Cystic Lesions of the Pancreas

Garcea, Giuseppe; Ong, Seok Ling; Arora, Rajesh; Neal, Christopher P.; Pollard, C.; Berry, David P.; Dennison, Ashley R.

doi:10.1159/000134279

Cited by 173 publications

(53 citation statements)

References 78 publications

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“…KRAS . pancreatic cyst Cystic lesions of the pancreas can either be inflammatory or proliferative [1]. Differentiating between low-and high-risk pre-malignant tumors can be difficult and the consequences of missing the chance for a curative resection in patients who are suitable can be devastating.…”

mentioning

confidence: 99%

Activating mutations ofGNASandKRASin cystic fluid can help detect intraductal papillary mucinous neoplasms of the pancreas

Frampton

Stebbing

Gall

et al. 2015

Expert Review of Molecular Diagnostics

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Evaluation of: Singhi AD, Nikiforova MN, Fasanella KE, et al. Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. Clin. Cancer Res. 20(16), 4381-9 (2014).Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have a risk of malignant transformation following an adenoma-carcinoma sequence. Surgical resection is often required, especially for main pancreatic duct IPMNs (MD-IPMNs). There is an urgent need for novel biomarkers to reliably differentiate IPMNs from more benign pancreatic cysts and therefore avoid unnecessary surgery. DNA sequencing has demonstrated that guanine nucleotide binding protein alpha stimulating (GNAS) activity polypeptide 1 mutations play a driving role in IPMN development. GNAS mutations have been shown to be highly specific for IPMNs, whereas oncogenic KRAS mutations have been associated with mucinous differentiation. The evaluated article by Singhi et al. helps to define the role of these mutations as biomarkers in preoperative endoscopic ultrasound fine-needle aspiration samples for detecting IPMNs. They found that the presence of a GNAS and/or a KRAS mutation was highly specific and sensitive for IPMNs. Cystic lesions of the pancreas can either be inflammatory or proliferative [1]. Differentiating between low-and high-risk pre-malignant tumors can be difficult and the consequences of missing the chance for a curative resection in patients who are suitable can be devastating. To prevent this, many centers recommend routine excision of all suspicious pancreatic cystic tumors (PCTs), potentially exposing patients with benign disease to the unjustifiable risks of major surgery. PCTs can be classified into non-mucinous tumors with negligible malignant potential, such as the serous cystadenomas (SCA), and those with significant malignant potential, such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). The mucinous cysts have the potential to give rise to in situ or invasive carcinoma, via an adenoma-carcinoma sequence. Thus, a correct pre-operative diagnosis and evaluation of a PCT is crucial for clinical decision-making.Endoscopic ultrasound fine-needle aspiration (EUS-FNA) has become an essential tool for cytopathologic confirmation of pancreatic lesions, and pre-operative planning. Recent meta-analysis has shown that pooled specificity for cytology is 93% (95% CI: 90-95) with a sensitivity of 54% (95% CI: 49-59) for a mucinous cyst [2]. Carcinoembryonic antigen (CEA) levels are raised in mucinous cyst fluid while low in non-mucinous lesions, and the optimum threshold of 192 ng/ml has high discriminatory accuracy [3]. Pooled specificity for CEA measurement is 88% (95% CI: 83-91), with a sensitivity of only 63% (95% CI: 59-67) for mucinous differentiation [ [4][5][6]. Of note, these experiments have revealed frequent activating mutations of GNAS and KRAS in IPMNs. Indeed, GNAS mutations appear to be a hallmark molecular alteration of IPMNs (prevalencẽ 66%) [6]. However, the ability and clinical usefulness of i...

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confidence: 99%

Activating mutations ofGNASandKRASin cystic fluid can help detect intraductal papillary mucinous neoplasms of the pancreas

Frampton

Stebbing

Gall

et al. 2015

Expert Review of Molecular Diagnostics

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“…Pseudocysts may be differentiated morphologically from cystic tumours in that they do not have an epithelial lining. 3,5 They arise following acute/chronic pancreatitis or pancreatic trauma. Pseudocysts typically contain necrotic tissue including necrotic fat, neutrophils and are surrounded by granulation tissue forming a fibrotic wall.…”

Section: Pancreatic Pseudocystmentioning

confidence: 99%

“…2 Fitness for surgery, life expectancy and risk/benefit ratio to be considered. 3 Pseudocyst to be excluded before proceeding with pancreatic resection. 4 'High' CEA cut-off chosen to provide high specificity for mucinous/malignant lesion (CEA cut-offs may be assay and population dependent).…”

Section: Physical Properties Of Pancreatic Cyst Fluid Specimensmentioning

confidence: 99%

“…2 Many of these cysts are asymptomatic and are discovered incidentally when the patient is being investigated for an unrelated problem. 3 Awareness of these lesions has increased in recent years, in part due to widespread use of high resolution abdominal imaging. Diagnosis and management of pancreatic cysts can be challenging although Clinical Laboratory Services, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UK the understanding of the natural history and optimal management of the various types of cyst is improving.…”

Section: Introductionmentioning

confidence: 99%

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A review of pancreatic cyst fluid analysis in the differential diagnosis of pancreatic cyst lesions

Boot

2013

Ann Clin Biochem

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Diagnosis and management of pancreatic cyst lesions is challenging as there is currently no investigation that offers both high diagnostic sensitivity and high specificity for the identification of potentially malignant lesions. Accurate classification of these lesions is vital in order to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of lesions that are malignant/pre-malignant. Pancreatic cyst fluid analysis has an important role in diagnosis, although all currently available investigations based on fluid analysis have significant limitations. Cytological analysis can reveal features that are specific for a certain class of cyst, but offers limited sensitivity in detecting malignant/premalignant cysts. Measurement of tumour markers, particularly carcinoembryonic antigen can also be informative. Concentrations of cyst fluid carcinoembryonic antigen tend to be higher in malignant/pre-malignant cysts, although there is a wide overlap between the various classes of cyst. A number of studies have suggested that diagnostic carcinoembryonic antigen cut-offs can be chosen that provide a high degree of specificity but limited sensitivity. Studies of the analytical validity of tumour marker assays in pancreatic cyst fluid analysis have highlighted discrepancies in some fluid specimens, which require further investigation. DNA analysis also has a role. In particular, K-Ras-2 mutational analysis appears to provide high specificity for detection of malignant/pre-malignant lesions. A number of diagnostic algorithms have been published, integrating use of available investigations in order to achieve the optimum discrimination of benign and potentially malignant cysts. Research into new biochemical markers and optimal use of available pancreatic cyst fluid analyses is ongoing.

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“…These lesions can be caused by injury, infection, or congenital anomalies. Pancreatic cystic neoplasms (PCNs) account for 10% to 15% of all pancreatic cystic lesions (Garcea et al, 2008). PCNs are a diverse group of neoplasms, including serous cystic neoplasms (SCNs), mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs), mucin solid pseudopapillary neoplasms, cystic endocrine neoplasms, and acinar cell cystadenocarcinomas.…”

Section: Introductionmentioning

confidence: 99%

Pancreatic cystic neoplasms: a review of preoperative diagnosis and management

Bai

Zhang

Masood

et al. 2013

J. Zhejiang Univ. Sci. B

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Pancreatic cystic neoplasms (PCNs) are a diverse group of neoplasms in the pancreas, and are more increasingly encountered with widespread abdominal screening and improved imaging techniques. The most common types of PCNs are serous cystic neoplasms (SCNs), mucinous cystic neoplasms (MCNs), and intraductal papillary mucinous neoplasms (IPMNs). Clinicians frequently feel bewildered in the differential diagnosis and subsequent management among the various types of lesions in the pancreas, which may lead to overtreatment or delayed treatment. The current review provides recent developments in the understanding of the three most common types of PCNs, the latest modalities used in preoperative diagnosis and differential diagnosis, as well as the most up to date management. Suggestions for diagnosis and differential diagnosis of SCNs, MCNs, and IPMNs are also provided for young surgeons. Better understanding of these neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients.

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Cystic Lesions of the Pancreas

Cited by 173 publications

References 78 publications

Activating mutations ofGNASandKRASin cystic fluid can help detect intraductal papillary mucinous neoplasms of the pancreas

Activating mutations ofGNASandKRASin cystic fluid can help detect intraductal papillary mucinous neoplasms of the pancreas

A review of pancreatic cyst fluid analysis in the differential diagnosis of pancreatic cyst lesions

Pancreatic cystic neoplasms: a review of preoperative diagnosis and management

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