Bilateral pulmonary infiltrates without lymphadenopathy: A fatal case of lung adenocarcinoma and amivantamab-induced pneumonitis

Lung cancer can present radiologically as diffuse lung infiltrates, often mimicking pneumonia or interstitial lung disease (ILD). This atypical presentation may result in prolonged treatment with antibiotics or corticosteroids before malignancy is considered. Amivantamab, an EGFR-MET bispecific antibody, is an effective treatment of EGFR exon 20-mutated non-small cell lung cancer (NSCLC), but carries a risk of drug-induced pneumonitis, a rare yet potentially fatal complication. In our case, a 72-year-old woman presented with a persistent six-month cough, initially treated as bronchitis without imaging. Despite multiple antibiotic courses, her symptoms worsened, leading to imaging that revealed bilateral lung infiltrates without lymphadenopathy, lowering clinical suspicion for malignancy. An initial bronchoscopy with bronchoalveolar lavage (BAL) cytology was negative for malignancy, further delaying oncologic evaluation. Ultimately, a surgical lung biopsy confirmed the diagnosis of lung adenocarcinoma. She was diagnosed with stage IV disease and treated with carboplatin, pemetrexed, and pembrolizumab, but tumor progression led to amivantamab initiation. After six months of therapy, she developed progressive dyspnea and diffuse ground-glass opacities, consistent with drug-induced pneumonitis. Despite high-dose corticosteroids, her respiratory status rapidly deteriorated, ultimately resulting in fatal respiratory failure. • Lung cancer manifesting as bilateral infiltrates can mimic pneumonia, ILD, aspiration or inhalational injury. A high degree of suspicion is essential in patients with refractory symptoms or persistent imaging abnormalities, especially when they do not respond to conventional treatment of pneumonia or ILD. • The absence of a smoking history or lymphadenopathy on imaging should not preclude oncologic evaluation, particularly histopathologic evaluation. • Amivantamab is an effective therapy for EGFR exon 20-mutated NSCLC, but its risk of pneumonitis, though rare, can be fatal.