Background: 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.

Methods: 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.

Results: 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%.

Conclusion: 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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