Pancreatic cytopathology plays an important role in the diagnosis and management of patients with solid and cystic lesions of the pancreas.
To serve as a practical guide to pancreatic cytopathology for the practicing pathologist. Data Sources.-A comprehensive assessment of the medical literature was performed.
We review pancreatic cytopathology, with specific discussions of its role in patient management, specimen types and specimen processing, specific diagnostic criteria, and the use of ancillary testing and advanced techniques.
"Expressing these issues statistically, the reported sensitivity of EUS-FNA ranges from 78%-95% with specificity reported to be 75-100% [17,18,20-25]. Though the specificity of biliary brush cytology is high, the sensitivity can be low with ranges of 46% to 73% reported [10,16,26,27]. The sensitivity of EUS-FNA cytology decreases to 62% in chronic pancreatitis and to only 50% in cases of chronic pancreatitis with obstructive jaundice . "
[Show abstract][Hide abstract] ABSTRACT: Background
Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.
Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0–300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.
The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.
A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.
"PCFNA biopsy has a bigger specificity, and at lower frequency in comparison with taking brush swabs during the endoscopic retrograde cholangiopancreatography (ECPW). A brush biopsy is a kind of an examination which enables to identify a group of patients with lesions of dysplastic ductal epithelium like a pancreatic intraepithelial neoplasia (PaIN)s and IPMN), however differentiation between atypia/cytological dysplasia with a regeneration atypia is often very difficult   . "
[Show abstract][Hide abstract] ABSTRACT: The technological progress within the range of methods of pancreas imaging and their more common accessibility selects a group of patients requiring a microscopic diagnosis. Percutaneous fine needle aspiration biopsy under the control of ultrasonography (PCFNA/USG) is the method commonly used in determining the character of a focal pancreatic lesion. Aim of the Work. An assessment of the accessibility of PCFNA biopsy in the assessment of solid and cystic changes in a pancreas and the correlation of the results of imaging examination, cytological smear and concentration of a serous marker CA19-9. Material and Methodology. In our material we analysed 43 cases of tumors of the pancreas among the patients who were at the average age of 59 ± 10.4 (14 women, 28 men) diagnosed by PCFNA biopsy. Results. In a group we are 23 cases of cancer, 12 cases of inflammation and 7 cases of cellular atypia for which 2 cases of IPMN were included. The sensitivity of the method was 92.5% but specificity was 68%. In our opinion PCFNA/USG is a method of the comparable sensitivity and specificity with fine needle aspiration biopsy with EUS control and its efficiency depends to a considerable degree on experience and interdisciplinary collaboration.
Gastroenterology Research and Practice 12/2012; 2012:908963. DOI:10.1155/2012/908963 · 1.75 Impact Factor
"Pancreatic cancer is the 4th commonest cause of cancer-related death accounting for 33,000 deaths per year in the US , ,  and at least 6,000 deaths per year in the UK . Currently surgical resection remains the only treatment associated with the potential for cure . However, most patients have locally advanced or metastatic disease at presentation and are therefore not surgical candidates , ; the actual resection rate is less than 10% . "
[Show abstract][Hide abstract] ABSTRACT: MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated.
Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets.
Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change.
Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers.
PLoS ONE 02/2012; 7(2):e32068. DOI:10.1371/journal.pone.0032068 · 3.23 Impact Factor
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