Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland carcinoma constituting 1–3% of all malignant salivary tumors, first described by Kleinsasser et al in 1968 [1]. SDC primarily affects males in the sixth to seventh decade and arises more often within the parotid gland, either de novo or from ex pleomorphic adenoma. 1,2

SDC frequently shows an aggressive clinical behavior, presenting as a rapidly enlarging neck mass, with/ without facial nerve palsy, extensive lymph node and distant metastasis. Management of such an aggressive neoplasm requires radical surgery and postoperative radiation therapy in the early stage of the tumor to prolong survival. Therefore, establishing an accurate preoperative diagnosis by fine-needle aspiration (FNA) is important. 3

SDC is an aggressive malignant neoplasm of salivary gland origin and can develop either de novo or secondary to malignant transformation within a long-standing pleomorphic adenoma.4 Studies (utilizing targeted NGS) that have compared de-novo SDCs and SDC arising from PA, found that SDCs ex PA demonstrate TP53 mutations or ERBB2 copy number gain, while de-novo SDCs showed combined HRAS/PIK3CA mutations without ERBB2 amplification. 5,6

Fine needle aspiration biopsy (FNA) yields samples that are often hyper cellular and show three-dimensional clusters as well as flat sheets of large, polygonal cells, sometimes displaying a cribriform pattern. The tumor cells show round to oval, highly pleomorphic nuclei, coarse chromatin, and prominent nucleoli. Mitotic figure can be identified and necrosis is frequently present.3

On immunohistochemistry, tumor cells express CK7, GATA3 and mammaglobin, resembling high grade ductal carcinoma of the breast.1 In addition, SDCs show strong expression of androgen receptor (AR) by IHC, with a reported expression rate of 69-100%. This can help in the differential diagnosis between SDC and invasive breast carcinoma, high grade mucoepidermoid carcinoma, acinic cell carcinoma, and squamous cell carcinoma.1 The current case showed diffuse (>90%) AR expression both in the cytology as well as the resection specimen, thereby aiding in reaching a specific diagnosis of SDC on cytology, instead of just high-grade salivary gland neoplasm.

In addition, several recent studies have shown that patients with AR+ SDC may benefit from androgen deprivation therapy (ADT).2 Therefore, AR immunohistochemistry can be beneficial both as a diagnostic marker as well as a predictive biomarker to select patients for ADT. 2,4

In conclusion, this case study highlights the importance of immunohistochemistry in diagnosing SDC on cytology, differentiating it from other morphologic mimics, and rendering a precise diagnosis.