侵袭性催乳素瘤(APRL)由于其高的再生率和潜在的危及生命的并发症而提出了重大的临床挑战。在这项研究中,我们介绍了一例患有APRL的患者,该患者接受了多种治疗方式的试验,目的是通过证实我们与以往文献的经验,对APRL的分子异常和管理进行综述.
共审查了268篇文章,纳入了46篇。病例报告和系列,包括研究APRLs的分子和/或遗传分析的研究。根据欧洲内分泌学学会指南,特别注意包括描述属于APRL亚型的催乳素瘤的研究;但是,作者没有将肿瘤标记为“侵袭性”或“非典型”。另外,我们提供一例病例报告,1例56岁的男性患者接受侵入性APRL治疗,该患者对多种治疗方式具有抗性.
文献综述显示APRLs的多个分子异常,包括ADAMTS6、MMP-9、PITX1、VEGF、POU6F2,CDKN2A,和Rb基因。错配修复基因,微小RNA的下调,以及包括RASSF1A在内的特定基因的超甲基化,发现p27和MGMT与泌乳素瘤的侵袭性直接相关。APRL受体分析表明,低水平的雌激素受体(ER)和生长抑素受体(SSTR5)和表皮生长因子受体(EGFR)的增加与侵袭性增加和更高的增殖活性有关。我们的患者对PD-L1,MSH2和MSH6的免疫组织化学染色呈阳性,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,服用多巴胺激动剂,肿瘤继续进展。患者服用帕唑帕尼,结果为阳性反应,患者在6个月内保持无进展。然而,随后的观察显示肿瘤进展.患者开始使用PD-L1抑制剂派姆单抗,然而肿瘤继续进展。
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理和确定精确医学治疗的潜在靶标至关重要。
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.