Abstract
BACKGROUND: Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare malignancies affecting the pancreas. The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components, each constituting 30% or more of the tumor volume. Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination. A well-differentiated neuroendocrine tumor (NET) component is rarely reported in MiNENs. CASE SUMMARY: Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas. The two tumors show distinct histology and significant differentiation discrepancy (poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET), and also present as metastases in separate lymph nodes. Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma, but no genetic alterations in the NET, suggesting divergent origins for these two components. Although tumors like this meet the diagnostic criteria for MiNEN, clinicians often find the diagnosis and staging confusing and impractical for clinical management. CONCLUSION: Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.