Background: Prolactinomas are benign neoplasms usually responsive to dopamine agonist therapy.
Rarely, these tumors exhibit aggressive features, including local invasiveness, high
proliferation profile, resistance to medical therapy, and recurrence after surgery.
Progression into carcinomas has also been reported. Understanding the molecular underpinnings
of these tumors is critical to elucidate their pathogenesis and to create targeted
therapy. This study aims to describe the treatment of an aggressive prolactinoma with
pazopanib, followed by a literature review of the molecular findings in aggressive
prolactinomas.
Methods: Our clinical database was retrospectively reviewed for patients with aggressive prolactinomas.
The PubMed library was searched and screened for published literature pertaining to
molecular biomarkers and targeting in aggressive prolactinomas. Screening for duplicates,
non-English language, and relevance was conducted.
Results: We present one clinical case from our center demonstrating aggressive characteristics
with thorough molecular characterization, and novel treatment modalities. We found
77 published articles that met our search criteria for molecular targeting in aggressive
prolactinomas. Genomic and molecular sequencing of the tumor detected complex abnormalities
in 18 chromosomes, involving the CDKN2A, CDKN2B, and TP53 genes, with increased PD-L1
expression. The patient was treated with pazopanib, a multitargeted receptor tyrosine
kinase inhibitor, with a therapeutic response. Published articles that were reviewed
include genetic, epigenetic, cell surface receptor, molecular pathway, and proteomic
studies.
Conclusion: Aggressive prolactinomas are complex tumors that require a multidisciplinary approach
for their treatment. Here we present the unusual case of an aggressive prolactinoma,
with insight into its molecular abnormalities and with a good result after a novel
treatment modality. Numerous articles have been published describing the molecular
targets and/or potential biomarkers. Although some progress has been made, further
studies are required to understand the molecular mechanisms and manage these aggressive
tumors effectively, aiming toward precision medicine.
