PNETs

Pancreatic neuroendocrine tumors (pNETs) are neoplasms arising from pancreatic neuroendocrine cells, typically the islet cells. They are rare and can be functional, secreting hormones, or nonfunctional. The annual incidence is about 1–2 per 100,000 people. A portion occurs in the context of genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1).

Functional pNETs produce hormones that cause distinct syndromes: insulinomas (hypoglycemia), gastrinomas (peptic ulcers), glucagonomas, VIPomas, and somatostatinomas. Nonfunctional tumors do not secrete active hormones and may present with vague abdominal symptoms or be discovered incidentally.

Diagnosis combines biochemistry, imaging, and histology. Hormone-related tests are used when a functional tumor is suspected. Chromogranin A can aid detection but is nonspecific. Cross-sectional imaging (CT or MRI) and endoscopic ultrasound help determine size and extent; functional imaging such as 68Ga-DOTATATE PET/CT is used for somatostatin receptor activity. Tumors are graded by Ki-67 index and mitotic rate into well-differentiated neuroendocrine tumors (G1–G3) and poorly differentiated carcinomas, with staging by TNM.

Treatment depends on stage and grade. Localized pNETs are usually managed with surgical resection; enucleation may be used for small insulinomas. Advanced disease may require liver-directed therapies, somatostatin analogs for symptom control, and systemic therapies such as everolimus or sunitinib. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is an option for somatostatin receptor–positive tumors; CAPTEM chemotherapy is used in select cases.

Prognosis is variable and strongly influenced by stage and grade. Regular follow-up with imaging and biomarkers is common to monitor response and detect recurrence.