Aims: Salivary duct carcinoma (SDC) often arises in pleomorphic adenoma (PA). Putative precursors, including low-grade cribriform cystadenocarcinoma (LGCCC) and ductal carcinoma in-situ (DCIS), are more controversial. Rearrangement of PLAG1 or HMGA2 is seen in 50-70% of PAs, but this has not been investigated in SDC. Using a large collection of SDCs from a single institution, we aimed to study these genes by fluorescence in-situ hybridization (FISH), and to correlate the presence of precursor lesions/intraductal proliferations with gene alterations.
Methods and results: Forty-four SDCs were stained for smooth muscle actin, CK14, and p63, and examined with PLAG1 and HMGA2 FISH. Eight cases were SDC ex-PA; ten had a hyalinized nodule (HN), which is suspicious for PA; six arose in association with LGCCC; and twenty were 'de-novo' SDCs. Ten cases had PLAG1 rearrangement/amplification (22.7%) and eight had HMGA2 (18.2%) rearrangement/amplification. The positive cases were four SDC ex-PAs, eight SDCs with an HN, and five 'de-novo' SDCs. Twenty-three SDC ex-PAs were present in total (52.3%). All six SDC ex-LGCCCs were FISH-negative. Myoepithelial staining surrounded all LGCCCs, and demonstrated DCIS in 17 cases. Eleven DCIS lesions were in SDC ex-PAs or FISH-positive 'de-novo' SDCs. These cases represent 'cancerization' of ducts. Only six FISH-negative 'de-novo' SDCs showed DCIS.
Conclusions: A large proportion of SDCs arise in PAs (with or without residual evidence of a PA). A small proportion of SDCs arise in LGCCCs. Cases showing DCIS often represent cancerization.
Keywords: HMGA2; PLAG1; ductal carcinoma in situ; low-grade cribriform cystadenocarcinoma; pleomorphic adenoma; precursor; salivary duct carcinoma.
© 2013 John Wiley & Sons Ltd.