Case Report: When syphilis imitates cancer: a case of misdiagnosed cutaneous T-cell lymphoma

Syphilis is an infectious disease caused by Treponema pallidum, which is regarded as one of the most significant imitators in daily clinical practice. Its manifestations are various, comprising numerous autoimmune, inflammatory, and neoplastic disorders. Here we present a case of a 27-year-old male initially suspected of cutaneous T-cell lymphoma (CTCL) based on lymphadenopathy, systemic weight loss, ulcerative cutaneous lesions, and fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) findings of hypermetabolic nodes above and below the diaphragm. Histopathological analysis suggested pleomorphic lymphoid proliferation, while imaging supported the suspicion of malignancy. However, subsequent biopsies revealed plasmacytic and lymphocytic infiltration without clonality, and treponemal serologies confirmed secondary syphilis. The patient was referred for anti-treponemal therapy resulting in the resolution of the initial symptoms. This case presents how syphilis can closely imitate hematologic malignancy, particularly CTCL, both clinically and histopathologically. We also review and prepare a summary of published reports of syphilis mimicking malignancies and propose a structured diagnostic algorithm. We believe that the early inclusion of syphilis in differential diagnosis is critical to avoid misdiagnosis and delays in initiating appropriate therapy.