18F-FAPI-74 PET/CT findings of an inflammatory branchial cleft cyst mimicking cervical metastasis from carcinoma of unknown primary: A case report

Fibroblast-activation protein inhibitor (FAPI) positron-emission tomography (PET) is emerging as a promising alternative to ¹⁸F-fluorodeoxyglucose (FDG) PET for head-and-neck cancer. Herein, we describe the case of a 51-year-old man with a cystic level-II neck mass that was intensely FDG-avid and even more avid on ¹⁸F-FAPI-74 PET. FDG-PET was performed as standard imaging modality to search for the primary tumor, while ¹⁸F-FAPI-74 PET was conducted as part of a clinical trial to detect potential occult lesions missed by FDG. While cytology suggested metastatic squamous-cell carcinoma and FDG PET revealed asymmetric tonsillar uptake, raising suspicion of an occult oropharyngeal primary tumor, ¹⁸F-FAPI-74 PET demonstrated an absence of tracer uptake in Waldeyer's ring. The patient subsequently underwent ipsilateral palatine-tonsillectomy, lingual-tonsil biopsy, and radical neck dissection. Histopathological examination definitively excluded malignancy, identifying the lesion as an inflamed branchial cleft cyst with marked fibroblast proliferation, and confirmed that both tonsils were benign. Consequently, the preoperative cytology suggesting metastatic squamous cell carcinoma was determined to be a false-positive finding. This case underscores the potential of ¹⁸F-FAPI-74 PET to exclude tonsillar primaries in carcinomas of unknown primary origin, while highlighting that fibrotic inflammation can cause false-positive uptake.