Primary squamous cell carcinoma of the salivary gland: immunohistochemical analysis and comparison with metastatic squamous cell carcinoma

Abstract

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.

Keywords: Metastatic squamous cell carcinoma; Primary squamous cell carcinoma; Salivary gland.

Fig. 1.

Histologic features of primary squamous cell carcinoma (SCC) and metastatic SCC of the salivary gland. (A, B) Keratinization, keratin pearls, and intercellular bridges are observed in primary SCC (A, case #8; inset, ×100) and metastatic SCC (B, case #15; left, original SCC; right, metastatic SCC). (C, D) Representative tumor border and tumoral microenvironment in primary and metastatic SCC. Primary SCC shows serrated sharp borders (C, case #5; inset, peritumoral inflammation and desmoplasia), while metastatic SCC shows a bosselated smooth boundary (D, case #14; inset, ×200). (E, F) Tumor necrosis is irregularly distributed in primary SCC (E, case #8; inset, ×200) and centrally located in metastatic SCC (case #16). (G) Primary SCC continuing to transitional or pseudostratified ductal epithelium (case #5). (H) The transitional area of salivary duct carcinoma in SCC is observed in a metastatic lymph node (case #7).

Fig. 2.

Results of immunohistochemical staining in primary squamous cell carcinoma (SCC) and metastatic SCC. (A) Immunopositive reaction to c-erbB2 in primary SCC (case #5). (B, C) Immunopositive response to androgen receptor staining in the salivary duct carcinoma component of the primary tumor (B, case #6) and metastatic tumor (case #7) in primary SCC. (D) Focal positivity for gross cystic disease fluid protein 15 in a metastatic tumor of primary SCC in a lymph node (case #7).