Diagnostic issues in neuroendocrine neoplasms of the lung

Bronchopulmonary neuroendocrine neoplasms (BP-NENs) account for approximately 30% of all NENs. Although BP-NENs and NENs of the gastroenteropancreatic organs (GEP-NENs) share morphological and molecular features, they differ in terms of their terminology and classification. Bronchopulmonary neuroendocrine tumors (BP-NETs) have classically been termed as carcinoid and grouped into typical (TC) and atypical carcinoid (AC) based on the presence or absence of necrosis and mitotic count. In the most recent World Health Organization (WHO) classification for NENs of endocrine organs (WHO 2022), BP-NETs-NET G1 and G2-are introduced as synonyms of TC and AC, respectively. However, the Ki-67 index, which defines the grade of NETs in digestive organs, is only discussed in the descriptive text and not included into the criteria for classification of BP-NENs. In addition, well-differentiated NENs with high mitotic counts which correspond to NET G3 in the GEP organ system are not defined. This review discusses the role of Ki-67 for a proper classification of BP-NETs/carcinoids.