Implications of the World Health Organization definition of atypia on surgically treated functional and non-functional pituitary adenomas.

Abstract

The World Health Organization (WHO) defines atypical pituitary adenomas as tumours with a MIB-1 labelling index ≥3%, p53 positivity and increased mitotic activity. Although a few reports have described the clinical and radiological correlates of atypia in pituitary adenomas, its impact on postoperative outcomes is not clearly defined. We reviewed preoperative and postoperative records of patients undergoing surgery for pituitary adenomas. Postoperative outcomes for functional adenomas (FPAs) were assessed according to contemporary definitions of remission and recurrence. For non-functional pituitary adenomas (NFPAs), extent of resection and disease progression were defined on the basis of postoperative magnetic resonance imaging. Of 394 patients included for analysis, 29 cases (7.4%) fulfilled criteria for atypia. Patients with atypical tumours were significantly younger than those with typical adenomas. Remission was possible in 47.4% of FPAs, and was unrelated to the presence of atypia. In NFPAs, local invasiveness was negatively associated with extent of resection (OR, 0.255; 95% CI, 0.086-0.753; p < 0.001). In 93 NFPAs followed postoperatively with serial imaging over a mean duration of 37.5 months, disease progression/recurrence was significantly associated with the presence of atypia (OR, 5.058; 95% CI, 1.273-20.098; p = 0.021) on multivariate analysis. Patients with atypical non-functional pituitary adenomas are at risk for postoperative recurrence and disease progression, suggesting a need for adjuvant therapy. However, only a small fraction of pituitary tumours demonstrate atypia, as defined by the WHO, limiting its clinical utility.