RESUMO
PURPOSE: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. EXPERIMENTAL DESIGN: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. RESULTS: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). CONCLUSIONS: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.
Assuntos
Biomarcadores Tumorais/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mutação/genética , Cisto Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Cromograninas , Líquido Cístico/química , Líquido Cístico/metabolismo , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cisto Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Cuidados Pré-Operatórios , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Adulto JovemRESUMO
A 51-year-old Caucasian female with a 7-year history of intermittent abdominal pain and diarrhoea presented to our service. Before presentation, she had been successfully treated for Helicobacter pylori infection, but later developed new oesophageal ulcerations with exudative lesions that were positive for herpes simplex virus, and candida oesophagitis had developed. Biopsies showed chronic inactive gastritis with gastric intestinal metaplasia. MRI revealed a solid 3.4×3 cm lesion in the caudate lobe of the liver, with a 7-mm pancreatic cyst. The aspirated pancreatic cyst cytology was benign. On exploratory laporatomy, the lesion appeared confined to the caudate lobe, and a resection was performed. The pathology was consistent with a well-differentiated neuroendocrine carcinoma with vascular invasion and involvement of the liver capsule, although resection margins were negative. The patient had complete symptomatic improvement. This case re-affirms the high index of suspicion needed to make the diagnosis of gastrinoma. If caught in time, surgical removal of primary hepatic gastrinoma can be curative.