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Clinical and therapeutic implications of cavernous sinus invasion in pituitary adenomas

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Abstract

Invasion of the cavernous sinus by pituitary adenomas impedes complete surgical resection, compromises biochemical remission, and increases the risk of further tumor recurrence. Accurate preoperative MRI-based diagnosis or intraoperative direct inspection of cavernous sinus invasion are essential for optimal surgical planning and for tailoring postoperative therapeutic strategies, depending on whether a total resection has been achieved, or tumoral tissue has been left in surgically inaccessible locations. The molecular mechanisms underlying the invasive behavior of pituitary adenomas remain poorly understood, hindering the development of targeted therapies. Some studies have identified genes overexpressed in pituitary adenomas invading the cavernous sinus, offering insights into the acquisition of invasive behavior. Their main limitation however lies in comparing purely intrasellar specimens obtained from invasive and non-invasive adenomas. Further, precise anatomical knowledge of the medial wall of the cavernous sinus is crucial for grasping the mechanisms of invasion. Recently, alongside the standard intrasellar surgery, extended endoscopic intracavernous surgical procedures with systematic selective resection of the medial wall of the cavernous sinus have shown promising results for invasive secreting pituitary adenomas. The first- and second-generation somatostatin agonist ligands and cabergoline are used with variable efficacy to control secretory activity and/or growth of intracavernous remnants. Tumor regrowth usually requires surgical reintervention, sometimes combined with radiotherapy or radiosurgery which is applied despite their benign nature. Unraveling the molecular pathways driving invasive behavior of pituitary adenomas and their tropism to the cavernous sinuses is the key for developing efficient innovative treatment modalities that could reduce the need for repeated surgery or radiotherapy.

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Acknowledgements

With financial support from the French National Research Agency (ANR) and ITMO Cancer of Aviesan within the framework of the 2021–2030 Cancer Control Strategy, on funds administred by Inserm.

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Authors and Affiliations

  1. INSERM U1185, Physiologie et Physiopathologie Endocriniennes, Université Paris-Saclay, 94276, Le Kremlin-Bicêtre, France

    Etienne Lefevre, Fanny Chasseloup, Mirella Hage, Philippe Chanson & Peter Kamenický

  2. Service de Neurochirurgie, AP-HP, Hôpital Pitié-Salpêtrière, 75013, Paris, France

    Etienne Lefevre

  3. Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des maladies Rares de l’Hypophyse, AP-HP, Hôpital Bicêtre, 94276, Le Kremlin-Bicêtre, France

    Fanny Chasseloup, Philippe Chanson & Peter Kamenický

  4. Department of Neurosurgery, University Hospital Erlangen, 91054, Erlangen, Germany

    Michael Buchfelder

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E.L., F.C., and P.K. wrote the main manuscript. M.B. prépare Fig. 1 and E.L. prepared Fig. 2. All authors reviewed the manuscript.

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Lefevre, E., Chasseloup, F., Hage, M. et al. Clinical and therapeutic implications of cavernous sinus invasion in pituitary adenomas. Endocrine (2024). https://doi.org/10.1007/s12020-024-03877-2

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