Valea Ana, Sandru Florica, Petca Aida, Dumitrascu Mihai Cristian, Carsote Mara, Petca Razvan-Cosmin, Ghemigian Adina
Department of Endocrinology, 'I. Hatieganu' University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Department of Endocrinology, Clinical County Hospital, 400000 Cluj-Napoca, Romania.
Exp Ther Med. 2022 Jan;23(1):74. doi: 10.3892/etm.2021.10997. Epub 2021 Nov 24.
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 (, aryl hydrocarbon receptor interacting protein , succinate dehydrogenase ( 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.
侵袭性泌乳素瘤（APRL）是侵袭性垂体瘤的一个亚组（占所有垂体肿瘤的10%），其定义为：基于放射学和/或组织学特征的侵袭性、与典型腺瘤相比更高的增殖率、对标准药物/方案迅速产生耐药性以及早期复发风险增加。这是一篇关于APRL的临床表现和治疗的叙述性综述。入院时，提示性特征可能包括血清泌乳素升高、肿瘤直径较大（主要>4 cm）、男性、诊断时年龄较小（<20岁）以及遗传易感性[1型多发性内分泌腺瘤（MEN1）、芳烃受体相互作用蛋白（AIP）、琥珀酸脱氢酶（SDH）基因突变]。通过评估E-钙黏蛋白、基质金属蛋白酶（MMP）-9和血管内皮生长因子（VEGF）状态可提示潜在的预后因素。此外，在治疗过程中，APRL可能与多巴胺激动剂（DA）耐药（在所有泌乳素瘤中占10%-20%）、垂体切除术后复发、有丝分裂计数>2、Ki-67增殖指数≥3%、需要放疗、尽管进行了多模式治疗但在控制泌乳素水平和肿瘤生长方面缺乏反应有关。然而，这些因素单独作为APRL诊断的替代指标均不成立。对于四线治疗，需要使用口服烷化剂化疗药物替莫唑胺，其可使75%的病例肿瘤缩小、血清泌乳素降低，但仅有8%的病例泌乳素水平恢复正常。关于治疗持续时间仍存在争议；对于五线治疗，即替莫唑胺治疗后的干预措施也存在争议。最近的数据表明，可采用生长抑素类似物（帕瑞肽）、检查点抑制剂（伊匹木单抗、纳武单抗）、酪氨酸激酶抑制剂（TKIs）（拉帕替尼）和mTOR抑制剂（依维莫司）等替代方案。APRL是一种复杂的疾病，仍然具有挑战性，多模式治疗至关重要。
