Invasive carcinoma that has arisen in pleomorphic adenoma (carcinoma ex PA) is most frequently high grade and often shows undifferentiated or salivary duct carcinoma patterns, though any salivary malignancy may arise. Carcinoma arising in pleomorphic adenoma may exhibit the same gene fusions as pleomorphic adenoma, including PLAG1 and HMGA2 fusions. Unfortunately, PLAG1 fusions (including cryptic fusions, [4]) are only found in a proportion of pleomorphic adenomas. Multiple copy number alterations are typically seen in high-grade carcinomas and there may be amplification of HMGA2 and MDM2. In relation to therapy for unresectable or metastatic carcinoma ex PA, molecular typing for HER2 and AR where salivary duct carcinoma arises can be performed and may inform targeted therapy.

Although slow growing, adenoid cystic carcinoma typically spreads by perineural invasion and lacks an immune stromal response. Local recurrence is common and distant metastasis may occur late in the course of the disease. The MYB-NFIB fusion is the genomic hallmark of adenoid cystic carcinoma, and activation of MYB and MYBL1 by increased copy number or proximity to other genes is thought to be the major driver. Mutation frequency in other genes is low [5]. Both KIT and EGFR may be overexpressed but are rarely mutated and therapy against these tyrosine kinase inhibitors is not effective.

The biological behaviour of mucoepidermoid carcinoma has a broad spectrum and histological grading has prognostic utility (WHO in press). The hallmark genomic events in mucoepidermoid carcinoma are translocations involving the transcriptional coactivator genes MAML2 and CRTC1/3. Additionally, mutations of HRAS have been found in around 20 % of mucoepidermoid carcinomas, most often in high grade tumours. Mucoepidermoid carcinomas that are MAML2-CRTC1/3 fusion positive have a more favourable outcome than fusion negative tumours [3]. Genomic studies can subdivide fusions positive mucoepidermoid carcinomas into two subgroups; those with a low copy number have a good prognosis whilst those with numerous copy number alterations pursue an aggressive clinical course and show poor outcomes. Precise histological classification of high grade salivary carcinomas is difficult and some MAML2 and CRTC1/3 fusion negative carcinomas that were currently classified as poorly differentiated mucoepidermoid carcinoma may in reality fit better into the adenocarcinoma NOS type.