Molecular analysis of pancreatic cystic neoplasm in routine clinical practice.
BACKGROUND
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.


AIM
To determine the impact of molecular analysis on the detection of mucinous cysts and malignancy.


METHODS
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.


RESULTS
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 KRAS and/or GNAS 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 (P = 0.086) for the diagnosis of mucinous cystic lesions. Mutations in KRAS and GNAS 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 KRAS and/or GNAS, although they were not related to malignancy (P > 0.05). None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance (P > 0.05).


CONCLUSION
Molecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous. Mutations were not able to detect malignant lesions.
['Herranz Pérez|Raquel|R|', 'de la Morena López|Felipe|F|', 'Majano Rodríguez|Pedro L|PL|', 'Molina Jiménez|Francisca|F|', 'Vega Piris|Lorena|L|', 'Santander Vaquero|Cecilio|C|']
Molecular analysis Mucinous cyst Pancreatic cysts Next-generation sequencing Pancreatic cancer Pancreatic cyst fluid