Shuyue Ren

Introduction Insulinoma‐associated protein 1 (INSM1) is a newly characterized sensitive and specific immunohistochemical marker for neuroendocrine (NE) tumors. Whereas more traditional NE markers, such as chromogranin A and synaptophysin, are cytoplasmic, INSM1 is uniquely nuclear and thus could serve as a useful addition to NE tumor workup. While application of immunohistochemical studies to cytology specimens is becoming increasingly relevant, knowledge of the effects of the certain fixatives as well as the pattern and intensity of immunoexpression are important considerations. Methods Sixteen cases of pancreatic neuroendocrine tumor (PanNET) diagnosed between 2015 and 2021 underwent both fine‐needle aspiration, which was subsequently prepared in CytoLyt®‐fixed cytology cell block (CCB), and surgical resection, in which specimens were prepared into formalin‐fixed paraffin embedded blocks (FFPE). For all samples, INSM1 immunoreactivity was classified according to staining intensity and extent, then compared between CCBs and matched FFPEs. Results All 16 FFPE specimens demonstrated strong and diffuse INSM1 immunoreactivity, while only 10/16 (62.5%) CCBs were positive. Of those 10, only 2/10 (20%) demonstrated strong and diffuse reactivity. Conclusion The choice of fixative has a demonstrable effect on the immunoreactivity of INSM1 in PanNET. Even though the sensitivity is lower in CytoLyt®‐fixed cell block specimens, the addition of INSM1 is useful, especially in challenging cases that may be negative for one or more of the traditional NE markers.