‘Atypical’ pituitary adenomas – clinical value of the WHO pathological criteria (#193)
Background: Identification of aggressive pituitary tumours is important in that it may influence the approach to patient management. The 2004 WHO pathological criteria defined the ‘atypical’ pituitary adenoma (a tumour with increased mitotic rate, Ki67 and p53 expression) in an attempt to identify a group of tumours that may behave more aggressively.
Objectives: To determine the prevalence of ‘atypical’ pituitary tumours amongst a 10 year cohort of pituitary tumours. To evaluate how well the WHO criteria predict clinically aggressive pituitary tumours.
Methods: Pathological data was collected on all patients who underwent pituitary surgery between January 2000 and December 2009. Tumours with Ki67 >3%, nuclear p53 staining >40% and mitotic rate >2 per 10 high-power fields were classified as meeting atypical criteria according to the WHO.
Data was collected from patient records, including tumour subtype, size, Hardy’s grade and clinical outcome. Aggressive tumours were defined as those with progressive growth despite >3 standard therapies (medical, surgery, radiotherapy).
Results: 12/92 tumours (13%) had ‘atypical’ features. Two had Ki67 >3%, 7 had extensive nuclear p53 staining and none had an increased mitotic rate. No case demonstrated more than one atypical criterion.
Average clinical follow-up was 74.3 months. Three patients with aggressive pituitary tumours were identified: none had Ki67 >3%, increased mitotic rate or extensive nuclear p53 staining, one had other abnormal morphological features. Twelve patients had tumour recurrence during follow-up, none of which met any of the WHO atypical criteria.
Conclusions: 13% of a 10-year cohort of pituitary tumours displayed atypical features as defined by the 2004 WHO criteria. However, none became aggressive in the follow-up period. Furthermore, the WHO criteria failed to identify those tumours that did become aggressive. We recommend additional validation of the WHO criteria be performed in larger cohorts. The current WHO criteria may need to be refined with consideration of additional biomarkers of aggression.