Sensitivity and specificity of INSM1 compared with Chromogranin and Synaptophysin in neuroendocrine carcinomas of the head and neck region

Background : The head and neck region is an area where neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) can arise. NECs have several mimickers, which make their diagnosis challenging. Accurate diagnosis typically relies on morphology, supported by established markers such as synaptophysin (SYN) or chromogranin A (CGA), each with varying sensitivity and specificity. Insulinoma-associated protein 1 (INSM1) is a newer marker that has shown good sensitivity and specificity in various organs. Despite its promising potential, there are very few studies when compared to other organs. Methods : This case-control study tested INSM1, SYN, and CGA on 14 NEC samples and 109 non-NEC samples to evaluate their sensitivity and specificity. Results: INSM1 demonstrated an overall sensitivity of 92.9%, compared to 78.5% for CGA (P = 0.157) and 100.0% for SYN (P = 0.317). INSM1 exhibited a specificity of 96.3%, compared to 100% for both CGA (P = 0.045) and SYN (P = 0.045). Among non-NEC cases, scattered staining (< 10% of tumor cells) was observed with INSM1, while 4 non-NEC cases showed positive staining for INSM1. All non-NEC cases were negative for CGA and SYN. Conclusion: INSM1 demonstrates good sensitivity, comparable to SYN and CGA, with no statistically significant differences observed between these markers. However, the specificity of INSM1 shows statistically significant differences. Notably, one case of EBV-positive nonkeratinizing squamous cell carcinoma of the nasopharynx exhibited INSM1 positivity in 40% of tumor cells. As such, INSM1 should not be used as a standalone marker for diagnosis. Furthermore, caution is warranted when interpreting results with staining ≤10%, as this may reduce the reliability of a positive finding.