Abstract
Syphilis, a systemic infection caused by Treponema pallidum, can present with atypical and severe manifestations in people living with the human immunodeficiency virus (HIV), posing significant diagnostic challenges. We report the case of a patient with acquired immunodeficiency syndrome (AIDS) who presented with a chest wall mass. Imaging findings were initially suggestive of a malignancy. However, subsequent evaluation, guided by positive serum syphilis antibodies despite non-specific inflammatory changes on histology and a negative metagenomic next-generation sequencing (mNGS) result, led to the diagnosis of a syphilitic gumma, which was confirmed by immunohistochemical staining. The lesion entirely resolved following penicillin therapy. This case highlights a critical clinical insight: syphilis must be considered in the differential diagnosis of mass lesions in immunocompromised hosts, and immunohistochemical staining is imperative for definitive diagnosis.