Current concepts in the classification of thoracic neuroendocrine tumours

Bronchopulmonary neuroendocrine tumours (NETs) share features with extrathoracic NETs and comprise a spectrum of neuroendocrine neoplasms, most of which are also mirrored by counterparts in the thymus. Accurate classification remains difficult on morphological criteria alone, as overlapping and transitional phenotypes occur and reproducibility of classification is marred by ambiguity, heterogeneity and sampling error, and artefacts, especially in cytology and small biopsy specimens. While there have been significant advances in the immunohistochemical and molecular characterization and phenotyping of thoracic NETs in recent years, and this holds great promise for the development of therapeutically relevant categories, this has not yet led to a shift in pathology practice. In this review, the current World Health Organization (WHO) classification of thoracic NETs will be discussed, areas of diagnostic difficulty highlighted, an overview of recent evidence for clinically relevant immunohistochemical and molecular phenotypes provided, and their potential for introduction into routine practice discussed.