Syphilis in Hematopathology Practice: A Diagnostic Challenge

Context.— Syphilis, a reemerging disease caused by the spirochete Treponema pallidum, is becoming more frequent in surgical pathology and hematopathology practices. Hematopathologists typically receive lymph node biopsies from patients with syphilis who have localized or diffuse lymphadenopathy. Occasionally, syphilis infection in the aerodigestive tract can show a prominent lymphoplasmacytic infiltrate and mimic lymphoma. Besides the varying and occasional atypical morphology, the fact that clinical suspicion tends to be low or absent when histologic evaluation is requested adds to the importance of making this diagnosis. Objective.— To summarize histologic features of syphilitic lymphadenitis and syphilis lesions in the aerodigestive tract, and to review differential diagnosis and potential diagnostic pitfalls. Data Sources.— Literature review via PubMed search. Conclusions.— Characteristic histologic findings in syphilitic lymphadenitis include thickened capsule with plasma cell–rich inflammatory infiltrate, reactive follicular and paracortical hyperplasia with prominent lymphoplasmacytic infiltrate, and vasculitis. Lymph nodes, however, can show a number of other nonspecific histologic features, which frequently makes the diagnosis quite challenging. In the aerodigestive tract, syphilis is characterized by plasma cell–rich infiltrates. Immunohistochemistry for T pallidum is the preferred method for detecting spirochetes; however, this immunohistochemical stain shows cross-reactivity with other treponemal and commensal spirochetes. Differential diagnosis of syphilis in lymph nodes and the aerodigestive tract is broad and includes reactive, infectious, and neoplastic entities. Pathologists should be aware of the histologic features of syphilis and keep this challenging entity in the differential diagnosis.