Neither the term neuroendocrine tumor nor the term carcinoid specify, whether the patient suffers from a benign or malignant tumor. Even today the pathologist cannot always determine if a well-differentiated (Ki-67≤2%) carcinoid is a benign or a malignant tumor. Often it is the clinical course that allows us to determine, after months or years, whether the carcinoid behaves in a benign or malignant way. Evidence for malignant behaviour is the occurrence of metastases. Infiltration of the muscular layers, involvement of the vessels (angioinvasion) and the histological loss of good differentiation hint to malignancy, too.

Degree of differentiation of neuroendocrine tumors

The degree of histological differentiation of carcinoids and islet cell tumors is important both for prognosis and treatment. The pathologist determines the degree of differentiation by immuno-histological staining of the tumor. The proliferative activity and proportion of tumor cells which stain positive for the proliferation marker Ki-67 are used as "markers". Well-differentiated tumors are considered G1 neuroendocrine tumors, if they show a histological proliferation rate of <2% or demonstrate a Ki-67 index of ≤2%. Patients with G1 carcinoids have a good overall prognosis. Tumors with a proliferation rate between 2% and 20% are considered G2 neuroendocrine tumors. In Europe G2 tumors are usually considered to be well-differentiated, in the U.S.A. G2 tumors are considered to be moderate-differentiated. The majority of tumors with a proliferation rate of more than 20% (G3) are poorly differentiated or even undifferentiated neuroendocrine carcinomas; those are generally associated with a less favorable prognosis.

Prof. Dr. med. Hans Scherübl


Center of Neuroendocrine Tumors
Prof. Dr. med. Hans Scherübl
Vivantes Klinikum Am Urban
Academic Teaching Hospital of Charité-University Medicine, Berlin
Dieffenbachstraße 1
10967 Berlin, Germany
Tel: + 49 30 130 225201
Fax: + 49 30 130 225205
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