侵袭性催乳素瘤(APRL)因其高复发率和潜在的危及生命的并发症而对临床带来显著挑战。本研究介绍了一例APRL患者的多种治疗方法试验，旨在通过与以往文献的经验相结合提供APRL的分子异常和管理综述。总共审查了268篇文章，纳入46篇。包括病例报告、系列病例和研究APRL的分子和/或遗传分析的研究。特别注意纳入根据欧洲内分泌学会指南而属于APRL亚型的催乳素瘤的研究，然而，作者没有将肿瘤标记为"侵袭性"或"非典型"。此外，我们还介绍了一例56岁男性患者，他患有侵袭性APRL，对多种治疗方法都无效。文献回顾发现，APRL的多种分子异常包括ADAMTS6、MMP-9、PITX1、VEGF、POU6F2、CDKN2A和Rb基因的突变和/或失调。错配修复基因、microRNA的下调和特定基因（包括RASSF1A、p27和MGMT）的高甲基化与催乳素瘤的侵袭性直接相关。APRL受体分析显示，雌激素受体（ER）水平低和生长抑素受体（SSTR5）和表皮生长因子受体（EGFR）增加与侵袭性和较高的增殖活性相关。我们的患者免疫组织化学染色呈阳性表达PD-L1、MSH2和MSH6，而微阵列分析显示CDKN2A和POU6F2基因突变。尽管接受了两次手术切除、放射治疗和多巴胺受体激动剂治疗，肿瘤仍在进展。患者接受了帕索帕尼布治疗，产生了积极的反应，患者持续6个月无进展。然而，随后的观察发现肿瘤再次进展。患者开始接受PD-L1抑制剂佩姆布鲁妥治疗，但肿瘤仍在进展。APRL是复杂的肿瘤，需要多学科的管理方法。了解这些肿瘤的分子基础对于理解其发病机制并确定个体化医疗治疗的潜在目标至关重要。Copyright © 2023 Medina, Zohdy, Porto, Revuelta Barbero, Bray, Maldonado, Rodas, Mayol, Morales, Neill, Read, Pradilla, Ioachimescu and Garzon-Muvdi.

Aggressive prolactinomas (APRLs) pose a significant clinical challenge due to their high rate of regrowth and potentially life-threatening complications. In this study, we present a case of a patient with an APRL who had a trial of multiple therapeutic modalities with the aim to provide a review of molecular abnormalities and management of APRLs by corroborating our experience with previous literature.A total of 268 articles were reviewed and 46 were included. Case reports and series, and studies that investigated the molecular and/or genetic analysis of APRLs were included. Special care was taken to include studies describing prolactinomas that would fall under the APRL subtype according to the European Society of Endocrinology guidelines; however, the author did not label the tumor as "aggressive" or "atypical". Addiontionally, we present a case report of a 56-year-old man presented with an invasive APRL that was resistant to multiple treatment modalities.Literature review revealed multiple molecular abnormalities of APRLs including mutations in and/or deregulation of ADAMTS6, MMP-9, PITX1, VEGF, POU6F2, CDKN2A, and Rb genes. Mismatch repair genes, downregulation of microRNAs, and hypermethylation of specific genes including RASSF1A, p27, and MGMT were found to be directly associated with the aggressiveness of prolactinomas. APRL receptor analysis showed that low levels of estrogen receptor (ER) and an increase in somatostatin receptors (SSTR5) and epidermal growth factor receptors (EGFR) were associated with increased invasiveness and higher proliferation activity. Our patient had positive immunohistochemistry staining for PD-L1, MSH2, and MSH6, while microarray analysis revealed mutations in the CDKN2A and POU6F2 genes. Despite undergoing two surgical resections, radiotherapy, and taking dopamine agonists, the tumor continued to progress. The patient was administered pazopanib, which resulted in a positive response and the patient remained progression-free for six months. However, subsequent observations revealed tumor progression. The patient was started on PD-L1 inhibitor pembrolizumab, yet the tumor continued to progress.APRLs are complex tumors that require a multidisciplinary management approach. Knowledge of the molecular underpinnings of these tumors is critical for understanding their pathogenesis and identifying potential targets for precision medical therapy.Copyright © 2023 Medina, Zohdy, Porto, Revuelta Barbero, Bray, Maldonado, Rodas, Mayol, Morales, Neill, Read, Pradilla, Ioachimescu and Garzon-Muvdi.