When Syphilis Imitates Cancer: A Case of Misdiagnosed Cutaneous T-Cell Lymphoma and Literature Review

Syphilis is a chronic infectious disease caused by Treponema pallidum which stands as one of the most significant imitators in clinical medicine. Its wide variety of manifestations can mimic autoimmune, inflammatory, and neoplastic disorders. Hereby 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 highlights how syphilis can closely imitate hematologic malignancy, particularly CTCL, at both clinical and histopathological levels. We also review published reports of syphilis masquerading as malignancies and propose a structured diagnostic algorithm. We believe that the early inclusion of syphilis in differential diagnosis is critical to avoid misdiagnosis and appropriate treatment delays.