Abstract Introduction Large cell lung carcinoma with rhabdoid features (LCLC-RP) is a rare (0.1-1%) and highly aggressive variant of non-small cell lung cancer. We report a rapidly fatal case, highlighting the tumor’s aggressive nature, co-mutations associated with therapy resistance, and limitations of palliative airway stenting in fulminant endoluminal disease. Case Description A 50-year-old male with a 30-pack-year smoking history presented with subacute dyspnea, cough, and low-grade fevers. Initial imaging showed a 7.7-cm right-upper-lobe (RUL) mass with mediastinal adenopathy. Endobronchial ultrasound-guided biopsies (Stations 4-R, 7; FNA) confirmed poorly differentiated carcinoma with rhabdoid morphology: Pan-Keratin TTF-1, Napsin A, synaptophysin, and p40 negative; high proliferative index (Ki-67 ∼60%). Mismatch-repair proteins were intact; PD-L1 tumor-proportion score was 1%. Comprehensive molecular profiling noted co-mutations in KRAS-Q61H with loss-of-function alterations in STK11 and KEAP1, copy-number losses in CDKN2A/B, MTAP, and SMARCA4, low tumor mutational burden (3.7/Mb), and no actionable fusions or drivers. Within three weeks, PET/CT revealed rapid tumor progression with new bilateral pulmonary nodules and a large right pleural effusion (removed 950 mL of malignant effusion). Urgent bronchoscopy performed: argon-plasma-coagulation (APC) debulking of the distal trachea and right-sided bronchi, serial dilation of the right mainstem/bronchus intermedius to 12 mm, and deployment of a covered 12 × 30-mm Ultraflex stent in the bronchus intermedius. Post-procedure, the right mainstem/bronchus intermedius and RML/RLL were patent; the RUL remained partially occluded. Despite initial improvement of airflow, within 48 hours the stent was re-occluded by tumoral ingrowth, precipitating acute hypoxemic respiratory failure requiring BiPAP (FiO2 100%). Given rapid decline, escalation to intubation or systemic therapy was not pursued; he transitioned to comfort care and passed away in hospice. Discussion Displaying aggressive nature of LCLC-RP from mild symptoms to terminal respiratory failure in four weeks. This is likely due to the concurrent KRAS activation, with STK11/KEAP1 mutation loss, which are linked to poor outcomes. Along with resistance to immune-checkpoint inhibitors. Consistent with this, our patient’s tumor had low PD-L1 expression and low TMB, suggesting minimal expected benefit from immunotherapy. Even when technically successful, palliative debulking and stenting may fail quickly in hyper-proliferative endobronchial disease, as shown by re-occlusion within 48 hours. This case highlights the need for early recognition of LCLC-RP, expedited multidisciplinary planning, and consideration of clinical-trial referral or novel strategies (e.g., approaches for SMARCA4-deficient tumors) at diagnosis to avoid loss of the treatment window. This abstract is funded by: None
Uppalapati et al. (Fri,) studied this question.