Pancreatic Intraductal Mucinous Neoplasm Research Articles

Ductal hamartoma of the pancreas: A clinicopathologic study

BackgroundBenign ductular proliferative lesions that resemble hepatic von-Meyenburg Complexes(VMC)/bile duct hamartomas have been noted to occur in the pancreas, but their incidence, clinicopathologic features and pathogenesis remains unknown. We present herein 3 patients that presented as cysts and call them pancreatic ductal hamartomas (PDH). MethodsThree cases of PDH were identified form a multi-institutional collaborative group, and their clinicopathological were reviewed. In addition, we also examined 115 consecutive pancreatic resections at our institutions for the presence of incidental PDHs. ResultsThe lesions were detected in each case during imaging for abdominal symptoms or grossing. The clinical suspicion was intra-ductal pancreatic mucinous cystic neoplasm (IPMN) in each case that led to pancreatectomy. The cyst fluid CEA was elevated in 2 of the patients tested. The patient age and gender were 73/M (case1), 68/F (case2) and 73/M (case3). In case1 besides the larger cystic lesion, numerous tiny lesions (0.1–0.3 cm) were seen throughout the pancreas. In case2 this was the only lesion, while in case3 there was another gastric-type IPMN with high-grade dysplasia. PDH were identified in 5(4.3%) of 115 consecutive pancreatectomy specimens. The PDHs measured 0.1–2.3 cm, and the histology is characterized by proliferation of irregular ductal structures lined by bland flattened to low columnar epithelium, variable cystic change and inspissated luminal secretions. The lining epithelium varied from non-mucinous pancreatico-biliary type to mucinous gastric foveolar-type, with occasional squamous metaplasia. SummaryPDH are seen in 4.5% of all pancreatectomy specimens and detected incidentally, but occasionally may become large and/or cystic enough leading to pancreatectomy. Their relationship to pancreatic carcinoma or IPMN remains currently unknown.

ThP4.14 - Updated surveillance guidance for Intra-ductal Pancreatic Mucinous Neoplasm (IPMN) – a 10-year cohort study in a tertiary care Surgical unit

Abstract Aims To investigate the adequacy of current frequency of surveillance of IPMN in a single tertiary surgical unit Methods This was a retrospective cohort study over a 10-year period (2013-2023), patient age range 30-85 years old. The data collected included gender, age at diagnosis, size(mm) of largest cyst, high risks(HRF) or worrisome features(WRF) and interventions required. Analysis undertaken pertaining to the incidence of IPMN with malignant potential as well as progression of disease on surveillance. Results Total of 61 patients. On presentation - Cyst size <1cm – 51%, 1-2cm- 33%, 2-3cm- 16%. <1cm group - no growth on surveillance scans and no interventions required. 1-2cm group - 35% had HRF, 25% of which underwent surgical intervention. 15% showed WF of which 33% required surgical intervention. 2-3cm group - 20% of patients with WF showed growth in cyst size. 40% of patients with WF - underwent surgery. Conclusion The malignant potential of IPMN correlates with the initial cyst size. Guidelines recommend that cysts <1cm should be under 2-yearly surveillance. However, when compared to those with cyst>1cm, none of the patients with cyst size<1cm displayed progression. Therefore, we propose that for patients with an initial cyst size of less than 1cm, who are above the age of 70 and/or Performance status (PS) =>2 – no active surveillance is required. If the PS <2 and patients are less than 70 years old, we recommend 5-yearly surveillance. For patients with cyst size >1cm, we recommend adhering to the current guidance. With this revised guidance, already scarce resources may be better utilised.

697 Updated Surveillance Guidance for Intra-Ductal Pancreatic Mucinous Neoplasm (IPMN) – a 10-Year Cohort Study in a Tertiary Care Surgical Unit

697 Updated Surveillance Guidance for Intra-Ductal Pancreatic Mucinous Neoplasm (IPMN) – a 10-Year Cohort Study in a Tertiary Care Surgical Unit

Consequences of a Surveillance Strategy for Side-branch Intraductal Pancreatic Mucinous Neoplasms: Long-term Follow-up of One Thousand Cysts.

To quantify the rate of progression in surveilled cysts and assess what factors should indicate delayed resection. Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs) are increasingly discovered, making it challenging to identify which patients require resection, thus avoiding inappropriate treatment. Most incidental lesions are surveyed, yet the consequences of that decision remain uncertain. A prospectively maintained database of pancreatic cystic neoplasms was queried for patients with SB-IPMN. Patients with ≥2 imaging studies >6 months apart were included. Clinically relevant progression (CR-progression) was defined by symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth ≥5mm in 2 years is considered CR-progression; size ≥3cm alone is not. Between 1997 and 2023, 1337 patients were diagnosed with SB-IPMN. Thirty-seven (2.7%) underwent up-front surgery; 1000 (75.0%) had >6 months of surveillance.The rate of CR-progression was 15.3% (n = 153) based on size increase (n = 63, 6.3%), main-duct involvement (n = 48, 4.8%), symptoms (n = 8, 5.0%), or other criteria (n = 34, 3.4%). At a median follow-up of 6.6 years (interquartile range: 3.0-10.26), 17 patients (1.7%) developed IC. Those with CR-progression developed IC in 11.1% (n = 17) and high-grade dysplasia (HGD) in 6.5% (n = 10). Nearly half of the cancers were not contiguous with the surveyed SB-IPMN.Size ≥3cm was not associated with HGD/IC ( P = 0.232). HGD/IC was least common in CR-progression determined by size growth (6.3%) versus main-duct involvement (24%) or other (43%, P < 0.001)Patients with CR-progression demonstrated improved survival (overall survival) with resection on time-to-event ( P < 0.001) and multivariate Cox regression (hazard ratio = 0.205, 0.096-0.439, P < 0.001) analyses. Overall survival was not improved with resection in all patients ( P = 0.244). CR-progression for SB-IPMNs is uncommon, with the development of cancer anywhere in the pancreas being rare. Initial size should not drive resection. Long-term and consistent nonoperative surveillance is warranted, with surgery currently reserved for CR-progression, knowing that the majority of these still harbor low-grade pathology.

Chromo-pancreatoscopy for preoperative evaluation of main duct intraductal pancreatic mucinous neoplasm

Chromo-pancreatoscopy for preoperative evaluation of main duct intraductal pancreatic mucinous neoplasm

Endoscopic diagnosis of santoriniceles with reverse pancreas divisum

A 77-year-old woman presented with her third episode of acute pancreatitis. Serum CA 19-9 was markedly elevated: 608 U/L (reference range <43 U/L). Branch duct type intraductal pancreatic mucinous neoplasms were suspected, owing to the appearance of multiple cystic lesions communicating with the dilatated pancreatic duct on magnetic resonance imaging. EUS confirmed a communication between the multilocular cysts and the dilatated duct of Santorini (A), but no communication between the ducts of Santorini and Wirsung was observed.

A Mimicker of Intraductal Papillary Mucinous Carcinoma of the Pancreas

Question: A 79-year-old asymptomatic man formerly diagnosed with branch duct (BD) type intraductal pancreatic mucinous neoplasms (IPMNs) was admitted owing to the appearance of a mural nodule in one of the IPMNs on abdominal ultrasound examination. Serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were normal. An abdominal contrast-enhanced computed tomography scan detected 2 cysts and 1 cyst in the pancreas body and head, respectively. These cystic lesions were visualized by magnetic resonance cholangiopancreatography as multilocular cysts connected with the main pancreatic duct and were thus diagnosed as BD-type IPMNs (Figure A).

Small, low-grade ampullary neuroendocrine tumor presenting with metastasis and multiple synchronous tumors in a patient with neurofibromatosis type 1: a case report with literature review

ABSTRACTNeurofibromatosis type 1 (NF1) is a tumor syndrome and one of the most common genetic disorders. Patients have an increased risk of developing neurologic and gastrointestinal (GI) neoplasms, but GI lesions are often underrecognized since most cases are asymptomatic. It is extremely rare to see multiple types of abdominal tumors synchronously in NF1. In this case, we describe a patient presenting with a small, low-grade periampullary neuroendocrine tumor (NET) that underwent endoscopic submucosal dissection and later pancreaticoduodenectomy (Whipple procedure). This led to findings of lymph node and distant metastasis of her NET, and the incidental discovery of gastrointestinal stromal tumors, extensive pancreatic intraepithelial neoplasia, and main duct and side branch intraductal pancreatic mucinous neoplasm. The synchronous presence of these lesions has not been reported in the literature.

Intraductal Pancreatic Mucinous Neoplasms: A Tumor-Biology Based Approach for Risk Stratification.

Pancreatic ductal adenocarcinoma is one of the most lethal human cancers. Its precursor lesions include pancreatic intra-epithelial neoplasia, mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm (IPMN). IPMNs usually present as an incidental finding at imaging in 2.6% of the population and, according to the degree of dysplasia, they are classified as low- or high-grade lesions. Since the risk of malignant transformation is not accurately predictable, the management of these lesions is based on morphological and clinical parameters, such as presence of mural nodule, main pancreatic duct dilation, presence of symptoms, or high-grade dysplasia. Although the main genetic alterations associated to IPMNs have been elucidated, they are still not helpful for disease risk stratification. The growing body of genomic and epigenomic studies along with the more recent development of organotypic cultures provide the opportunity to improve our understanding of the malignant transformation process, which will likely deliver biomarkers to help discriminate between low- and high-risk lesions. Recent insights on the topic are herein summarized.

Intraoperative pancreatoscopy for surgical planning in a patient with ansa pancreatica and mixed-type intraductal pancreatic mucinous neoplasm

Intraoperative pancreatoscopy for surgical planning in a patient with ansa pancreatica and mixed-type intraductal pancreatic mucinous neoplasm

Identification of key lncRNAs in the tumorigenesis of intraductal pancreatic mucinous neoplasm by coexpression network analysis.

Intraductal papillary mucinous neoplasm (IPMN) is an intraepithelial precancerous lesion of pancreatic ductal adenocarcinoma (PDAC) that progresses from adenoma to carcinoma, and long noncoding RNAs (lncRNA) might be involved in the tumorigenesis. In this study, we obtained the expression profiles of more than 4000 lncRNAs by probe reannotation of a microarray dataset. As a correlation network‐based systems biology method, weighted gene coexpression network analysis (WGCNA) was used to find clusters of highly correlated lncRNAs in the tumorigenesis of IPMN, which covered four stepwise stages from normal main pancreatic duct to invasive IPMN. In the most relevant module (R2 = −0.75 and P = 5E‐05), three hub lncRNAs were identified (HAND2‐AS1, CTD‐2033D15.2, and lncRNA‐TFG). HAND2‐AS1 and CTD‐2033D15.2 were negatively correlated with the tumorigenesis (P in one‐way ANOVA test = 1.45E‐07 and 1.39E‐0.5), while lncRNA‐TFG were positively correlated with the tumorigenesis (P = 3.99E‐08). The validation set reached consistent results (P = 2.66E‐03 in HAND2‐AS1, 1.47E‐04 in CTD‐2033D15.2 and 6.23E‐08 in lncRNA‐TFG). In functional enrichment analysis, the target genes of microRNAs targeting also these lncRNAs were overlapped in multiple biological processes, pathways and malignant diseases including pancreatic cancer. In survival analysis, patients with higher expression of HAND2‐AS1‐targeted and CTD‐2033D15.2‐targeted microRNAs showed a significantly poorer prognosis in PDAC, while high expression of lncRNA‐TFG‐targeted microRNAs demonstrated an obviously better prognosis (log‐rank P < .05). In conclusion, by coexpression network analysis of the lncRNA profiles, three key lncRNAs were identified in association with the tumorigenesis of IPMN, and those lncRNAs might act as early diagnostic biomarkers or therapeutic targets in pancreatic cancer.

Cystic Pancreatic Lesions: A Review of Diagnosis and Management

AbstractPancreatic cysts are commonly seen with increasing use of cross-sectional imaging. They range from a benign inflammatory process that can produce pseudocysts to malignant lesions such as mucinous cystadenocarcinoma. Other common pancreatic cysts include intraductal pancreatic mucinous neoplasms and serous cystadenomas. Optimized imaging protocol dedicated to imaging the pancreas is required, such as multiphasic computed tomography, magnetic resonance imaging/magnetic resonance cholangiopancreatography, or endoscopic ultrasound, to fully detect and characterize the lesions. A confident diagnosis can be made on imaging when features such as calcifications, pancreatic duct diameter, main duct communication, and mural nodules are assessed. Additionally, pathologic evaluation from fluid/tissue sampling aid in diagnosis. Optimal management of pancreatic cysts is achieved based on the imaging features, conveying key findings in the radiology report, pathologic evaluation, and clinical factors.

2804 Outcomes in Intra-Ductal Papillary Mucinous Neoplasms in the New York Harbor Veteran Population: An Update

INTRODUCTION: Over the last few years there has been an increase in the frequency of findings of intra-ductal papillary mucinous neoplasms (IPMNs). This is likely due to the increased use of advanced abdominal imaging as well as in increase in the quality of these images. In most cases, decisions are based on consensus rather than evidence based as to how to proceed with regard to follow up imaging, biopsy, or even surgical resection. At ACG 2017, we presented the outcomes of and natural history of patients with IPMNs in the Brooklyn VA. Since that presentation, we have an update regarding further data points as well as in increase in the number of patients we analyzed. METHODS: Retrospective chart review was performed on patients with diagnosis, based on coding) of pancreatic cyst, pancreatic lesion, and intra-ductal pancreatic mucinous neoplasm from the New York Harbor Veterans Affairs Hospital from 2000 to 2015. 767 patients were initially flagged, and based on either radiology reports or clinic notes 104 were determined to actually have an IPMN. We looked at basic demographics, risk factors and survival data. RESULTS: Baseline characteristics are outlined in Table 1 of the 104 patients formally diagnosed with an IPMN. In summary, 101 are male. The average age at the time of initial diagnosis was 71.5 years old, the median age was 72 years old. The average Body Mass index was 27.3. The subjects in this study were overwhelmingly African American (40.6%) and White (42.6%). There was a small Hispanic component (14.6%). There were no Asian patients in the study. Nine patients underwent surgical resection. 33 patients died and the median time to survival was not able to be calculated at this time. The average age at the time of death was 78.9 years old. In the 33 patients that died only 6 Patients (5.7% of total patients diagnosed) died from pancreatic causes. CONCLUSION: The management of IPMNs presents a clinical challenge for gastroenterologists today. To date, the levels of evidence in which the current guidelines are based on is poor. Our study is limited by factors such as advanced age, gender and multiple comorbidities preventing further invasive interventions. It is due to these factors, that our study is not applicable to the general population. Therefore, we recommend further larger multicenter trials with a diverse cohort to establish the risk of IPMN’s and their effect on mortality from pancreatic cancer.

GNAS but Not Extended RAS Mutations Spectrum are Associated with a Better Prognosis in Intraductal Pancreatic Mucinous Neoplasms.

The management of intraductal papillary mucinous neoplasms (IPMNs) is mainly based on imaging features and clinical symptoms, and remains challenging. The aim of this study was to assess GNAS, RAS family (KRAS, NRAS and HRAS), BRAF, and PIK3CA mutation status in resected IPMNs and correlate it with clinicopathological characteristics and patient survival. Overall, 149 consecutive unselected patients who underwent pancreatectomy for IPMNs were included. After dissection from formalin-fixed and paraffin-embedded tumors, GNAS mutational screening was assessed by allelic discrimination using Taqman® probes and confirmed by SNaPshot analysis. RAS family, BRAF, and PIK3CA mutational screening was assessed by high resolution melt and Sanger sequencing. Gastric- and intestinal-type IPMNs were the most frequent lesions (52% and 41%, respectively). Intestinal-type IPMNs were more frequently associated high-grade dysplasia (49%) and were the only IPMNs associated with colloid-type carcinoma. All pancreatobiliary IPMNs were invasive lesions, located in the main pancreatic duct. GNAS-activating mutations were strongly associated with the intestinal phenotype (p < 10-4), while RAS pathway mutations were not associated with any particular phenotype. Mutations within other members of the epidermal growth factor receptor (EGFR) pathway were very rare (2%). GNAS-mutated IPMNs were rarely invasive (11%) and almost exclusively (83%) of the colloid type. For invasive lesions, multivariate analyses determined that only node negativity was associated with improved cancer-specific survival, but, in univariate analysis, GNAS mutation was associated with prolonged survival. In patients selected for surgery, GNAS mutation analysis and tumor phenotype can help to better predict patient prognosis. In the near future, a more precise mutational analysis of IPMNs might help to better tailor their management.

A comparison of the Sendai and Fukuoka guidelines for side branch intraductal pancreatic mucinous neoplasms at a single institution

A comparison of the Sendai and Fukuoka guidelines for side branch intraductal pancreatic mucinous neoplasms at a single institution

Covering the Cover

Covering the Cover

The BRG1/SOX9 axis is critical for acinar cell-derived pancreatic tumorigenesis.

Chromatin remodeler Brahma related gene 1 (BRG1) is silenced in approximately 10% of human pancreatic ductal adenocarcinomas (PDAs). We previously showed that BRG1 inhibits the formation of intraductal pancreatic mucinous neoplasm (IPMN) and that IPMN-derived PDA originated from ductal cells. However, the role of BRG1 in pancreatic intraepithelial neoplasia-derived (PanIN-derived) PDA that originated from acinar cells remains elusive. Here, we found that exclusive elimination of Brg1 in acinar cells of Ptf1a-CreER; KrasG12D; Brg1fl/fl mice impaired the formation of acinar-to-ductal metaplasia (ADM) and PanIN independently of p53 mutation, while PDA formation was inhibited in the presence of p53 mutation. BRG1 bound to regions of the Sox9 promoter to regulate its expression and was critical for recruitment of upstream regulators, including PDX1, to the Sox9 promoter and enhancer in acinar cells. SOX9 expression was downregulated in BRG1-depleted ADMs/PanINs. Notably, Sox9 overexpression canceled this PanIN-attenuated phenotype in KBC mice. Furthermore, Brg1 deletion in established PanIN by using a dual recombinase system resulted in regression of the lesions in mice. Finally, BRG1 expression correlated with SOX9 expression in human PDAs. In summary, BRG1 is critical for PanIN initiation and progression through positive regulation of SOX9. Thus, the BRG1/SOX9 axis is a potential target for PanIN-derived PDA.

Outcomes in Intra-ductal Papillary Mucinous Neoplasms in the New York Harbor Veteran Population

Introduction: Intra-ductal papillary mucinous neoplasms (IPMN) have become more frequently and incidentally diagnosed in recent years due to increases in imaging procedures. With recommendations based on weak evidence, the only consistent recommendation is for surgical intervention in patients with main duct lesions, branch duct lesions greater than 3 cm, or a solid component of the cyst. The intent of our study is to evaluate the natural history of incidental pancreatic cysts and to determine if these lesions have an effect on morbidity and mortality. Methods: Retrospective chart review was performed on patients with diagnosis of pancreatic cyst, pancreatic lesion, and intra-ductal pancreatic mucinous neoplasm from the New York Harbor Veterans Affairs Hospital from 2000 to 2015. Of 767 patients, 116 were randomly selected for further analysis. Charts were reviewed for outcomes which included progression of IPMN into disease or death of patient from pancreatic or other causes. Results: Of the 116 patients with pancreatic cysts, 47 patients were diagnosed with IPMN. Baseline characteristics are outlined in Table 1. In summary, all patients were male, more than half of patients were over age 70 at diagnosis and more than half had BMI greater than 25. There were few Hispanic (7%) or Asian (0%) patients, with most patients self-identifying as white (42.6%) or black (40.4%). In terms of patient outcomes (Table 2), only 8 of 47 patients had passed away at time of publication, with 3 passing from a pancreatic etiology, 2 being pancreatic cancer. Only 17 (36.2%) patients underwent EUS to further evaluate the cysts and 4 of these 17 had FNA sampling of the cyst. Out of 47 patients, 4 underwent surgical removal of pancreatic lesions and all 4 pathology samples showed IPMN without malignancy.Table: Table. Baseline CharacteristicsTable: Table. IPMN characteristics and outcomesConclusion: Currently, management of IPMNs is based on consensus rather than strong evidence. This study preliminarily supports the evolution of management to conservatively observing these lesions. However, as with many published studies on IPMNs, this study has limitations such as advanced age, all male sample and multiple comorbidities preventing further invasive interventions. Because of this, our findings cannot be applied to the general population. Therefore we recommend further larger multicenter trials to establish the risk of IMPN's developing into pancreatic cancer, specifically in the aging population.

Abstract 3518: Brg1 plays a critical role in PanIN formation through regulating Sox9 expression

Abstract Background: Mutations of SWI/SNF chromatin remodeling complexes are one of the hallmarks of human pancreatic ductal adenocarcinoma (PDA). Brahma related gene 1 (Brg1) is a catalytic ATPase subunit of SWI/SNF complexes and Brg1 is silenced in about 10% of human PDA. Recent study revealed that Brg1 inhibits formation of intraductal pancreatic mucinous neoplasm (IPMN) and IPMN-derived PDA in the context of oncogenic Kras and that IPMNs originate from adult pancreatic ductal cells, demonstrating a tumor suppressive role of Brg1. However, the role of Brg1 in the formation of pancreatic intraepithelial neoplasia (PanIN) from acinar cells and PanIN-derived PDA is not fully understood. Aim: To investigate the functional role of Brg1 in the formation of PanIN Methods and Results: We generated Ptf1a-CreER; KrasG12D; Brg1f/f (KBC) mice, in which Brg1 is deleted exclusively in adult pancreatic acinar cells along with expression of oncogenic Kras upon tamoxifen induction of Cre activity and assessed spontaneous acinar-to-ductal metaplasia (ADM) and PanIN formation. We found that ADM and PanIN formation was significantly decreased in KBC mice compared with littermate controls. Next, we induced caerulein-acute pancreatitis to KBC mice and assessed for pancreatitis-induced tumorigenesis. We found that PanINs were decreased in KBC mice compared with littermate controls, although pancreatitis-induced ADMs were widely observed in KBC mice. Since Brg1 is known to critical regulator of p53, mutant p53 allele was crossed with KBC mice. Unexpectedly, even in the context of mutant p53, loss of Brg1 significantly deceased PanIN formation. These results suggest that Brg1 plays a tumor-supportive role in acinar cell-derived PanIN formation in various contexts. Primary acinar cell culture experiments revealed that ADM formation was markedly reduced in the absence of Brg1 and that Sox9 expression was downregulated in Brg1-depleted acinar cells. Furthermore, we confirmed that Sox9 expression is downregulated in Brg1-depleted ADMs/PanINs compared with Brg1-retained ADMs/PanINs by immunohistochemistry. To determine the functional relationship between Brg1 and Sox9, we generated Ptf1a-CreER; KrasG12D; Brg1f/f; Sox9OE mice, in which Sox9 is constitutively overexpressed. Remarkably, Sox9 overexpression canceled the phenotype of decrease in PanIN formation by Brg1 deletion. Furthermore, to investigate whether Brg1/Sox9 axis is observed in human PanIN-derived PDAs, we performed immunohistochemistry of Brg1 and Sox9 in human PanIN-derived PDAs. In 27 human PDAs, all of 5 PDAs with low Brg1 expression had low Sox9 expression. Conclusions: Our results suggest that Brg1 plays a critical role in acinar cell-derived PanIN formation in part through regulating Sox9 expression positively. Our data underscore a cell-type specific, context-dependent role of Brg1 in the initiation of PDA formation. Citation Format: Motoyuki Tsuda, Akihisa Fukuda, Satoshi Ogawa, Kenji Masuo, Norihiro Goto, Yukiko Hiramatsu, Yu Muta, Kozo Ikuta, Yoshito Kimura, Yoshihide Matsumoto, Yutaka Takada, Takuto Yoshioka, Takahisa Maruno, Haruhiko Akiyama, Kyoichi Takaori, Shinji Uemoto, Tsutomu Chiba, Hiroshi Seno. Brg1 plays a critical role in PanIN formation through regulating Sox9 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3518. doi:10.1158/1538-7445.AM2017-3518

Insights into the Pathogenesis of Pancreatic Cystic Neoplasms.

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.