Abstract Introduction Lepidic mucinous adenocarcinoma (LMA) is a rare histologic subtype, accounting for roughly 5% of lung adenocarcinomas. It frequently manifests as multifocal or diffuse pneumonia-like infiltrates, posing significant diagnostic challenges. Although LMA most commonly occurs in non-smokers, we report an uncommon case of multifocal LMA in a 53-year-old female with a seventy-six pack year smoking history who presented with persistent hypoxia and diffuse cavitary nodules on imaging – findings that initially mimicked chronic infection. Description A 53-year-old woman with a history of chronic obstructive pulmonary disease, and extensive tobacco use presented with progressive dyspnea and cough unresponsive to multiple antibiotic courses, leading to repeated emergency department visits and admissions. Chest CT revealed innumerable bilateral centrilobular nodules with cavitation and perilymphatic thickening, initially interpreted as an infectious or inflammatory process. A comprehensive infectious workup was negative, including acid fast bacillus, fungal, and viral studies. Although QuantiFERON-TB was positive, three consecutive sputum cultures were negative for active tuberculosis.Bronchoscopy revealed mucus plugging but no endobronchial lesions, however, cytology did come back suspicious for malignancy. Due to worsening hypoxia, the patient underwent video-assisted thoracoscopic wedge biopsy, which revealed multifocal lepidic mucinous adenocarcinoma involving the right upper and middle lobes. She remained oxygen-dependent but clinically stable and was referred for oncology evaluation and next-generation sequencing. Her prior asbestos and mold exposure during home renovation raised the possibility of additive environmental risk factors. Discussion This case adds to the literature on LMA by describing an uncommon malignancy with an atypical presentation that initially resembled chronic infection. The diffuse, cavitary, and nodular pattern on imaging prompted repeated antibiotic trials and contributed to a diagnostic delay, highlighting the challenge of distinguishing malignancy from infection in patients with complex pulmonary histories. Early pursuit of tissue diagnosis is critical when pulmonary infiltrates persist despite appropriate antimicrobial therapy. Multifocal LMA remains a diagnostic and therapeutic challenge due to its variable radiographic appearance manifestations and limited evidence to guide management. This case highlights the importance of maintaining a broad differential diagnosis when evaluating non-resolving pulmonary disease and demonstrates the value of a multidisciplinary approach – including pulmonology, oncology, and thoracic surgery – for timely diagnosis and coordinated care. Equally important, early integration of palliative care can provide essential support in managing symptom burden, psychological distress, and aligning treatment with patient-centered goals following a new diagnosis of advanced malignancy. This abstract is funded by: None
Heydari et al. (Fri,) studied this question.