Endoscopic Ultrasound-guided Fine-needle Aspiration Research Articles

The diagnostic utility of methylthioadenosine phosphorylase immunohistochemistry for pancreatic ductal adenocarcinoma in FNA and small biopsy specimens.

Accurate diagnosis of pancreatic lesions by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy can be challenging. Although surrogate immunohistochemical markers for genetic alterations associated with pancreatic ductal adenocarcinoma (PDAC) have been identified, they have modest sensitivity. Biallelic loss of CDKN2A occurs in up to 46% of PDACs, and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) has been identified as a reliable surrogate marker for this alteration. The current study evaluates the utility of MTAP IHC for the diagnosis of PDAC. In total, 136 cases of EUS-FNA cell block or core biopsy targeting solid pancreatic masses were identified. MTAP IHC was performed and evaluated for complete loss of expression in neoplastic cells. These results were correlated with available clinical next-generation sequencing that was performed on a subset of cases. Complete loss of MTAP expression was identified in 23 of 80 (29%) PDACs. A subset of cases classified as suspicious (4 of 21) and atypical (4 of 22) showed MTAP loss. All morphologically indeterminate cases with MTAP loss were confirmed as PDAC on resection/additional sampling. No benign samples (n=13) showed loss of MTAP. In samples that had available clinical next-generation sequencing data (n=13), copy number loss of CDKN2A was detected in all cases that had loss of MTAP expression (n=4). Loss of MTAP was identified in approximately 30% of PDAC small biopsy specimens. As loss of MTAP expression is not expected in nonneoplastic cells, and these findings suggest that MTAP IHC can support a diagnosis of PDAC in small biopsy samples.

Grading pancreatic adenocarcinomas on fine needle aspiration cytology. The outstanding issues.

The three-tier grading scheme described in "The Papanicolaou Society of Cytopathology (PSC) System for reporting Pancreaticobiliary Cytopathology" (TPSCRPBC) which remained unchanged following the WHO Reporting System for Pancreaticobiliary Cytopathology (WRPBC) was evaluated on pancreatic adenocarcinomas (PACs) reported on endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC). The Papanicolaou and May Grunwald Giemsa-stained smears from 116 cases of PACs were graded using the three-tier grading scheme laid down by TPSCRPBC/WRPBC. Cases exhibiting multiple grades were assigned primary, secondary and tertiary grades. Each case was assigned a grade score, either by adding the primary and secondary grades, by adding the primary and tertiary grades when the tertiary grade was 3 or by doubling the grade when only one grade existed. Necrosis was estimated semi-quantitatively. The inter-observer reproducibility in grading was evaluated using Kappa and Kendall's tau-c. Correlations between the various grades, the stage of the tumour and the amount of necrosis were assessed using Spearman rho and Kendall's tau-b. 31.89% of cases showed one grade, and 68.11% showed at least two grades. 16.38% showed three grades. The two commonest grade scores were 3 and 5. The inter-observer reproducibility for grading and grade scoring was satisfactory. A positive correlation was noted between the grades and the amount of necrosis. No significant correlation was found between the grades, grade scores and the stage of the tumours. The TPSCRPBC/WRPBC grading scheme can be suitably applied to PACs with good inter-observer reproducibility. Cases often show multiple grades in the same tumour.

Tissue processing of endoscopic ultrasound-guided fine-needle aspiration specimens from solid pancreatic lesions.

Now that tissue cores can be obtained using fine-needle biopsy (FNB) needles, the ways tissues are handled for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are changing. Direct smear, touch smear of core tissues, and centrifugation have been used for cytological examinations, and liquid-based cytology (LBC), which allows immunostaining and genetic tests that use residual samples, is emerging as an alternative. We emphasize that liquid cytology (Cytospin™ cytology and LBC) is still important, because it enables the diagnosis of pancreatic ductal adenocarcinoma (PDAC) when cancerous cells are scarce in specimens. Cell blocks are being replaced by core tissues obtained via FNB needles. Recent reports indicate that rapid on-site evaluation (ROSE) is not necessary when FNB needles are used, and macroscopic on-site evaluation is used to evaluate specimen adequacy. Macroscopic findings of specimens are helpful in the diagnostic workup and for clarifying specimen-handling methods. In addition to the red strings and white cores observed in PDAC, mixed red and white strings, gray tissues, and gelatinous tissues are observed. Gray (necrotic) tissues and gelatinous (mucus) tissues are more suitable than histology for cell block or cytological processing. Tumor cells in neuroendocrine tumors (NETs) are numerous in red strings but cannot be observed macroscopically. ROSE might thus be necessary for lesions that may be NETs. Core tissues can be used for genetic tests, such as those used for KRAS mutations and comprehensive genomic profiling. Cytological materials, including slides and LBC specimens, can also be genetic test materials.

Challenges of cytopathological pancreas diagnostics

The cytologic diagnostics of solid and cystic pancreatic lesions with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is an integral part of the clinical workup and the decision of asurgical versus aconservative approach. Cystic lesions are increasingly being diagnosed due to improved imaging and represent numerous neoplastic as well as non-neoplastic epithelial and non-epithelial entities, which differ in biological behavior and prognosis. In particular, the differentiation of mucinous and non-mucinous cysts is significant for further clinical management. Regressive cellular changes, gastrointestinal contaminants, and overlapping morphologic changes of reactively altered ductal epithelial cells and cells of well-differentiated neoplasms and preneoplasms are special challenges of cytological diagnostics. For auniform cytological classification of findings, an internationally developed seven-level classification system has been published and co-published by the World Health Organization (WHO). This classification system takes into account both morphological findings and further procedures on cytological material such as next-generation sequencing and immunocytochemistry and is based on the WHO classification for pancreatic tumors. Against this background, important cytologic diagnostic criteria of various solid and cystic lesions relevant in clinical practice are presented in this article, considering diagnostic possibilities and pitfalls as well as differential diagnoses.

Endoscopic ultrasound-guided fine-needle aspiration for pancreatic cystic lesions: a comprehensive review.

Advancements in diagnostic radiology have amplified the incorporation of these techniques into routine clinical practice. Concurrently, the frequency of incidentally identifying pancreatic cystic lesions (PCLs) has surged. PCLs encompass diverse categories contingent upon their origin. Among them, branch duct-intraductal papillary mucinous neoplasms (BD-IPMN) and mucinous cystic neoplasms (MCN) are categorized as mucinous cystic lesions that have malignant potential. Even solid neoplasms occasionally show cystic degeneration. Therefore, precise differential PCL diagnosis is crucial to optimize clinical management strategies and detect malignant transformations. Endoscopic ultrasound (EUS) affords comprehensive visualization of the pancreas with high-resolution ultrasound, complemented by fine-needle aspiration (FNA) under real-time EUS guidance, which is a minimally invasive procedure for obtaining pathological samples. This synergy has established EUS and EUS-FNA as vital procedures in the management of PCLs, enabling differentiation of PCLs. Cyst fluid analysis has played a pivotal role in deciding the optimal management strategy. The efficacy of cytological analysis is limited by scant cytologic material. The "string sign" test evaluates fluid viscosity, and its simplicity warrants initial consideration. Amylase and tumor markers, such as CEA, have been studied, but they yield varied sensitivity and specificity. Glucose and genetic mutations (KRAS, GNAS) exhibit promise, while comprehensive genomic profiling underscores genetic insights. Through-the-needle biopsy and needle-based confocal laser endomicroscopy also show high diagnostic yield. EUS-FNA, however, entails risks like infection and needle tract seeding, emphasizing the need for proper utilization. Pancreatic cyst fluid analysis augments diagnostic accuracy and informs clinical decisions, making it a valuable adjunct to imaging.

Diagnostic Value of Concurrent Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Fine-Needle Core Biopsy in Cytology Categories of Pancreatic Solid Lesions: An Institutional Experience

Abstract Introduction/Objective Endoscopic ultrasound is the current standard of care in the evaluation of pancreatic solid lesions. Two methods have been employed in obtaining EUS-guided pancreatic specimens; fine needle aspiration (EUS-FNA) and fine needle core biopsy (EUS-FNB). EUS-FNA may have certain limitations, including the inability to assess the histological architecture and a limited sample size for immunohistochemical staining on cell blocks. EUS- FNB, which employs a larger needle for core biopsy, was developed to address these limitations. However, it is still uncertain which method is better suited for specific lesions. In this study, we evaluated the diagnostic efficacy of concurrent EUS-FNA and EUS-FNB from pancreatic solid lesions. Methods/Case Report We reviewed our institutional database for cases that had EUS-FNA from pancreatic solid lesions with a subsequent definitive diagnosis on histology. Similarly, the concurrent EUS-FNB findings were recorded. The cases were categorized based on the World Health Organization pancreaticobiliary cytology reporting system. Furthermore, the absolute risk of malignancy (ARM) of each diagnostic category (defined as the presence of high-grade dysplasia or worse on the histologic follow-up) was calculated. Results (if a Case Study enter NA) A total of 108 cases were reviewed for the study from 1/1/2019 to 6/1/2022. The patients were 47% male and 53% female with an average age of 68. No case was categorized as non-diagnostic or neoplastic high-grade. There were 20 benign, 7 atypical, 3 neoplastic low-grade, 6 suspicious for malignancy, and 72 malignant cases, and the associated ARM related to each category was 40%, 86%, 33%, 33%, and 96% respectively. Concurrent EUS-FNB was performed in 23 cases in total (12 in malignant and 11 in other categories). EUS-FNB exhibited 95% positive and 100% negative predictive values (PPV and NPV) in all categories combined and 89% PPV and 100% NPV in non-malignant and indeterminate categories (categories II, III, IV, VI) for correlating to the histologic follow-up. Conclusion Cases diagnosed in all categories except the malignant category demonstrated ARM rates higher than expected. When approaching a solid pancreatic lesion, EUS-FNB may increase the diagnostic value, especially in cases of non-malignant and indeterminate categories. Moreover, categorizing the cases in the benign category may require additional supporting data, and placing them in the nondiagnostic category may be more appropriate warranting re-sampling if there is a clinical vs pathologic discrepancy.

Metastatic Mullerian adenocarcinoma involving the pancreas initially misdiagnosed as an intraductal papillary mucinous neoplasm (IPMN): A case report, and lessons learned

Abstract Introduction/Objective Metastases to the pancreas from Mullerian primaries are rare and can be confused with primary pancreatic malignancies. Methods/Case Report A 49-year-old woman presented with right lower abdominal pain. She denied any prior history of malignancy but had undergone hysterectomy and bilateral salpingo-oophorectomy for unknown reasons. CT scan revealed an 8.9 cm predominantly cystic mass in the pancreas, highly suspicious of an invasive mucinous neoplasm. EUS-guided FNA of the pancreas showed large, complex papillary fronds of mucinous epithelial cells in a background of abundant extracellular mucin, findings that were interpreted as an intraductal papillary mucinous neoplasm (IPMN) with foci of high-grade dysplasia and possible adenocarcinoma. A subsequent PET/CT scan demonstrated a 3.9 cm hepatic mass and a 3.8 cm perihepatic lesion. FNA of the liver was interpreted as metastatic pancreatic adenocarcinoma. Despite aggressive treatment, her disease progressed. Molecular profiling of her liver tumor demonstrated a pathogenic KRAS G12D mutation and a PDGFRA variant of uncertain significance. Genomic (DNA) and transcriptomic (RNA) analysis indicated a 96% probability that the patient had ovarian or fallopian tube adenocarcinoma and a 4% probability of uterine endometrial adenocarcinoma rather than metastatic pancreatic adenocarcinoma. A panel of immunocytochemical stains was performed on the pancreas and liver FNAs. The tumor cells were strongly positive for CK7, CK19, ER, and WT1, focally positive for PAX8 (nuclear) and P53 (wild-type), and negative for CK20, CDX2, and SATB2. Results (if a Case Study enter NA) NA Conclusion These findings corroborated the molecular analysis suggesting that the patient had metastatic Mullerian adenocarcinoma rather than metastatic pancreatic adenocarcinoma. Her oncologic treatment was adjusted accordingly.

Needle-tract seeding following endoscopic ultrasound-guided fine-needle aspiration using a 25G needle for pancreatic tail cancer.

Needle-tract seeding following endoscopic ultrasound-guided fine-needle aspiration using a 25G needle for pancreatic tail cancer.

Efficacy of Endoscopic Ultrasound-Guided Fine Needle Aspiration with and without Stylet and Suction for Cytopathological Diagnosis of Different Solid Lesions.

Efficacy of Endoscopic Ultrasound-Guided Fine Needle Aspiration with and without Stylet and Suction for Cytopathological Diagnosis of Different Solid Lesions.

New treatment for gastric duplication cyst: Endoscopic ultrasonography-guided fine-needle aspiration combined with lauromacrogol sclerotherapy: A case report

BACKGROUND Gastric duplication cysts are very rare disease that are mainly diagnosed by endoscopic ultrasonographic fine-needle aspiration biopsy. In the past, this disease was usually treated with traditional surgery and rarely with minimally invasive endoscopic surgery. However, minimally invasive endoscopic therapy has many advantages, such as no skin wound, organ preservation, postoperative pain reduction, early food intake, fewer postoperative complications, and shorter post-procedure hospitalization. CASE SUMMARY We report a case of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) combined with lauromacrogol sclerotherapy for pyloric obstruction due to gastric duplication cysts. CONCLUSION EUS-FNA combined with lauromacrogol sclerotherapy provides a new option for the treatment of gastrointestinal duplication cysts.

Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs)

BackgroundMain-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs. MethodsWe performed a retrospective study of 369 patients who underwent resections for MD- or MT-IPMN at two tertiary centers (2000–2019). Multivariable logistic regression analyses were performed for postoperative adverse events to compare the risks between intervention (ERCP, EUS-FNA with branch duct (BD) aspirated, EUS-FNA with MD aspirated from the duct directly or cyst/mass arising from MD) versus no-intervention group. Results33.1 % of patients had a preoperative ERCP and 69.4 % had EUS-FNA. Postoperative adverse events included: 30-day readmission (12.7 %), delayed gastric emptying (13.8 %), pancreatic fistula (10.3 %), abdominal abscess (5.7 %), cardiopulmonary adverse events (11.4 %), and mortality (1.4 %). The model was adjusted for potential confounders. There were no significant differences between the ERCP and no-ERCP groups for specific adverse events. Compared to no-EUS-FNA groups, groups of EUS-FNA with BD aspiration and EUS-FNA with MD aspiration from the main pancreatic duct directly or cyst/mass arising from MD did not show a significant increase in specific adverse events. ConclusionsPostoperative adverse events were not significantly increased among patients who had ERCP or EUS-FNA before surgical resection for MD- or MT-IPMNs. Endoscopic procedures directly sampling the MD can be safely pursued for diagnostic purposes in selected cases.

Usefulness of endoscopic ultrasound-guided fine needle aspiration of pancreatic ductal adenocarcinoma to obtain satisfactory samples for genetic study

Usefulness of endoscopic ultrasound-guided fine needle aspiration of pancreatic ductal adenocarcinoma to obtain satisfactory samples for genetic study

Scope position is a determining factor for diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration for mass lesions in the pancreatic head

Scope position is a determining factor for diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration for mass lesions in the pancreatic head

Comparison of FNA-based conventional cytology specimens and digital image analysis in assessment of pancreatic lesions.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is one of the most important diagnostic tools for investigation of suspected pancreatic masses, although the interpretation of the results is controversial. In recent decades, digital image analysis (DIA) has been considered in pathology. The aim of this study was to assess the DIA in the evaluation of EUS-FNA based cytopathological specimens of pancreatic masses and comparing it with conventional cytology analysis by pathologist. This study was performed using cytological slides related to EUS-FNA samples of pancreatic lesions. The digital images were prepared and then analyzed by ImageJ software. Factors such as perimeter, circularity, area, minimum, maximum, mean, median of gray value, and integrated chromatin density of cell nucleus were extracted by software ImageJ and sensitivity, specificity, and cutoff point were evaluated in the diagnosis of malignant and benign lesions. In this retrospective study, 115 cytology samples were examined. Each specimen was reviewed by a pathologist and 150 images were prepared from the benign and malignant lesions and then analyzed by ImageJ software and a cut point was established by SPSS 26. The cutoff points for perimeter, integrated density, and the sum of three factors of perimeter, integrated density, and circularity to differentiate between malignant and benign lesions were reported to be 204.56, 131953, and 24643077, respectively. At this cutting point, the accuracy of estimation is based on the factors of perimeter, integrated density, and the sum of the three factors of perimeter, integrated density, and circularity were 92%, 92%, and 94%, respectively. The results of this study showed that digital analysis of images has a high accuracy in diagnosing malignant and benign lesions in the cytology of EUS-FNA in patients with suspected pancreatic malignancy and by obtaining cutoff points by software output factors; digital imaging can be used to differentiate between benign and malignant pancreatic tumors.

S1221 The Diagnostic Outcomes of Endoscopic Ultrasound-Guided Fine Needle Aspiration vs Fine Needle Biopsy for Pancreatic Cystic Lesions

S1221 The Diagnostic Outcomes of Endoscopic Ultrasound-Guided Fine Needle Aspiration vs Fine Needle Biopsy for Pancreatic Cystic Lesions

S3385 Diagnosis of Littoral Cell Angioma of the Spleen With Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy

S3385 Diagnosis of Littoral Cell Angioma of the Spleen With Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy

S2043 Pancreatic Mesothelial Cyst Diagnosed via Endoscopic Ultrasound-Guided Fine Needle Aspiration and Through-The-Needle Biopsy

S2043 Pancreatic Mesothelial Cyst Diagnosed via Endoscopic Ultrasound-Guided Fine Needle Aspiration and Through-The-Needle Biopsy

S3396 Diagnosis of Recurrent Ewing Sarcoma With Endoscopic Ultrasound-Guided Fine Needle Aspiration of a Lung Mass: A Case Report

S3396 Diagnosis of Recurrent Ewing Sarcoma With Endoscopic Ultrasound-Guided Fine Needle Aspiration of a Lung Mass: A Case Report

B-343 Validation of Glucose Test in Pancreatic Cyst Fluid

Abstract Background Pancreatic cysts may be detected in 40 to 50 percent of patients who undergo abdominal magnetic resonance imaging for unrelated reasons. Mucinous cysts such as intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are known precursor lesions of pancreatic ductal adenocarcinoma. Therefore, it is imperative to identify mucinous cysts from nonmucinous cysts. In addition to cytology analysis, biomarker analysis in cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration can also provide information for the differential diagnosis of a mucinous cyst. Carcinoembryonic antigen (CEA) has been used as the biomarker to differentiate mucinous and nonmucinous pancreatic cysts with a sensitivity of around 63% and specificity of around 88%. Recently, glucose in pancreatic cyst fluid has been shown to have a better sensitivity (92%) and specificity (87%) in the differentiation of mucinous cysts using a threshold of <50 mg/dL. Therefore, it is consequential for clinical laboratories to validate glucose tests in pancreatic cyst fluid samples. In this study, we report the validation of the glucose test in pancreatic cyst fluid samples using the glucose assay on an automated chemistry analyzer. Methods The glucose assay, GLUC3, on Roche Cobas c702 analyzer was used to measure glucose in pancreatic cyst fluid samples. For linearity and recovery studies, cyst fluid samples were spiked with stock glucose solutions of known concentrations in a way that the spiked fluid samples always contained no less than 90% of the cyst fluid. Linearity was determined by assaying nine samples with glucose concentrations from 0–718 mg/dL. For the recovery study, various amounts of glucose were added to a cyst fluid sample containing undetectable glucose. The expected glucose concentrations in these samples are 23.2, 46.4, 92.7, and 159 mg/dL, respectively. Intra-run and inter-run precisions were determined by measuring glucose ten times in a run and in 10 separated runs, respectively, in 9 cyst fluid samples containing various amounts of glucose ranging from 0–718 mg/dL. The effect of hemoglobin was tested by spiking one cyst fluid sample with a hemolysate. Stability was determined by testing one sample at 0 and 24 h at room temperature, respectively. Results The assay was linear from 0–718 mg/dL of glucose with a slope of 1.05 and an intercept of 3.5. The recovery ranged from 103% to 111% in samples containing 23.2, 46.4, 92.7, and 159 mg/dL glucose, respectively. Both the intra-run and inter-run precisions for the nine samples with different glucose concentrations had a coefficient of variation of <5%. The samples were stable at room temperature for the study period of 24 h. No interference was observed at hemoglobin of 477 mg/dL. Conclusion Our study indicates that the glucose assay, GLUC3, on Roche Cobas c702 analyzer can be used to measure glucose in pancreatic cyst fluid samples. Our results show that glucose measurement in pancreatic cyst fluid had a good recovery and reproducible results with precision being <5%. This test may aid in the differential diagnosis of pancreatic mucinous cysts.

Predictors of malignant intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is the most common pancreatic cystic neoplasm with a tendency to malignancy,and the 5-year survival rate of patients with invasive IPMN is less than 40%. Therefore,early detection of malignant cases and surgical intervention will significantly improve patient outcomes. The clinical guidelines recommended risk factors for IPMN malignancy according to imaging characteristics,clinical manifestations and serum tumor markers,among which dilation of the main pancreatic duct≥10 mm,the presence of solid components or enhanced mural nodules,and obstructive jaundice were recognized as high-risk factors. However,clinical practice has shown that the risk factors recommended by the current guidelines are not highly accurate in predicting IPMN malignancy,and the main problem is that the guidelines are less specific and allow follow-up cases to undergo unnecessary surgical resection. In recent years,the development of new technologies and methods such as genomics,radiomics,and artificial intelligence has greatly promoted the research progress of IPMN. Endoscopic ultrasound-guided fine needle aspiration of cystic fluid combined with molecular detection such as DNA and RNA,as well as radiomics combined with machine learning modeling,have shown superiority in improving the prediction accuracy of malignant IPMN,and will become an important tool to assist the diagnosis and treatment of IPMN in the future.