Background Primary squamous cell carcinoma (SCC) of the salivary gland is a rare disease, and distinguishing primary SCC from metastatic SCC is difficult. This study investigated the histological and immunohistochemical differences between primary and metastatic salivary gland SCC to improve the accuracy of diagnosis and to explore the pathogenesis of this disease. Methods Data of 16 patients who underwent surgery for SCC of salivary glands between 2000 and 2018 at Asan Medical Center were retrieved. Eight patients had a history of SCC at other sites, and eight patients had only salivary gland SCC. Immunostaining for p16, p53, androgen receptor (AR), gross cystic disease fluid protein 15 (GCDFP-15), and c-erbB2, as well as mucicarmine staining, were compared between the two groups. Results Most tumors were located in the center of the salivary glands with extraparenchymal extension. The histology of primary SCC of the salivary gland was consistent with moderately differentiated SCC with extensive desmoplastic reaction and peritumoral inflammation. Involvement of the salivary gland ducts and transition into the ductal epithelium were observed in two cases. Metastatic SCC resembled the primary tumor histologically and was associated with central necrosis. Both groups exhibited negative mucin staining. Two, one, and one primary SCC case exhibited AR, GCDFP-15, and c-erbB2 positivity, respectively. Conclusions A subset of primary SCCs originated in salivary ducts or was related to salivary duct carcinoma. Distinguishing primary from metastatic SCC of the salivary gland is difficult using histologic features and immunoprofiles. A comprehensive review of the medical history is essential.

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