Case Presentation: A 45 year-old Cambodian female with no past medical history presented to the clinic with a mild cough. Her medical history was notable for never smoking, occasional alcohol use, and no recreational drug use. She had no known occupational exposures and no family history of malignancy. Initial treatment for gastroesophageal reflux disease and asthma were ineffective. Chest x-ray revealed a left lower lobe infiltrate concerning for a pneumonia which did not resolve with appropriate antibiotics. The patient had worsening fatigue and shortness of breath over the course of the month. CT Chest subsequently showed bilateral pulmonary emboli, pleural effusions, mediastinal and hilar lymphadenopathy and a pericardial effusion. She was admitted to the hospital and initiated on heparin for anticoagulation. Fluid cytology from thoracentesis revealed poorly differentiated adenocarcinoma of pulmonary origin. Her course was complicated by heaviness in her left arm with no focal deficits on neurologic exam. MRI of her brain showed no metastases but multiple subacute to acute strokes. She then developed acute respiratory failure requiring BiPAP with resolution after bilateral catheter drainage placement. FISH analysis was positive for ROS-1 rearrangement and negative for ALK and EGFR mutations. She was promptly started on crizotinib and discharged home for continued outpatient follow-up with oncology.
Discussion: This case depicts a young Asian female who never smoked with rapid progression of newly diagnosed adenocarcinoma within two months of symptom onset. EGFR mutations are commonly tested in Asian patients with new NSCLC but ROS-1 rearrangements encompass a newer, small, yet highly relevant subgroup of NSCLCs. The recent approval for crizotinib for the treatment of this type of lung cancer has been associated with substantial and durable responses (3), which highlights the need to identify and test for this mutation regularly. As demonstrated by this case report, this type of lung cancer can present in young, healthy, never smokers with no family history with nonspecific symptoms such as a cough. A high level of suspicion must therefore be maintained by physicians in order to identify low-risk patients with ROS-1 positive NSCLC in order to prevent a delay in treatment and further complications as witnessed by this patient’s bilateral pulmonary emboli, malignant pericardial effusion and several strokes.
Conclusions: Lung cancer continues to be the leading cause of cancer worldwide, with non-small cell lung cancers (NSCLC) accounting for an estimated 85% of all lung cancer types. Several key driver gene mutations have been identified in NSCLCs, which have allowed for more accurate classification and improved treatment options based on each specific mutation. Recently, chromosomal rearrangements involving ROS-1, a receptor tyrosine kinase of the insulin receptor family, have been found and defined as driver mutations in 1-2% of all NSCLCs (1). ROS-1 mutations have a higher prevalence in younger patients who are never-smokers with a new diagnosis of adenocarcinoma (2). These rearrangements are defining a unique class of patients who otherwise have a low likelihood of developing lung cancer, associated with high morbidity.