Rare Pancreatic/Peripancreatic Cystic Lesions Can Be Accurately Characterized by EUS with Through-the-Needle Biopsy-A Unique Pictorial Essay with Clinical and Histopathological Correlations.

Due to their aspecific macroscopic appearance, uncommon pancreatic cystic lesions (PCLs) are often misdiagnosed as mucinous lesions and improperly resected. We aimed to evaluate the endoscopic ultrasound (EUS)-guided through-the-needle biopsy (TTNB) capacity of the preoperative diagnosis of uncommon PCLs. Overall, 136 patients with PCLs who underwent EUS-TTNB between 2016 and 2022 were retrospectively identified. Common histotypes (e.g., IPMN, serous cystadenoma, and mucinous cystadenoma) were excluded and 26 (19.1%) patients (15 female, mean age 52.9 ± 10.4) were analyzed. The EUS findings, adverse events (AEs), and TTNB outcomes in uncommon PCLs were evaluated. The cysts histotype was accurately diagnosed by TTNB in 24/26 (92.3%) cases (seven cystic neuroendocrine tumors, four squamoid cysts, three acinar cells cystadenomas, two lymphoepithelial cysts, two mucinous non-neoplastic cysts, two bronchogenic cysts, two cystic lymphangiomas, one solid-pseudopapillary neoplasm, and one schwannoma). In the remaining two cases, lymphangioma was eventually diagnosed after resection. Surgery was performed in 15/26 (57.7%) patients. The mean follow-up of non-surgical patients was 32.5 months. One severe acute case of pancreatitis (3.8%) that required surgery occurred after EUS-TTNB. Uncommon pancreatic/peripancreatic lesions represent the 19.1% of PCLs in our series, with mainly benign histotypes. TTNB demonstrated a high diagnostic performance with a low rate of AEs in this setting, representing a reliable tool with which to avoid useless surgery.

Challenges in diagnosis and treatment of multiple atypical parathyroid tumors in a patient with extrapyramidal symptoms: case report and literature review.

Background: Atypical parathyroid tumors (APTs) are rare entities. We report the case of a patient with multiple APT presenting with extrapyramidal symptoms and a delayed hypercalcemic crisis. Case Description: A 72-year-old man presented to a tertiary referral center's emergency room (ER) following two episodes of temporary loss of consciousness. He had a history of ideomotor sluggishness, lethargy, extrapyramidal symptoms and dysphagia, which started 6 months prior. Serum calcium levels at presentation were normal. Four days later the patient developed a rapidly evolving respiratory failure requiring orotracheal intubation, severe hypercalcemia (up to 19.8 mg/dL) and increased serum parathyroid hormone (PTH) (151 pmol/L). A neck ultrasound (US) showed two lesions posteroinferiorly to the right and left thyroid lobe. Since hypercalcemia proved to be refractory to medical therapy, the patient underwent urgent bilateral neck exploration with subtotal parathyroidectomy for suspect parathyroid carcinoma (PC). Histopathological examination showed three nodular lesions consistent with a diagnosis of APT in each excised parathyroid. Four months after surgery, the patient is alive and well with no signs of recurrence. Neurological follow-up visits documented the absence of extrapyramidal signs. Conclusions: Our patient showed an unusual presentation of primary hyperparathyroidism (PHPT) sustained by multiple concurrent APTs. A low suspicion threshold should be maintained to avoid delay in diagnosis. The present case adds to the body of literature on APTs, contributing to a greater understanding of this rare disease.

Endoscopic ultrasound fine-needle biopsy to assess DAXX/ATRX expression and alternative lengthening of telomeres status in non-functional pancreatic neuroendocrine tumors.

BACKGROUND/OBJECTIVES: Death domain-associated protein (DAXX) and/or α-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes mutations and alternative lengthening of telomeres (ALT) activation are associated with more aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PanNETs). We aimed to evaluate the reliability of such markers on endoscopic-ultrasound fine-needle biopsy (EUS-FNB) specimens. METHODS: Patients who underwent EUS-FNB and subsequent surgical resection for PanNETs between January 2017 and December 2019 were retrospectively identified. Immunohistochemistry (IHC) to evaluate DAXX/ATRX expression and fluorescence in situ hybridization (FISH) for ALT status were performed. Primary outcome was the concordance rate of markers expression between EUS-FNB and surgical specimens. Secondary aims were association between markers and lesion aggressiveness, their diagnostic performance in predicting aggressiveness, and agreement of preoperative and post-surgical Ki67-based grading. RESULTS: Forty-one NF-PanNETs (mean diameter 36.1 ± 26.5 mm) were included. Twenty-four showed features of lesion aggressiveness. Concordance of expressions of DAXX, ATRX, and ALT status between EUS-FNB and surgical specimens were 95.1% (κ = 0.828; p < 0.001), 92.7% (κ = 0.626; p < 0.001), and 100% (κ = 1; p < 0.001), respectively. DAXX/ATRX loss and ALT-positivity were significantly (p < 0.05) associated with metastatic lymphnodes and lymphovascular invasion. The combination of all tumor markers (DAXX/ATRX loss + ALT-positivity + grade 2) reached an accuracy of 73.2% (95%CI 57.1-85.8) in identifying aggressive lesions. Pre- and post-operative ki-67-based grading was concordant in 80.5% of cases (k = 0.573; p < 0.001). CONCLUSION: DAXX/ATRX expression and ALT status can be accurately evaluated in a preoperative setting on EUS-FNB samples, potentially improving the identification of patients with increased risk and poorer prognosis.

New digital confocal laser microscopy may boost real-time evaluation of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from solid pancreatic lesions: Data from an international multicenter study.

BACKGROUND: Pancreatic cancer is an aggressive malignancy and a leading cause of cancer death worldwide; its lethality is partly linked to the difficulty of early diagnosis. Modern devices for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) were recently developed to improve targeting and sampling of small lesions, but innovative technologies for microscopic assessment are still lacking. Ex vivo fluorescence confocal laser microscopy (FCM) is a new digital tool for real-time microscopic assessment of fresh unfixed biological specimens, avoiding conventional histological slide preparation and potentially being highly appealing for EUS-FNB specimens. METHODS: This study evaluated the possible role of FCM for immediate evaluation of pancreatic specimens from EUS-FNB. It involved comparison of the interobserver agreement between the new method and standard histological analysis during international multicenter sharing of digital images. Digital images from 25 cases of EUS-FNB obtained with real-time FCM technology and 25 paired digital whole-slide images from permanent conventional paraffin sections were observed by 10 pathologists from different Institutions in Europe, Japan, and the United States, in a blinded manner. The study evaluated 500 observations regarding adequacy, morphological clues, diagnostic categories, and final diagnosis. FINDINGS: Statistical analysis showed substantial equivalence in the interobserver agreement among pathologists using the two techniques. There was also good inter-test agreement in determining sample adequacy and when assigning a diagnostic category. Among morphological features, nuclear enlargement was the most reproducible clue, with very good inter-test agreement. INTERPRETATION: Findings in this study are from international multicenter digital sharing and are published here for the first time. Considering the advantages of FCM digital diagnostics in terms of reduced time and unaltered sample maintenance, the ex vivo confocal laser microscopy may effectively improve traditional EUS-FNB diagnostics, with significant implications for planning modern diagnostic workflow for pancreatic tumors. FUNDING: This study was not supported by any funding source.

"Pure" hepatoid tumors of the pancreas harboring CTNNB1 somatic mutations: a new entity among solid pseudopapillary neoplasms.

Hepatoid tumors (HTs) represent a rare group of neoplasms that are histologically similar to hepatocellular carcinoma but arise outside the liver. The current World Health Organization classification recognizes the hepatoid morphology of pancreatic tumors only as a possible variant of pancreatic ductal adenocarcinoma (PDAC). Here, we describe two cases of "pure" HT of the pancreas showing common features and characterized by indolent biological behavior. These tumors were roundish nodules with pushing borders, hyaline globules, and pure hepatoid histology; they were diffusely positive for ß-catenin and LEF1 on immunohistochemistry. At next-generation sequencing, both neoplasms harbored only one pathogenic somatic mutation that affected the CTNNB1 gene at exon 3 and showed a loss of heterozygosity on chromosomes 18 and 21. By integrating macroscopic and microscopic features, along with their molecular profiles, we advocate that such tumors represent a distinct entity from PDAC and should be considered a new variant of solid pseudopapillary neoplasms. The recognition of this new neoplastic category may have immediate implications not only for tumor taxonomy but also for clinical practice.

Limited Role of Hair Cortisol and Cortisone Measurement for Detecting Cortisol Autonomy in Patients With Adrenal Incidentalomas.

Several studies demonstrated the diagnostic accuracy of hair glucocorticoid measurement in patients with overt Cushing syndrome, but few data are available for patients with adrenal incidentaloma (AI) and cortisol autonomy. The aim of our study was to assess whether measurement of 5 corticosteroid hormones with the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method in the keratin matrix is useful to stratify patients with AI by the presence of autonomous cortisol secretion [ACS] (defined as serum cortisol after 1 mg dexamethasone suppression test (DST) > 138 nmol/l) or possible ACS [PACS] (defined as serum cortisol after 1 mg DST > 50 nmol/l but ≤138 nmol/l). We analysed data of 67 AI patients (32 with cortisol autonomy) and 81 healthy subjects. We did not find any significant statistical difference comparing hair cortisol, cortisone, and 20ß-dihydrocortisol concentrations between healthy controls and AI patients, while 6ß-hydroxycortisol and 11-deoxycortisol were undetectable. Moreover, no significant difference was found in hair cortisol, cortisone, and 20ß-dihydrocortisol levels of AI patients with or without cortisol autonomy. Finally, we did not find any correlation in patients with AI between hormonal concentrations in the keratin matrix and serum, salivary, and urinary cortisol levels, or with body mass index. In conclusion, our findings suggest that hair glucocorticoid measurement is not suitable as a diagnostic test for cortisol autonomy (ACS and PACS).

Dual-Tracer (68Ga-DOTATOC and 18F-FDG-)-PET/CT Scan and G1-G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Single-Center Retrospective Evaluation of 124 Nonmetastatic Resected Cases.

INTRODUCTION: The combined use of 68gallium (68Ga)-DOTA-peptides and 18fluorine-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans in the workup of pancreatic neuroendocrine tumors (PanNETs) is controversial. This study aimed at assessing both tracers' capability to identify tumors and to assess its association with pathological predictors of recurrence. METHODS: Prospectively collected, preoperative, dual-tracer PET/CT scan data of G1-G2, nonmetastatic, PanNETs that underwent surgery between January 2013 and October 2019 were retrospectively analyzed. RESULTS: The final cohort consisted of 124 cases. There was an approximately equal distribution of males and females (50.8%/49.2%) and G1 and G2 tumors (49.2%/50.8%). The disease was detected in 122 (98.4%) and 64 (51.6%) cases by 68Ga-DOTATOC and by 18F-FDG PET/CT scans, respectively, with a combined sensitivity of 99.2%. 18F-FDG-positive examinations found G2 tumors more often than G1 (59.4 vs. 40.6%; p = 0.036), and 18F-FDG-positive PanNETs were larger than negative ones (median tumor size 32 mm, interquartile range [IQR] 21 vs. 26 mm, IQR 20; p = 0.019). The median Ki67 for 18F-FDG-positive and -negative examinations was 3 (IQR 4) and 2 (IQR 4), respectively (p = 0.029). At least 1 pathological predictor of recurrence was present in 74.6% of 18F-FDG-positive cases (vs. 56.7%; p = 0.039), whereas this was not found when dichotomizing the PanNETs by their dimensions (≤/>20 mm). None of the 2 tracers predicted nodal metastasis. The receiver operating characteristic curve analysis showed that 18F-FDG uptake higher than 4.2 had a sensitivity of 49.2% and specificity of 73.3% for differentiating G1 from G2 (AUC = 0.624, p = 0.009). CONCLUSION: The complementary adoption of 68Ga-DOTATOC and 18F-FDG tracers may be valuable in the diagnostic workup of PanNETs despite not being a game-changer for the management of PanNETs ≤20 mm.

Bcl-10, trypsin and synaptophysin helps recognize acinar cell and mixed acinar neuroendocrine cell carcinoma of the pancreas on both preoperative cytological samples and needle biopsy specimens.

OBJECTIVE: Acinar cell carcinoma (ACC) of the pancreas are known to be rare and difficult to be recognize because they mimic other unrelated tumors (neuroendocrine, solid pseudopapillary) with different clinical behavior. Especially in the setting of inoperable patients, fine needle aspiration cytology (FNAC), core needle biopsy (FNAB) and immunocyto/histochemistry (ICC/IHC) play a crucial role in the differential diagnosis. The biological material available for ICC tests obtained by minimal invasive procedures is usually limited. Aim of the current study was to evaluate diagnostic panel based on a limited number of ICC markers for typing preoperatively ACC of the pancreas. METHODS: Of 1820 needle sampling procedures performed and related to pancreatic lesions, 21 cases were extracted with a confirmed diagnosis of ACC on histology. Of them,12 were pure ACC and 9 mixed acinar-neuroendocrine carcinoma (MANEC). Smears of ACC, MANEC and a control group composed of 34neuroendocrine, 7solid pseudopapillary, 50ductal and 4 adenosquamous carcinoma were assessed with an ICC panel made up of BCL10, trypsin, synaptophysin, chromograninA, ß-catenin. RESULTS: On cytology, BCL10 sensitivity and specificity for ACC was 100%. Trypsin correctly recognized 90% of the cases. Synaptophysin was helpful to correctly identify all the cases with a mixed neuroendocrine component. No significant cross-reaction was observed between BCL10 and trypsin in any of the control group case. CONCLUSIONS: BCL10 is a determinant marker for the diagnosis of acinar cell carcinoma and mixed acinar neuroendocrine cell carcinoma of the pancreas in a pre-operative citologic/histologic setting.

Case Report: Microangiopathic Hemolytic Anemia With Normal ADAMTS13 Activity.

Thrombotic microangiopathies (TMAs) include a heterogeneous group of diseases characterized by abnormalities in the vessel walls of arterioles and capillaries resulting in microvascular thrombosis that typically presents with a microangiopathic hemolytic anemia (MAHA) and severe thrombocytopenia. We describe here the case of an 82-year-old woman, who came to our attention for a clinical condition consistent with thrombotic microangiopathy. Even if initially highly suggestive for a thrombotic thrombocytopenic purpura (TTP), the elevated ADAMTS13 activity together with the alteration of the main coagulation parameters (D-dimer elevation, fibrinogen consumption, slightly prolonged prothrombin time), induced us to consider several other diseases in the differential diagnostic process. The case evolved toward a suspected overlapped secondary hemophagocytic syndrome, though the hyperferritinemia was finally interpreted within the frame of a cytokine storm. After a complex diagnostic workup, the clinical and biochemical parameters guided us toward the diagnosis of a cancer-related microangiopathic hemolytic anemia (CR-MAHA) secondary to a relapsing breast cancer with multiple metastatic localizations. Prednisone 1 mg/kg body weight was started, and several units of fresh frozen plasma were infused, obtaining a good control of the hemolysis. No specific oncological therapies were, however, possible, due to the older age and the critically compromised general condition of the patient; therefore, after clinical stabilization, the patient was discharged for treatment in a palliative care Hospital.

Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors.

BACKGROUND/OBJECTIVES: Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens. METHODS: Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed. RESULTS: Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482). CONCLUSION: Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.

SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease.

Mitochondrial acyl-coenzyme A species are emerging as important sources of protein modification and damage. Succinyl-CoA ligase (SCL) deficiency causes a mitochondrial encephalomyopathy of unknown pathomechanism. Here, we show that succinyl-CoA accumulates in cells derived from patients with recessive mutations in the tricarboxylic acid cycle (TCA) gene succinyl-CoA ligase subunit-ß (SUCLA2), causing global protein hyper-succinylation. Using mass spectrometry, we quantify nearly 1,000 protein succinylation sites on 366 proteins from patient-derived fibroblasts and myotubes. Interestingly, hyper-succinylated proteins are distributed across cellular compartments, and many are known targets of the (NAD+)-dependent desuccinylase SIRT5. To test the contribution of hyper-succinylation to disease progression, we develop a zebrafish model of the SCL deficiency and find that SIRT5 gain-of-function reduces global protein succinylation and improves survival. Thus, increased succinyl-CoA levels contribute to the pathology of SCL deficiency through post-translational modifications.

MondoA regulates gene expression in cholesterol biosynthesis-associated pathways required for zebrafish epiboly.

The glucose-sensing Mondo pathway regulates expression of metabolic genes in mammals. Here, we characterized its function in the zebrafish and revealed an unexpected role of this pathway in vertebrate embryonic development. We showed that knockdown of mondoa impaired the early morphogenetic movement of epiboly in zebrafish embryos and caused microtubule defects. Expression of genes in the terpenoid backbone and sterol biosynthesis pathways upstream of pregnenolone synthesis was coordinately downregulated in these embryos, including the most downregulated gene nsdhl. Loss of Nsdhl function likewise impaired epiboly, similar to MondoA loss of function. Both epiboly and microtubule defects were partially restored by pregnenolone treatment. Maternal-zygotic mutants of mondoa showed perturbed epiboly with low penetrance and compensatory changes in the expression of terpenoid/sterol/steroid metabolism genes. Collectively, our results show a novel role for MondoA in the regulation of early vertebrate development, connecting glucose, cholesterol and steroid hormone metabolism with early embryonic cell movements.

In most animals, a protein called MondoA closely monitors the amount of glucose in the body, as this type of sugar is the fuel required for many life processes. Glucose levels also act as a proxy for the availability of other important nutrients. Once MondoA has detected glucose molecules, it turns genetic programmes on and off depending on the needs of the cell. So far, these mechanisms have mainly been studied in adult cells. However, recent studies have shown that proteins that monitor nutrient availability, and their associated pathways, can control early development. MondoA had not been studied in this context before, so Weger et al. decided to investigate its role in embryonic development. The experiments used embryos from zebrafish, a small freshwater fish whose early development is easily monitored and manipulated in the laboratory. Inhibiting production of the MondoA protein in zebrafish embryos prevented them from maturing any further, stopping their development at an early key stage. This block was caused by defects in microtubules, the tubular molecules that act like a microscopic skeleton to provide structural support for cells and guide transport of cell components. In addition, the pathway involved in the production of cholesterol and cholesterol-based hormones was far less active in embryos lacking MondoA. Treating MondoA-deficient embryos with one of these hormones corrected the microtubule defects and let the embryos progress to more advanced stages of development. These results reveal that, during development, the glucose sensor MondoA also controls pathways involved in the creation of cholesterol and associated hormones. These new insights into the metabolic regulation of development could help to understand certain human conditions; for example, certain patients with defective cholesterol pathway genes also show developmental perturbations. In addition, the work highlights a biological link between cholesterol production and cellular responses to glucose, which Weger et al. hope could one day help to identify new cholesterol-lowering drugs.

Primary pancreatic lymphoma: Clinical presentation, diagnosis, treatment, and outcome.

Primary pancreatic lymphoma (PPL) is a rare disease representing 0.1% of malignant lymphomas, which lacks well-defined diagnostic and therapeutic protocols. OBJECTIVES: To describe PPL clinical, diagnostic and histological characteristics, together with therapy and outcome, in a relatively large series of patients. METHODS: The study includes 39 PPL patients, aged ≥15 years, observed from January 2005 to December 2018, in 8 Italian Institutions. RESULTS: The main symptoms were abdominal pain (58%) and jaundice (47%). Lactate dehydrogenase serum levels were elevated in 43% of patients. Histological specimens were mostly obtained by percutaneous (41%) or endoscopic (36%) biopsy, with diffuse large B-cell lymphoma being the most frequent (69%) histological diagnosis. Chemotherapy was administered alone in 65% of patients, with radiotherapy in 17%, or after surgery in 9%. The 2-year overall survival (OS) was 62%, the 2-year progression-free survival (PFS) 44%. Debulking surgery (with or without chemotherapy) was associated with a significant worse OS. Three (9.4%) of 32 high-grade patients experienced a central nervous system (CNS) relapse. CONCLUSIONS: PPL is rare, often high-grade, with symptoms and localization similar to other pancreatic malignancies. Biopsy should be the preferred diagnostic method. High-grade PPL should undergo CNS prophylaxis.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and grading of pancreatic neuroendocrine tumors: a retrospective analysis of 110 cases.

BACKGROUND: Data on the reliability of the Ki-67 index and grading calculations from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic neuroendocrine tumors (PanNETs) are controversial. We aimed to assess the accuracy of these data compared with histology. METHODS: Cytological analysis from EUS-FNA in patients with suspected PanNETs (n = 110) were compared with resection samples at a single institution. A minimum of 2000 cells were considered to be adequate for grading. Correlation and agreement between cytology and histology in grading and Ki-67 values, respectively, were investigated. Secondary outcomes included the diagnostic performance of EUS-FNA. RESULTS: EUS-FNA samples were adequate for PanNET diagnosis and PanNET grading in 98/110 (89.1 %) and 77/110 (70.0 %) patients, respectively; thus, 77 samples were adequate for comparing cytology vs. histology. There were 67 (62.0 %), 40 (36.4 %), and 1 (0.9 %) patients with a final diagnosis of G1, G2, and G3 tumors, respectively. EUS-FNA grading was concordant with surgical pathology in 81.8 % of patients; under- and overgrading occurred in 15.6 % and 2.6 %, respectively. The overall level of agreement for grading was moderate (Cohen's κ = 0.59, 95 % confidence interval [CI] 0.34 - 0.78). Spearman's rho for Ki-67 in tumors ≤ 20 mm and > 20 mm was strong and moderate, respectively (rho = 0.68, 95 %CI 0.47 - 0.83; rho = 0.59, 95 %CI 0.35 - 0.75). The Bland - Altman plot showed that the Ki-67 values were comparable and reproducible between the two measurements. CONCLUSIONS: Although they were not available for a significant number of patients, grading and Ki-67 values from cytology correlated with histology moderately to strongly.

Randomized trial comparing fork-tip and side-fenestrated needles for EUS-guided fine-needle biopsy of solid pancreatic lesions.

BACKGROUND AND AIMS: The aim of this study was to compare the performance of EUS-guided fine-needle biopsy using fork-tip or side-fenestrated needles in patients with solid pancreatic lesions. METHODS: A randomized controlled study was conducted in a single academic center on patients who underwent sampling with fork-tip or side-fenestrated 22-gauge or 25-gauge needles. Three passes were performed, each independently evaluated by a blinded pathologist and by endosonographers for macroscopic on-site evaluation (MOSE). The primary outcome was histologic yield; secondary aims were safety, diagnostic yield, sample quality, number of needle passes required to establish a diagnosis, and reliability of MOSE. RESULTS: One hundred ninety-two patients were enrolled. Both 22-gauge and 25-gauge fork-tip needles retrieved significantly higher rates of histologic samples than side-fenestrated needles (P < .013). Safety and diagnostic accuracy were comparable in the 2 arms, whereas sample quality (tissue integrity and blood contamination) was significantly better in the fork-tip group (P < .0001). The median number of diagnostic passes was lower using fork-tip needles (P = .054). The agreement between MOSE and pathologic evaluation was almost perfect in the fork-tip group and fair in the side-fenestrated group. CONCLUSIONS: Both needles showed equivalent safety and diagnostic accuracy. However, fork-tip needles provided a higher rate of extremely good-quality histologic samples and required fewer needle passes to reach a diagnosis. MOSE is a highly reliable tool when fork-tip needles are used compared with side-fenestrated needles. (Clinical trial registration number: NCT03622229.).

Is triple-positive serology for Epstein-Barr virus (VCA-IgG, VCA-IgM, EBNA-IgG) a specific feature of angioimmunoblastic T-cell lymphoma?

PURPOSE: We assessed the frequency of triple-positive serology (viral capsid antigen [VCA]-immunoglobulin G [IgG], VCA-immunoglobulin M, Epstein-Barr nuclear antigen-IgG) for Epstein-Barr virus (EBV) in a small number of patients with angioimmunoblastic T-cell lymphoma (AITL) at disease onset. METHODS: Nine patients with newly diagnosed AITL were retrospectively enrolled in the present study. For all of them, EBV serology data were available. RESULTS: Of 9 patients, 7 (77.7%) had a triple-positive serology (VCA-IgG, VCA-IgM, EBNA-IgG ) for EBV. These patients were characterized by bone marrow involvement, high incidence of thrombocytopenia, and poor prognosis according to Revised International Prognostic Index and Prognostic Index for Angioimmunoblastic T-cell Lymphoma scores. CONCLUSION: Assessment of both viremia and serology for EBV could be useful in patients with clinical and laboratory data suggesting lymphoma diagnosis; furthermore, although our data need to be validated in a larger cohort of patients, triple positivity for EBV serology might help to direct the diagnosis toward AITL.

Diagnostic concordance between whole slide imaging and conventional light microscopy in cytopathology: A systematic review.

Many studies have examined the diagnostic concordance of whole slide imaging (WSI) and light microscopy (LM) for surgical pathology. In cytopathology, WSI use has been more limited, mainly because of technical issues. The aim of this study was to review the literature and determine the overall diagnostic concordance of WSI and LM in cytopathology. A systematic search of PubMed, Scopus, and the Cochrane Library was performed, with data extracted from the included articles. A quality assessment of studies was performed with a modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. The primary outcome was concordance for the diagnoses rendered by WSI and LM as shown by the concordance rate with the original diagnosis, intra-observer and interobserver concordance with the κ coefficient, or a percentage. Secondary outcomes included the time taken to reach a diagnosis and the quality and perception of WSI. A descriptive survey was provided. Among 1867 publications, a total of 19 studies (1%) were included. Overall, the concordance between WSI and the original diagnosis was 84.1%, the intra-observer concordance between WSI and LM was 92.5% with a κ coefficient of 0.66, and the interobserver κ coefficient was 0.69. The time to reach a diagnosis was longer with WSI in all studies. The quality of WSI was good, but diagnostic confidence and cytologist preference were higher for LM. In conclusion, the concordance of WSI with LM is acceptable and in line with systematic reviews in surgical pathology. However, the time required for scanning and technical issues represent barriers to complete adoption. It is foreseeable that technical advances and rigorous validation study design will help to improve the diagnostic concordance of WSI with LM in cytopathology.

Systemic mastocytosis associated with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis: Report of three cases.

The association of systemic mastocytosis with another hematologic neoplasia of myeloid or lymphoid origin is recognized as an advanced subvariant of mastocytosis. Here, we report the association of indolent or smoldering systemic mastocytosis with three cases of myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis, a recently recognized disease characterized by SF3B1 mutations. The hierarchical pattern of KIT, SF3B1, JAK2, and additional mutations was studied in whole and fractionated subpopulations of peripheral blood cells and whole bone marrow. In two cases, we could demonstrate a multilineage D816V KIT mutation, involving all myeloid lineages in one patient and also the lymphoid series in the other. Two patients displaying both SF3B1 and V617F JAK2 mutations had a very poor prognosis. Another patient bearing SF3B1, but not V617F JAK2 mutation, had a favorable response to erythropoietin treatment and long survival.