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Archives of Pathology & Laboratory... Mar 2022Pancreatic cystic lesions are increasingly diagnosed. Among other criteria, they are often distinguished in mucinous versus nonmucinous cysts. Mucinous pancreatic cystic...
CONTEXT.—
Pancreatic cystic lesions are increasingly diagnosed. Among other criteria, they are often distinguished in mucinous versus nonmucinous cysts. Mucinous pancreatic cystic lesions have received increasing attention, especially those known as precursors of pancreatic ductal adenocarcinoma. However, the group of nonmucinous cystic lesions of the pancreas includes numerous entities that may pose a diagnostic challenge. Their accurate diagnosis and classification are crucial for adequate patient management.
OBJECTIVE.—
To review the spectrum of nonmucinous cystic lesions of the pancreas, taking into consideration their epidemiology and typical clinical context, their characteristic gross morphology and histomorphology, as well as their immunohistochemical and molecular profile.
DATA SOURCES.—
Literature was searched and reviewed with MEDLINE via PubMed. Macroscopic and microscopic images were obtained from the archives of the Institute of Pathology, Heinrich Heine University and University Hospital of Duesseldorf, Germany.
CONCLUSIONS.—
Nonmucinous cysts of the pancreas comprise numerous, mostly rare entities displaying different biological behaviors. The most frequent are serous cystic neoplasms, solid-pseudopapillary neoplasms, cystic neuroendocrine tumors, and pancreatitis-associated pseudocysts. Accurate diagnosis can be achieved if characteristic clinical context, histomorphology, and immunoprofile are taken into account.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Cyst; Pancreatic Ducts; Pancreatic Neoplasms
PubMed: 33503226
DOI: 10.5858/arpa.2020-0446-RA -
Journal of the American College of... Jan 2020Direct-to-consumer BRCA testing will increase BRCA diagnoses and subsequent abdominal imaging. It is unclear whether BRCA carriers are at higher risk of developing...
BACKGROUND
Direct-to-consumer BRCA testing will increase BRCA diagnoses and subsequent abdominal imaging. It is unclear whether BRCA carriers are at higher risk of developing pancreatic cysts (PCs) or cyst-associated pancreatic ductal adenocarcinoma (PDAC). We investigated the prevalence of PCs in BRCA-tested patients, and whether BRCA-carriers have higher rates of PDAC when PCs are found.
STUDY DESIGN
This is a retrospective cross-sectional study of patients with BRCA testing and abdominal imaging between 1996 and 2018. Pancreatic cysts were identified on original imaging reports. Prevalence and risk characteristics of PCs, as well as incidence of PDAC, were compared between BRCA+, BRCA-, and BRCA-untested patients.
RESULTS
Pancreatic cysts were identified in 4,045 patients among 128,164 unique patients with abdominal imaging, including 33 patients with PCs in 1,113 BRCA-tested patients. There was no difference in PC prevalence between BRCA+, BRCA-, and untested patients (3.6%, 2.6%, 3.2%, respectively; p = 0.64). Pancreatic cysts were diagnosed in BRCA+ patients at a younger age (57.1 vs 65.3 years, p < 0.001); however, there was no difference in risk stratification compared with BRCA- or untested patients by consensus criteria. Across the population of imaged patients, patients with PCs had significantly higher rates of PDAC compared with those without PCs (18.2% vs 2.4%, p < 0.001). Incidence of cyst-associated PDAC was similar in BRCA+ and BRCA- patients (13.3% vs 22.2%, p = 0.84).
CONCLUSIONS
BRCA+ patients have similar rates of PCs, high-risk features in their cysts, and PDAC as BRCA- and untested patients. BRCA+ patients likely do not require dedicated abdominal imaging to evaluate for PCs and should follow management guidelines similar to those as the untested general population if an incidental PC is identified.
Topics: Abdomen; Adult; Aged; Carcinoma, Pancreatic Ductal; Cross-Sectional Studies; Female; Genes, BRCA1; Genes, BRCA2; Humans; Male; Middle Aged; Mutation; Pancreatic Cyst; Pancreatic Neoplasms; Retrospective Studies; Risk Assessment
PubMed: 31672679
DOI: 10.1016/j.jamcollsurg.2019.09.019 -
Archives of Pathology & Laboratory... Mar 2020Histopathologic diagnosis of adenocarcinoma of the prostate is based on light-microscopic examination of hematoxylin-eosin-stained tissue sections. Multiple factors,... (Review)
Review
CONTEXT.—
Histopathologic diagnosis of adenocarcinoma of the prostate is based on light-microscopic examination of hematoxylin-eosin-stained tissue sections. Multiple factors, including preanalytic and analytic elements, affect the ability of the pathologist to accurately diagnose prostatic adenocarcinoma. False-negative diagnosis, that is, failure to diagnose prostatic adenocarcinoma, may have serious clinical consequences. It is important to delineate and understand those factors that may affect and cause histopathologic false-negative diagnoses of prostatic adenocarcinoma.
OBJECTIVES.—
To review common factors involved in histopathologic underdiagnosis of prostatic adenocarcinoma, including the following: (1) tissue processing and sectioning artifacts, (2) minimal adenocarcinoma, (3) deceptively benign appearing variants of acinar adenocarcinoma, (4) single cell adenocarcinoma, and (5) treatment effects.
DATA SOURCES.—
Data sources included published, peer-reviewed literature and personal experiences of the senior author.
CONCLUSIONS.—
Knowledge of the reasons for histopathologic false-negative diagnosis of adenocarcinoma of the prostate is an important component in the diagnostic assessment of prostate tissue sections. Diagnostic awareness of the histomorphologic presentations of small (minimal) adenocarcinoma; deceptively benign appearing variants including atrophic, foamy gland, microcystic, and pseudohyperplastic variants; single cell carcinoma; and treatment effects is critical for establishment of a definitive diagnosis of adenocarcinoma and the prevention of false-negative diagnoses of prostate cancer.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cytodiagnosis; Diagnosis, Differential; False Negative Reactions; Humans; Male; Pancreatic Cyst; Prostatic Neoplasms; Sensitivity and Specificity
PubMed: 31729886
DOI: 10.5858/arpa.2019-0456-RA -
Current Gastroenterology Reports Apr 2019Pancreatic cystic lesions represent a growing public health dilemma, particularly as our population ages and cross-sectional imaging becomes more sensitive. Mucinous... (Review)
Review
PURPOSE OF REVIEW
Pancreatic cystic lesions represent a growing public health dilemma, particularly as our population ages and cross-sectional imaging becomes more sensitive. Mucinous cysts carry a clinically significant risk of developing pancreatic cancer, which carries an extremely poor prognosis. Determining which cysts will develop cancer may be challenging, and surgical resection of the pancreas carries significant morbidity. The goal of this paper is to review the rationale for cyst ablation and discuss prior and current research on cyst ablation techniques and efficacy. Indications, contraindications, and factors related to optimal patient selection are outlined.
RECENT FINDINGS
Endoscopic ultrasound-guided chemoablation of pancreatic cysts has been performed in neoplastic cysts, with varying levels of efficacy. Safety concerns arose due to the risk of pancreatitis in alcohol-based treatments; however, the most recent data using a non-alcohol chemoablation cocktail suggests that ablation is effective without the need for alcohol, resulting in a significantly more favorable adverse event profile. Endoscopic ultrasound-guided chemoablation of neoplastic pancreatic cysts is a promising, minimally invasive approach for treatment of cysts, with recent significant advances in safety and efficacy, suggesting that it should play a role in the treatment algorithm.
Topics: Ablation Techniques; Antineoplastic Agents; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Endosonography; Humans; Pancreatic Cyst; Pancreatic Neoplasms; Ultrasonography, Interventional
PubMed: 31016391
DOI: 10.1007/s11894-019-0686-5 -
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 -
Clinical and Translational... Apr 2019Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer...
OBJECTIVES
Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration.
METHODS
Pathology of 80 resected pancreatic cysts was reviewed. Expression of COX-2, cPLA2, and AKT was quantified by tissue immunohistochemistry immunoreactivity scores (IRSs). IRS values were compared between cyst types and (in 30 cases) with matched cyst fluid PGE2 concentrations.
RESULTS
The mean IRS was higher in the epithelium of mucinous vs nonmucinous cysts for COX-2 (6.1 ± 4.7 vs 3.2 ± 2.8, P = 0.01) and cPLA2 (6.9 ± 3.0 vs 2.9 ± 2.9, P < 0.001). Cyst epithelial COX-2 expression was higher in mucinous cysts with low-grade dysplasia vs those with high-grade dysplasia or invasive carcinoma (IRS 8.0 ± 3.9 vs 1.5 ± 2.9, P < 0.001), whereas the opposite was found for cPLA2 (6.2 ± 3.0 vs 8.6 ± 2.3, P = 0.005). Cyst fluid PGE2 concentrations did not correlate with either the IRS or a history of low- to moderate-dose ASA use.
CONCLUSIONS
COX-2 and cPLA2 are overexpressed in the epithelium of mucinous pancreatic cysts. COX-2 and/or cPLA2 inhibition might prevent the emergence or progression of mucinous pancreatic cysts, but higher doses of ASA or nonsteroidal anti-inflammatory drugs may be necessary to substantially inhibit cyst epithelial COX-2 activity.
Topics: Adult; Aged; Aged, 80 and over; Aspirin; Carcinoma, Pancreatic Ductal; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Cyst Fluid; Dinoprostone; Epithelium; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Phospholipases A2, Cytosolic; Proto-Oncogene Proteins c-akt; Retrospective Studies; Young Adult
PubMed: 31009406
DOI: 10.14309/ctg.0000000000000028 -
Birth Defects Research. Part C, Embryo... Jun 2014Primary cilia and their anchoring basal bodies are important regulators of a growing list of signaling pathways. Consequently, dysfunction in proteins associated with... (Review)
Review
Primary cilia and their anchoring basal bodies are important regulators of a growing list of signaling pathways. Consequently, dysfunction in proteins associated with these structures results in perturbation of the development and function of a spectrum of tissue and cell types. Here, we review the role of cilia in mediating the development and function of the pancreas. We focus on ciliary regulation of major pathways involved in pancreatic development, including Shh, Wnt, TGF-β, Notch, and fibroblast growth factor. We also discuss pancreatic phenotypes associated with ciliary dysfunction, including pancreatic cysts and defects in glucose homeostasis, and explore the potential role of cilia in such defects.
Topics: Animals; Cilia; Disease Models, Animal; Glucose Metabolism Disorders; Humans; Organogenesis; Pancreas; Pancreatic Cyst; Phenotype; Signal Transduction
PubMed: 24864023
DOI: 10.1002/bdrc.21063 -
Journal of Gastrointestinal and Liver... Jun 2011An increased number of pancreatic cysts are being diagnosed due to the increased usage of cross-sectional imaging. Endoscopic ultrasound (EUS)-guided fine needle... (Review)
Review
An increased number of pancreatic cysts are being diagnosed due to the increased usage of cross-sectional imaging. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology and molecular analysis of these cystic lesions have led to their better detection and characterization. The aim of this review is to assess the value of cyst fluid analysis for the differential diagnosis of pancreatic cystic lesions, in view of the recent progresses of molecular analysis methods. Pancreatic cysts can be either simple (retention) cysts, pseudocysts and cystic neoplasms, while these are further subdivided into serous cystadenomas, mucinous cystic neoplasms (MCNs) or intraductal papillary mucinous neoplasms (IPMNs). EUS is now being used to investigate cystic pancreatic lesions, particularly by means of EUS guided cyst aspiration and sampling of the cyst wall or septa, as well as mural nodules. Cyst fluid can be further studied after aspiration in order to analyze cytology, viscosity, extracellular mucin, other tumor markers (CEA, CA 19-9,CA 15-3, Ca 72-4, etc.), enzymes (amylase, lipase), as well as DNA analysis of DNA quality/content or mutational analysis to study allelic imbalance/LOH (loss of heterozygosity) and K-ras mutations. After careful review of the published studies, a conclusion was reached that the use of tumor and molecular markers in conjunction with multimodality detection methods such as CT, MR and EUS-FNA allows risk stratification, while being also cost-effective.
Topics: Cyst Fluid; Diagnosis, Differential; Humans; Pancreatic Cyst
PubMed: 21725515
DOI: No ID Found -
World Journal of Gastroenterology Jul 2019Carcinoembryonic antigen (CEA) and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms. Genetic testing and microforceps... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Carcinoembryonic antigen (CEA) and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms. Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.
AIM
To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.
METHODS
We performed a literature search in Medline, Scopus, and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts, with endoscopic ultrasound with fine-needle aspiration (EUS-FNA) prior to surgery and surgical pathology as reference standard for diagnosis. We evaluated the diagnostic accuracy for: 1- benign cysts; 2- mucinous low-risk cysts; 3- high-risk cysts, and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis. We also assessed publication bias, heterogeneity, and study quality.
RESULTS
Eight studies, including 1206 patients, of which 203 (17%) referred for surgery who met the inclusion criteria were analyzed in the systematic review, and seven studies were included in the meta-analysis. Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts. Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts, with sensitivities of 0.89 (95%CI: 0.79-0.95) and 0.57 (95%CI: 0.42-0.71), specificities of 0.88 (95%CI: 0.75-0.95) and 0.88 (95%CI: 0.80-0.93) and AUC of 0.9555 and 0.92, respectively. The diagnostic yield was higher in microforceps biopsies than in genetic analysis (0.73 0.54, respectively) but the rates of correctly identified cysts were identical (0.73 with 95%CI: 0.62-0.82 0.71 with 95%CI: 0.49-0.86, respectively).
CONCLUSION
Genetic testing and microforceps biopsies are useful second tests, with identical results in benign pancreatic cysts. Genetic analysis performs better for low- and high-risk cysts but has lower diagnostic yield.
Topics: Cyst Fluid; Diagnosis, Differential; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Genetic Testing; Humans; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Preoperative Period; Sensitivity and Specificity
PubMed: 31341368
DOI: 10.3748/wjg.v25.i26.3450 -
Gastroenterology Mar 2022To successfully implement imaging-based pancreatic cancer (PC) surveillance, understanding the timeline and morphologic features of neoplastic progression is key. We...
BACKGROUND & AIMS
To successfully implement imaging-based pancreatic cancer (PC) surveillance, understanding the timeline and morphologic features of neoplastic progression is key. We aimed to investigate the progression to neoplasia from serial prediagnostic pancreatic imaging tests in high-risk individuals and identify factors associated with successful early detection.
METHODS
We retrospectively examined the development of pancreatic abnormalities in high-risk individuals who were diagnosed with PC or underwent pancreatic surgery, or both, in 16 international surveillance programs.
RESULTS
Of 2552 high-risk individuals under surveillance, 28 (1%) developed neoplastic progression to PC or high-grade dysplasia during a median follow-up of 29 months after baseline (interquartile range [IQR], 40 months). Of these, 13 of 28 (46%) presented with a new lesion (median size, 15 mm; range 7-57 mm), a median of 11 months (IQR, 8; range 3-17 months) after a prior examination, by which time 10 of 13 (77%) had progressed beyond the pancreas. The remaining 15 of 28 (54%) had neoplastic progression in a previously detected lesion (12 originally cystic, 2 indeterminate, 1 solid), and 11 (73%) had PC progressed beyond the pancreas. The 12 patients with cysts had been monitored for 21 months (IQR, 15 months) and had a median growth of 5 mm/y (IQR, 8 mm/y). Successful early detection (as high-grade dysplasia or PC confined to the pancreas) was associated with resection of cystic lesions (vs solid or indeterminate lesions (odds ratio, 5.388; 95% confidence interval, 1.525-19.029) and small lesions (odds ratio, 0.890/mm; 95% confidence interval 0.812-0.976/mm).
CONCLUSIONS
In nearly half of high-risk individuals developing high-grade dysplasia or PC, no prior lesions are detected by imaging, yet they present at an advanced stage. Progression can occur before the next scheduled annual examination. More sensitive diagnostic tools or a different management strategy for rapidly growing cysts are needed.
Topics: Adult; Aged; Aged, 80 and over; Disease Progression; Early Detection of Cancer; Endosonography; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Metastasis; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Precancerous Conditions; Retrospective Studies; Risk Factors; Time Factors; Tomography, X-Ray Computed; Tumor Burden; Watchful Waiting
PubMed: 34678218
DOI: 10.1053/j.gastro.2021.10.014