Medullary colonic carcinomas present with early-stage disease and do not express neuroendocrine markers by immunohistochemistry

BACKGROUND: Medullary colonic carcinoma (MCC) is a rare and distinct phenotype of colorectal cancers characterized histologically by sheets of malignant cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, exhibiting prominent infiltration by lymphocytes and neutrophilic granulocytes. We present the clinicopathologic and immunohistochemical characteristics of this rare tumor in our patient population. METHODS: Eleven cases diagnosed with MCC from 1996-2020 met the diagnostic histologic criteria and had tissue blocks available for further analysis. Immunohistochemistry for mismatch repair deficiency, CDX2, synaptophysin, and chromogranin, and microsatellite instability testing by polymerase chain reaction were performed. Additional clinical information was obtained from the electronic medical records. RESULTS: The median age at diagnosis was 69 years. MCC was more common in women (64%) than men (36%) and all (100%) cases involved the right colon. The median carcinoembryonic antigen level at diagnosis was 2.8 ng/mL. Lymphovascular invasion and perineural invasion occurred in 64% and 9% of cases, respectively. Synaptophysin and chromogranin showed no expression in any of the cases (0%), and CDX2 was only expressed in 18% of cases by immunohistochemistry. Most patients (73%) presented with stage II disease and 7 (64%) cases were microsatellite instability-high. Only lymph node metastasis showed an association with overall survival (OS) (hazard ratio 0.04, 95% confidence interval 0.0003-0.78; P=0.035). During a median follow up of 1.25 years, the median OS was not estimable as the survival curve did not reach the median point of survival, indicating that more than half of the patients were still alive at the end of the study. CONCLUSION: Based on our experience, neuroendocrine markers, including synaptophysin and chromogranin, are not expressed in MCC, and many patients present with early-stage disease.