Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool

Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens. Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF) of commonly altered genes (BRAF, CDKN2A, CTNNB1, GNAS, RAS, PIK3CA, PTEN, SMAD4, TP53 and VHL) was evaluated for their ability to identify and grade mucinous PCL. Results: Cytology showed a diagnostic sensitivity of 43.5% for mucinous PCL due in part to the impact of non-diagnostic (28.8%) and negative (50.5%) specimens. Incorporating an algorithmic approach or molecular analysis markedly increased the accuracy of cytologic evaluation. Detection of mucinous PCL by molecular analysis was 93.3% based on the detection of KRAS and/or GNAS gene mutations (p = 0.0001). Additional genes provided a marginal improvement in sensitivity but were associated with cyst type (e.g. VHL) and grade (e.g. SMAD4). In the surgical cohort, molecular analysis and the proposed algorithm showed comparable sensitivity (88.9% vs. 100%). Conclusions: Incorporating somatic molecular analysis in the cytologic evaluation of EUS-FNA increases diagnostic accuracy for detection, classification and grading of PCL. This approach has the potential to improve patient management

The Role of Tim-3 Receptor in CD8+ T cells Cytotoxicity in Chronic HIV Infection

The Tim-3+ T cells in HIV infection are dysfunctional in proliferation or cytokine production. Here, we evaluated the effects of Tim-3 expression on the cytotoxicity of CD8+ T cells in HIV infection by examining 1) the ability of Tim-3+ CD8+ T cells to make perforin and 2) the direct ability of Tim-3+ CD8+ T cells to kill HIV infected CD4+ target cells. Tim-3+ CD8+ T cells maintained higher levels of perforin. However, these cells were defective in their ability to degranulate. Blocking the Tim-3 signalling pathway enhanced the cytotoxic capabilities of HIV specific CD8+ T cells by increasing: their degranulation capacity, their ability to release perforin, their ability to target activated granzyme B to HIV antigen expressing CD4+ T cells and their ability to suppress HIV infection of CD4+ T cells. Thus, the Tim-3 receptor can down-regulate the CD8+ T cell cytotoxicity through inhibition of degranulation and perforin/granzyme secretion.MAS

Crystal‐storing histiocytosis and associated marginal zone lymphoma with extensive plasmacytic differentiation

Key Clinical Message Crystal‐storing histiocytosis (CSH) is a non‐neoplastic histiocytic proliferation that results from the intra‐lysosomal accumulation of immunoglobulins as crystals. CSH is frequently associated with various B‐cell lymphomas or plasma cell neoplasms. CSH can potentially obscure underlying lymphoproliferative neoplasms. This association should always be considered and the tissue should be carefully evaluated

Central Odontogenic Fibroma of Mandible: A Case report

Background and Aims: Central odontogenic fibroma is a rare odontogenic neoplasm that originates from odontogenic ectomesenchyme. Most cases occur in the mandible and between the ages of 11 and 39 years. The neoplasm shows a definite female preponderance, with a ratio of 2.2:1 and has a very low recurrence rate. The aim of this article was to report a case of this rare lesion which was accidental found. Case Report: A 11-year-old female, during her orthodontic treatment and without any complain and any sign or symptoms, performed a panoramic image for assessing the permanent teeth buds. In the panoramic view a unilocular radiolucent lesion with well-defined and corticated borders in the right mandibular body region was evident. The lesion was treated with simple excision. Simple type of central odontogenic fibroma histopathologic features was observed in the microscopic view. Conclusion: Although the central odontogenic fibroma is a rare benign neoplasm, however, a careful evaluation of radiographic images is important for early detection of lesions because the patient may have no clinical symptoms such as swelling, pain and paresthesia

Rosai-Dorfman Disease of the Breast

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is a rare benign proliferative disorder of histiocytes that typically involves the lymph nodes and can also involve extranodal sites. Rosai-Dorfman disease confined to the breast is extremely rare, but important to recognize as it can mimic malignancy. We present the case of a 63-year-old woman who presented with a palpable breast lump that was highly suspicious for malignancy based on mammogram and ultrasound appearance. Biopsy revealed inflammatory tissue with lymphoplasmacytic and histiocytic predominance. The diagnosis of Rosai-Dorfman was made based on characteristic staining of histiocytes with S-100 and the presence of emperipolesis. Early recognition of this benign disease entity spared the patient further investigation and surgical intervention

Radical Subjectivism as the Epistemological Foundation of Novel Entrepreneurial Action

Explaining change has always been one of the greatest challenges in social sciences. With a particular focus on economic change, Schumpeter introduced novelty as the key to fundamental changes and subsequent economic development. Recognizing the corresponding epistemological foundations of a novel phenomenon is the starting point for understanding itself, its process, conditions, and prerequisites. Hence, in this paper, first we discuss the assumptions governing novelty and novel phenomena. Then, we compare the three major approaches used to explain entrepreneurial phenomena in the literature, namely neoclassic, neo-Austrian, and radical subjectivism, and we explain the appropriate novelty-based epistemological foundation of entrepreneurship. To better understand radical subjectivism, we discuss its five fundamental assumptions, namely “imaginative choice,” “plans based on past experiences and future expectations”, “heterogeneity and in equilibrium”, “the metaphor of the world as a kaleidoscope” and “the creation of order”. finally, the implications of these assumptions are set forth for future research on economics and entrepreneurship

MDS/MPN-Unclassifiable with t(X;17)(q28;q21) and KANSL1-MTCP1/CMC4 Fusion Gene

Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) is a poorly characterized entity among overlap myeloid syndromes. Recent studies have shown heterogeneous mutational profiles in this group being able to subclassify them into entities closely related to the more well-established disorders under the umbrella term of the MDS/MPN group. Recurrent cytogenetic alterations are, nonetheless, rare in MDS/MPN-U. Here, for the first time, we report a case of MDS/MPN-U with a t(X;17)(q28;q21) chromosomal rearrangement leading to the KANSL1-MTCP1 fusion gene

Deep Learning Accurately Quantifies Plasma Cell Percentages on CD138-Stained Bone Marrow Samples

The diagnosis of plasma cell neoplasms requires accurate, and ideally precise, percentages. This plasma cell percentage is often determined by visual estimation of CD138-stained bone marrow biopsies and clot sections. While not necessarily inaccurate, estimates are by definition imprecise. For this study, we hypothesized that deep learning can be used to improve precision. We trained a semantic segmentation-based convolutional neural network (CNN) using annotations of CD138+ and CD138- cells provided by one pathologist on small image patches of bone marrow and validated the CNN on an independent test set of image patches using annotations from two pathologists and a non-deep learning commercial software. On validation, we found that the intraclass correlation coefficients for plasma cell percentages between the CNN and pathologist #1, a non-deep learning commercial software and pathologist #1, and pathologists #1 and #2 were 0.975, 0.892, and 0.994, respectively. The overall results show that CNN labels were almost as accurate as pathologist labels at a cell-by-cell level. Once satisfied with performance, we scaled-up the CNN to evaluate whole slide images (WSIs), and deployed the system as a workflow friendly web application to measure plasma cell percentages using snapshots taken from microscope cameras

The effects of anatomical location and distance from dental implants on the quality and quantity of metal artifacts in cone beam computed tomography scans: a cross-sectional study

Abstract Background Artifacts in cone beam computed tomography (CBCT) images can cause disruptions in diagnosis and treatment. Multiple factors influence the artifacts, including the quality and technology of devices, positions, patient-related factors, device settings, and bone density. Besides, anatomical area and distance from the implant affect the artifacts. This study aimed to investigate the effects of anatomical location and distance from the implant on the quality and quantity of artifacts. Methods A total of 200 CBCT images of patients with titanium implants and prostheses in the anterior and posterior regions of the maxilla and mandible were evaluated in this study. Four areas were assessed for each implant in three apical, middle, and cervical regions with distances of 3 mm, 4 mm, and 5 mm from the implant. Besides, the impact of adjacent implants on the artifacts was investigated. An ANOVA test with post hoc Bonferroni correction was used to analyze variable differences between subgroups. Results The differences were statistically significant, except for the difference between the posterior areas of the upper and lower jaws. A comparison of different areas revealed that most artifacts were related to the anterior maxilla, followed by anterior mandibular regions. The results of covariance analysis indicated that region and location had independent effects on the amount of artifacts. Conclusions Artifacts are more frequent in the anterior region compared to the posterior site. They are also more frequent in the maxilla than the mandible and cervical areas close to the implant than the middle and apical regions