Title : Multifocal invasive syphilis in an HIV-positive male mimicking septic emboli and testicular malignancy: A diagnostic and therapeutic challenge
Abstract:
Background:
Syphilis, a sexually transmitted infection caused by Treponema pallidum, remains a diagnostic challenge due to its diverse clinical presentations and ability to mimic various infectious and malignant conditions. In immunocompromised patients, particularly those with HIV, its manifestations can be even more atypical and aggressive. We present a rare and complex case of multifocal tissue-invasive syphilis involving the bone, testis, lungs, and central nervous system in a newly diagnosed HIV-positive male, initially suspected to have septic emboli and metastatic testicular cancer.
Case Presentation:
A 39-year-old male with no significant medical history presented with right foot pain of several weeks’ duration and progressive right testicular swelling over several months. Imaging revealed destructive bony lesions, a heterogeneous testicular mass, and multiple pulmonary nodules. Initial differentials included septic emboli, disseminated fungal infection, or metastatic malignancy. Serological testing revealed a new HIV diagnosis (viral load: 124,443 copies/mL; CD4: 312/μL) and a high-titer reactive RPR (1:1024). CSF analysis confirmed neurosyphilis (reactive VDRL 1:8), and testicular ultrasound revealed a 2.8 cm mass suspicious for malignancy. CT and bone scans further supported a multifocal process. He was treated with 14 days of intravenous penicillin G followed by intramuscular benzathine penicillin. Remarkable clinical and radiographic improvement was noted, including regression of the testicular mass, thus avoiding an unnecessary orchiectomy. Histopathology of a biopsied lymph node showed reactive plasmacytosis without evidence of malignancy or treponemal organisms. Broad-range PCR testing on lymph tissue later returned negative for T. pallidum.
Discussion:
This case underscores the protean nature of syphilis and its capacity to mimic oncologic, septic, and granulomatous diseases, especially in HIV-positive individuals. In the setting of syphilitic orchitis, misdiagnosis may lead to unwarranted radical surgeries such as orchiectomy. While urologic guidelines recommend orchiectomy for suspicious testicular masses, a testicular-sparing approach is increasingly recognized as appropriate in high-risk STI populations. The diagnostic conundrum is further complicated by low sensitivity of histological staining and occasional false negatives on PCR assays. Hence, clinical acumen, high suspicion, and therapeutic trials may be crucial in diagnosis. Additionally, this case highlights the underrecognized prevalence of syphilitic bone involvement and the potential role of advanced imaging in identifying atypical lesions.
Conclusion:
Clinicians should maintain a high index of suspicion for syphilis in immunocompromised patients presenting with systemic, multifocal lesions mimicking malignancy or embolic disease. A conservative and multidisciplinary approach can avert unnecessary invasive procedures and improve outcomes. This case exemplifies the evolving landscape of syphilis in the HIV era and reinforces the importance of integrating infectious disease perspectives in the evaluation of complex systemic presentations.
