared in 5 patients within 5 months to 4 years after diagnosis (mean 22 mo), distant metastases were noted in 7 patients with invasion of orbit (2 cases), and in 1 case each metastasis to the neck soft tissues, liver, lungs, mediastinum, and thoracic vertebra was noted. We describe for the first time EWSR1 gene rearrangement in a subset of myoepithelial carcinomas arising in minor and major salivary glands. The EWSR1-rearranged CCMC represents a distinctive aggressive variant composed predominantly of clear cells with frequent necrosis. Most EWSR1-rearranged CCMCs of salivary glands are characterized by poor clinical outcomes. FAU - Skalova, Alena AU - Skalova A AD - *Department of Pathology, Faculty of Medicine in Plzen, Charles University daggerdaggerBioptic Laboratory Ltd, Molecular Pathology Laboratory, Plzen parallelThe Fingerland Department of Pathology, Faculty of Medicine and University Hospital, Charles University in Prague, Hradec Kralove, Czech Republic daggerDepartment of Pathology, University Health Network, Toronto, ON double daggerDepartment of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC section signDepartment of Anatomical Pathology, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada paragraph signInstitute of Pathology, University Hospital, Erlangen, Germany #Department of Pathology, N.N. Alexandrov's Research Center of Oncology and Medical Radiology, Minsk, Republic of Belarus **Department of Pathology, Medical University of Gdansk, Poland double daggerdouble daggerDepartment of Pathology, Cytopathos, Slovakia section sign section signDepartment of Pathology, University of Zagreb, Croatia parallel parallelDepartment of Pathology, National Cancer Institute, Fondazione "G.Pascale", Naples, Italy. FAU - Weinreb, Ilan AU - Weinreb I FAU - Hyrcza, Martin AU - Hyrcza M FAU - Simpson, Roderick H W AU - Simpson RH FAU - Laco, Jan AU - Laco J FAU - Agaimy, Abbas AU - Agaimy A FAU - Vazmitel, Marina AU - Vazmitel M FAU - Majewska, Hanna AU - Majewska H FAU - Vanecek, Tomas AU - Vanecek T FAU - Talarcik, Peter AU - Talarcik P FAU - Manajlovic, Spomenka AU - Manajlovic S FAU - Losito, Simona N AU - Losito SN FAU - Steiner, Petr AU - Steiner P FAU - Klimkova, Adela AU - Klimkova A FAU - Michal, Michal AU - Michal M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - 0 (Biomarkers, Tumor) RN - 0 (Calmodulin-Binding Proteins) RN - 0 (EWSR1 protein, human) RN - 0 (RNA-Binding Protein EWS) RN - 0 (RNA-Binding Proteins) SB - IM MH - Adenoma, Pleomorphic/chemistry/*genetics/mortality/pathology/therapy MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/analysis/*genetics MH - Calmodulin-Binding Proteins/*genetics MH - Carcinoma/chemistry/*genetics/mortality/secondary/therapy MH - Disease-Free Survival MH - Female MH - *Gene Rearrangement MH - Genetic Predisposition to Disease MH - Humans MH - Immunohistochemistry MH - *In Situ Hybridization, Fluorescence MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Myoepithelioma/chemistry/*genetics/mortality/secondary/therapy MH - Necrosis MH - Neoplasm Recurrence, Local MH - Phenotype MH - Predictive Value of Tests MH - RNA-Binding Protein EWS MH - RNA-Binding Proteins/*genetics MH - Salivary Gland Neoplasms/chemistry/*genetics/mortality/pathology/therapy MH - Time Factors MH - Treatment Outcome EDAT- 2015/01/13 06:00 MHDA- 2015/04/10 06:00 CRDT- 2015/01/13 06:00 PHST- 2015/01/13 06:00 [entrez] PHST- 2015/01/13 06:00 [pubmed] PHST- 2015/04/10 06:00 [medline] AID - 10.1097/PAS.0000000000000364 [doi] PST - ppublish SO - Am J Surg Pathol. 2015 Mar;39(3):338-48. doi: 10.1097/PAS.0000000000000364.