Neuroendocrine neoplasms: Evolving concepts and terminology

The terminology pertaining to neuroendocrine tumours has long been a confusing and controversial one. Traditional terms such as 'carcinoid', 'atypical carcinoid', and even 'oat-cell carcinoma' are used in different ways by various observers, and they are often misunderstood by clinical physicians as well. These drawbacks of the existing nomenclature set the stage for potential therapeutic errors. In response to this problem, a simplified nosological system has evolved in reference to neuroendocrine neoplasms; it divides such lesions into two groups: epithelial (group 1) and non-epithelial (group 2). With rare exceptions (such as parathyroid adenoma and pituitary adenoma) group 1 tumours are all termed 'neuroendocrine carcinomas', because it is well known that they share a capacity for malignant behaviour. The risk that they will, in fact, pursue an untoward clinical course is further quantified by assigning one of three grades. Hence, one derives such designations as 'grade 2 neuroendocrine carcinoma' as a replacement for 'atypical carcinoid' and 'grade 3 neuroendocrine carcinoma, small-cell type' in place of 'oat-cell carcinoma'. Pathological criteria for the spectrum of neuroendocrine carcinomas have been codified and are provided in this review. In contrast, traditional diagnostic terms for group 2 tumours, including paragangliomas, neuroblastomas, primitive neuroectodermal tumours, and other lesions with neural/non-epithelial characteristics, have been retained in the current nosological scheme.