Pancreatic Neuroendocrine Microtumors: Etiology, Diagnostic Criteria, and Differential Diagnosis

Pancreatic neuroendocrine microtumors represent small, well-differentiated neuroendocrine neoplasms (<5 mm) that are widely regarded as early lesions within the spectrum of pancreatic neuroendocrine tumorigenesis; however, their biological behavior remains a matter of an ongoing debate.

Although frequently associated with hereditary tumor syndromes such as multiple endocrine neoplasia type 1 and von Hippel-Lindau disease, pancreatic neuroendocrine microtumors also occur sporadically and are increasingly detected incidentally. In this review, we summarize their histopathological features, including key differential diagnoses, outline current insights into their molecular pathogenesis, and highlight unresolved issues in their clinical and diagnostic management.

Pancreatic neuroendocrine microtumors are small, low-proliferative neoplastic lesions arising in the islets of Langerhans and are considered precursor lesions of fully developed pancreatic neuroendocrine tumors. Increased proliferative activity and lymph node metastases are exceedingly rare. In contrast to non-neoplastic, hyperplastic islets, they show an altered distribution of islet cell hormones, which represents a key feature distinguishing them from their principal differential diagnosis.