In 2010, the classification of gastrointestinal neuro-endocrine tumours was changed from a classification based on the grade of differentiation to a classification based on the ki 67 index. Both methods provide prognostic information, but the ki 67 staining is a more reproducible method. Grade of differentiation was mentioned less often in pathology reports after 2010.
However, well-differentiated tumours with a higher ki 67 index exist, especially in the pancreas. Poorly differentiated carcinomata and well differentiated neuroendocrine tumours in the pancreas have a clearly different genetic background, the former harbouring abnormalities in DAXX/ATRX or MEN1, the latter in TP53, SMAD4 or RB1. Therefore, the WHO 2017 classification has introduced a new classification for neuroendocrine neoplasms of the pancreas with well-differentiated NET G1 (ki 67 index < 3), G2 (ki 67 index < 20) and G3 (ki 67 index above 20) as opposed to poorly differentiated NEC, small or large cell (also with ki 67 index above 20).
The WHO update for gastrointestinal tumours, including NET outside of the pancreas, has not been published yet. Probably the same changes will be introduced.
Poorly differentiated neuroendocrine carcinomata respond to specific therapies. One large Scandinavian trial has nicely shown different response rates on combination therapy with platinum-etoposide in subgroups of G3 NEN.
In the well differentiated NEN, treatment choices include octreotide analogues, everolimus, peptide receptor radionucleide therapy, debulking surgery and locally ablative therapies (selective internal radiation therapy or cold embolization), temodal-capecitabine, streptozotocin-based chemotherapy and sunitinib. All these therapies have proven to be effective in somewhat different populations and there is no evidence on optimal sequence of treatments.
The prognosis of patients with functioning tumours is often determined by the syndrome. Patients with carcinoid syndrome can develop pellagra or right heart failure. Telotristat etiprate blocks the binding of tryptophan to TPH, reducing the production of serotonin. This leads to a signifcant decrease in diarrhea in patients with carcinoid syndrome and possibly has a positive impact on the evolution of carcinoid heart disease.
