142 Medullary Carcinoma or Neuroendocrine component? The INSM1 Dilemma in Colonic Neoplasia

Introduction/Objective Insulinoma-associated protein 1 (INSM1) is a highly sensitive marker for neuroendocrine differentiation. However, emerging reports show it may be expressed in non-neuroendocrine malignancies and can be a diagnostic pitfall. The purpose of this report is to highlight a case of medullary carcinoma of the colon with diffuse INSM1 expression. Methods/Case Report A 69-year-old woman was found to have a hepatic flexure mass on colonoscopy. No metastatic disease was identified on imaging, and she underwent right hemicolectomy. Pathologic evaluation revealed a 6.7 cm poorly differentiated carcinoma with areas of syncytial growth, prominent lymphoid response, and no nodal involvement (pT2N0). Immunohistochemistry showed diffuse nuclear INSM1 positivity, focal synaptophysin and chromogranin expression, and Ki-67 proliferation index >90%, initially raising concern for a poorly differentiated neuroendocrine carcinoma (PDNEC) component. MSI-testing by immunohistochemistry showed loss of MLH1 and PMS2. Based on morphology and MLH1/PMS2 loss, a diagnosis of medullary carcinoma was rendered after expert consultation. This avoided potential post-operative chemotherapy had there been a PDNEC component. Results NA Conclusion Diffuse INSM1 expression in colorectal medullary carcinoma can be misinterpreted as PDNEC and may have implications for adjuvant therapy. Syncytial growth and MSI-high status are diagnostic clues, and expert consultation is recommended in challenging cases.