NET: What gastroenterologists should know

Even gastroenterologists may struggle with this very special and heterogeneous group of neoplasms. But a correct diagnosis is usually within their grasp.

Important facts about neuroendocrine tumours

• They are originally derived from the neuroectoderm. The exact aetiology is unclear.
• In principle, NETs can occur throughout the body, but the main site of manifestation is the gastrointestinal tract.
• Some tumours are functionally active and secrete hormones. They often cause non-specific symptoms.
• A large proportion of functionally inactive NETs remain asymptomatic for a long time.

Despite the increasing incidence and prevalence of gastrointestinal NETs, the tumours are often difficult to grasp. They are usually discovered by chance during routine endoscopies, or an attentive colleague is drawn to them by non-specific symptoms. Once the suspicion has been raised, precise staging and grading is necessary to assess the severity and to choose the right therapy.

How are NETs detected?

The means of choice for diagnostic confirmation are endoscopy, including endoscopic ultrasound (EUS) and, if necessary, CT, MRI and PET. For most gastric, duodenal and rectal lesions, locoregional staging is sufficient, whereas NETs of the jejunum and ileum should always be assessed with cross-sectional and functional imaging. The tumour marker chromogranin A (CgA), on the other hand, should not be relied upon for staging due to limited sensitivity and specificity.

Biopsy and staging are followed by grading. According to the WHO's classification, different tumour grades are distinguished on the basis of mitotic index and Ki-67 proliferation index. The higher the mitotic rate and the Ki-67 index, the more aggressive the tumour and the worse the prognosis. The authors recommend referral to a specialised centre for all G2 and G3 NETs.

When endoscopy, when surgery?

The only curative therapy for all NETs is complete resection, either surgically or endoscopically. The localisation and tumour size are decisive. Small, solitary and well-differentiated neoplasms in the stomach, small and large intestine can often be removed endoscopically. With increasing tumour size, the risk of nodular metastases increases. Here, surgery is more likely to be recommended. In the case of jejunal and ileal NETs, surgical resection is generally advised, regardless of size, as these neoplasms have a high metastatic potential and often occur multicentrally.

Tumour-free resection margins are important for the success of the treatment. If they are not reached endoscopically, surgery is performed. If necessary, further treatments are indicated. This should be discussed in a multidisciplinary tumour panel.

Conclusion for medical practice

Gastrointestinal neuroendocrine tumours are becoming increasingly common. The likelihood of encountering them in the course of a gastroenterologist's career is therefore high. The most important thing is to think about their possibility in the first place. Especially in the case of unclear findings and non-specific symptoms, NETs should be considered as a differential diagnosis.