# Human Meningiomas Reveal No Evidence of Neuroendocrine Differentiation

## TL;DR

This study finds no evidence that meningiomas, a type of brain tumor, have neuroendocrine features, despite some similarities to neuroendocrine tumors.

## Contribution

The study provides new evidence against neuroendocrine differentiation in meningiomas using multiple immunohistochemical markers and electron microscopy.

## Key findings

- NSE was detected in 91% of meningiomas, but other neuroendocrine markers like chromogranin A and synaptophysin were mostly absent.
- No secretory granules were detected in meningioma specimens using transmission electron microscopy.
- NSE and chromogranin B showed correlations with SSTR2 immunoreactivity and varied by tumor grade and subtype.

## Abstract

Meningiomas are heterogeneous tumors and studies suggest that meningiomas might be part of MEN1 syndrome. The tumors express somatostatin receptors (SSTRs) comparable to that seen in neuroendocrine neoplasms. We aimed to explore neuroendocrine differentiation in meningiomas by investigating the following neuroendocrine markers: neural cell adhesion molecule (CD56/NCAM), chromogranin A, chromogranin B, chromogranin C, neuron‐specific enolase (NSE), secretagogin, and synaptophysin. Our findings were related to WHO grade, tumor subtype, and SSTR2 immunoreactivity. Tissue microarrays from 162 patients with intracranial meningioma underwent immunohistochemical analyses. Immunoreactivity was assessed with manual and digital analyses. Transmission electron microscopy (TEM) was used to detect secretory granules in one tumor specimen. NSE, CD56, and chromogranin B were detected in 91%, 44%, and 16% of meningiomas, respectively. The other neuroendocrine markers were mostly negative. NSE immunoreactivity was higher in WHO grade 2 tumors (p = 0.027) and differed among subtypes with highest and lowest immunoreactivity in meningothelial and fibrous subtypes, respectively. Chromogranin B (p = 0.006) and NSE (p = 0.003) were positively correlated to SSTR2 immunoreactivity. No secretory granules were detected. Manual and digital evaluation showed excellent agreement. Our study does not support the hypothesis of neuroendocrine differentiation in meningiomas, as chromogranin A and synaptophysin were mostly absent.