Pituitary neuroendocrine tumors (PitNETs) represent a heterogeneous group of intracranial neoplasms arising from the anterior pituitary gland. While most tumors are benign, certain subsets can display aggressive behavior marked by invasiveness, treatment resistance, and familial clustering. The current World Health Organization (WHO) classification emphasizes the role of lineage-specific transcription factors in better identifying cell types. However, this methodology is not sufficient to ensure fully accurate prediction of tumor behavior; therefore, new, more in-depth methods are required to improve diagnostic reliability and treatment decision-making. A narrative review was carried out to evaluate the literature on PitNET classification schemas and their molecular signatures. Attention was placed on classification research and developments that impact current clinical management. Evidence indicates improvement in the molecular classification of PitNETs, not just from lineage-specific transcription factors, but also from advances in genomic, transcriptomic, and epigenetic profiling. These newer techniques have revealed that PitNETs are driven by a complex interplay of alterations, including somatic mutations, germline predisposition genes, copy number variations, and poorly regulated signaling pathways. Each of these general findings plays a role in influencing tumor behavior, controlling lineage differentiation, and determining response to therapy. These findings indicate the need for integrating molecular characteristics with clinical data to improve risk stratification and guide personalized treatment. Clinical data combined with molecular classification systems is redefining our understanding of PitNET behavior and improving clinical decision-making by increasing our diagnostic accuracy and advancing our knowledge of individualized patient tumor biology. Continued research and development of comprehensive predictive approaches are necessary to achieve reliable outcome prediction and improve therapeutic decision-making for all patients.
Kidwell et al. (Sun,) studied this question.