Accurate diagnosis of salivary duct carcinoma requires a high index of suspicion and clinicopathologic correlation. Hallmark genetic changes that may provide novel therapeutic options are being explored. One hundred ninety salivary gland malignancies at Royal Prince Alfred Hospital (from 1989-2014) were reviewed. Human epidermal growth factor receptor 2 (HER2) and androgen receptor status were determined along with multigene profiling. Twenty-three salivary duct carcinomas were identified, predominantly in men in their fifth to ninth decades of life. Facial nerve palsy (12%) and cervical lymph node metastases (82%) were present, and 96% received postoperative adjuvant therapy. Histologically, the tumors resembled high-grade invasive and in situ ductal carcinoma of the breast. Micropapillary, papillary, sarcomatoid, oncocytic, and mucinous variants were seen. The tumors showed androgen receptor (70%), HER2 amplification (30%), and HRAS, AKT1, PIK3CA, and NRAS mutations (22%; cumulative). The 5-year disease-free survival was 36%. Salivary duct carcinoma demonstrates a wide histopathologic spectrum. Treatment strategies need to take androgen receptor, HER2 amplification, and PIK3CA mutation into account. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1838-E1847, 2016.
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