Aggressive nonfunctioning pituitary neuroendocrine tumors

Brain Tumor Pathol. 2022 Oct;39(4):183-199. doi: 10.1007/s10014-022-00441-6. Epub 2022 Jun 20.


Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.

Keywords: Aggressiveness; Corticotropinomas; NF-PitNETs; Poorly differentiated PIT-1 lineage tumors; Somatotropinomas.

Publication types

  • Review

MeSH terms

  • Humans
  • Neuroendocrine Tumors* / pathology
  • Pituitary Neoplasms* / genetics
  • Pituitary Neoplasms* / pathology
  • Transcription Factors
  • World Health Organization


  • Transcription Factors