Sun Dongjin, Li Yumei, Cao Zhixing
Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Pathology, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Front Oncol. 2025 Feb 13;15:1472017. doi: 10.3389/fonc.2025.1472017. eCollection 2025.
Peutz-Jeghers syndrome (PJS) is characterized by an increased risk of gynecologic tumors. Gastric-type endocervical adenocarcinoma (GEA) is a rare non-human papillomavirus (HPV)-related tumor. We reported an uncommon case of a 39-year-old woman with PJS who developed GEA, superficial cervical vaginal myofibroblastoma, sex cord-stromal tumors with annular tubules of the ovaries, and cervical and vaginal high-grade squamous interepithelial neoplasia (HSIL). Before being verified GEA, the patient had been experiencing suspicious symptoms for over 9 years, with nabothian cysts and vaginitis being misdiagnosed. HSIL displayed widespread p16 immunostaining, and HPV DNA screening confirmed HPV-18 infection, although GEA was negative. Further, we verified mutation and amplification of GEA by fluorescence hybridization (FISH). was the most commonly mutated gene. The therapy with the anti-HER2 antibody trastuzumab was suggested based on HER2 amplification. We also analyzed the somatic mutations of GEA by whole genome sequencing (WES). There were 157 single nucleotide variations (SNVs) and 215 indels, with all of them being heterozygotes. Nonsynonymous and frameshift insertions were the most common kinds of mutations. The germine gene mutation was found, which may play an important role in tumor development. According to gene function enrichment analyses, the genomic changes primarily implicated general transcription or expression pathways and cell cycle pathways. In addition, the JAK2/STAT3 pathway could be a major focus of targeted therapy for GEA patients with PJS. Our findings show that the patient with PJS can have a variety of unusual gynecologic tumors. Patients with PJS must have routine gynecological, ultrasonographic, and cytological examinations to detect precursor or early-stage lesions. The patient's abnormal symptoms must be treated early with caution. A comprehensive genomic study reveals the potential causative genetic factors, therapeutic targets, and chemotherapy resistance of GEA. Further research will focus on the main driving genes, molecular mechanisms, and molecular target therapy in more patients.
黑斑息肉综合征（PJS）的特征是妇科肿瘤风险增加。胃型宫颈腺癌（GEA）是一种罕见的与人乳头瘤病毒（HPV）无关的肿瘤。我们报告了一例罕见病例，一名39岁患有PJS的女性，她同时发生了GEA、浅表性宫颈阴道肌成纤维细胞瘤、卵巢环状小管性索间质肿瘤以及宫颈和阴道高级别鳞状上皮内瘤变（HSIL）。在确诊为GEA之前，患者出现可疑症状已超过9年，宫颈腺囊肿和阴道炎被误诊。HSIL显示广泛的p16免疫染色，HPV DNA筛查证实为HPV - 18感染，尽管GEA为阴性。此外，我们通过荧光原位杂交（FISH）验证了GEA的突变和扩增。 是最常发生突变的基因。基于HER2扩增，建议使用抗HER2抗体曲妥珠单抗进行治疗。我们还通过全基因组测序（WES）分析了GEA的体细胞突变。共有157个单核苷酸变异（SNV）和215个插入缺失，均为杂合子。非同义突变和移码插入是最常见的突变类型。发现了胚系 基因突变，其可能在肿瘤发生发展中起重要作用。根据基因功能富集分析，基因组变化主要涉及一般转录或表达途径以及细胞周期途径。此外，JAK2/STAT3途径可能是PJS相关GEA患者靶向治疗的主要靶点。我们的研究结果表明，患有PJS的患者可能会出现多种不寻常的妇科肿瘤。PJS患者必须进行常规妇科、超声和细胞学检查，以检测前驱病变或早期病变。患者的异常症状必须谨慎早期治疗。全面的基因组研究揭示了GEA潜在的致病遗传因素、治疗靶点和化疗耐药性。进一步的研究将聚焦于更多患者的主要驱动基因、分子机制和分子靶向治疗。
