title: Consistent PLAG1 and HMGA2 abnormalities distinguish carcinoma ex-pleomorphic adenoma from its de novo counterparts.
abstract: Carcinoma ex-pleomorphic adenoma (CA ex-PA) is a malignant salivary gland tumor that arises in association with pleomorphic adenoma (PA). Both PA and CA ex-PA have a broad spectrum of histology, and distinction from their histologic mimics may be difficult based on morphology alone. PLAG1 and HMGA2 abnormalities are the most common genetic events in both PA and CA ex-PA; however, the use of PLAG1 and HMGA2 as adjunct molecular tests has not been well established. Fluorescence in situ hybridization for PLAG1 and HMGA2 was performed on 22 CA ex-PA (10 myoepithelial carcinomas [MECAs], 10 salivary duct carcinomas [SDCs], 1 carcinoma with squamoglandular features, and 1 mixed MECA-adenocarcinoma not otherwise specified), 20 de novo carcinomas (11 MECAs and 9 SDCs), 16 PAs, and 11 PA-histologic mimics. All except 3 CAs ex-PA (86%) were positive for PLAG1 or HMGA2 rearrangements/amplifications. In contrast, 18 (90%) of 20 de novo carcinomas lacked abnormalities in PLAG1 or HMGA2 (P < .01). PLAG1 or HMGA2 rearrangements were identified in 6 (67%) of 9 hypocellular myxoid PAs and in 2 (29%) of 7 cellular PAs. Furthermore, all morphologic mimics of PA were negative for PLAG1 or HMGA2. PLAG1 and HMGA2 rearrangements are the most common genetic events in CA ex-PA regardless of the histologic subtype. Unlike CA ex-PA, de novo carcinomas were negative for PLAG1 and HMGA2. Interestingly, rearrangements of PLAG1/HMGA2 were identified in most hypocellular PAs but only in a small subset of cellular PAs. Fluorescence in situ hybridization for PLAG1 or HMGA2 can be used to distinguish between PA and CA ex-PA and their morphologic mimics.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065. Electronic address: katabin@makcc.org.
authors.forename: Nora
authors.initials: N
authors.lastname: Katabi
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065.
authors.forename: Ronald
authors.initials: R
authors.lastname: Ghossein
authors.affiliation: Department of Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065.
authors.forename: Alan
authors.initials: A
authors.lastname: Ho
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065.
authors.forename: Snjezana
authors.initials: S
authors.lastname: Dogan
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065.
authors.forename: Yun-Shao
authors.initials: YS
authors.lastname: Sung
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065. Electronic address: antonesc@mskcc.org.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D008949:Adenoma, Pleomorphic / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D044584:Carcinoma, Ductal / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D008940:Mitotic Index; D009208:Myoepithelioma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; C500986:EWSR1 protein, human; D025743:HMGA2 Protein; C104382:PLAG1 protein, human; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins
keywords: Carcinoma ex pleomorphic adenoma; HMGA2; Myoepithelial carcinoma; PLAG1; Salivary duct carcinoma