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Pituitary Tumors: An Update in the Pathogenetic Mechanisms, the Diagnostic Methods and the Therapeutic Approaches

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 3291

Special Issue Editor

Prof. Dr. Dimitrios Kanakis

E-Mail Website
Guest Editor
Pathology, University of Nicosia Medical School, Nicosia, Cyprus
Interests: neurooncology; neurodegenerative diseases; traumatic brain injury/chronic traumatic encephalopathy; demyelinating diseases; neurodevelopmental disorders; neuromuscular disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors has introduced several changes with respect to neoplasms arising in the pituitary gland.

On the one hand, the previously used term “Pituitary Adenomas (PAs)”, for the neoplasms arising in the anterior lobe, has been replaced by the newly developed term “Pituitary Neuroendocrine Tumors (PitNETs)”. In addition, the term “metastatic PitNET” has been favored as an alternative to “Pituitary Carcinoma”. Furthermore, in the current classification, a detailed histological subtyping is proposed according to the tumor cell lineage, cell type and other relevant characteristics. In this context, the use of immunohistochemistry, for the pituitary transcription factors (PIT1, TPIT, SF1, GATA3 and ERα), is recommended, in order to identify the major lineage-defined PitNET types and subtypes.

On the other hand, important changes have also included posterior lobe tumors. Thus, the terms spindle cell oncocytoma, granular cell tumor and sellar ependymoma have been replaced by the terms oncocytic pituicytoma, granular pituicytoma and ependymal pituicytoma, as the former are now considered variants of the classical pituicytoma.

Finally, tumors with a hypothalamic neuronal differentiation are recognized either as neurocytomas or gangliocytomas, showing the characteristic histological picture as elsewhere in the Central Nervous System (CNS).

The aforementioned significant changes and others that have been adopted in the new classification are the result of the continuous research in the field of pituitary tumors, which has allowed us to elucidate, at least to some extent, their pathogenesis. Undoubtedly, the acquired knowledge has influenced immensely the development of novel diagnostic approaches, used for their identification and more accurate characterization, which in turn has also contributed to the development of more precise treatment strategies.

It is the aim of this Special Issue to demonstrate the recent achievements in the pathogenesis, diagnosis and treatment of these neoplasms. Therefore, any contribution in the form of a research or review paper is encouraged and welcomed.

Prof. Dr. Dimitrios Kanakis
Guest Editor

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Keywords

  • pituitary neuroendocrine tumors (PitNETs)
  • pituitary transcription factors
  • PIT1
  • TPIT
  • SF1
  • GATA3
  • ERα
  • pituicytoma
  • hypothalamic neurocytoma
  • hypothalamic gangliocytoma

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Published Papers (3 papers)

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Research

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13 pages, 1872 KiB  
Article
MicroRNA Is Downregulated in Invasive Non-Functioning Pituitary Adenomas
by Aleksandra Derwich-Rudowicz, Aleksandra Żbikowska, Marek Ruchała, Mirosław Andrusiewicz, Jakub Moskal and Nadia Sawicka-Gutaj
Int. J. Mol. Sci. 2025, 26(9), 4408; https://doi.org/10.3390/ijms26094408 - 6 May 2025
Viewed by 401
Abstract
The study aimed to analyze hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p expression in the serum of patients with invasive non-functioning pituitary adenomas (NFPAs) and prolactinomas, as candidates for non-invasive biomarkers. The study included 62 patients with NFPAs and 18 with [...] Read more.
The study aimed to analyze hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p expression in the serum of patients with invasive non-functioning pituitary adenomas (NFPAs) and prolactinomas, as candidates for non-invasive biomarkers. The study included 62 patients with NFPAs and 18 with macroprolactinoma who qualified for transsphenoidal surgical resection. MicroRNAs were isolated from serum samples. The expression levels of hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p were determined using TaqMan MicroRNA assays. The statistical analyses were performed with MedCalc. The total concentration of microRNA was significantly lower in NFPAs than in the CG (p = 0.0419). ROC curve analysis showed that the cutoff point of miRNA lower than 10.73 predicted the PA (sensitivity = 70.0%; specificity = 57.7%; AUC = 0.629; p = 0.052). No correlation between selected miRNAs and tumor type was found: hsa-miR-143-3p (p = 0.4610), hsa-miR-16-5p (p = 0.8767), and hsa-miR-423-5p (p = 0.1459). miRNA expression also did not correlate with invasiveness (cavernous or sphenoid sinus invasion, optic chiasm compression). Although the total expression of microRNA was significantly lower in NFPAs, hsa-miR-16-5p, hsa-miR-143-3p, and hsa-miR-423-5p are not useful as non-invasive biomarkers in patients with invasive non-functioning pituitary adenomas and prolactinomas. Full article
(This article belongs to the Special Issue Pituitary Tumors: An Update in the Pathogenetic Mechanisms, the Diagnostic Methods and the Therapeutic Approaches)
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Review

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15 pages, 2486 KiB  
Review
A Brief Overview of Molecular Biology in Pituitary Adenomas with a Focus on Aggressive Lesions
by Ligia Gabriela Tataranu
Int. J. Mol. Sci. 2025, 26(8), 3717; https://doi.org/10.3390/ijms26083717 - 15 Apr 2025
Viewed by 492
Abstract
Arising from the anterior lobe of the hypophysis, pituitary neuroendocrine tumors (PitNETs), previously known as pituitary adenomas, constitute an intricate and heterogeneous entity. Although they are defined as benign pathology, these tumors can often invade neighboring structures and demonstrate aggressive behavior. The continuous [...] Read more.
Arising from the anterior lobe of the hypophysis, pituitary neuroendocrine tumors (PitNETs), previously known as pituitary adenomas, constitute an intricate and heterogeneous entity. Although they are defined as benign pathology, these tumors can often invade neighboring structures and demonstrate aggressive behavior. The continuous advancement of molecular biology has begun to shed light on the genetic mutations behind the development and evolution of this pathology, providing a better understanding. Notwithstanding, the rising occurrence in recent decades can mainly be attributed to advanced diagnostic techniques; however, these tumors continue to increase in prevalence and incidence, creating a heavy burden on healthcare systems. Consequently, the need for further studies is dire, primarily due to a lack of tailored therapeutic approaches. Thus, this article aims to offer a brief overview of the molecular biology behind these complex tumors to contribute, even on a small scale, to more comprehensive care. Full article
(This article belongs to the Special Issue Pituitary Tumors: An Update in the Pathogenetic Mechanisms, the Diagnostic Methods and the Therapeutic Approaches)
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21 pages, 2166 KiB  
Review
DNA Methylation in Pituitary Adenomas: A Scoping Review
by Morten Winkler Møller, Mathias Just Nortvig, Mikkel Schou Andersen and Frantz Rom Poulsen
Int. J. Mol. Sci. 2025, 26(2), 531; https://doi.org/10.3390/ijms26020531 - 10 Jan 2025
Cited by 1 | Viewed by 1078
Abstract
Pituitary adenomas are a diverse group of neoplasms with variable clinical behavior. Despite advances in genetic analysis, understanding the role of epigenetic modifications, particularly DNA methylation, remains an area under investigation. This scoping review aimed to update and synthesize the current body of [...] Read more.
Pituitary adenomas are a diverse group of neoplasms with variable clinical behavior. Despite advances in genetic analysis, understanding the role of epigenetic modifications, particularly DNA methylation, remains an area under investigation. This scoping review aimed to update and synthesize the current body of literature on DNA methylation in pituitary adenomas, focusing on methodological advancements and clinical correlations. A systematic search conducted across multiple databases, including Embase, Scopus, MEDLINE, and CENTRAL, identified 107 eligible studies. Early methods, such as methylation-restricted digestion and methylation-specific PCR (MSP), have evolved into more comprehensive approaches, such as chip-based DNA methylation analysis. Key findings suggest that genes like POMC, SOCS-1, and RASSF1A show a significant association between methylation and clinical behavior. However, methylation patterns alone are insufficient to fully explain tumorigenesis. Emerging data suggest that DNA methylation might serve as a prognostic marker for invasive growth and recurrence, but further longitudinal studies are needed. This review highlights the need for future research to explore the methylome more thoroughly and to better define the clinical impact of epigenetic modifications in pituitary adenomas. Full article
(This article belongs to the Special Issue Pituitary Tumors: An Update in the Pathogenetic Mechanisms, the Diagnostic Methods and the Therapeutic Approaches)
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