NENs are commonly called neuroendocrine tumours or carcinoids, but the correct term is NENs as tumours and carcinoid refer to specific NET subtypes. The term neuroendocrine refers to specific aspects of the cell and does not allow us to understand what kind of cancer we face, how it will respond to treatments and how aggressive it will be.
NENs originate from the diffuse neuroendocrine system, that is from a set of cells with similar morphological characteristics (they have aspects in part neurological and in part endocrine). Since this system spreads throughout the body, NENs can occur anywhere. In two thirds of cases, they arise in the gastro-enteric-pancreatic (GEP) tract, especially in the small intestine.
NENs include various diseases that differ in clinical and biological terms. Their management requires the expertise of several specialists (pathologist, medical oncologist, surgeon, nuclear medicine physician, endocrinologist, gastroenterologist, interventional radiologist, nutritionist, radiation oncologist). It is crucial that these professionals cooperate as part of a multidisciplinary team that establishes a comprehensive therapeutic strategy appropriate for the individual patient.
At IEO, we have been involved in clinical management and clinical research in patients with NENs for about 20 years. Our approach has always been multidisciplinary. Dedicated professionals have been created for each diagnostic and therapeutic specialty. We use various competencies to characterise the disease, define the patient clinical frame and the immediate and late objectives of care.
It is crucial that a dedicated pathologist is certain of the diagnosis and of some features which indicate the aggressiveness of the disease. Therefore, when possible, patients who have already had a histological diagnosis elsewhere are asked for a review by our pathologists.
From a clinical perspective, NENs are divided into two groups, functioning and non-functioning, depending on whether there is a presence or absence of a clinical syndrome related to the production and release into the circulation of one or more hormones by the tumour.
Syndromes associated with functioning NENs are various, the best known is the carcinoid syndrome, that most often appears as redness of the face (so-called flushing) and diarrhoea.
From am anatomic-pathological perspective, GEP NENs are classified into three groups, based on the proliferation index (that is the amount of tumour cells in the reproduction phase). Ki67 <2% and/or mitotic index <2 HPF (high power fields) = G1; Ki67 3-20% and/or mitotic index 2-20 HPF = G2; and Ki67> 20% and/or mitotic index> 20 HPF = G3. The first two groups, G1 and G2, are also called NEUROENDOCRINE TUMOURS (NET), while the third group, G3, forms the NEUROENDOCRINE CARCINOMAS (NEC).
Pulmonary NENs have a different classification, also prepared by WHO, which breaks them down as follows; typical carcinoid and atypical carcinoid (less aggressive forms), large cell neuroendocrine carcinoma and small cell neuroendocrine carcinoma (the most aggressive).
Carcinomas usually evolve rapidly and are treated with chemotherapy. G1 tumours and typical carcinoid tumours are generally slow in evolution, and are treated with non-intensive medical therapies, such as somatostatin analogues (octreotide or lanreotide). G2 tumours and atypical carcinoid tumours can behave differently and are treated according to their specific characteristics.