Sulfur granule‑negative pulmonary Schaalia odontolytica infection that mimics lung cancer with lack of radiological response to β‑lactam therapy: a case report

Abstract Background Pulmonary actinomycosis is frequently misdiagnosed as lung cancer or pulmonary tuberculosis. Classic sulfur granules are the hallmark pathological markers of this disease, while sulfur granule-negative cases pose substantial diagnostic challenges. Although metagenomic next-generation sequencing (mNGS) enables rapid pathogen identification, low‑abundance pathogen reads in bronchoalveolar lavage fluid (BALF) pose challenges for clinical interpretation. Moreover, no unified guidelines define surgical timing for encapsulated abscesses showing lack of radiological response to standard β-lactam regimens. This atypical case of Schaalia odontolytica infection highlights important clinical challenges and may provide diagnostic and surgical references for clinicians. Case presentation A 65-year-old male with long‑standing type 2 diabetes mellitus (T2DM) and suboptimal glycemic control presented with a 12-month history of productive cough and intermittent hemoptysis. Chest computed tomography (CT) revealed an upper-lobe mass highly suspicious for lung cancer. Special staining of bronchoscopically collected secretions yielded positive Gram and Grocott methenamine silver (GMS) staining, whereas BALF mNGS only detected 79 sequencing reads of S. odontolytica. Four-month guideline-concordant penicillin therapy showed no measurable reduction of the lesion. After multidisciplinary team (MDT) discussion and positron emission tomography-computed tomography (PET-CT) to characterize disease extent and identify additional suspicious lesions, the patient underwent video-assisted thoracoscopic surgery (VATS) right upper lobectomy. Intraoperative pus culture and repeated high-abundance mNGS confirmed the pathogen. The patient received an additional 24‑week postoperative course of oral amoxicillin‑clavulanate, and remained clinically and radiologically recurrence‑free at six‑month follow‑up. Conclusions Combined special histochemical staining and mNGS may aid diagnostic evaluation for sulfur granule-negative pulmonary actinomycosis mimicking lung cancer. Low BALF sequencing reads cannot rule out invasive infection complicated by encapsulated abscess. Timely surgical resection, combined with prolonged postoperative antimicrobial therapy, may benefit carefully selected patients with lesions showing lack of radiological response to standard β‑lactam therapy, providing practical diagnostic and therapeutic insights for clinicians managing indeterminate pulmonary masses highly suspicious for malignancy.