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.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
carcinoma ex pleomorphic adenoma;
Document Type: Research Article
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
Publication date: January 1, 2018