A 58-year-old male smoker presents with chest pain and hemoptysis. Chest X-ray shows a central hilar mass with mediastinal widening. Bronchoscopic biopsy reveals small round cells with scant cytoplasm and high mitotic rate. Immunohistochemistry is positive for chromogranin A and synaptophysin. Which single feature most reliably distinguishes this SCLC from limited-stage disease?

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