Targeting DLL3 in Extrapulmonary Neuroendocrine Carcinoma: Bridging the Gap from Diagnosis to Emerging Biomarker-Driven Therapy

Dr. Strosberg introduces the case of James, a 64-year-old man with hypertension presenting with progressive abdominal pain, 12-pound unintentional weight loss, and fatigue over 6 weeks. Imaging reveals a 4.2-centimeter colonic mass with peritoneal lymph nodes and hepatic lesions. Colonoscopy-guided biopsy confirms poorly differentiated carcinoma of colonic origin, with positive chromogranin A and CK20 immunostaining, Ki-67 proliferation index of 82%, mitotic rate exceeding 20 per high-powered field, and confirmed metastatic disease. Somatostatin receptor expression is negative with mildly elevated chromogranin A levels.

Dr. Strosberg discusses clinical practice approaches when encountering patients like James with colonic masses demonstrating very high Ki-67 indices and neuroendocrine immunohistochemical markers. When pathologists confirm poorly differentiated carcinoma with characteristic Ki-67 exceeding 55% to 70% and appropriate morphology, metastatic disease typically requires medical oncology management with cytotoxic chemotherapy as the primary intervention.