Analysis of PLAG1 & HMGA2 Rearrangement in Salivary Duct Carcinoma and an Examination of the Role of Precursor Lesions
Armita Bahrami, Bayardo Perez-Ordonez, James Dalton, Zhirong Yin, Ilan Weinreb. St. Jude Children's Research Hospital, Memphis, TN; University Health Network, Toronto, ON, Canada
Background: Salivary duct carcinoma (SDC) is amongst the most common tumors arising in pleomorphic adenoma (PA). Other putative precursors, including low grade cribriform cystadenocarcinoma (LGCCC) and high grade ductal carcinoma in-situ (DCIS) are more controversial. The majority of SDC appear to arise de novo. Recently DCIS was implicated in the majority of SDC. Some LGCCC show microinvasion but only rare examples have a widely invasive component. PA are known to have rearrangement of the PLAG1 or HMGA2 genes in 50-70% of cases. This has been shown to be retained in carcinoma ex PA. A study of PLAG1 and HMGA2 genes in SDC with a variety of putative precursors has not been performed to date.
Design: A TMA was built with duplicate cores of 44 SDC. All cases were reviewed for potential PA and intraductal lesions and were stained with SMA, CK14 and p63. Custom BAC probes were used to evaluate PLAG1 and HMGA2 genes by FISH. A case was considered positive when >20% of cells had a split signal indicating rearrangement of the respective gene.
Results: The patients ranged from 33-86 years old (mean 66.8). SDC ex PA was present in 8 cases. An additional 10 cases had an "obsolete" hyalinized nodule, suspicious for PA. Six SDCs arose in association with a LGCCC-like component. The remaining 20 cases were de novo SDC. A total of 10 cases had PLAG1 (22.7%) and 8 had HMGA2 (18.2%) rearrangment/amplification, respectively. One showed both genes involved. Of these 17 positive cases there were 4 definitive SDC ex PA, 8 SDC with a hyalinized nodule and 5 apparent de novo SDC. There were 6 FISH negative SDC ex PA. A total of 23 SDC ex PA were therefore present in the cohort (52.3%). All 3 cases with testable PA and SDC components were FISH positive in both elements. All 6 SDC ex LGCCC were FISH negative. Myoepithelial staining was present around all LGCCC-like components. It also demonstrated DCIS in 17 other cases. Of these, 11 were present in SDC ex PA or FISH positive apparent de novo SDC. These cases are interpreted as "cancerization" of ducts as it is unlikely to represent a precursor in the presence of a PA. Only 6 FISH negative apparent de novo SDCs showed DCIS (13.6% of the cohort). Pure de novo SDC represented 7 cases (15.9% of the cohort).
Conclusions: A large proportion of SDC arise in PA, which are either visible, show an "obsolete" hyalinized nodule or no trace of PA. A small proportion of SDC arise in LGCCC. Most cases showing DCIS represent cancerization but a minority of cases may show true DCIS.
Category: Head & Neck
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 148, Tuesday Morning