Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Epithelial-Myoepithelial Carcinoma

Frequent Morphologic and Molecular Evidence of Preexisting Pleomorphic Adenoma, Common HRAS Mutations in PLAG1-intact and HMGA2-intact Cases, and Occasional TP53, FBXW7, and SMARCB1 Alterations in High-grade Cases

El Hallani, Soufiane MD, PhD*; Udager, Aaron M. MD, PhD; Bell, Diana MD; Fonseca, Isabel MD§; Thompson, Lester D.R. MD; Assaad, Adel MD; Agaimy, Abbas MD#; Luvison, Alyssa M. BS*; Miller, Caitlyn BS*; Seethala, Raja R. MD*; Chiosea, Simion MD*

The American Journal of Surgical Pathology: January 2018 - Volume 42 - Issue 1 - p 18–27
doi: 10.1097/PAS.0000000000000933
Original Articles

We hypothesized that there is a relationship between the preexisting pleomorphic adenoma [PA]), histologic grade of epithelial-myoepithelial carcinomas (EMCAs), and genetic alterations. EMCAs (n=39) were analyzed for morphologic and molecular evidence of preexisting PA (PLAG1, HMGA2 status by fluorescence in situ hybridization, FISH, and FGFR1-PLAG1 fusion by next-generation sequencing, NGS). Twenty-three EMCAs were further analyzed by NGS for mutations and copy number variation in 50 cancer-related genes. On the basis of combined morphologic and molecular evidence of PA, the following subsets of EMCA emerged: (a) EMCAs with morphologic evidence of preexisting PA, but intact PLAG1 and HMGA2 (12/39, 31%), (b) Carcinomas with PLAG1 alterations (9/39, 23%), or (c) HMGA2 alterations (10/39, 26%), and (d) de novo carcinomas, without morphologic or molecular evidence of PA (8/39, 21%). Twelve high-grade EMCAs (12/39, 31%) occurred across all subsets. The median disease-free survival was 80 months (95% confidence interval, 77-84 mo). Disease-free survival and other clinicopathologic parameters did not differ by the above defined subsets. HRAS mutations were more common in EMCAs with intact PLAG1 and HMGA2 (7/9 vs. 1/14, P<0.001). Other genetic abnormalities (TP53 [n=2], FBXW7 [n=1], SMARCB1 deletion [n=1]) were seen only in high-grade EMCAs with intact PLAG1 and HMGA2. We conclude that most EMCAs arose ex PA (31/39, 80%) and the genetic profile of EMCA varies with the absence or presence of preexisting PA and its cytogenetic signature. Progression to higher grade EMCA with intact PLAG1 and HMGA2 correlates with the presence of TP53, FBXW7 mutations, or SMARCB1 deletion.

*Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA

Department of Pathology, Michigan Medicine, Ann Arbor, MI

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX

§Pathological Anatomy Institute, Faculdade de Medicina, Universidade de Lisboa & Serviço de Anatomia Patológica, Instituto Português de Oncologia Francisco Gentil, Lisboa, Portugal

Department of Pathology, Southern California Permanente Medical Group, Woodland Hills, CA

Department of Pathology, Virginia Mason Hospital, Seattle, WA

#Institute of Pathology, University Hospital, Erlangen, Germany

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Simion Chiosea, MD, UPMC, Presbyterian University Hospital, A610-2, 200 Lothrop St, Pittsburgh, PA 15213 (e-mail:

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.