Neuroendocrine tumors (NETs) are a diverse group of rare neoplasms originating from neuroendocrine cells found throughout the body. These tumors can develop in almost any organ and can range from slow-growing, indolent tumors to aggressive, high-grade neuroendocrine carcinomas (NECs).
Though NETs can occur within almost any organ, over 60% reportedly occur in the gastrointestinal tract. Other common sites include the lungs and pancreas; NETs can also occur in the head, neck, thymus, thyroid, breast, skin, and genitourinary system. While rare in some locations, NETs should be considered in the differential diagnosis of well-differentiated tumors in virtually any tissue, especially when neuroendocrine markers are present.
Learn more about the sites of NET.
Serum chromogranin A and neuron-specific enolase have traditionally been used as biomarkers in clinical practice for NETs throughout the body; however, specificity and sensitivity are considered limited. As such, research is ongoing into other biomarkers that can be used for tumor detection, including serotonin, which is highly specific for NETs in the ileum; serotonin is not strongly associated with NETs affecting the thymus or optic nerve.
Other emerging markers (such as pancreastatin, progastrin-releasing peptide, and the multianalyte NETest) are also being investigated for their potential to improve diagnostic sensitivity, monitor disease progression, and assess treatment response. Click here for a chart of various neuroendocrine biomarkers by organ.
Learn more about NET biomarkers.
According to the most recent NANETS guidelines, there is no "definitive preference" for MRI or CT when imaging NETs. However, the guidelines note that MRI tends to have greater sensitivity than CT for liver metastasis detection and evaluating blood vessel invasion, despite CT typically offering higher spatial resolution than MRI.
Although MRI, CT, and ultrasound can be part of for imaging NETs, as modality should be tailored to the clinical question, tumor location, and patient-specific factors, the guidelines note that multiphase CT is the cornerstone for primary neuroendocrine identification, staging, and response assessment.
Learn more about imaging for NETs.
According to the WHO's neuroendocrine neoplasm classification, grade 1 NETs in the gastrointestinal and pancreatobiliary tracts must have a Ki-67 index value < 3%. They must also have fewer than two mitoses per 2 mm². Grade 2 gastrointestinal NETs have between two and 20 mitoses per 2 mm² and a Ki-67 index value between 3% and 20%; anything higher than that would be considered grade 3. This is consistent with recent literature.
If the NETs are poorly differentiated and have > 20 mitoses per 2 mm² and > 20% Ki-67, they would be considered NECs and classified further by their cell morphology as either small cell or large cell types.
Learn more about grading NETs.
For treatment of unresectable midgut NETs presenting with carcinoid syndrome or elevated urinary 5-HIAA levels, NANETS recommends somatostatin analogues as the initial therapy. NANETS also recommends continuing somatostatin analogues alongside other therapies, such as peptide receptor radionuclide therapy, mTOR Inhibitors, or liver-directed treatments; this is usually based on disease progression, tumor burden, and patient-specific factors.
Platinum-based chemotherapy, alone or in conjunction with other treatments, is more often initially used in poorly-differentiated NECs.
Oral serotonin synthesis inhibitors are approved for adults for the treatment of certain symptoms associated with carcinoid syndrome that are not managed with somatostatin analogues. Interferon therapy is usually recommended following somatostatin analogue treatment.
Learn more about the treatment of NETs.
Editor's Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.
