Abstract Background Lepidic adenocarcinoma, a histologic subtype of pulmonary adenocarcinoma, is characterized by neoplastic proliferation along intact alveolar septa. On imaging, it commonly presents as multifocal ground-glass opacities, often mimicking infectious or inflammatory lung disease. The presence of a micropapillary component, however, confers aggressive behavior with aerogenous spread, lymphovascular invasion, and poor prognosis. Early recognition and histologic confirmation are essential to avoid diagnostic delay and inappropriate management. Case Presentation A 79-year-old male with hypertension, hyperlipidemia, TIA, gout, benign prostatic hyperplasia, GERD, and a history of smoking presented with progressive dyspnea and hypoxemia. Two months earlier, he had been empirically treated with a Medrol Dosepak and mucolytics for presumed bronchitis. On pulmonary evaluation, room-air SpO2 was 73% with diffuse rhonchi and rales. CT chest revealed multifocal ground-glass opacities without a discrete mass and with underlying bullous emphysematous changes. Despite albuterol therapy, symptoms persisted, and a six-minute walk test demonstrated desaturation to 73%, improving to 90% on 10 L/min oxygen. He was admitted for bronchoscopy and further evaluation. Transbronchial biopsy confirmed adenocarcinoma with lepidic and micropapillary patterns. He remained intubated post-procedure and was later extubated to high-flow oxygen but remained oxygen dependent. Corticosteroids were initiated for presumed lymphangitic spread without improvement. Given diffuse aerogenous involvement, he was not a candidate for surgical resection or stereotactic body radiation therapy (SBRT). Oncology recommended palliative chemotherapy, but the patient elected for home hospice. Discussion This case highlights the diagnostic challenge of lepidic adenocarcinoma, which may mimic non-malignant lung disease and delay oncologic evaluation. Unlike typical nodular adenocarcinomas, lepidic tumors spread aerogenously, producing diffuse ground-glass infiltrates rather than a single lesion. Such radiologic patterns often prompt empiric antibiotics or steroids. The coexistence of lepidic and micropapillary growth thus creates a paradoxical clinical profile. It is radiographically subtle yet biologically invasive. The absence of radiographic mass, poor steroid response, and progressive hypoxemia in this patient emphasized the importance of early tissue diagnosis when diffuse opacities remain unexplained. Conclusion Lepidic-predominant adenocarcinoma should be considered in patients with diffuse ground-glass opacities and refractory hypoxemia unresponsive to empiric therapy. Early biopsy and histologic subtyping are essential, as mixed lepidic-micropapillary morphology signifies poor prognosis and dictates management. Recognizing this entity can prevent diagnostic delay and guide timely oncologic intervention. This abstract is funded by: None
Naqvi et al. (Fri,) studied this question.