Case Presentation: The patient is an 83 year-old Caucasian man with a history of hypertension, tobacco use, and COPD who presented to the emergency department with a four day history of chest pain, shortness of breath, and mild non-productive cough. His chest pain was constant and had no exacerbating or alleviating factors. He denied any fever or chills.
On admission he exhibited mild tachycardia and tachypnea, and required 2 liters of supplemental oxygen. His basic chemistry panel and CBC were within normal limits. An EKG and serial troponins were unremarkable. However, his lactate dehydrogenase was 3250 U/L. A chest radiograph demonstrated a right mediastinal opacity, determined to be a 10.9 x 6.7 cm mass on computed tomography. Interestingly, this mass was not present on a chest radiograph obtained two months prior. A positron emission tomography scan demonstrated multiple areas of hypermetabolic activity, including a large mediastinal lesion, multiple lung lesions, bilateral supraclavicular adenopathy, and diffuse marrow involvement. Biopsy of a left supraclavicular lymph node demonstrated a poorly differentiated carcinoma, positive for synaptophysin and chromogranin. This was most consistent with a large cell neuroendocrine carcinoma of the lung. The tumor was negative for EGFR, ALK rearrangements, ROS1 rearrangement, and PD-L1 expression. Chemotherapy with carboplatin and etoposide was started urgently due to the rapid growth of the tumor. However the patient chose to transition to comfort cares about one week after chemotherapy started and died shortly thereafter due to respiratory failure.
Discussion: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor of the lung that is distinct from small cell lung cancer (SCLC), and accounts for about 3% of lung cancers. Due to its rarity, understanding of the natural history of LCNECs is limited. This case exemplifies the rapid progressiveness of LCNECs. At the time of diagnosis, 60-80% of patients have known lymph node involvement, while 40% have frankly metastatic disease. Paraneoplastic and carcinoid syndromes are rarely associated with LCNECs, and patients may have symptoms of chest pain, dyspnea, or productive cough. SCLC-based chemotherapy (e.g. carboplatin/etoposide) is currently utilized for advanced disease, with expected response in 30-60% of patients. The prognosis of LCNEC is poor with a median survival rate around 9-10 months. LCNEC is increasingly recognized to have distinct molecular subsets. Using these subsets in future studies may improve chemotherapy selection for LCNEC.
Conclusions: Understanding of the natural history of LCNECs is limited due to its heterogeneous biology. This case illustrates the rapidity of tumor development in LCNEC. Additionally, due to the biological heterogeneity of LCNECs, optimal chemotherapeutic regimens remain an active area of investigation.