Case of the Month

Answer to February's Case of the Month

B. Treponema pallidum

The lymph node shows syphilitic lymphadenitis, one of the clinical manifestations of syphilis. Syphilis is a venereal disease caused by the spirochete Treponema pallidum, which was first clinically recognized in the 15^th century and T. pallidum discovered as a causative agent at the beginning of the 20^th century. Today, the incidence of primary and secondary syphilis is on the rise, with an 81 percent increase in reported cases in the United States from 2014 to 2018. Syphilis can be a challenging disease for clinicians to diagnose, which has led to its nickname – “The Great Mimicker” – because its symptoms and clinical findings overlap with many other conditions.

Clinically, syphilis has three stages, as well as latent stages that can occur either between the primary and secondary stages or after the resolution of the secondary stage. Syphilis is sexually transmissible in the primary and secondary stages. The primary stage is characterized by indurative and ulcerative syphilitic chancre, occurring at the site of contact with a partner’s infectious lesion – most commonly th genital area, rectum, or oral cavity. Secondary syphilis is characterized by nonpruritic rash (characteristically on palms and soles), mucosal lesions (condyloma latum), fever, lymphadenopathy, and occasionally alopecia, periostitis, hepatitis, and nephritis. Tertiary syphilis occurs in approximately 30 percent of infected patients anywhere from two to 50 years after initial infection, and can manifest as central nervous system disease (e.g., meningovascular disease or tabes dorsalis), gummas (tumorous lesions), cardiovascular syphilis, and ocular or otic syphilis.

As the number of cases in the community increases, pathologists see more syphilitic lesions (from all clinical stages of disease) under the microscope, which can present a diagnostic challenge. Lesions can be seen in almost any organ and can overlap histologically with other conditions – so syphilis should be considered in many differential diagnoses. Syphilitic lymphadenitis can be seen in all stages of disease. The most commonly observed histologic changes include follicular and paracortical hyperplasia, interfollicular plasmacytosis, capsular thickening (frequently prominent, as in this case) with plasma cell infiltration, and obliterative vasculitis. Some cases can show collections of epithelioid histiocytes or well-formed granulomas and stromal and vascular hyperplasia. In the tertiary stage, lymph nodes can show gummatous lymphadenitis, characterized by prominent necrosis surrounded by epithelioid histiocytes and multinucleated giant cells. In the affected lymph nodes, spirochetes can be demonstrated using Warthin-Starry staining, immunofluorescence, or immunohistochemical stain (the preferred method). Differential diagnosis of syphilitic lymphadenitis includes other causative agents of necrotizing and non-necrotizing granulomatous inflammation (e.g., sarcoidosis or mycobacterial infections). Chlamydia trachomatis is a causative agent of lymphogranuloma venereum, causing necrotizing granulomatous lymphadenitis; Rickettsia rickettsia causes Rocky Mountain spotted fever; and lymph nodes involved in Mycobacterium avium-intracellulare infection usually show sheets of foamy macrophages filled with bacilli that can be demonstrated with Ziehl-Neelsen staining.

Submitted by Anamarija M. Perry, Associate Professor of Pathology, and Lauren B. Smith, Professor and Director of Hematopathology at the University of Michigan, Ann Arbor, Michigan, USA.