Histoplasma-Associated Mediastinal Granulomatous Disease With Superimposed Viridans Group Streptococcal Suppurative Lymphadenitis Mimicking Malignancy: A Case Report.

A 41-year-old incarcerated male with multiple comorbidities presented with severe constitutional symptoms, including persistent fever, pleuritic chest pain, and significant unintentional weight loss. Diagnostic evaluation revealed a large, irregular posterior mediastinal mass on chest CT, characterized by calcifications, heterogeneous low-attenuation areas, and internal air locules extending to the subcarinal region adjacent to the lower thoracic esophagus. These findings initially raised concerns for an esophageal pathology complicated by potential perforation; however, an esophagram excluded esophageal rupture. Laboratory studies demonstrated persistent thrombocytosis, hypoalbuminemia, anemia, elevated inflammatory markers, and a low-positive Histoplasma antibody titer (1:8), suggestive of fungal involvement. Further evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) obtained purulent material from an enlarged subcarinal lymph node, supporting the presence of an active bacterial infection. Microbiological analysis demonstrated moderate growth of viridans group streptococci, which correlated with Gram-stain findings of Gram-positive cocci in chains. Although scant Staphylococcus epidermidis was also recovered, it was considered likely to represent contamination and was therefore not regarded as the primary pathogen. Treatment with broad-spectrum intravenous antibiotics alongside systemic antifungal therapy led to significant clinical and radiological improvement. Follow-up CT imaging demonstrated marked reduction of the mediastinal mass, resolution of internal air locules, and improvement in lymphadenopathy and pleural effusions. This case report emphasizes the diagnostic complexity of infectious mediastinal masses that closely mimic malignancies. It further highlights the importance of integrating comprehensive clinical, radiological, serological, and microbiological data to establish an accurate diagnosis and guide appropriate targeted treatment.