Aggressive prolactinoma (Review)

  • Authors:
    • Ana Valea
    • Florica Sandru
    • Aida Petca
    • Mihai Cristian Dumitrascu
    • Mara Carsote
    • Razvan-Cosmin Petca
    • Adina Ghemigian
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  • Published online on: November 24, 2021
  • Article Number: 74
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Aggressive prolactinoma (APRL) is a subgroup of aggressive pituitary tumors (accounting for 10% of all hypophyseal neoplasia) which are defined by: invasion based on radiological and/or histological features, a higher proliferation profile when compared to typical adenomas and rapidly developing resistance to standard medication/protocols in addition to an increased risk of early recurrence. This is a narrative review focusing on APRL in terms of both presentation and management. Upon admission, the suggestive features may include increased serum prolactin with a large tumor diameter (mainly >4 cm), male sex, early age at diagnosis (<20 years), and genetic predisposition [multiple endocrine neoplasia type 1 (MEN1), aryl hydrocarbon receptor interacting protein (AIP), succinate dehydrogenase (SDHx) gene mutations]. Potential prognostic factors are indicated by assessment of E-cadherin, matrix metalloproteinase (MMP)-9, and vascular endothelial growth factor (VEGF) status. Furthermore, during management, APRL may be associated with dopamine agonist (DA) resistance (described in 10-20% of all prolactinomas), post-hypophysectomy relapse, mitotic count >2, Ki-67 proliferation index ≥3%, the need for radiotherapy, lack of response in terms of controlling prolactin levels and tumor growth despite multimodal therapy. However, none of these as an isolated element serves as a surrogate of APRL diagnosis. A fourth-line therapy is necessary with temozolomide, an oral alkylating chemotherapeutic agent, that may induce tumor reduction and serum prolactin reduction in 75% of cases but only 8% have a normalization of prolactin levels. Controversies surrounding the duration of therapy still exist; also regarding the fifth-line therapy, post-temozolomide intervention. Recent data suggest alternatives such as somatostatin analogues (pasireotide), checkpoint inhibitors (ipilimumab, nivolumab), tyrosine kinase inhibitors (TKIs) (lapatinib), and mTOR inhibitors (everolimus). APRL represents a complex condition that is still challenging, and multimodal therapy is essential.
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Valea A, Sandru F, Petca A, Dumitrascu MC, Carsote M, Petca R and Ghemigian A: Aggressive prolactinoma (Review). Exp Ther Med 23: 74, 2022
Valea, A., Sandru, F., Petca, A., Dumitrascu, M.C., Carsote, M., Petca, R., & Ghemigian, A. (2022). Aggressive prolactinoma (Review). Experimental and Therapeutic Medicine, 23, 74.
Valea, A., Sandru, F., Petca, A., Dumitrascu, M. C., Carsote, M., Petca, R., Ghemigian, A."Aggressive prolactinoma (Review)". Experimental and Therapeutic Medicine 23.1 (2022): 74.
Valea, A., Sandru, F., Petca, A., Dumitrascu, M. C., Carsote, M., Petca, R., Ghemigian, A."Aggressive prolactinoma (Review)". Experimental and Therapeutic Medicine 23, no. 1 (2022): 74.