Are There CT Imaging Features That Can Distinguish Primary Pulmonary Squamous Cell Carcinoma from Solitary Lung Metastasis of Head and Neck Squamous Cell Carcinoma?

Background/Objectives: Distinguishing primary lung squamous cell carcinoma (PLSCC) from metastatic head and neck squamous cell carcinoma (MHNSCC) to the lungs is challenging for pathologists, especially when patients present with a solitary lung nodule. The purpose of this study was to identify CT imaging features that differ between PLSCC from solitary MHNSCC to the lungs, using next-generation sequencing (NGS) and human papillomavirus in situ hybridization analysis as the gold reference standard. Methods: This retrospective, single-institution cross-sectional study included patients with a biopsy-proven PLSCC or solitary MHNSCC from July 2013 to May 2022, who underwent NGS or in situ hybridization, and baseline CT or PET/CT. Each scan was evaluated by at least two radiologists. Nodular, pleural, and ancillary CT features, as well as maximum standardized uptake value (SUVmax) from PET/CTs, were recorded. Associations between imaging features and pathology were examined using either the Wilcoxon rank-sum or Fisher’s exact test. Results: In total, 81 patients were included (median 66 years; 64 male); 36/81 (44%) had PLSCC and 45/81 (56%) had MHNSCC. PLSCC was associated with a larger size (median, 3.3–3.6 cm vs. 1.4–1.6 cm, p < 0.001), and the presence of post obstructive atelectasis (p = 0.002), pleural retraction (p < 0.001), pleural tags (p = 0.02), and pleural surface involvement (p = 0.02). MHNSCC presented as smaller peripheral nodules (p = 0.003) with lower SUVmax (p = 0.01). Conclusions: Several CT imaging features as well as SUVmax from PET/CT were significantly different between PLSCC and solitary MHNSCC and their potential discriminatory ability warrants evaluation in future studies.