Invasive Ureaplasma urealyticum infection mimicking diffuse large B-cell lymphoma relapse: A case report

Ureaplasma spp. are typically benign colonizers of the urogenital tract but may cause invasive disease in immunocompromised patients. In rare cases, such infections may mimic malignancy and lead to significant diagnostic delay. Diagnosis is challenging due to non-specific clinical manifestations, poor visibility on Gram stain, and limitations of standard culture methods. We report a rare case of invasive Ureaplasma urealyticum infection in a patient in complete remission after rituximab-based chemoimmunotherapy for diffuse large B-cell lymphoma transformed from follicular lymphoma. The infection manifested as a progressively destructive soft tissue lesion involving the scrotum and abdominal wall and was suspected to represent lymphoma progression. Conventional microbiologic investigations remained negative, and the diagnosis was ultimately established through microbiome analysis based on 16S rRNA gene amplicon sequencing. Antimicrobial susceptibility testing guided prolonged dual-agent therapy with doxycycline and moxifloxacin, resulting in complete resolution. Clinicians should consider invasive Ureaplasma infection in immunocompromised patients with persistent culture-negative infections or PET-positive lesions suggestive of malignancy, as early molecular diagnostics may prevent diagnostic delay and unnecessary invasive procedures.