Case Presentation: Previously healthy, never-smoker, COVID vaccinated, 45yo male with a history of hypertension presented to urgent care for one month history of shortness of breath on exertion, mild cough, and some weight loss. At urgent care, oxygen saturation was found to be 77% on room air and was transferred to Bronson Hospital for further workup and management.On exam, the patient was speaking in full sentences and was healthy-appearing although hypoxic. Initial lab findings included leukocytosis. Chest XR was notable for diffuse, bilateral airspace disease and follow-up CT demonstrated extensive micro-nodularity and consolidations concerning for atypical infections including miliary Tuberculosis, Histoplasmosis and COVID pneumonia. CT detected sclerotic bone lesions throughout spine and sternum, and two hypodense liver lesions. The patient required supplemental oxygen via high flow nasal cannula to maintain O2 saturation above 92%. He persistently denied shortness of breath and any additional symptoms. Empiric pneumonia treatment included azithromycin, ceftriaxone, and dexamethasone. A comprehensive infectious workup included RIDP and testing for: TB, legionella, pneumocystis, HSV, CMV, VZV, Brucella, Bartonella, Mycoplasma pneumonia, Q fever, Coccidiodes, Blastomyces, Histoplasma, Staphylococcus aureus and HIV. The patient was also tested for: ANCA vasculitis; calcitriol and ACE levels for sarcoidosis; thyroid abnormalities; and specimens of lung tissue were analyzed. Significant findings included: positive EBV antibodies and elevated ESR and CRP.Specimens from bronchoscopy were significant for primary adenocarcinoma of the lung with 0% of tumor cells positive for PDL1. CT abdomen/pelvis, brain MRI, and total body bone scan revealed diffuse metastases to the brain (over 60 distinct lesions), liver, bones, and a left adrenal mass. The patient continued to deny additional symptoms including pain, focal neurologic symptoms, visual or motor disturbances. Radiation oncology was consulted and the patient elected to proceed with palliative whole brain radiation. He was discharged home to follow up with oncology and radiation-oncology.

Discussion: Lung cancer is the leading cause of cancer-related deaths in the United States. Common presentations include cough, weight loss, dyspnea, chest pain, hemoptysis, bone pain and hoarseness. In the United States approximately 19% of female and 9% of male nonsmokers will develop lung cancer. Amongst nonsmokers, non-small cell lung cancer, particularly adenocarcinoma, is the most prevalent. Some patients may develop cancer secondary to occupational and environmental exposures, while others have no known risks. In NSCLC, better prognoses are associated with early stage disease, minimal weight loss (< 5%), functional status and female gender. Certain tumor biomarkers also contribute to disease prognosis. EGFR and ERCC1 expression is associated with better prognoses, while the presence of K-ras expression is associated with worse prognosis. Additional markers, such as PD-L1, can be targeted with immunotherapy.

Conclusions: In the case of our patient, a delayed diagnosis confounded by lack of PD-L1 expression confers a poor prognosis. While he remained largely asymptomatic and pain-free despite his cancer severity, his case exemplifies the remarkable reserve that the human body possesses. This reserve may have delayed his diagnosis and, while impressive, it ultimately resulted in a poorer outcome for this patient.

IMAGE 1: Axial Chest CT showing extensive infiltrates throughout lungs

IMAGE 2: Bone scan showing numerous distant bone metastases