Diagnosis of Syphilis in Paraffin-Embedded Skin Biopsies: Comparison of Treponema pallidum Immunohistochemistry and Polymerase Chain Reaction in Primary and Secondary Stages of Disease

Syphilis remains one of the most prevalent sexually transmitted infections. Serology is the diagnostic gold standard, but skin biopsies aid in ambiguous cases. Treponemas can be detected in tissue by immunohistochemistry (IHC) and polymerase chain reaction (PCR); however, their comparative performance across disease stages has not been extensively studied. This retrospective study of 48 formalin-fixed, paraffin-embedded (FFPE) skin biopsies from syphilis cases compared Treponema pallidum IHC and PCR. Of 48 biopsies, 42 (88%) were positive by T. pallidum–specific PCR, whereas IHC identified 45 (94%; p = 0.04). Organisms were denser in primary syphilis (p = 0.03) and predominantly involved the lower third of the epidermis. In 7 of 45 biopsies (15%), treponemas were only detected in the dermis (all secondary syphilis). Therefore, Treponema pallidum IHC demonstrated a slight advantage over PCR, but low Treponema density in about 40% and epidermal absence in nearly 20% of secondary syphilis biopsies highlight a substantial risk of overlooking treponemas on IHC. Systematic assessment including endothelium and perivascular areas is essential.