Endocrinology and Metabolic Diseases, Aldo Moro University of Bari, Bari, Italy.
Thyroid. 2011 Nov;21(11):1273-7. doi: 10.1089/thy.2011.0063. Epub 2011 Aug 30.
Peutz-Jeghers syndrome (PJS) is a rare dominantly inherited disease characterized by the association of gastrointestinal hamartomatous polyposis, mucocutaneous hyperpigmentation, and increased risk of cancer at different target organs. Its occurrence with differentiated thyroid cancer, particularly papillary thyroid carcinoma (PTC), even if rare, has been described.
We here present a case of PTC observed in a PJS patient and a review of the literature aiming at discussing the utility of thyroid surveillance in the management of these patients. A 22-year-old woman presenting with hyperpigmented lesions of the lips and hamartomatous polyps in the stomach, duodenum, jejunum, and ileum, leading to the suspicion of PJS, was submitted to genetic analysis. Mutation scanning of the Liver Kinase B1 (LKB1) gene identified the presence of the truncating mutation E265X, thus confirming the clinical diagnosis. Beside the endoscopic, radiologic, and echographic evaluations required by the standard surveillance guidelines, the patient had a neck ultrasound (US), which showed a 5×4×6 mm hypoechoic nodule in the right thyroid lobe. The nodule contained microcalcifications and a perinodular vascular pattern. The cytological preparations derived from US-guided fine-needle aspiration biopsy of the nodule demonstrated the presence of PTC. The patient underwent a video-assisted total thyroidectomy and the histological examination revealed a follicular variant of papillary microcarcinoma. Radioactive iodine therapy was not performed because of the small size of the lesion. The patient was started on levothyroxine therapy to keep the serum thyrotropin levels suppressed. Both the sequencing and the multiplex ligation-dependent probe amplification analysis could not identify any LKB1 mutation in the tumor specimen, and the methylation-specific polymerase chain reaction assay excluded hypermethylation of the LKB1 promoter as the mechanism of inactivation for the remaining normal allele in the tumor.
Although other mechanisms of LKB1 silencing may be responsible for its inactivation in the thyroid cancer, we cannot rule out that the occurrence of thyroid carcinoma could be a coincidental finding in this patient. However, the case here presented suggests that US of the thyroid could possibly become an integral part of the evaluation and the follow-up program adopted for PJS patients.
Peutz-Jeghers 综合征（PJS）是一种罕见的常染色体显性遗传疾病，其特征是胃肠道错构瘤性息肉、黏膜皮肤色素沉着过度以及不同靶器官癌症风险增加。已描述了其与分化型甲状腺癌，尤其是甲状腺乳头状癌（PTC）的偶发相关性。
我们在此报告了一例 PJS 患者中观察到的 PTC 病例，并对文献进行了综述，旨在讨论对这些患者进行甲状腺监测的效用。一名 22 岁女性因唇部色素沉着过度病变和胃、十二指肠、空肠和回肠的错构性息肉就诊，疑诊为 PJS，随后进行了基因分析。肝激酶 B1（LKB1）基因突变扫描发现存在截断突变 E265X，从而确认了临床诊断。除了符合标准监测指南要求的内镜、影像学和超声评估外，患者还进行了颈部超声（US）检查，显示右甲状腺叶有一个 5×4×6mm 的低回声结节。该结节含有微钙化和周围结节的血管模式。US 引导下细针抽吸活检获得的细胞学标本显示存在 PTC。患者接受了视频辅助全甲状腺切除术，组织学检查显示滤泡型乳头状微癌。由于病变较小，未进行放射性碘治疗。患者开始接受左甲状腺素治疗，以保持血清促甲状腺激素水平抑制。肿瘤标本的测序和多重连接依赖性探针扩增分析均未发现 LKB1 突变，而甲基化特异性聚合酶链反应检测排除了 LKB1 启动子的高甲基化作为肿瘤中剩余正常等位基因失活的机制。
尽管 LKB1 沉默的其他机制可能导致其在甲状腺癌中失活，但我们不能排除甲状腺癌的发生可能是该患者的偶然发现。然而，本病例提示甲状腺 US 可能成为评估和随访 PJS 患者的方案的一部分。
