Non-Functioning Pancreatic Neuroendocrine Tumours

This chapter will focus on neuroendocrine tumours (NETs) of the lung and pancreas (panNETs) (non-functioning) summarizing the current understanding, diagnosis, and management recommendations of these two subgroups NETs (functioning panNETs and other NET subtypes will be covered separately in subsequent chapters). Lung NETs are the most common subtype of NETs outside the gastroenteropancreatic (GEP) axis, and there has been an alarming rise in its incidence in recent years. Lung NETs are categorized into well-differentiated typical carcinoid (TC), well-differentiated atypical carcinoid (AC), poorly differentiated small cell lung carcinoma (SCLC) and poorly differentiated large cell neuroendocrine carcinoma (LCNEC); which has a significant implication on the treatment recommended. Meanwhile panNETs are classified morphologically into well-differentiated NETs (grades 1-3) and poorly differentiated NECs (grade 3). The majority of lung NETs and panNETs are non-functioning by virtue of absence of carcinoid syndrome and lack of positive serum neuroendocrine biomarkers. In both, histopathological, biochemical, and complete radiological work-up including the use of nuclear medicine imaging are pivotal in confirming the diagnosis. The last decade has witnessed rapid advances in systemic treatment options available for both lung NETs and panNETs with the advent of somatostatin analogues (SSAs), various targeted therapies, and chemotherapy; and also liver-directed therapies and other nuclear medicine ‘theranostics’. In view of the heterogeneity in NETs, each patient’s treatment pathway should be personalized, and it is recommended for all subtypes of NETs to be managed in high-volume centres in close partnership with a specialized multidisciplinary team.