CytoLyt? Fixation Impedes INSM-1 Immunoreactivity Compared to Formalin Fixation

Background Insulinoma-associated protein 1 (INSM-1) is an immunohistochemical (IHC) marker commonly used to confirm cytomorphological concordant neuroendocrine tumors/carcinomas (NET/NEC), demonstrating high utility in small samples. Previous reports have suggested comparable INSM-1 staining in CytoLyt®-fixed cell blocks and formalin-fixed surgical pathology specimens. This study aimed to assess INSM-1 immunoreactivity using both fixation methods and investigate potential factors contributing to its variable expression. Materials and Methods A retrospective query was performed (03/31/21 to 05/31/22) for NET/NEC cases that had both Formalin and CytoLyt® fixed cell blocks. We collected clinical data and reporting of immunostains for each case. INSM-1 staining was evaluated in both fixation methods, and reported as positive, negative, or equivocal. Equivocal INSM-1 staining was further scored as a percentage of 1-100% and intensity of weak (faint staining), moderate (darker staining), and strong (dense staining). Results Our search identified 20 cases from diverse body sites, including mediastinal lymph nodes (40%), pancreas (35%), lung (20%), and porta hepatis lymph nodes (5%). All cases exhibited a widespread positivity (over 90%) in formalin-fixed cell blocks. In contrast, CytoLyt® fixed cells showed a negative stain in 65% of cases, and 30% exhibited an equivocal positivity. Conclusion While INSM-1 is previously reported as a sensitive (75–100%) and specific (82.7–100%) marker for NET/NECs, our study found a reduced immunohistochemical staining in CytoLyt®-fixed cell blocks. Consequently, false negative INSM-1 IHC results in CytoLyt®-fixed cell block material may pose a pitfall in the diagnosis of NET/NEC.