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Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!

Matthias Dottermusch
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Abstract

The introduction of the term pituitary neuroendocrine tumor (PitNET) to replace pituitary adenoma has sparked a versatile debate among experts. The controversy surrounding this nomenclature change includes the question of whether these tumors' biological identity truly corresponds to neuroendocrine tumors. In this meta-analysis, DNA methylation data were interrogated to clarify whether the old or new nomenclature more accurately reflects the epigenome of these tumors. Publicly available DNA methylation data of 100 NETs, 100 PitNETs/adenomas, and 100 adenomas of various origins and lineages were compiled from 18 different publications. Epigenomic signatures characteristic of NETs and adenomas were defined and compared to those of PitNETs/adenomas. Promoter CpG methylation levels were investigated for hallmarks of cellular differentiation. Comparative DNA methylation analyses demonstrated that all 100 PitNETs/adenomas aligned more closely with NETs than with adenomas. Focusing on promoter-associated CpGs moreover confirmed robust epigenomic features associated with neuroendocrine differentiation in PitNETs/adenomas. These findings indicate that PitNETs/adenomas resemble NETs rather than adenomas on the epigenomic level and support PitNET as the biologically more accurate term. Of note, appropriately addressing the broad spectrum of clinical behaviors in these tumors remains a critical issue in the current pituitary tumor classification framework and nomenclature.

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HumansPituitary NeoplasmsNeuroendocrine TumorsAdenomaDNA MethylationEpigenomeMethylationPitNETPituitaryJournal ArticleMeta-Analysis

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BibTeXRIS

Matthias Dottermusch. 2025-10-08. Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!. https://doi.org/10.1007/s12022-025-09879-8

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