Aims To investigate the clinicopathological features, molecular characteristics and diagnostic criteria of primary salivary duct carcinoma of the lung (LSDC).

Methods We analysed the clinicopathological and molecular features of five cases of LSDC retrieved from the archives of Shanghai Pulmonary Hospital from 2020 to 2022, and reviewed the relevant literature.

Results All patients were men, with an average age of 66 years (age range: 49–79 years), and all lesions were central masses with a mean maximum diameter of 42.6 mm (range: 16–70 mm). Morphologically, LSDC comprised of intraductal and invasive components. Both the intraductal and invasive components of LSDC can exhibit papillary, micropapillary, cribriform, tubule structures and solid proliferation. The intraductal component can exhibit Roman bridge structures, which were usually accompanied by central comedo-like necrosis. Immunohistochemically, LSDCs consistently expressed cytokeratin (CK)7 (5 of 5) and showed variable positivity of androgen receptor (AR) (5 of 5) focally or diffusely; additionally, the tumour cells expressed human epidermal growth factor receptor 2 (HER2) (3+, n=3; 2+, n=2), GATA-binding protein 3 (3 of 5), and gross cystic disease fluid protein-15 (1 of 5), and all of which were negative for thyroid transcription factor-1, napsin A, p40, CK5/6 and p63. The residual basal/myoepithelial cells surrounding the in situ carcinoma expressed p40, CK5/6 and p63. TP53 mutation and HER2 gene amplification (3 of 5) were the most frequent genetic alterations in LSDC. All patients who underwent surgical lobectomies were alive without recurrence or metastasis.

Conclusions LSDC is a highly rare malignant tumour. The distinctive architecture of in situ carcinoma and tumour cells expressing AR can provide diagnostic indications for LSDC.