Variability and Lack of Prognostic Value Associated With Atypical Pituitary Adenoma Diagnosis: A Systematic Review and Critical Assessment of the Diagnostic Criteria

Neurosurgery. 2018 Oct 1;83(4):602-610. doi: 10.1093/neuros/nyx541.


Background: Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk histopathological features than typical PAs. In July 2017, the WHO published an update to their classification of pituitary tumors and abandoned the APA terminology.

Objective: To assess the prevalence and outcomes of patients diagnosed with APA through a literature review. Focus was placed on variation in the application of the previous WHO criteria and on rates of recurrence.

Methods: A systematic review of PubMed (2004-July 2017) was performed to identify studies reporting prevalence and clinical characteristics/outcomes of APA. Eight studies were analyzed for prevalence. Six studies reporting histopathological details were analyzed in depth.

Results: Of the 7105 included patients, 373 (5.2%) met criteria for APA (prevalence range: 3%-15%). Only 2 of 8 studies utilized identical grading criteria, demonstrating a lack of standardized application. Most APAs (84%) were macroadenomas, with 52% invasive on magnetic resonance imaging. Nonfunctional PAs were most common (37%), followed by prolactinomas (23%) and Growth Hormone adenomas (21%). Recurrence/progression occurred in 21% of APA patients (follow-up range 37-75 mo). Only 2 of 8 studies reported an association between APA diagnosis and recurrence/progression.

Conclusion: Based on diagnostic variability and lack of association with clinical outcomes, refinement of criteria for APA was necessary. The WHO update eliminates the ambiguity in APA diagnosis in favor of criteria that emphasize clinical behavior (invasion, recurrence, and resistance to treatment) and molecular markers. Our review supports abandonment of the previous APA designation due to limited prognostic utility.

Publication types

  • Systematic Review

MeSH terms

  • Adenoma / classification*
  • Adenoma / pathology*
  • Adult
  • Aged
  • Female
  • Humans
  • Middle Aged
  • Pituitary Neoplasms / classification*
  • Pituitary Neoplasms / pathology*
  • Prognosis