Abstract

Background: Pulmonary papillomas account for less than 1% of lung tumors. Among them, pulmonary mixed squamous and glandular papilloma (PMSGP) is the rarest subtype and is prone to misdiagnosis, particularly when showing increased 18F-fluorodeoxyglucose (FDG) uptake on PET/CT. Case presentation: We report a 48-year-old male presenting with persistent dry cough. Computed tomography (CT) revealed a large, peripherally located right lung mass (4.5 cm) with lobulated margins. PET/CT demonstrated markedly increased FDG uptake (SUVmax: 26), strongly suggesting malignancy. Histologically, the tumor showed multiple papillary structures composed of squamous cells positive for CK5/6, p63, and CK19, and glandular cells positive for CEA and TTF-1. Ki-67 was low (< 1%), p53 showed a wild-type pattern, and BRAF, p16, and HPV-PCR were negative, consistent with PMSGP. No recurrence was observed after 3 years of follow-up. Discussion: This represents one of the highest reported SUVmax values in PMSGP, accompanied by unusual features including large size and peripheral location. This case highlights an important diagnostic pitfall on PET/ CT, as benign lesions may demonstrate intense FDG uptake and mimic lung carcinoma. In addition, necrosis and stromal mucin may create pseudo-invasive features, increasing the risk of overdiagnosis, especially in small biopsy. Conclusion: PMSGP is a rare entity that may exhibit features suggestive of malignancy. A high SUVmax does not exclude a benign lesion; therefore, integrated clinicopathological and radiological evaluation is essential to avoid misdiagnosis and overtreatment.