The Ki-67 antigen in the new 2021 World Health Organization classification of lung neuroendocrine neoplasms

Prof. Rosai’s work has permeated the surgical pathology in many fields, including the 2017 World Health Organization classification on tumors of endocrine organs and pulmonary neuroendocrine cell pathology, with stimulating contributions which have also anticipated the subsequent evolution of knowledge. Among the many studies authored by Prof. Rosai, we would like to recall one of which whose topic has been encased in the new 2021 World Health Organization classification on lung tumors. This is an eminently practical paper dealing with the use of the proliferation antigen Ki-67 in lung neuroendocrine neoplasms. While these neoplasms are primarily ranked upon histologic features and Ki-67 labeling index does not play any role in classification, diagnostic dilemmas may however arise in severely crushed biopsy or cytology samples where this marker proves helpful to avoid misdiagnoses of carcinoids as small cell carcinoma. Another application of Ki-67 labeling index endorsed by the 2021 World Health Organization classification regards, alongside mitotic count, the emerging recognition of lung atypical carcinoids with increased mitotic or proliferation rates, whose biological boundaries straddle a subset of large cell neuroendocrine carcinoma. This article focuses on these two practical applications of the proliferation marker Ki-67 in keeping with the 2021 World Health Organization classification, which provides standards for taxonomy, diagnosis and clinical decision making in lung neuroendocrine neoplasm patients.