Herranz Pérez Raquel, de la Morena López Felipe, Majano Rodríguez Pedro L, Molina Jiménez Francisca, Vega Piris Lorena, Santander Vaquero Cecilio
Department of Gastroenterology and Hepatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid 28006, Spain.
Molecular Biology Laboratory, Department of Gastroenterology and Hepatology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid 28006, Spain.
World J Gastrointest Endosc. 2021 Feb 16;13(2):56-71. doi: 10.4253/wjge.v13.i2.56.
Cystic pancreatic lesions consist of a wide variety of lesions that are becoming increasingly diagnosed with the growing use of imaging techniques. Of these, mucinous cysts are especially relevant due to their risk of malignancy. However, morphological findings are often suboptimal for their differentiation. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) with molecular analysis has been suggested to improve the diagnosis of pancreatic cysts.
To determine the impact of molecular analysis on the detection of mucinous cysts and malignancy.
An 18-month prospective observational study of consecutive patients with pancreatic cystic lesions and an indication for EUS-FNA following European clinical practice guidelines was conducted. These cysts included those > 15 mm with unclear diagnosis, and a change in follow-up or with concerning features in which results might change clinical management. EUS-FNA with cytological, biochemical and glucose and molecular analyses with next-generation sequencing were performed in 36 pancreatic cysts. The cysts were classified as mucinous and non-mucinous by the combination of morphological, cytological and biochemical analyses when surgery was not performed. Malignancy was defined as cytology positive for malignancy, high-grade dysplasia or invasive carcinoma on surgical specimen, clinical or morphological progression, metastasis or death related to neoplastic complications during the 6-mo follow-up period. Next-generation sequencing results were compared for cyst type and malignancy.
Of the 36 lesions included, 28 (82.4%) were classified as mucinous and 6 (17.6%) as non-mucinous. Furthermore, 5 (13.9%) lesions were classified as malignant. The amount of deoxyribonucleic acid obtained was sufficient for molecular analysis in 25 (69.4%) pancreatic cysts. The amount of intracystic deoxyribonucleic acid was not statistically related to the cyst fluid volume obtained from the lesions. Analysis of and/or showed 83.33% [95% confidence interval (CI): 63.34-100] sensitivity, 60% (95%CI: 7.06-100) specificity, 88.24% (95%CI: 69.98-100) positive predictive value and 50% (95%CI: 1.66-98.34) negative predictive value ( = 0.086) for the diagnosis of mucinous cystic lesions. Mutations in and were found in 2/5 (40%) of the lesions classified as non-mucinous, thus recategorizing those lesions as mucinous neoplasms, which would have led to a modification of the follow-up plan in 8% of the cysts in which molecular analysis was successfully performed. All 4 (100%) malignant cysts in which molecular analysis could be performed had mutations in and/or , although they were not related to malignancy ( > 0.05). None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance ( > 0.05).
Molecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous. Mutations were not able to detect malignant lesions.
胰腺囊性病变包含多种类型，随着成像技术的广泛应用，其诊断率日益提高。其中，黏液性囊肿因其恶变风险而备受关注。然而，形态学表现往往不足以实现其鉴别诊断。有人提出，结合分子分析的内镜超声细针穿刺活检（EUS-FNA）有助于提高胰腺囊肿的诊断水平。
确定分子分析对黏液性囊肿及恶性病变检测的影响。
依据欧洲临床实践指南，对连续的胰腺囊性病变患者进行为期18个月的前瞻性观察研究，这些患者均有EUS-FNA指征。这些囊肿包括直径>15 mm且诊断不明、随访中有变化或具有可疑特征（其结果可能改变临床管理）的囊肿。对36个胰腺囊肿进行了EUS-FNA检查，包括细胞学、生化、葡萄糖分析以及采用二代测序的分子分析。在未进行手术的情况下，结合形态学、细胞学和生化分析结果，将囊肿分为黏液性和非黏液性。恶性病变定义为手术标本上细胞学检查为恶性、高级别异型增生或浸润性癌，临床或形态学进展，转移或在6个月随访期内与肿瘤并发症相关的死亡。比较二代测序结果与囊肿类型及恶性病变的关系。
纳入研究的36个病变中，28个（82.4%）被分类为黏液性，6个（17.6%）为非黏液性。此外，5个（13.9%）病变被分类为恶性。25个（69.4%）胰腺囊肿获取的脱氧核糖核酸量足以进行分子分析。囊内脱氧核糖核酸量与从病变中获取的囊液量无统计学关联。对 和/或 的分析显示，诊断黏液性囊性病变的敏感度为83.33%[95%置信区间（CI）：63.34 - 100]，特异度为60%（95%CI：7.06 - 100），阳性预测值为88.24%（95%CI：69.98 - 100），阴性预测值为50%（95%CI：1.66 - 98.34）（ = 0.086）。在分类为非黏液性的病变中，2/5（40%）检测到 和 突变，因此将这些病变重新分类为黏液性肿瘤，这将导致8%成功进行分子分析的囊肿的随访计划发生改变。在可进行分子分析的所有4个（100%）恶性囊肿中，均检测到 和/或 突变，尽管这些突变与恶性病变无关（ > 0.05）。分析的其他突变均无法在统计学上显著检测到黏液性或恶性囊肿（ > 0.05）。
分子分析可改善胰腺囊肿黏液性或非黏液性的分类。突变无法检测出恶性病变。
