MKI67 and acromegaly: In 2017, Donoho et al. [44] proposed to diagnose aggressive acromegaly in their review as (1) rapid tumor growth, age less than 30 years at diagnosis, progressive increase in size despite therapy, and resistance to medical therapy; (2) imaging features, including extrasellar invasiveness and Knosp classification [7, 45]; (3) histopathological features, such as increased Ki-67 labeling index, increased expression of p53, and sparsely granulation.