A brain lesion with tumor cells expressing cytokeratin, chromogranin, and synaptophysin most likely metastasized from which primary cancer?

• A. Glioblastoma multiforme
• B. Melanoma
• C. Renal cell carcinoma
• D. Small cell carcinoma of the lung

Answer: (D)

Immunohistochemical profiling helps identify where a metastatic brain tumor originated by matching marker patterns. Cytokeratin signals epithelial origin, while chromogranin and synaptophysin indicate neuroendocrine differentiation. A brain lesion that coexpresses epithelial markers with neuroendocrine markers points to a neuroendocrine tumor of a distant organ, most commonly small cell carcinoma of the lung, as the primary source. Glioblastoma multiforme is a primary brain tumor and would typically show GFAP positivity rather than neuroendocrine markers. Melanoma would usually express S-100 and related melanoma markers rather than chromogranin/synaptophysin, and renal cell carcinoma often lacks neuroendocrine markers. Thus, the pattern described best fits metastasis from small cell lung cancer.