A 62-year-old woman with a 40-pack-year smoking history is found to have small cell lung cancer on biopsy. Immunohistochemistry is performed to confirm neuroendocrine differentiation. Which of the following is the most common neuroendocrine marker expressed in small cell lung cancer?

Explanation

## Neuroendocrine Markers in Small Cell Lung Cancer **Key Point:** Synaptophysin is the most frequently and reliably expressed neuroendocrine marker in SCLC, present in >95% of cases. It is the gold standard marker for confirming neuroendocrine differentiation in lung cancer. ### Comparison of Neuroendocrine Markers in SCLC | Marker | Sensitivity in SCLC | Specificity | Clinical Use | Notes | |--------|---------------------|-------------|--------------|-------| | **Synaptophysin** | >95% | High | Gold standard for NE differentiation | Most reliable; present in nearly all SCLC | | **Chromogranin A** | 80–90% | High | Confirmatory; also serum marker | May be elevated in serum; useful for monitoring | | **CD56 (NCAM)** | 85–95% | Moderate | Confirmatory; also in other NE tumors | Less specific than synaptophysin | | **Calcitonin** | <5% | Very high | Rare; associated with paraneoplastic syndrome | Only in subset with ectopic hormone production | ### Pathologic Basis **Synaptophysin** is a synaptic vesicle protein found in all neuroendocrine cells. In SCLC: - Present in nearly 100% of cases - Marks the neuroendocrine origin of the tumor - Appears as cytoplasmic staining on immunohistochemistry - Used in diagnostic panels alongside chromogranin A and CD56 **High-Yield:** The diagnostic panel for SCLC typically includes **synaptophysin + chromogranin A + CD56**. Positivity for at least 2 of these 3 markers confirms neuroendocrine differentiation and SCLC diagnosis. **Clinical Pearl:** Chromogranin A can also be measured in serum and may serve as a **tumor marker for monitoring response to therapy** in SCLC patients, but synaptophysin is the tissue-based gold standard for diagnosis. **Mnemonic:** **SCC** = **S**ynaptophysin (most common), **C**hromogranin A (confirmatory), **C**D56 (confirmatory). All three are markers of neuroendocrine differentiation, but synaptophysin is present first and most reliably. [cite:Robbins 10e Ch 15]