scholarly journals Pre-Operative Imaging and Pathological Diagnosis of Localized High-Grade Pancreatic Intra-Epithelial Neoplasia without Invasive Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 945
Author(s):  
Ryota Sagami ◽  
Kentaro Yamao ◽  
Jun Nakahodo ◽  
Ryuki Minami ◽  
Masakatsu Tsurusaki ◽  
...  
Keyword(s):  
Pancreatic Duct ◽  
Invasive Carcinoma ◽  
Current Knowledge ◽  
Precancerous Lesions ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Ducts ◽  
High Grade ◽  
Cytologic Examination ◽  
Imaging Characteristics ◽  
Retention Cysts

Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.

scholarly journals A hypoechoic, tumor-like lesion in the pancreatic head and neck on endoscopic ultrasonography may be due to a high-grade pancreatic intraepithelial neoplasia/carcinoma in situ

2021 ◽  
pp. 50
Author(s):  
◽  
◽  
◽  
Keyword(s):  
Head And Neck ◽  
Pancreatic Duct ◽  
Carcinoma In Situ ◽  
Pancreatic Head ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
High Grade ◽  
Pancreatic Intraepithelial Neoplasia ◽  
Cytologic Examination

High-grade pancreatic intraepithelial neoplasia (HG PanIN)/carcinoma in situ (CIS) in the pancreatic body and tail can induce parenchymal atrophy through chronic inflammatory changes presenting as a Hypoechoic area on EUS (Hypocho) or focal pancreatic parenchymal atrophy (FPPA) on computed tomography (CT) and magnetic resonance imaging (MRI). We herein discussed two patients with a hypoechoic area in the pancreatic head and neck on EUS resembling pancreatic ductal adenocarcinoma (PDAC). The lesions consisted of dense fibrosis and fat infiltration with pancreatic parenchymal atrophy around the HG PanIN/CIS in the main pancreatic duct (MPD), which penetrated the lesion and showed mild stenosis and upstream dilation. CT and MRI were unable to visualize the lesions. A specimen was obtained from one lesion by fine-needle aspiration under EUS (EUS-FNA) guidance for histopathological and cytological analysis, but the tests returned negative for adenocarcinoma. However, serial pancreatic-juice aspiration cytologic examination (SPACE) revealed adenocarcinoma in both lesions, prompting surgical resection. Histopathological examination revealed non-invasive HG PanIN/CIS in the MPD surrounded by dense fibrosis and fat deposition in the area of parenchymal atrophy. The CIS was restricted to the area of parenchymal atrophy.These two cases are noteworthy in illustrating a hypoechoic area appearing on EUS as a tumor-like lesion resembling PDAC. EUS-FNA has recently been used histopathologically to diagnose a pancreatic lesion. However, in the present and similar cases, EUS-FNA can only reveal secondary changes due to CIS unless the pancreatic duct covered by the CIS is accidentally punctured. We should bear in mind that CIS can appear as a hypoechoic area resembling PDAC on EUS, and that SPACE is the best method for diagnosing CIS in such cases.

scholarly journals Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marta Cáceres ◽  
Rita Quesada ◽  
Mar Iglesias ◽  
Francisco X. Real ◽  
Maria Villamonte ◽  
...  
Keyword(s):  
Pancreatic Duct ◽  
Premalignant Lesions ◽  
Ductal Adenocarcinoma ◽  
High Grade ◽  
Histological Changes ◽  
Pancreatic Duct Ligation ◽  
Duct Ligation ◽  
Risk Patients ◽  
Flat Lesions ◽  
Over Time

Abstract Pancreatic duct ligation (PDL) in the murine model has been described as an exocrine pancreatic atrophy-inducing procedure. However, its influence has scarcely been described on premalignant lesions. This study describes the histological changes of premalignant lesions and the gene expression in a well-defined model of pancreatic ductal adenocarcinoma by PDL. Selective ligation of the splenic lobe of the pancreas was performed in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice (PDL-Kras mice). Three experimental groups were evaluated: PDL group, controls and shams. The presence and number of premalignant lesions (PanIN 1–3 and Atypical Flat Lesions—AFL) in proximal (PP) and distal (DP) pancreas were studied for each group over time. Microarray analysis was performed to find differentially expressed genes (DEG) between PP and PD. Clinical human specimens after pancreaticoduodenectomy with ductal occlusion were also evaluated. PDL-Kras mice showed an intense pattern of atrophy in DP which was shrunk to a minimal portion of tissue. Mice in control and sham groups had a 7 and 10-time increase respectively of risk of high-grade PanIN 2 and 3 and AFL in their DP than PDL-Kras mice. Furthermore, PDL-Kras mice had significantly less PanIN 1 and 2 and AFL lesions in DP compared to PP. We identified 38 DEGs comparing PP and PD. Among them, several mapped to protein secretion and digestion while others such as Nupr1 have been previously associated with PanIN and PDAC. PDL in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice induces a decrease in the presence of premalignant lesions in the ligated DP. This could be a potential line of research of interest in some cancerous risk patients.

scholarly journals Proposal for Endoscopic Ultrasonography Classification for Small Pancreatic Cancer

Diagnostics ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 15 ◽  
Author(s):  
Shuzo Terada ◽  
Masataka Kikuyama ◽  
Shinya Kawaguchi ◽  
Hideyuki Kanemoto ◽  
Yoshihiro Yokoi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Duct ◽  
Endoscopic Ultrasonography ◽  
Invasive Carcinoma ◽  
High Sensitivity ◽  
Needle Aspiration ◽  
Tumor Type ◽  
Cytologic Examination ◽  
Small Pancreatic Cancer ◽  
Invasive Carcinomas

Backgrounds: Endoscopic ultrasonography (EUS) is used to observe the stricture of the main pancreatic duct (MPD) and in diagnosing pancreatic cancer (PC). We investigate the findings on EUS by referring to the histopathological findings of resected specimens. Materials and Methods: Six patients with carcinoma in situ (CIS) and 30 patients with invasive carcinoma of 20 mm or less were included. The preoperative EUS findings were classified as follows. A1: Simple stricture type—no findings around the stricture; A2: Hypoecho stricture type—localized hypoechoic area without demarcation around the stricture; A3: Tumor stricture type—tumor on the stricture; B: Dilation type—the dilation of the pancreatic duct without a downstream stricture; C: Parenchymal tumor type—tumor located apart from the MPD. Results: Classes A1 and A2 consisted of 2 CISs, and 4 invasive carcinomas included two cases smaller than 5 mm in diameter. Most of the cancers classified as A3 or C were of invasive carcinoma larger than 5 mm in diameter. All cancers classified as B involved CIS. Serial pancreatic-juice aspiration cytologic examination (SPACE) was selected for all types of cases, with a sensitivity of 92.0%, while EUS-guided fine needle aspiration cytology (EUS-FNA) was only useful for invasive carcinoma, and its sensitivity was 66.7%. Conclusions: Stricture without a tumor could be a finding for invasive PC and pancreatic duct dilation without a downstream stricture could be a finding indicative of CIS. Carcinoma smaller than 5 mm in diameter could not be recognized by EUS. SPACE had a high sensitivity for diagnosing small PC.

scholarly journals Effectiveness of Focal Pancreatic Parenchymal Atrophy in Diagnosing High-Grade Pancreatic Intraepithelial Neoplasia/Carcinoma in Situ

2021 ◽  
Vol 9 (8) ◽  
Author(s):  
Masataka Kikuyama ◽  
Jun Nakahodo ◽  
Goro Honda ◽  
Shinichiro Horiguchi ◽  
Mizuka Suzuki ◽  
...  
Keyword(s):  
Carcinoma In Situ ◽  
Histopathological Examination ◽  
Imaging Finding ◽  
Early Stage ◽  
Pancreatic Head ◽  
Intraepithelial Neoplasia ◽  
Ductal Adenocarcinoma ◽  
High Grade ◽  
Cytologic Examination

To improve the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), the diagnosis of early-stage PDAC is essential. In particular, the diagnosis of high-grade intraepithelial pancreatic neoplasia/carcinoma in situ (HG-PanIN/CIS) is the best option. However, it is almost impossible to directly observe HG-PanIN/CIS. Thus, identifying a secondary imaging finding due to the disorder is important. Focal pancreatic parenchymal atrophy (FPPA) and hypoechoic area have been reported as preferred secondary signs. We studied 50 patients to clarify the effectiveness of FPPA in diagnosing HG-PanIN/CIS. Most patients had the opportunity to undergo further examination due to the presence of a cyst. Among the 50 patients, 23 (46%) had positive results for serial pancreatic-juice aspiration cytologic examination (SPACE), which has high sensitivity and specificity for diagnosing PADC; 20 of the 23 (87.0%) patients underwent surgery to resect the pancreatic part including the FPPA. Distal pancreatectomy and pancreatoduodenectomy were performed in 19 patients and one patient, respectively. In 13 of the 20 (65%) patients, histopathological examination revealed HG-PanIN/CIS in the pancreatic ductal epithelium of the resected specimens. FPPA could indicate HG-PanIN/CIS, but not satisfactorily. One of the factors for the unsatisfactory results might be the difficulty in identifying FPPA in the pancreatic head area. On the other hand, a pancreatic cyst, especially in the area of FPPA, could lead to the diagnosis of HG-PanIN/CIS. The size of the cyst does not affect the diagnosis of HG-PanIN/CIS.

High-Grade Pancreatic Intraepithelial Neoplasia in a Patient With Familial Adenomatous Polyposis

2005 ◽  
Vol 129 (11) ◽  
pp. 1398-1400 ◽  
Author(s):  
Chakshu Gupta ◽  
Paul F. Mazzara
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Precancerous Lesions ◽  
English Literature ◽  
Intraepithelial Neoplasia ◽  
Colorectal Adenomas ◽  
Pancreatic Ducts ◽  
High Grade ◽  
Adenomatous Polyposis ◽  
Pancreatic Intraepithelial Neoplasia ◽  
Increased Risk

Abstract Familial adenomatous polyposis (FAP) is caused by mutation of the adenomatous polyposis coli (APC) gene and is characterized by multiple colorectal adenomas and tumors of other organs and sites. A 58-year-old woman with FAP syndrome and previous total colectomy presented for routine follow-up examination. Abdominal ultrasound and subsequent endoscopic evaluation revealed ampullary and duodenal polyps, as well as inhomogeneity of the pancreatic head. A pancreaticoduodenectomy confirmed multiple duodenal adenomas. In addition, high-grade pancreatic intraepithelial neoplasia (PanIN-3) was found in the smaller pancreatic ducts. Pancreatic precancerous lesions have only rarely been described in FAP, including 2 pancreatic duct adenomas and 2 intraductal papillary mucinous neoplasms. A review of the world English literature revealed no reports of PanIN-3 in association with FAP. Further studies are required to determine if patients with FAP are at increased risk for pancreatic premalignant lesions.

scholarly journals A Serous Cystic Neoplasm of the Pancreas Coexisting with High-Grade Pancreatic Intraepithelial Neoplasia Mimicking an Intraepithelial Papillary Mucinous Neoplasm: A Case Report

2017 ◽  
Vol 10 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Aya Kawanishi ◽  
Kenichi Hirabayashi ◽  
Hirotaka Kono ◽  
Yumi Takanashi ◽  
Atsuko Hadano ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Pancreatic Duct ◽  
Intraductal Papillary Mucinous Neoplasm ◽  
Main Pancreatic Duct ◽  
Cystic Lesion ◽  
Cystic Neoplasm ◽  
Pancreatic Ducts ◽  
High Grade ◽  
Mucinous Neoplasm ◽  
Serous Cystic Neoplasm

Serous cystic neoplasms of the pancreas are rare exocrine pancreatic neoplasms, most of which are benign and do not communicate with the pancreatic duct. Pancreatic intraepithelial neoplasm (PanIN) is considered a precursor of ductal adenocarcinoma that is microscopically recognized in pancreatic ducts. A 67-year-old Japanese woman presented with a 10-mm multilocular cystic lesion at the pancreatic body. Magnetic resonance pancreatography showed stenosis of the main pancreatic duct at the pancreatic body and dilatation of the distal side of the main pancreatic duct. Furthermore, communication between the cystic lesion and the main pancreatic duct was suspected based on magnetic resonance pancreatography findings. Distal pancreatectomy was performed under the preoperative diagnosis of intraductal papillary mucinous neoplasm. Histologically, the cystic lesion was lined with a non-atypical cuboidal or flat epithelium with clear cytoplasm and was thus diagnosed as a serous cystic neoplasm. High-grade PanIN lesions with stromal fibrosis were observed at the main and branch pancreatic ducts. Histological examination revealed no communication between the serous cystic neoplasm and the pancreatic ducts. Immunohistochemically, the epithelium of the serous cystic neoplasm showed positive anti-von Hippel-Lindau antibody staining, whereas the epithelium of the PanIN showed negative staining. A serous cystic neoplasm coexisting with another pancreatic neoplasm is rare. When dilatation of the main or branch pancreatic ducts coexists with a serous cystic neoplasm, as in this case, the lesion clinically mimics an intraductal papillary mucinous neoplasm.

scholarly journals Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Camille Verocq ◽  
Marie-Lucie Racu ◽  
Dominique Bafort ◽  
Gloria Butorano ◽  
Luis Perez-Casanova Garcia ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Pancreatic Duct ◽  
Intraductal Papillary Mucinous Neoplasm ◽  
Invasive Carcinoma ◽  
Medullary Carcinoma ◽  
High Grade Dysplasia ◽  
Low Grade ◽  
High Grade ◽  
Mucinous Neoplasm ◽  
Gastric Type

Abstract Background Pancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations. Case presentation We report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy. Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body. Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate. Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test. Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations. The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression. Conclusions The present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.

scholarly journals Senolytic elimination of Cox2-expressing senescent cells inhibits the growth of premalignant pancreatic lesions

Gut ◽  
2021 ◽  
pp. gutjnl-2020-321112
Author(s):  
Dror Kolodkin-Gal ◽  
Lior Roitman ◽  
Yossi Ovadya ◽  
Narmen Azazmeh ◽  
Benjamin Assouline ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Precancerous Lesions ◽  
Intraepithelial Neoplasia ◽  
Preventive Therapy ◽  
Ductal Adenocarcinoma ◽  
Potential Contribution ◽  
Pancreatic Intraepithelial Neoplasia ◽  
Promoting Effect ◽  
Paracrine Effects ◽  
Bcl2 Family

ObjectiveCellular senescence limits tumourigenesis by blocking the proliferation of premalignant cells. Additionally, however, senescent cells can exert paracrine effects influencing tumour growth. Senescent cells are present in premalignant pancreatic intraepithelial neoplasia (PanIN) lesions, yet their effects on the disease are poorly characterised. It is currently unknown whether senolytic drugs, aimed at eliminating senescent cells from lesions, could be beneficial in blocking tumour development.DesignTo uncover the functions of senescent cells and their potential contribution to early pancreatic tumourigenesis, we isolated and characterised senescent cells from PanINs formed in a Kras-driven mouse model, and tested the consequences of their targeted elimination through senolytic treatment.ResultsWe found that senescent PanIN cells exert a tumour-promoting effect through expression of a proinflammatory signature that includes high Cox2 levels. Senolytic treatment with the Bcl2-family inhibitor ABT-737 eliminated Cox2-expressing senescent cells, and an intermittent short-duration treatment course dramatically reduced PanIN development and progression to pancreatic ductal adenocarcinoma.ConclusionsThese findings reveal that senescent PanIN cells support tumour growth and progression, and provide a first indication that elimination of senescent cells may be effective as preventive therapy for the progression of precancerous lesions.

scholarly journals Pancreatic Cancers with High Grade Tumor Budding Exhibit Hallmarks of Diminished Anti-Tumor Immunity

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1090
Author(s):  
Hassan Sadozai ◽  
Animesh Acharjee ◽  
Thomas Gruber ◽  
Beat Gloor ◽  
Eva Karamitopoulou
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Disease Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Budding ◽  
Ductal Adenocarcinoma ◽  
Low Grade ◽  
High Grade ◽  
Mesenchymal Transition

Tumor budding is associated with epithelial-mesenchymal transition and diminished survival in a number of cancer types including pancreatic ductal adenocarcinoma (PDAC). In this study, we dissect the immune landscapes of patients with high grade versus low grade tumor budding to determine the features associated with immune escape and disease progression in pancreatic cancer. We performed immunohistochemistry-based quantification of tumor-infiltrating leukocytes and tumor bud assessment in a cohort of n = 111 PDAC patients in a tissue microarray (TMA) format. Patients were divided based on the ITBCC categories of tumor budding as Low Grade (LG: categories 1 and 2) and High Grade (HG: category 3). Tumor budding numbers and tumor budding grade demonstrated a significant association with diminished overall survival (OS). HG cases exhibit notably reduced densities of stromal (S) and intratumoral (IT) T cells. HG cases also display lower M1 macrophages (S) and increased M2 macrophages (IT). These findings were validated using gene expression data from TCGA. A published tumor budding gene signature demonstrated a significant association with diminished survival in PDAC patients in TCGA. Immune-related gene expression revealed an immunosuppressive TME in PDAC cases with high expression of the budding signature. Our findings highlight a number of immune features that permit an improved understanding of disease progression and EMT in pancreatic cancer.

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