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Archives of Pathology & Laboratory... Mar 2022Although most pancreatic and bile duct neoplasms are solid, mucinous cystic neoplasms and intraductal neoplasms have been increasingly recognized even when clinically... (Review)
Review
CONTEXT.—
Although most pancreatic and bile duct neoplasms are solid, mucinous cystic neoplasms and intraductal neoplasms have been increasingly recognized even when clinically silent, thanks to the increased use of sensitive imaging techniques. Cystic and intraductal neoplasms of the pancreas are often resectable and curable and constitute about 5% of all pancreatic neoplasms. Owing to their preinvasive nature and different biology, recognition of these entities remains a major priority. Mucinous cystic neoplasms are histologically and clinically distinct from other cystic pancreatic neoplasms. Pancreatic intraductal neoplasms encompass 3 major entities: intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Intraductal papillary neoplasms of bile ducts are also preinvasive mass-forming neoplasms with both similarities and differences with their pancreatic counterparts. All of these pancreatobiliary neoplasms have diverse and distinctive clinicopathologic, genetic, and prognostic variations.
OBJECTIVE.—
To review the clinical, pathologic, and molecular features of mucinous cystic and intraductal neoplasms of the pancreatobiliary tract.
DATA SOURCES.—
Literature review, diagnostic manuals, and guidelines.
CONCLUSIONS.—
This review will briefly describe well-known clinical and pathologic features and will focus on selected recently described aspects of morphology, grading, classification, and genomic alterations of cystic and intraductal neoplasms of the pancreatobiliary tract.
Topics: Bile Duct Neoplasms; Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Prognosis
PubMed: 35192699
DOI: 10.5858/arpa.2021-0399-RA -
Cirugia Y Cirujanos 2023Pancreatic cancer is the seventh leading cause of death worldwide, with ductal adenocarcinoma as the most frequent neoplasm. Half of the patients who are diagnosed have... (Review)
Review
BACKGROUND
Pancreatic cancer is the seventh leading cause of death worldwide, with ductal adenocarcinoma as the most frequent neoplasm. Half of the patients who are diagnosed have metastases at the time of diagnosis.
OBJECTIVE
A review of the treatment of resectable pancreatic adenocarcinoma with oligometastatic disease was carried out in order to present an overview of the existing evidence.
METHOD
A bibliographic search was carried in PubMed/Medline, Clinical Key and Index Medicus vhith MESH terms, from the year 1993 to 2022.
RESULTS
Patients with liver or lung metastases due to pancreatic ductal adenocarcinoma who undergo surgery and chemotherapy have a longer survival in carefully selected patients.
CONCLUSIONS
The evidence regarding surgery in patients with pancreatic ductal adenocarcinoma and oligometastasis is limited and further randomized controlled trials are needed for both scenarios. As well as established criteria that help the selection of patients who can receive this type of treatment.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Carcinoma, Pancreatic Ductal; Lung Neoplasms
PubMed: 37084317
DOI: 10.24875/CIRU.22000364 -
World Journal of Gastroenterology Aug 2019the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic... (Review)
Review
the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.
Topics: Bile Duct Neoplasms; Biliary Tract; Biomarkers, Tumor; Carcinogenesis; Carcinoma in Situ; Carcinoma, Pancreatic Ductal; Cholangiocarcinoma; Disease Progression; Humans; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Stem Cells
PubMed: 31496617
DOI: 10.3748/wjg.v25.i31.4343 -
Pancreas Sep 2020Worldwide, approximately half a million people are diagnosed with pancreatic cancer every year, with mortality rates of more than 90%. T cells within pancreatic tumors... (Review)
Review
Worldwide, approximately half a million people are diagnosed with pancreatic cancer every year, with mortality rates of more than 90%. T cells within pancreatic tumors are generally infrequent and incapable of eliciting antitumor immunity. Thus, pancreatic cancer is considered an "immunologically cold" tumor. However, recent studies clearly show that when T-cell immunity in pancreatic cancer is sufficiently induced, T cells become effective weapons. This fact suggests that to improve pancreatic cancer patients' clinical outcomes, we need to unveil the complex immune biology of this disease. In this review, we discuss the elements of tumor immunogenicity in the specific context of pancreatic malignancy.
Topics: Antigen-Presenting Cells; Antigens, Neoplasm; Cytotoxicity, Immunologic; Humans; Lymph Nodes; Models, Immunological; Pancreatic Neoplasms; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Tumor Microenvironment
PubMed: 32833941
DOI: 10.1097/MPA.0000000000001621 -
Turk Patoloji Dergisi 2022Most pancreatic tumors are epithelial, and, among these, more than 90% are of ductal origin. However, a variety of mesenchymal tumors may involve the pancreas and may... (Review)
Review
OBJECTIVE
Most pancreatic tumors are epithelial, and, among these, more than 90% are of ductal origin. However, a variety of mesenchymal tumors may involve the pancreas and may manifest different clinicopathological characteristics. The literature on mesenchymal tumors in the pancreas is largely limited to individual case reports or analyses of small series, predominantly focusing on radiologic features.
MATERIAL AND METHOD
Authors' institutional and consultation databases were reviewed to identify the mesenchymal tumors involving the pancreas.
RESULTS
Forty cases were identified; twenty-five (63%) tumors were benign/borderline, and the remaining fifteen (37%) were malignant. Of the benign/borderline tumors; 9 were solitary fibrous tumors, 6 gastrointestinal stromal tumors (GISTs), 4 schwannomas, 2 desmoid type fibromatosis, 1 lymphangioma, 1 ganglioneuroma, 1 inflammatory myofibroblastic tumor, and 1 low grade mesenchymal neoplasm. Malignant tumors included 6 cases of leiomyosarcomas, 4 liposarcomas, 2 rhabdomyosarcomas, 1 epithelioid angiosarcoma, 1 malignant peripheral nerve sheet tumor, and 1 undifferentiated pleomorphic sarcoma. Four cases (multicystic schwannoma, desmoid fibromatosis, lymphangioma and inflammatory myofibroblastic tumor) were preoperatively misdiagnosed as a primary epithelial tumor of the pancreas.
CONCLUSION
Mesenchymal tumors rarely involve the pancreas. They are usually benign/borderline neoplasms but may be diagnostically challenging, especially clinically/radiologically, as they may form cystic and/or large lesions in the pancreas. Mesenchymal tumors should be considered in both the clinical/radiological and pathological differential diagnosis of pancreatic lesions.
Topics: Diagnosis, Differential; Humans; Neoplasms, Glandular and Epithelial; Pancreas; Pancreatic Neoplasms; Precancerous Conditions
PubMed: 35001360
DOI: 10.5146/tjpath.2022.01567 -
Modern Pathology : An Official Journal... Sep 2023Early detection and treatment of invasive carcinoma arising in association with intraductal papillary mucinous neoplasm (IPMN), which is biologically and...
Early detection and treatment of invasive carcinoma arising in association with intraductal papillary mucinous neoplasm (IPMN), which is biologically and (epi)genetically distinct from conventional pancreatic ductal adenocarcinoma, provide an opportunity to improve the prognosis of this lethal disease. Despite the successful application of programmed death (ligand) 1 (PD-[L]1)-blocking strategies in numerous cancers, the immune microenvironment of IPMN with associated invasive carcinoma remains elusive. Here, we investigated CD8 T cells, CD68 macrophages, PD-L1, and V-domain immunoglobulin suppressor of T-cell activation (VISTA) in 60 patients with IPMN with associated invasive carcinoma using immunohistochemistry, explored their correlations with clinicopathologic variables and prognosis, and compared them with those in 76 patients with IPMN without invasive carcinoma (60 low-grade and 16 high-grade lesions). Using antibodies against CD8, CD68, and VISTA, we evaluated tumor-infiltrating immune cells in 5 high-power fields (×400) and calculated the corresponding mean counts. PD-L1 with a combined positive score of ≥1 was regarded as positive, and VISTA expression on tumor cells (TCs) was deemed positive when ≥1% of TCs showed membranous/cytoplasmic staining. A reduction of CD8 T cells and an increase of macrophages were observed during carcinogenesis. Positive PD-L1 combined positive score and VISTA expression on TCs were 13% and 11% in the intraductal component of IPMN with associated invasive carcinoma, 15% and 12% in the associated invasive carcinoma, and 6% and 4% in IPMN without an invasive carcinoma, respectively. Interestingly, the PD-L1 positivity rate was the highest in a subset of associated invasive carcinomas (predominantly gastric-type-derived) and was associated with higher counts of CD8 T cells, macrophages, and VISTA immune cells. Accumulation of VISTA immune cells was observed in the intraductal component of IPMN with associated invasive carcinoma compared with that of low-grade IPMN, whereas in intestinal-type IPMN with associated invasive carcinoma, the number of these cells decreased during the transition from the intraductal component to the associated invasive carcinoma. Survival analysis revealed that a higher number of macrophages predicted poorer prognosis. In conclusion, our results might help in individualized immunotherapeutic strategies for these patients.
Topics: Humans; B7-H1 Antigen; CD8-Positive T-Lymphocytes; Pancreatic Intraductal Neoplasms; Adenocarcinoma, Mucinous; Pancreatic Neoplasms; Pancreas; Carcinoma, Pancreatic Ductal; Neoplasm Invasiveness; Tumor Microenvironment
PubMed: 37244388
DOI: 10.1016/j.modpat.2023.100223 -
Clinical Cancer Research : An Official... Apr 2023Intraductal papillary mucinous neoplasm (IPMN) is a precursor of pancreatic ductal adenocarcinoma. Low-grade dysplasia has a relatively good prognosis, whereas...
PURPOSE
Intraductal papillary mucinous neoplasm (IPMN) is a precursor of pancreatic ductal adenocarcinoma. Low-grade dysplasia has a relatively good prognosis, whereas high-grade dysplasia and IPMN invasive carcinoma require surgical intervention. However, diagnostic distinction is difficult. We aimed to identify biomarkers in peripheral blood for accurate discrimination.
EXPERIMENTAL DESIGN
Sera were obtained from 302 patients with IPMNs and 88 healthy donors. For protein biomarkers, serum samples were analyzed on microarrays made of 2,977 antibodies. A support vector machine (SVM) algorithm was applied to define classifiers, which were validated on a separate sample set. For microRNA biomarkers, a PCR-based screen was performed for discovery. Biomarker candidates confirmed by quantitative PCR were used to train SVM classifiers, followed by validation in a different sample set. Finally, a combined SVM classifier was established entirely independent of the earlier analyses, again using different samples for training and validation.
RESULTS
Panels of 26 proteins or seven microRNAs could distinguish high- and low-risk IPMN with an AUC value of 95% and 94%, respectively. Upon combination, a panel of five proteins and three miRNAs yielded an AUC of 97%. These values were much better than those obtained in the same patient cohort by using the guideline criteria for discrimination. In addition, accurate discrimination was achieved between other patient subgroups.
CONCLUSIONS
Protein and microRNA biomarkers in blood allow precise diagnosis and risk stratification of IPMN cases, which should improve patient management and thus the prognosis of IPMN patients. See related commentary by Löhr and Pantel, p. 1387.
Topics: Humans; Pancreatic Intraductal Neoplasms; Adenocarcinoma, Mucinous; Pancreatic Neoplasms; Pancreas; Carcinoma, Pancreatic Ductal; MicroRNAs; Biomarkers; Hyperplasia; Risk Assessment
PubMed: 36516200
DOI: 10.1158/1078-0432.CCR-22-2531 -
Medicina (Kaunas, Lithuania) Jan 2023: The aim of the study was to analyze the prevalence and characteristics of pancreatic cystic tumors (PCTs). : A retrospective analysis of the medical records of 124... (Observational Study)
Observational Study
: The aim of the study was to analyze the prevalence and characteristics of pancreatic cystic tumors (PCTs). : A retrospective analysis of the medical records of 124 patients, 102 (69%) women and 46 (31%) men, who had undergone surgery for pancreatic cystic tumors in 2014-2018. Among 148 pancreatic cysts, 24 (16%) were non-neoplasmatic and 124 (84%) were neoplasmatic. The neoplasmatic cysts ( = 124) were included in our analysis. There were five main types of PCTs: IPMN (intraductal papillary mucinous neoplasm) ( = 45), MCN (mucinous cystic neoplasm) ( = 30), SCN (serous cystic neoplasm) ( = 28), SPN (solid pseudopapillary neoplasm) ( = 8), and CPEN (cystic pancreatic endocrine neoplasm) ( = 8), as well as mixed-type tumors ( = 5). A statistically significant dependency between PCT type and age was proven (= 0.0001): IPMNs were observed in the older group of patients with an average age of 66.12 (40-79) years while SPNs were noted in the youngest group of patients with an average age of 36.22 (22-55) years. A statistically significant association between PCT type and gender ( = 0.0001) was found: IPMNs occurred among 24 (53.33%) men and 21 (46.6%) women. In the MCN and SPN groups, all patients were female (100%). Among the SCN group, the majority were women (27 (96.43%)), and there was only 1 (3.57%) man. A statistically significant dependency between PCT type and size was proven ( = 0.0007). The mean size of IPMNs was the smallest 2.95 (0.6-10 cm) and the mean size of MCNs was the largest 6.78 (1.5-19 cm). A statistically significant dependency between PCT type and tumor location was proven ( = 0.000238). The most frequent location of IPMN was the pancreatic head: 27 (60%). MCN was most frequently located in the pancreatic tail (18 (60%)). Most (10/28) SCNs were found in the pancreatic tail (10 (35.71%)). CPENs were most frequently located in the pancreatic tail (three (37.5%)) and pancreatic body and tail (three (37.5%)). SPNs were located commonly in the pancreatic head (five (62.5%)). The type of surgery depended on the tumor location. The most frequent surgery for IPMNs was pancreatoduodenectomy (44.4%), while for MCNs and SCNs, it was distal pancreatectomy (81%). The postoperative morbidity and mortality were 34.68% and 1.61%, respectively. Postoperative pancreatic fistula (POPF) was the most frequent (29%) complication. : IPMN was the most frequent resected PCT in our material. A statistically significant association between the type of cyst and location within the pancreas, size, local lymph node involvement, and patient's age and sex was proved. POPF was the most frequent postoperative complication. In patients with PCTs, due to substantial postoperative morbidity, adequate patient selection, considering both the surgical risk as well as the long-term risk of malignant transformation, is very important during qualification for surgery.
Topics: Humans; Female; Male; Aged; Adult; Retrospective Studies; Pancreatic Intraductal Neoplasms; Pancreas; Neoplasms, Cystic, Mucinous, and Serous; Pancreatic Neoplasms
PubMed: 36837443
DOI: 10.3390/medicina59020241 -
Pathology Oncology Research : POR Apr 2020The solid-pseudopapillary neoplasm of the pancreas is a rare but enigmatic entity occurring mainly in young women. Since the first description by V. Frantz in 1959 the... (Review)
Review
The solid-pseudopapillary neoplasm of the pancreas is a rare but enigmatic entity occurring mainly in young women. Since the first description by V. Frantz in 1959 the terminology of this tumor has continuously changed but it has remained simply descriptive, because the exact histogenesis is still obscure. Although in majority of cases the survival is excellent, nevertheless, the expected prognosis is not exactly predictable. In this review the authors aim to summarize its clinico-pathological features, the expected biological behavior, the molecular alterations, the immune phenotype and discuss the putative histogenesis. From diagnostic point of view, the salient histological characteristic findings are analyzed that would help to differentiate it from other, look-alike pancreatic tumors, and suggestions are made about the desirable content of the histological report.
Topics: Humans; Neoplasms, Cystic, Mucinous, and Serous; Pancreatic Neoplasms
PubMed: 31209654
DOI: 10.1007/s12253-019-00671-8 -
Signal Transduction and Targeted Therapy Oct 2023Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is...
Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.
Topics: Humans; Pancreatic Cyst; Cyst Fluid; Proteomics; Pancreatic Neoplasms; Glycoproteins; Neoplasms, Cystic, Mucinous, and Serous
PubMed: 37848412
DOI: 10.1038/s41392-023-01645-8