Materiały źródłowe

• #1 Pancreatic Cystic Lesions: A Focused Review on Cyst Clinicopathological Features and Advanced Diagnostics

  https://www.mdpi.com/2075-4418/13/1/65

  Pancreatic cystic lesions (PCLs) are being detected more frequently due to the increasing use of cross-sectional imaging. Our knowledge of different types of PCLs has grown dramatically in recent years. A multidisciplinary approach using a combination of radiological imaging, endoscopic ultrasound (EUS), cytology, cyst fluid analysis, and molecular profiling is most helpful in diagnosing and risk stratifying PCLs. Despite these advancements, challenges still exist in the appropriate classification of PCLs as benign versus precancerous and accurate risk-stratification of intraductal papillary mucinous neoplasm (IPMNs). Unwarranted resection of benign PCLs (up to 15% of pancreatectomies) causes unnecessary mortality and morbidity, and there is continued surgical overtreatment of branch duct-IPMNs where up to 50% of lesions only reveal low-grade dysplasia.

• #1 Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression

  https://www.mdpi.com/2072-6694/16/6/1183

  Pancreatic cysts are being identified with increasing frequency, and the prevalence increases with age to 10–25% by the 7th decade of life. They also have the potential for malignant transformation. […] The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. […] Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. […] Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected.

• #1 Pancreatic Cysts – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525979/

  Pancreatic cysts can be either neoplastic or non-neoplastic. […] Neoplastic cysts include intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasm, solid pseudopapillary neoplasm, and cystic pancreatic neuroendocrine tumors. […] The etiology of pancreatic cysts varies widely depending on if they are non-neoplastic or neoplastic. […] Neoplastic cysts include IPMN which includes main duct IPMN, branch duct IPMN, and mixed IPMN, mucinous cystic neoplasm, solid pseudopapillary neoplasm, and cystic pancreatic neuroendocrine tumors. […] IPMN: The three types of IPMN are main duct, branch duct, and mixed. Main duct IPMN is characterized by segmental or diffuse dilation of the main pancreatic duct to greater than 5 mm in diameter without any other causes of obstruction. […] Mucinous cystic neoplasms: Large, mucin-producing cysts that do not communicate with the ductal system.

• #1 Pancreatic Cysts and Pseudocysts – Pancreatic Diseases – Gastroenterology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.5.3.

  Pancreatic cysts are fluid collections located within or outside the pancreas that usually contain pancreatic secretions. They may be classified as true cysts or postinflammatory cysts (pseudocysts). […] True cysts have an epithelial lining. They may be further divided into: […] Retention cysts, which result from dilation of the pancreatic duct due to obstruction (this is frequent in chronic pancreatitis). […] Neoplastic cysts (account for 50% of all pancreatic cysts): Mucinous cystic neoplasms (MCN) (may be malignant), serous cystadenoma (SCA) (almost always nonmalignant), intraductal papillary mucinous neoplasms (IPMN) (some are considered to be precancerous lesions). […] Postinflammatory cysts or pseudocysts are a complication of acute pancreatitis.

• #1 Pancreatic Pseudocysts: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/184237-overview

  Pancreatic pseudocysts can be single or multiple. Multiple cysts are more frequently observed in patients with alcoholism, and they can be multiple in about 15% of cases. Size varies from 2-30 cm. About one third of pseudocysts manifest in the head of the gland, and two thirds appear in the tail. The fluid in pseudocysts has been well characterized as clear or watery, or it can be xanthochromic. The fluid in pseudocysts usually contains very high amounts of amylase, lipase, and trypsin, though the amylase level may decrease over time. […] The pathogenesis of pseudocysts seems to stem from disruptions of the pancreatic duct due to pancreatitis and extravasation of the enzymatic material. Two thirds of patients with pseudocysts have demonstrable connections to the pancreatic duct. In the other third, an inflammatory reaction is supposed to have sealed the connection so that it is not demonstrable. The cause of pseudocysts parallels the cause of acute pancreatitis; 75-85% of cases are caused by alcohol or gallstone diseaserelated pancreatitis. In children, pseudocysts and trauma are frequently associated.

• #1 What are Pancreatic Cysts? – Let’s Win Pancreatic Cancer

  https://letswinpc.org/symptoms/pancreatic-cysts/what-you-should-know-pancreatic-cysts/

  Like a cyst in any other part of the body, pancreatic cysts are water- or mucus-filled structures. While some people are predisposed to develop pancreatic cysts because of genetics, most arise from inflammation of the pancreas (also called pancreatitis). In most cases, these cysts are benign. […] The problem is, all of these things can also be associated with pancreatitis. You can even get focal massesa mass or lesion that develops at a circumscribed area of the organwith chronic pancreatitis. So theres a big degree of overlap between the characteristics of potentially premalignant cysts and inflammatory nonmalignant cysts. […] We can do endoscopic ultrasound, where we put a flexible scope through the mouth, down into the stomach so we can get a good view of the back wall of the stomach. We can draw samples of the pancreatic fluid and analyze it for biochemical markers such as CA 19-9 or carcinoembryonic antigen (CEA), which are predictive of cancer. We also have some novel approaches where we can take needle biopsies of the cyst wall to help better characterize the cyst.

• #1 Simple pancreatic cyst | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/simple-pancreatic-cyst?lang=us

  Simple pancreatic cysts, also known as true epithelial cysts or retention cysts, are unilocular cysts within the pancreas, lined by a monolayer of epithelium, which lack communication with the pancreatic ducts. […] The etiology remains unknown, however their diagnosis predominantly in a pediatric population strongly suggests that they are congenital. […] Simple pancreatic cysts are lined by a monolayer of cuboidal epithelium and contain simple fluid, without debris or hemorrhage, or superinfection. Indeed they are structurally identical to simple cysts in other viscera, e.g. renal. The fluid has few cells within it with mixed inflammatory cells. Analysis of the fluid demonstrates low levels of amylase, lipase and carcinoembryonic antigen (CEA). They are benign and do not show malignant transformation.

• #1 Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714518/

  GNAS mutation leads to disruption of the intrinsic hydrolytic activity of Gs, which results in constitutive activation of its function. […] This suggest that these mutations are probably acquired early in the pathogenesis of IPMN and additional mutations may be required for the disease progression. […] The goal of gaining a detailed understanding of the pathogenesis of neoplastic cysts and the pathways leading to cancer development is to 1) employ -omics approach to help in correctly diagnosing the type of cyst; 2) help in detecting if cancer has already developed in these lesions thus providing a clear indication for surgical approach; 3) predict of the biology of lesions with respect to progression to invasive lesions; and 4) attain the elusive goals of developing pharmacotherapy which may prevent development of invasive lesions.

• #1 Pancreatic Cystic Lesions: A Focused Review on Cyst Clinicopathological Features and Advanced Diagnostics

  https://www.mdpi.com/2075-4418/13/1/65

  Molecular analysis by next-generation sequencing (NGS) has evolved significantly in recent years with improved accuracy in the diagnosis and risk-stratification of PCLs. According to recent surgical series of PCLs, the most resected PCLs are mucinous neoplasms: IPMNs (45% of all resected PCLs) and mucinous cystic neoplasm (MCN, 16%). The most frequently resected non-mucinous neoplasms include serous cystic neoplasms (SCN, 16%), cystic neuroendocrine tumors (cNET, 5%), and solid pseudopapillary neoplasm (SPN, 3%). […] The three histologic subtypes of IPMNs are gastric type (~70%), intestinal type (~20%), and pancreatobiliary type (~10%). Somatic mutations in KRAS and GNAS are the two most common genetic alterations seen in IPMN, together seen in >95% of all IPMNs. KRAS mutation is an early event and nearly a prerequisite in the pathogenesis of ductal neoplasms, including pancreatic ductal adenocarcinomas (PDAC). Activating GNAS mutations are enriched in the intestinal subtype. Changes in tumor suppressor genes, such as TP53, CDKN2A and SMAD4, as well as mutations of mTOR genes (PTEN, PIK3CA, AKT1) are associated with advanced neoplasia (high-grade dysplasia and invasion).

• #1 Pancreatic Cystic Lesions: A Focused Review on Cyst Clinicopathological Features and Advanced Diagnostics

  https://www.mdpi.com/2075-4418/13/1/65

  Overall, about a third of resected IPMN are associated with invasive carcinoma. Main-duct IPMN (>10 mm) has higher rate of associated malignancy, up to 60%, whereas branch-duct IPMN (>3 cm) has a lower rate (15–20%). The two most common IPMN-associated invasive carcinomas are tubular (ductal) adenocarcinoma and colloid adenocarcinoma. […] The pathogenesis is unclear and thought to be related to ectopic embryonic remnants, which explains some “ancient” changes such as a thick fibrous wall and mural calcifications. Activating mutations in codon 12 of KRAS is seen in 50–66% of MCNs as well as loss of function in RNF43. Unlike IPMN, GNAS mutations are rarely seen in MCN. The gene mutations associated with advanced neoplasia in IPMN may be observed in MCN, including TP53, CDKN2A, SMAD4, and/or mTOR genes.

• #1 Prevalence, Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl15063

  It has been proposed that ectopic ovarian stroma in the pancreas tail, biliary tree and retroperitoneum, may release hormones and growth factors, stimulating local endodermally-derived epithelium to proliferate and form cystic tumors. […] The risk of malignancy in MCN is 17.5%. […] The basis for this universal recommendation of surgery is based on the fact that the majority of the patients are young and would otherwise require lengthy surveillance; most of the lesions are located in the body and tail of the pancreas where surgical management in high volume experienced centers carries negligible mortality and low morbidity; and unlike IPMN, MCN do not require surveillance after surgical resection (unless there is evidence of invasive cancer). […] BD-IPMNs are all considered premalignant, but the risk can vary based on the size, associated worrisome features (e.g., nodules), multiplicity, and the underlying epithelial subtype.

• #1 Lymphoepithelial Cysts of the Pancreas: a Report of 12 Cases and a Review of the Literature | Modern Pathology

  https://www.nature.com/articles/3880553

  Lymphoepithelial cyst (LEC) of the pancreas is a rare lesion of undetermined pathogenesis that had been documented almost exclusively in males. […] The pathogenesis and relationship to LECs of the salivary glands or other cystic pancreatic lesions are poorly understood. […] The etiopathogenesis of LECs is not known. Conditions that are typically associated with LEC of salivary glands, such as a history of Sjogren disease, HIV infection, or lymphoma have not been recorded in pancreatic LECs. […] A proposed mechanism of pathogenesis for LECs is the development from epithelial remnants in lymph nodes. […] The presence of small ductal elements in the lymphoid tissue of four cases in this study may lend further support to this hypothesis. […] It is unlikely that mesothelial invaginations, favored hypothesis of the splenic epidermoid cysts, would apply to LECs of the pancreas.

• #1 Lymphoepithelial Cysts of the Pancreas: a Report of 12 Cases and a Review of the Literature | Modern Pathology

  https://www.nature.com/articles/3880553

  Cystic transformation of pancreatic ducts that had undergone squamous metaplasia has been considered. […] It has also been suggested that LECs may be a form of teratoma; however, the presence and the distribution of lymphoid tissue would be most unusual for a teratoma. […] It has also been speculated that LECs may represent branchial cleft cysts that have been displaced and fused with the pancreas during embryogenesis. […] One hypothesis that is quite appealing is a continuation of a mechanistic explanation unifying those head and neck lesions that are characterized by cystic or glandular epithelial elements surrounded by lymphoid tissue into one generic category.

• #1 The Radiology Assistant : Pancreatic cystic Lesions

  https://radiologyassistant.nl/abdomen/pancreas/pancreas-cystic-lesions

  Cystic pancreatic lesions are increasingly identified due to the widespread use of CT and MRI. Certain pancreatic cysts represent premalignant lesions and may transform into mucin-producing adenocarcinoma. […] Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. […] This means that many pancreatic cysts remain undetermined and guidelines are needed for follow up and management. […] Mucinous cystic neoplasm – This is usually a unilocular cyst filled with mucin sometimes with wall calcification, exclusively seen in predominantly 40 60 year old women. […] Mucinous cystic neoplasm is a premalignant tumor – may transform into a mucinous cystadenocarcinoma.

• #1 Pancreatic Cyst: Symptoms, Causes, Types & Treatment

  https://my.clevelandclinic.org/health/diseases/pancreatic-cyst

  Pancreatic cysts are abnormal growths, which means that a genetic mutation occurred. But researchers dont know why these occur. They might be partly hereditary and partly triggered by other factors, like inflammation and aging. A small percentage of cysts directly relate to hereditary conditions. […] Certain mucinous neoplasms can secrete mucin into the pancreatic duct, causing it to swell and eventually clog. This prevents pancreatic enzymes from passing through the duct to your small intestine. The enzymes back up in your pancreas and irritate it, causing pancreatitis. […] A small percentage of cysts can turn into cancer, most commonly adenocarcinoma. Pancreatic cancer has a tendency to spread, so catching it early is key. […] Some pancreatic cysts may need to be removed if they cause complications or look suspicious for cancer. But pancreatic surgery comes with its own risks and side effects, so healthcare providers consider each cyst carefully. […] Certain types of cysts have a higher risk of becoming cancerous. A healthcare provider might need to remove them right away. Healthcare providers estimate the risk of cancer and weigh it against the risks of surgery for the individual, based on their general health.

• #1

  https://link.springer.com/article/10.1007/s10620-017-4603-1

  With the current epidemic of diagnosed pancreatic cystic neoplasms on the rise, a substantial amount of work has been done to unravel their biology, thus leading to implications on clinical decision making. Recent genetic profiling of resected human specimens has identified alterations in signaling pathways involving KRAS and GNAS signaling as early events in the pathogenesis of intraductal pancreatic mucinous neoplasms. […] Progressively, mutations in genes such as TP53, SMAD4, RNF43, and others are thought to characterize invasive and advanced lesions. The role of inflammation in fueling the growth and transformation of these cysts has also begun to be studied with greater interest. […] A number of promising clinical studies have attempted to integrate these genetic insights into classifying these cysts and treating patients. […] We have reviewed existing literature on similar lines besides commenting on some useful animal models that recapitulate molecular and phenotypic progression of these cysts.

• #1 Pancreatic cyst fluid harbors a unique microbiome | Microbiome | Full Text

  https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0363-6

  Pancreatic cysts are fluid-filled neoplasms that can be detected with a frequency of up to 2% in the general asymptomatic adult population and have a low, but not negligible risk for evolving into pancreatic ductal adenocarcinoma, while accounting for up to 5% of the total incidence of pancreatic cancerous lesions. […] Optimal clinical management of pancreatic cysts remains controversial, but there is consensus in the field that increased insight into the molecular pathogenesis of pancreatic cysts may guide development of rational strategies in this respect. Unfortunately, the etiology of pancreatic cysts remains largely obscure. […] The presence of such a bacterial ecosystem in pancreatic cysts raises important questions as to the role of the bacteria present in such cysts in the development of such structures. […] The study reveals previously undescribed bacterial diversity present in human pancreas and its cyst fluids. As specific bacteria are associated with this body site, we propose that such bacteria may carry the potential to influence the development of pathophysiological processes in the pancreas.

• #1 Pancreatic Cyst Symptoms, Causes and Treatment

  https://www.cancercenter.com/cancer-types/pancreatic-cancer/risk-factors/pancreatic-cysts

  Some genetic mutations that lead to the development of pancreatic cysts also increase cancer risk. These are called hereditary cancer syndromes. Almost all pancreatic cysts below 15 mm in size are not cancerous. […] The seriousness of pancreatic cysts varies dramatically, with some more prone to becoming cancerous than others. Most pancreatic cysts grow slowly–between 3mm and 6mm per year. Faster growing cysts may indicate they are at a higher risk of developing into cancer. […] The most common types of cysts found in the pancreas are those caused by injury or inflammation. These include pseudocysts, paraduodenal wall cysts and infection-related cysts. Inflammation-related cysts are a common complication of pancreatitis, a condition in which the pancreas has become inflamed. These cysts are noncancerous (benign).

• #1 Pancreatic Cysts | UCSF Robotic Surgery

  https://roboticsurgery.ucsf.edu/condition/pancreatic-cysts

  Some pancreatic cysts occur as a consequence of having pancreatitis, an inflammation of the pancreas. […] Most pancreatic cysts are benign (noncancerous) and do not cause symptoms. However, some are precancerous with the potential to develop into pancreatic cancer. It is therefore critically important to identify the type of cyst and whether it has malignant potential. […] Intraductal papillary mucinous neoplasms are the most common type of precancerous cyst. […] IPMNs produce proteins in large amounts that form mucus or mucin within the cyst lining and fluid. it is difficulty to predict when an IPMN will become malignant (cancerous). […] Mucinous cystic neoplasms are precancerous growths which start in the body and tail of the pancreas, and develop predominantly in women. […] Larger cysts with septations, tiny walls that divide the cyst into compartments, may be more likely to become malignant.

• #1 Cystic lesions of the pancreas | Modern Pathology

  https://www.nature.com/articles/3800706

  Intraductal papillary mucinous neoplasms (IPMNs) are characterized by cystic dilatation of pancreatic ducts in which an intraductal proliferation of neoplastic mucin-producing cells is usually arranged in papillary patterns. Mucin production by the neoplastic cells is usually associated with intraluminal mucin secretion which leads to cystic dilatation of the ducts, and at times, to mucin extrusion from the ampulla of Vater, a finding that is virtually diagnostic of an IPMN. […] IPMNs appear to be genetically much more stable than conventional infiltrating ductal adenocarcinomas, and lack (or exhibit at much lower levels) the molecular/genetic alterations of the latter. Mutations in the KRAS, p16 and TP53 genes are significantly less common in IPMNs, and SMADH4/DPC4 loss is not usually detected. […] The presence of ovarian stroma is diagnostic for mucinous cystic neoplasms and has almost become a requirement for the diagnosis of this tumor type.

• #1 Pancreatic cyst – Wikipedia

  https://en.wikipedia.org/wiki/Pancreatic_cyst

  The most common malignancy that can present as a pancreatic cyst is a mucinous cystic neoplasm. […] Intraductal papillary mucinous neoplasms (IPMN) involve the main pancreatic duct (main ductal IPMN) or its branches (branch duct IPMN) or both (mixed type IPMN). IPMNs are pre-malignant with main duct IPMNs having a 33-85% malignant potential and branch duct IPMNs having a 15% risk of malignancy at 15 years. […] Pancreatic mucinous cystic neoplasm usually involve the tail of the pancreas and 90% of cases involve women and they usually present in the 4-6th decade of life. They have a malignant potential of 10-34%. […] Pancreatic neuroendocrine tumors may sometimes undergo cystic degeneration forming cysts. These types of tumors arise from pancreatic endocrine cells, and 10% are functional, being able to secrete hormones.

• #1 Prevalence, Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl15063

  The mean frequency of malignancy (defined as high-grade dysplasia and invasive cancer) in surgically resected BD-IPMN is 25.5% (range, 6.3% to 46.5%) and the mean frequency of invasive cancer 17.7% (range, 1.4% to 36.7%). […] For patients with a definite diagnosis of a BD-IPMN or those with a strong suspicion of a presumed BD-IPMN, the next major challenge is risk-stratification for cancer development, a crucial determinant of either operative or nonoperative (surveillance) management. […] The presence of nodules on surgically resected BD-IPMNs is associated with increased risk of advanced pathology (high-grade dysplasia or invasive cancer) on those specimens. […] The other major strength of EUS in the evaluation of CNP, when compared with CT or MRI, is the ability to safely perform cyst fluid aspiration and analysis of cytology and tumor markers. […] The role of existing and newer pancreatic cyst fluid markers continues to be evaluated.

• #1 Cystic pancreatic lesions: MR imaging findings and management | Insights into Imaging | Full Text

  https://insightsimaging.springeropen.com/articles/10.1186/s13244-021-01060-z

  Moreover, it is characterized by a unique feature such as increased de novo development of pancreatic ductal adenocarcinoma (PDAC) elsewhere in the pancreas, suggesting the presence of diffuse pathologic changes predisposing to malignant transformation. […] IPMN is diagnosed at a mean age of 60 years, and it affects males slightly more frequently than females. […] IPMN is mostly detected in asymptomatic patients, but sometimes impaired outflow of pancreatic juice induced by hypersecretion of mucin may cause pain, may induce laboratory test abnormalities of pancreatitis and may cause acute pancreatitis itself, and thus, an IPMN may be discovered after an episode of acute pancreatitis. […] IPMN has heterogeneous malignant potential, and thus, the International Association of Pancreatology (IAP), with Fukuoka consensus in 2012, proposed two-tier criteria to predict malignancy.

• #1 Cystic Lesions of the Pancreas: Clinical and Pathologic Review of

  https://www.primescholars.com/articles/cystic-lesions-of-the-pancreas-clinical-and-pathologic-review-of-cases-in-a-five-year-period-97959.html

  Cystic lesions of the pancreas represent an important subgroup of pancreatic tumors. […] The increased detection of cystic lesions has also lead to the study of clinical and morphologic features that can help to distinguish between neoplastic and nonneoplastic processes and between benign and malignant cystic neoplasms. […] Cysts with mucinous lining are particularly important due to their inherent malignant potential. Mucinous cystic neoplasms are common, representing 10% to 45% of all pancreatic cystic neoplasms. […] In our study, the proportion of IPMN cases is higher, being the most frequent diagnosis (52.6%) followed by mucinous cystic neoplasms (13.4%). […] Mucinous cystic neoplasms are almost exclusive of premenopausal women, with a mean age of 48 years and a male to female ratio less than 1:20; they are located predominantly in the tail of the pancreas. […] Solid pseudopapillary tumor is included in the differential diagnosis of pancreatic cystic lesions because very commonly develops necrosis and cystic degeneration. […] Cystic neuroendocrine tumors are considered lesions with low malignant potential.

• #1

  https://link.springer.com/article/10.1007/s10620-021-07084-1

  On other end of the spectrum, mucin producing lesions, such as mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs), have malignant potential. […] MCNs carry a 10-39% risk of malignancy although less than 0.4% of cysts less than 3 cm in size without a nodule contain HGD or invasive cancer. […] Therefore, the European Study Group refined surgical resection criteria for MCN to those with size at least 4 cm, nodule, and/or symptoms. […] Intraductal papillary mucinous neoplasms (IPMN) have an equal gender distribution and often occur in the head of the pancreas as solitary or multifocal lesions. […] Malignant potential varies across these different types of IPMNs. […] These high rates of malignancy lead to recommendations for surgical resection of MD-IPMN and mixed-type IPMNs.

• #1 Pancreatic Cysts – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK525979/

  Solid pseudopapillary neoplasm: Large, well-demarcated, mixed cystic and solid tumors. […] Cystic pancreatic neuroendocrine tumor: Smaller, more likely nonfunctional, cystic lesions that may be associated with multiple endocrine neoplasia types 1. […] Mucinous nonneoplastic cyst: Mucin-producing cyst without malignant potential that is differentiated from mucinous cystic neoplasm by lack of ovarian-type stroma and from IPMN by lack of ductal communication.

• #1 Pancreatic Cystic Lesions: A Case-Based Approach

  https://www.gastroendonews.com/Review-Articles/Article/10-21/Pancreatic-Cystic-Lesions/64972

  The risk for malignancy in SPNs is estimated to be around 15%, based on data from 2 surgical series. […] Emerging Technologies […] In recent years, new markers from EUS-guided fluid samples from PCNs and new technical modalities of tissue acquisition and assessment have emerged that could improve our ability to accurately diagnose PCNs and understand their risk for malignant transformation. […] Although pancreatic cysts present a clinical challenge, familiarity with the different types of cysts and the ability to identify those with malignant potential are important.

• #1 Molecular Test Classify Pancreatic Cysts – Let’s Win Pancreatic Cancer

  https://letswinpc.org/symptoms/pancreatic-cysts/molecular-test-classify-pancreatic-cysts/

  Pancreatic cysts are very common, but only a small proportion of them are cancerous or can progress to cancer. […] Current guidelines for assessing whether a pancreatic cyst is cancerous mostly rely on imaging of features such as size and growth rate, and many argue that these tests are not sensitive enough. Researchers have turned to advanced sequencing technology to better distinguish pancreatic cystic lesions, in hopes of predicting their malignant potential and optimizing patient management. […] The resulting product, PancreaSeq Genomic Classifier, is a unique molecular test that targets 74 genes to evaluate five classes of genomic alterations including gene mutations, gene fusions, and gene expression believed to correlate with pancreatic lesions. […] Being able to identify the differences between benign cysts and potentially cancerous pancreatic neoplasms is so important when it comes to stratifying patients for appropriate surveillance protocols and management options, as well as easing their anxiety.

• #1 Pancreatic Cancer Risk Testing Using Pancreatic Cyst Fluid

  https://www.southcarolinablues.com/web/public/brands/medicalpolicyhb/external-policies/pancreatic-cancer-risk-testing-using-pancreatic-cyst-fluid/

  One method used to ascertain subtypes of PCN and to identify malignancy is the use of biomarkers in peripheral blood such as serum carbohydrate antigen (CA) 19-9. […] Serum CA 19-9 levels that exceed 37 U/ml, may provide information on potential malignancy or invasive IPMN. […] Cystic fluid analysis is also purported as useful to further analyze PCN by subtype. […] Analyses of pancreatic cystic fluid for this purpose may include CEA, CA 19-9, amylase and lipase, viscosity, mucin stain, and cytology (Khalid McGrath, 2023). […] Molecular analysis of DNA has been suggested as another way to gather important diagnostic information on pancreatic cysts. […] DNA markers such as GNAS and KRAS have evidenced specificity and sensitivity for diagnosis of whether a cyst is an IPMN (Scholten et al., 2018).

• #1 Molecular Test Classify Pancreatic Cysts – Let’s Win Pancreatic Cancer

  https://letswinpc.org/symptoms/pancreatic-cysts/molecular-test-classify-pancreatic-cysts/

  They looked for mutations in genes such as KRAS, BRAF, and PTEN mutations, as well as other complex genomic alterations and differential gene expression. […] The researchers then integrated the presence versus absence of these alterations to come up with a cystic precursor score and establish a genomic classifier for the risk of early pancreatic cancer. […] They found that the PancreaSeq test was not only accurate in predicting pancreatic cyst type and advanced neoplasia with sensitivity and specificity as high as 95 percent and 100 percent, respectively but that it also improved the sensitivity of current pancreatic cyst guidelines. […] The test also does an excellent job at identifying cystic pancreatic neuroendocrine tumors (CPanNETs) and may represent the foundation from which to build prognostic biomarkers for that condition. […] Our hope is that it catches cancer early while preventing unnecessary surgeries.

• #1 Pancreatic Cystic Lesions: A Case-Based Approach

  https://www.gastroendonews.com/Review-Articles/Article/10-21/Pancreatic-Cystic-Lesions/64972

  Pancreatic cysts are a biologically diverse group of lesions that have varying degrees of malignant potential. […] Despite our growing armamentarium of tests, there is no perfect test for quantifying the malignant potential of pancreatic cysts. […] The management of pancreatic cysts requires accurate risk stratification for malignant potential based on the presence or absence of symptoms and high-risk features on imaging. […] Determining whether a PCN is serous/nonmucinous or mucinous usually is the first step in risk stratification because mucinous cysts are considered premalignant. […] Mucinous cysts are lined by a columnar epithelium capable of producing mucus. […] The Cooperative Pancreatic Cyst study revealed that a CEA level cutoff of 192 ng/mL was the most accurate in differentiating mucinous from nonmucinous cysts.

• #1 Pancreatic Cystic Lesions: A Case-Based Approach

  https://www.gastroendonews.com/Review-Articles/Article/10-21/Pancreatic-Cystic-Lesions/64972

  An elevated pancreatic cyst fluid amylase level indicates a connection with the pancreatic duct and typically is noted in IPMNs and pseudocysts. […] Pancreatic inflammatory fluid collections are not lined by an epithelium and are a result of local complications of acute pancreatitis. […] PCNs, according to the World Health Organization histologic classification, are divided into 2 categories: serous (nonmucinous) and mucinous. […] The risk for invasive cancer in patients with MCNs depends on the presence of concerning features on preoperative imaging. […] The risk for malignancy associated with IPMNs depends on the type. […] The risk for malignant transformation of BD-IPMNs is much lower. […] Available guidelines recommend some form of long-term surveillance of patients with IPMNs.

• #1 Pancreatic cysts – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pancreatic-cysts/symptoms-causes/syc-20375993

  Pancreatic cysts are saclike pockets of fluid on or in your pancreas. The main categories of pancreatic cysts can be divided into two groups, nonneoplastic or neoplastic cysts. Each group includes many different subtypes of cysts, such as pseudocysts, serous cystadenomas and mucinous cystic neoplasms. Most aren’t cancerous, and many don’t cause symptoms. But some pancreatic cysts can be or can become cancerous. […] The cause of most pancreatic cysts is unknown. Some cysts are associated with rare illnesses, including polycystic kidney disease or von Hippel-Lindau disease, a genetic disorder that can affect the pancreas and other organs. […] Pseudocysts often follow a bout of a painful condition in which digestive enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the abdomen, such as from a car accident. […] Heavy alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. Abdominal injury is also a risk factor for pseudocysts.

• #1 Pancreatic Cystic Lesions: A Case-Based Approach

  https://www.gastroendonews.com/Review-Articles/Article/10-24/pancreas-pancreatic-cysts-lesions-imaging/75191

  Pancreatic cystic lesions are being found more frequently on cross-sectional imaging studies. Although many of these cysts are discovered incidentally in asymptomatic patients, many have a malignant potential. Coupled with the lack of a single diagnostic test for accurate risk stratification and the risks of surgical resection, this leads to diagnostic and management challenges for clinicians, highlighting the need for a multidisciplinary approach to optimize patient care. […] The incidence of pancreatic cystic lesions is increasing, partly due to the aging population, the increased use of cross-sectional imaging studies, and, perhaps, other reasons that are unclear. The prevalence of pancreatic cysts increases with age; it has an approximate overall incidence of 15% on MRI, with meta-analysis data showing this number increases from 9% in people aged 50 to 59 years to as high as 38% in those aged 80 years and older.

• #1 Pancreatic cysts: What they are and how they’re treated | MD Anderson Cancer Center

  https://www.mdanderson.org/cancerwise/pancreatic-cysts–what-they-are-and-how-they-are-treated.h00-159542901.html

  But if you have pancreas cysts, you are more likely to develop pancreatic cancer. […] There are two main genes associated with cysts in the pancreas: KRAS and GNAS. Kim says other genes associated with higher cancer risk, like BRCA mutations, can also play a role in cyst development. […] Were not sure why some people have cysts that develop into cancer and some dont, Kim says. Thats why he and his team are working to better understand the genetic link between pancreatic cysts and cancer.

• #1 Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714518/

  Due to increasing availability and use of cross-sectional imaging modalities, the diagnosis of pancreatic cystic neoplasms is on the rise. […] Research has shown that some of these cysts indeed have malignant potential. Thus, addressing these cysts surgically offers an opportunity to achieve, at least partially, the ever-elusive goal of preventing development of pancreatic cancer. […] A better understanding of the pathogenesis of pancreatic cyst and their progression to malignancy will help make an accurate diagnosis and predict behavior. This review addresses our current knowledge of the pathogenesis of pancreatic cysts. […] In this regard cystic neoplasms of the pancreas are no exceptions. A variety of studies have evaluated the mutational profile of cystic neoplasms of the pancreas with the goal to get an insight into their pathogenesis.

• #1 Diagnosis and management of pancreatic cystic lesions for the non-gastroenterologist | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/91/2/96

  Worrisome characteristics include main pancreatic duct dilation greater than or equal to 5 mm, cyst size greater than or equal to 3 cm, and the presence of a solid component or mural nodule in the PCL. […] PCLs that have the potential to become malignant are managed by active monitoring or surgical excision. […] PCLs with high-risk characteristics, and those with a known high risk of malignancy, such as main duct intraductal papillary mucinous neoplasms and solid pseudopapillary tumors, should be referred for surgical excision. […] The overall prognosis is favorable, with early detection and active surveillance serving as the cornerstones of management.

• #2 Pancreatic Cystic Lesions: A Case-Based Approach

  https://www.gastroendonews.com/Review-Articles/Article/10-24/pancreas-pancreatic-cysts-lesions-imaging/75191

  Pancreatic cystic lesions are being found more frequently on cross-sectional imaging studies. Although many of these cysts are discovered incidentally in asymptomatic patients, many have a malignant potential. Coupled with the lack of a single diagnostic test for accurate risk stratification and the risks of surgical resection, this leads to diagnostic and management challenges for clinicians, highlighting the need for a multidisciplinary approach to optimize patient care. […] The incidence of pancreatic cystic lesions is increasing, partly due to the aging population, the increased use of cross-sectional imaging studies, and, perhaps, other reasons that are unclear. The prevalence of pancreatic cysts increases with age; it has an approximate overall incidence of 15% on MRI, with meta-analysis data showing this number increases from 9% in people aged 50 to 59 years to as high as 38% in those aged 80 years and older.

• #2 Pancreatic cyst – Wikipedia

  https://en.wikipedia.org/wiki/Pancreatic_cyst

  A pancreatic cyst is a fluid filled sac within the pancreas. The prevalence of pancreatic cysts is 2-15% based on imaging studies, but the prevalence may be as high as 50% based on autopsy series. Most pancreatic cysts are benign and the risk of malignancy (pancreatic cancer) is 0.5-1.5%. Pancreatic pseudocysts and serous cystadenomas (which collectively account for 15-25% of all pancreatic cysts) are considered benign pancreatic cysts with a risk of malignancy of 0%. […] Causes range from benign to malignant. Pancreatic cysts can occur in the setting of pancreatitis, though they are only reliably diagnosed 6 weeks after the episode of acute pancreatitis. […] Main branch intraductal papillary mucinous neoplasms (IPMNs) are associated with dilatation of the main pancreatic duct, while side branch IPMNs are not associated with dilatation.

• #2 Pancreatic Cyst Etiology and Evaluation – Department of Surgery

  https://www.surgery.wisc.edu/2018/01/05/pancreatic-cyst-etiology-and-evaluation/

  Pancreatic cysts can be classified as either of non-epithelial or epithelial origin, and within each of those categories as non-neoplastic or neoplastic. […] The vast majority of pancreatic cysts fall into the category of neoplastic epithelial cysts. This group can be subdivided into those that are benign, pre-malignant and malignant: […] Pre-malignant cysts of epithelial origin include the two most challenging conditions mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN). […] Malignant epithelial cysts include invasive carcinomas that arise from either MCN or IPMN, cystic ductal adenocarcinomas, cystic neuroendocrine tumors, and solid pseudopapillary tumors. […] The risk of high-grade dysplasia, in-situ or invasive malignancy is on the order of 60-70%. […] Although they have malignant potential, the risk is low and dependent on specific cyst features.

• #2 Pancreatic Cyst: Symptoms, Causes, Types & Treatment

  https://my.clevelandclinic.org/health/diseases/pancreatic-cyst

  A pancreatic cyst is a fluid-filled growth on the inside or outside of your pancreas. There are different types, made of slightly different cellular materials. Some types are neoplastic, and others are nonneoplastic. Neoplastic cysts have the potential to become cancerous. Nonneoplastic types dont. […] Some pancreatic cysts seem to be related to inflammation (pancreatitis), but most occur for unknown reasons. Most pancreatic cysts wont cause any problems. Rarely, a neoplastic type of cyst can be the start of pancreatic cancer. This is more likely if you have a family history of pancreatic cancer. […] Less than 1% of pancreatic cysts turn into cancer. But up to 30% of pancreatic cysts have the potential to turn into cancer. This is why healthcare providers keep an eye on them. Most precancerous cysts grow and change very slowly, so regular surveillance is likely to spot cancerous changes early in the process.

• #2 Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714518/

  Recent efforts from clinical studies have identified key molecular driver mutations like KRAS and GNAS as early events. These findings along with mouse models that recapitulate morphological and natural history of progression from cystic lesions to malignancy is helping paint a clearer picture of this disease.

• #2 Pancreatic Cystic Lesions: A Focused Review on Cyst Clinicopathological Features and Advanced Diagnostics

  https://www.mdpi.com/2075-4418/13/1/65

  Overall, about a third of resected IPMN are associated with invasive carcinoma. Main-duct IPMN (>10 mm) has higher rate of associated malignancy, up to 60%, whereas branch-duct IPMN (>3 cm) has a lower rate (15–20%). The two most common IPMN-associated invasive carcinomas are tubular (ductal) adenocarcinoma and colloid adenocarcinoma. […] The pathogenesis is unclear and thought to be related to ectopic embryonic remnants, which explains some “ancient” changes such as a thick fibrous wall and mural calcifications. Activating mutations in codon 12 of KRAS is seen in 50–66% of MCNs as well as loss of function in RNF43. Unlike IPMN, GNAS mutations are rarely seen in MCN. The gene mutations associated with advanced neoplasia in IPMN may be observed in MCN, including TP53, CDKN2A, SMAD4, and/or mTOR genes.

• #2 Lymphoepithelial Cysts of the Pancreas: a Report of 12 Cases and a Review of the Literature | Modern Pathology

  https://www.nature.com/articles/3880553

  Cystic transformation of pancreatic ducts that had undergone squamous metaplasia has been considered. […] It has also been suggested that LECs may be a form of teratoma; however, the presence and the distribution of lymphoid tissue would be most unusual for a teratoma. […] It has also been speculated that LECs may represent branchial cleft cysts that have been displaced and fused with the pancreas during embryogenesis. […] One hypothesis that is quite appealing is a continuation of a mechanistic explanation unifying those head and neck lesions that are characterized by cystic or glandular epithelial elements surrounded by lymphoid tissue into one generic category.

• #2 What are Pancreatic Cysts? – Let’s Win Pancreatic Cancer

  https://letswinpc.org/symptoms/pancreatic-cysts/what-you-should-know-pancreatic-cysts/

  Like a cyst in any other part of the body, pancreatic cysts are water- or mucus-filled structures. While some people are predisposed to develop pancreatic cysts because of genetics, most arise from inflammation of the pancreas (also called pancreatitis). In most cases, these cysts are benign. […] The problem is, all of these things can also be associated with pancreatitis. You can even get focal massesa mass or lesion that develops at a circumscribed area of the organwith chronic pancreatitis. So theres a big degree of overlap between the characteristics of potentially premalignant cysts and inflammatory nonmalignant cysts. […] We can do endoscopic ultrasound, where we put a flexible scope through the mouth, down into the stomach so we can get a good view of the back wall of the stomach. We can draw samples of the pancreatic fluid and analyze it for biochemical markers such as CA 19-9 or carcinoembryonic antigen (CEA), which are predictive of cancer. We also have some novel approaches where we can take needle biopsies of the cyst wall to help better characterize the cyst.

• #2 Prevalence, Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl15063

  The mean frequency of malignancy (defined as high-grade dysplasia and invasive cancer) in surgically resected BD-IPMN is 25.5% (range, 6.3% to 46.5%) and the mean frequency of invasive cancer 17.7% (range, 1.4% to 36.7%). […] For patients with a definite diagnosis of a BD-IPMN or those with a strong suspicion of a presumed BD-IPMN, the next major challenge is risk-stratification for cancer development, a crucial determinant of either operative or nonoperative (surveillance) management. […] The presence of nodules on surgically resected BD-IPMNs is associated with increased risk of advanced pathology (high-grade dysplasia or invasive cancer) on those specimens. […] The other major strength of EUS in the evaluation of CNP, when compared with CT or MRI, is the ability to safely perform cyst fluid aspiration and analysis of cytology and tumor markers. […] The role of existing and newer pancreatic cyst fluid markers continues to be evaluated.

• #2 Cystic pancreatic lesions: MR imaging findings and management | Insights into Imaging | Full Text

  https://insightsimaging.springeropen.com/articles/10.1186/s13244-021-01060-z

  Once pseudocyst and WON have been excluded, a CPL communicating with MPD is an IPMN, while if not communicating could be a SCN, a MCN or a SPN and differential diagnosis, certain or presumptive, can be done on the basis of demographic data, location of the lesion and its morphological appearance. […] New imaging applications, with quantitative analysis thanks to texture analysis, have the potential to help to better stratify IPMNs, thus allowing a more correct management.

• #2

  https://link.springer.com/article/10.1007/s10620-017-4603-1

  With the current epidemic of diagnosed pancreatic cystic neoplasms on the rise, a substantial amount of work has been done to unravel their biology, thus leading to implications on clinical decision making. Recent genetic profiling of resected human specimens has identified alterations in signaling pathways involving KRAS and GNAS signaling as early events in the pathogenesis of intraductal pancreatic mucinous neoplasms. […] Progressively, mutations in genes such as TP53, SMAD4, RNF43, and others are thought to characterize invasive and advanced lesions. The role of inflammation in fueling the growth and transformation of these cysts has also begun to be studied with greater interest. […] A number of promising clinical studies have attempted to integrate these genetic insights into classifying these cysts and treating patients. […] We have reviewed existing literature on similar lines besides commenting on some useful animal models that recapitulate molecular and phenotypic progression of these cysts.

• #2 Pancreatic Cancer Risk Testing Using Pancreatic Cyst Fluid

  https://www.southcarolinablues.com/web/public/brands/medicalpolicyhb/external-policies/pancreatic-cancer-risk-testing-using-pancreatic-cyst-fluid/

  One method used to ascertain subtypes of PCN and to identify malignancy is the use of biomarkers in peripheral blood such as serum carbohydrate antigen (CA) 19-9. […] Serum CA 19-9 levels that exceed 37 U/ml, may provide information on potential malignancy or invasive IPMN. […] Cystic fluid analysis is also purported as useful to further analyze PCN by subtype. […] Analyses of pancreatic cystic fluid for this purpose may include CEA, CA 19-9, amylase and lipase, viscosity, mucin stain, and cytology (Khalid McGrath, 2023). […] Molecular analysis of DNA has been suggested as another way to gather important diagnostic information on pancreatic cysts. […] DNA markers such as GNAS and KRAS have evidenced specificity and sensitivity for diagnosis of whether a cyst is an IPMN (Scholten et al., 2018).

• #2 Pancreatic Cyst Symptoms, Causes and Treatment

  https://www.cancercenter.com/cancer-types/pancreatic-cancer/risk-factors/pancreatic-cysts

  Injuries and pancreatitis are the most common causes of pancreatic cysts. Pancreatitis can develop from a disease such as alcoholism, from having a gallstone lodge in a duct, or from trauma. Rarely, pancreatic cysts can be caused by an infection such as tuberculosis, tapeworms or other organisms. Some pancreatic cysts are linked to polycystic kidney disease, medullary cystic kidneys or cystic fibrosis. […] Pancreatic cysts are also associated with certain rare inherited and/or congenital syndromes (conditions the patient is born with).

• #2 Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714518/

  GNAS mutation leads to disruption of the intrinsic hydrolytic activity of Gs, which results in constitutive activation of its function. […] This suggest that these mutations are probably acquired early in the pathogenesis of IPMN and additional mutations may be required for the disease progression. […] The goal of gaining a detailed understanding of the pathogenesis of neoplastic cysts and the pathways leading to cancer development is to 1) employ -omics approach to help in correctly diagnosing the type of cyst; 2) help in detecting if cancer has already developed in these lesions thus providing a clear indication for surgical approach; 3) predict of the biology of lesions with respect to progression to invasive lesions; and 4) attain the elusive goals of developing pharmacotherapy which may prevent development of invasive lesions.

• #2

  https://link.springer.com/article/10.1007/s10620-021-07084-1

  Pancreatic cystic lesions (PCLs) represent a heterogenous group of lesions with varying degrees of malignant potential and a wide clinicopathologic spectrum that mandates careful diagnostic and therapeutic consideration. […] The diagnosis and management of PCLs remain problematic due to the variable biological behavior of these lesions, cost of surveillance, morbidity of surgical resection, lack of reliable diagnostics, and need for improved guidelines. […] Thus, advances in pancreatic cyst diagnostics and therapeutics with endoscopic ablation techniques require further study. […] While pancreatic cysts are increasingly being discovered, pancreatic cancer-related mortality has not improved. Hence, managing these PCLs has gained considerable attention as clinicians focus on stratifying the malignant potential of these cysts to prevent the mortality associated with progression to pancreatic cancer.

• #3 Lymphoepithelial Cysts of the Pancreas: a Report of 12 Cases and a Review of the Literature | Modern Pathology

  https://www.nature.com/articles/3880553

  Cystic transformation of pancreatic ducts that had undergone squamous metaplasia has been considered. […] It has also been suggested that LECs may be a form of teratoma; however, the presence and the distribution of lymphoid tissue would be most unusual for a teratoma. […] It has also been speculated that LECs may represent branchial cleft cysts that have been displaced and fused with the pancreas during embryogenesis. […] One hypothesis that is quite appealing is a continuation of a mechanistic explanation unifying those head and neck lesions that are characterized by cystic or glandular epithelial elements surrounded by lymphoid tissue into one generic category.

• #3 Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714518/

  GNAS mutation leads to disruption of the intrinsic hydrolytic activity of Gs, which results in constitutive activation of its function. […] This suggest that these mutations are probably acquired early in the pathogenesis of IPMN and additional mutations may be required for the disease progression. […] The goal of gaining a detailed understanding of the pathogenesis of neoplastic cysts and the pathways leading to cancer development is to 1) employ -omics approach to help in correctly diagnosing the type of cyst; 2) help in detecting if cancer has already developed in these lesions thus providing a clear indication for surgical approach; 3) predict of the biology of lesions with respect to progression to invasive lesions; and 4) attain the elusive goals of developing pharmacotherapy which may prevent development of invasive lesions.

• #4 Insights into the Pathogenesis of Pancreatic Cystic Neoplasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5714518/

  GNAS mutation leads to disruption of the intrinsic hydrolytic activity of Gs, which results in constitutive activation of its function. […] This suggest that these mutations are probably acquired early in the pathogenesis of IPMN and additional mutations may be required for the disease progression. […] The goal of gaining a detailed understanding of the pathogenesis of neoplastic cysts and the pathways leading to cancer development is to 1) employ -omics approach to help in correctly diagnosing the type of cyst; 2) help in detecting if cancer has already developed in these lesions thus providing a clear indication for surgical approach; 3) predict of the biology of lesions with respect to progression to invasive lesions; and 4) attain the elusive goals of developing pharmacotherapy which may prevent development of invasive lesions.

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