Spindle Cell Lipoma Arising from the Supraglottis: A Case Report and Review of the Literature.

Lipomas are common benign mesenchymal neoplasms. Although 13% of lipomas are found in the head and neck, only 0.6% have been reported in the larynx. Of all lipomas, the spindle cell variant is the least common. In the present study, we report a case of supraglottic spindle cell lipoma and review the literature of laryngeal spindle cell lipoma. A 35-year-old male presented with dysphagia and dyspnea and was found to have bilateral supraglottic lesions causing airway obstruction. The masses were resected endoscopically. Final pathology demonstrated mature adipocytes and spindle cells, with immunohistochemical patterns supportive of spindle cell lipoma. Spindle cell lipomas have rarely been reported in the upper airway. To our knowledge, this is the youngest patient reported to date. These lipomas are uncommon benign neoplasms and should be distinguished from aggressive mesenchymal neoplasms such as liposarcoma variants to guide appropriate conservative but curative therapy.

PSMA Expression in the Neovasculature Associated With Rectal Adenocarcinoma: A Potential Stromal Target for Nuclear Theranostics.

We report the case of a 63-year-old man who underwent MRI and Ga-PSMA-11 PET/CT for biochemical recurrence localization after radical prostatectomy (serum PSA, 0.25 ng/mL) and describe the incidental discovery of a rectal adenocarcinoma. Immunohistochemical analysis showed PSMA staining in the tumor-associated neovasculature, but not in normal vasculature, or tumor cells. After surgical removal, he was treated with salvage radiotherapy to the postoperative prostate bed. This case example has several implications: the findings confirm the expression of PSMA in the tumor-associated neovasculature of a rectal cancer, nonprostate cancers' stroma may represent a potentially relevant target for nuclear theranostics.

Midline carcinoma expressing NUT in malignant effusion cytology.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare and aggressive subset of poorly differentiated squamous cell carcinoma that is defined by t(15,19) and typically presents in the midline structures of the head, neck, and mediastinum. We report two cases of NMC that presented uniquely with malignant pleural and pericardial effusions including one with cardiac tamponade at presentation. The first case is of a 25-year-old male patient who presented with progressive dyspnea associated with palpitations and dizziness on standing, found to have large bilateral pleural effusions. The second case is of a previously healthy 29-year-old male patient who presented with progressive dyspnea, cough with expectoration, and a large right lower neck mass of 3 months onset, and a large left pleural effusion and left lung infiltrate on imaging studies. Both cases showed malignant cells on cytology suggestive of poorly differentiated carcinoma. Subsequent histopathological and immunochemistry studies were consistent with the diagnosis of NMC. Both patients had a rapid decline in status and suffered comorbidities secondary to their carcinoma, inevitably leading to their death. It is important to consider NUT midline carcinomas can present in a variety of clinical scenarios, and it is important to consider in the differential diagnoses when evaluating malignant effusion cytology. Utilization of ancillary testing with a broad immunostain profile including NUT studies, as well as fluorescent in-situ hydridization (FISH) studies are helpful and necessary in making the appropriate diagnosis.

International telecytology: Current applications and future potential.

International telecytology can improve patient care by increasing access to regional and international expertise in cytopathology. The majority of international telecytology studies published to date have been based on static telepathology platforms. Overall concordance rates for these studies ranged from 71% to 93%. This is comparable to the concordance rates published for other studies comparing diagnoses made by digital still images to reference glass slides, which vary from 80% to 95%. Static telepathology systems are relatively cheap and easy to use, and have the potential to increase access to international experts in developing countries with limited resources. In contrast, resource-rich academic and private medical centers can use whole slide digital imaging (WSI) for telecytology consultation, though few studies have been published addressing this topic. International telepathology consultation services with digital whole slide image capabilities have been established at several academic medical centers including the University of Pittsburgh Medical Center (UPMC) and the University of California at Los Angeles (UCLA), through the UCLA Center for Telepathology and Digital Pathology. In a small series of 20 telecytology cases submitted to UCLA from 2014 to 2017 (10 gynecologic and 10 fine needle aspiration cases), a meaningful diagnosis was rendered for 100% of cases, with 100% concordance between the submitting institution, versus consultation diagnosis provided by UCLA. These limited results are promising, and in the future both WSI and static telecytology consultation may have a place serving clinical needs in different practice settings.

Evaluation of the SharkCore® needle for EUS-guided core biopsy of pancreatic neuroendocrine tumors.

BACKGROUND AND OBJECTIVES: EUS guided core biopsy was once rarely performed but is now entering mainstream practice. Neuroendocrine tumors often warrant core biopsy as sufficient tissue must be obtained to allow for special staining to ensure a correct diagnosis. Traditionally these lesions were sampled with FNA needles. We performed a retrospective pilot study to evaluate the clinical value and efficacy of the a new EUS core needle biopsy needle as compared to a standard EUS FNA needle in the evaluation of patients with known or suspected neuroendocrine tumors. METHODS: A retrospective analysis of the first 10 patients (between January 2015 and April 2016) to undergo EUS-FNA with the SharkCore® needle at the University of Utah School of Medicine/Huntsman Cancer Center with neuroendocrine tumors. Each case was retrospectively reviewed by a board certified cytopathologist (BLW) for the following cytologic parameters on the aspirate smears or touch/squash preparations: overall cellularity [1 (low) to 3 (high)], percentage of obtained cells that were lesional/representative (<25%, 26%-50%, and >50%), relative ease of interpretation [1 (difficult) to 3 (easy)]. Pathologic material and reporting records were also reviewed for each case to confirm the number of needle passes to achieve diagnostic adequacy, the presence or absence diagnostic material on H&E slide (from cell block, if prepared), whether a definitive diagnosis was able to be rendered, and the presence or absence of a true core/core fragments (within the cell block, if prepared). RESULTS: A total of 20 patients underwent EUS-FNA for suspected neuroendocrine lesions. Ten patients underwent either transgastric or transduodenal EUS-FNA with the 22 gauge SharkCore® needle. The comparison cohort of 10 patients underwent either transgastric or transduodenal EUS-FNA with the standard 22 gauge Echotip® needle. The SharkCore® needle required a fewer mean number of needle passes to obtain diagnostic adequacy than the Echotip® (P=0.0074). For cases with cell blocks, the SharkCore® needle produced diagnostic material in 100% of cases, whereas Echotip® produced diagnostic material in 60% of cases. There was no significant difference between specimen cellularity, percentage of lesional material, or ease of interpretation between the two needle types. CONCLUSION: Our pilot investigation targeting patients with known or suspected pancreatic NETs indicates that the SharkCore® needle shows promise in obtaining suitable tissue for ancillary testing that can allow for more definitive pathologic interpretations on EUS FNA specimens. Fewer passes were needed with the core needle when compared to a standard needle.

DISTRIBUTIONAL IMPLICATIONS OF A NATIONAL CO2 TAX IN THE U.S. ACROSS INCOME CLASSES AND REGIONS: A MULTI-MODEL OVERVIEW.

This paper presents a multi-model assessment of the distributional impacts of carbon pricing. A set of harmonized representative CO2 taxes and tax revenue recycling schemes is implemented in five large-scale economy-wide general equilibrium models. Recycling schemes include various combinations of uniform transfers to households and labor and capital income tax reductions. Particular focus is put on equity - the distribution of impacts across household incomes - and efficiency, evaluated in terms of household welfare. Despite important differences in the assumptions underlying the models, we find general agreement regarding the ranking of recycling schemes in terms of both efficiency and equity. All models identify a clear trade-off between efficient but regressive capital tax reductions and progressive but costly uniform transfers to households; all agree upon the inferiority of labor tax reductions in terms of welfare efficiency; and all agree that different combinations of capital tax reductions and household transfers can be used to balance efficiency and distributional concerns. A subset of the models go further and find that equity concerns, particularly regarding the impact of the tax on low income households, can be alleviated without sacrificing much of the double-dividend benefits offered by capital tax rebates. There is, however, less agreement regarding the progressivity of CO2 taxation net of revenue recycling. Regionally, the models agree that abatement and welfare impacts will vary considerably across regions of the U.S. and generally agree on their broad geographical distribution. There is, however, little agreement regarding the regions which would profit more from the various recycling schemes.

A Survey of the Prevalence and Impact of Reporting Guideline Endorsement in Pathology Journals.

OBJECTIVES: To determine the prevalence of reporting guideline endorsement in pathology journals and to estimate the impact of guideline endorsement. METHODS: We compared the quality of reporting in two sets of studies: (1) studies published in journals that explicitly mentioned a guideline vs studies published in journals that did not and (2) studies that cited a guideline vs studies that did not. The quality of reporting in prognostic biomarker studies was assessed using the REporting recommendations for tumor MARKer prognostic studies (REMARK) guideline. RESULTS: We found that six (10%) of the 59 leading pathology journals explicitly mention reporting guidelines in the instructions to authors. Only one journal required authors to submit a checklist. There was significant variation in the rate at which various REMARK items were reported (P < .001). Journal endorsement was associated with more complete reporting (P = .04). Studies that cited REMARK had greater adherence to the REMARK reporting guidelines than studies that did not (P = .02). CONCLUSIONS: The prevalence of guideline endorsement is relatively low in pathology journals, but guideline endorsement may improve the quality of reporting.

Is current irrigation sustainable in the United States? An integrated assessment of climate change impact on water resources and irrigated crop yields.

While climate change impacts on crop yields has been extensively studied, estimating the impact of water shortages on irrigated crop yields is challenging because the water resources management system is complex. To investigate this issue, we integrate a crop yield reduction module and a water resources model into the MIT Integrated Global System Modeling framework, an integrated assessment model linking a global economic model to an Earth system model. We assess the effects of climate and socioeconomic changes on water availability for irrigation in the U.S. as well as subsequent impacts on crop yields by 2050, while accounting for climate change projection uncertainty. We find that climate and socioeconomic changes will increase water shortages and strongly reduce irrigated yields for specific crops (i.e., cotton and forage), or in specific regions (i.e., the Southwest) where irrigation is not sustainable. Crop modeling studies that do not represent changes in irrigation availability can thus be misleading. Yet, since the most water-stressed basins represent a relatively small share of U.S. irrigated areas, the overall reduction in U.S. crop yields is small. The response of crop yields to climate change and water stress also suggests that some level of adaptation will be feasible, like relocating croplands to regions with sustainable irrigation or switching to less irrigation intensive crops. Finally, additional simulations show that greenhouse gas (GHG) mitigation can alleviate the effect of water stress on irrigated crop yields, enough to offset the reduced CO2 fertilization effect compared to an unconstrained GHG emission scenario.

HER2 immunohistochemical and fluorescence in situ hybridization discordances in invasive breast carcinoma with micropapillary features.

The 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) recommendations for HER2 testing contain a recommendation for pathologists with respect to invasive micropapillary carcinoma. The guidelines suggest that HER2 immunohistochemical staining that is intense but incomplete and would be considered 1+ may actually be HER2-amplified by fluorescence in situ hybridization. Thus, pathologists should consider reporting the immunohistochemistry as equivocal (2+) and employ an alternative testing methodology. This recommendation is based largely on one paper wherein the authors tested a series of 22 micropapillary carcinomas that were considered 1+ by immunohistochemistry and identified HER2 amplification in one case (5%). In order to assess for a possible discordance between HER2 immunohistochemistry and fluorescence in situ hybridization, we evaluated a series of invasive carcinomas with micropapillary features using both methodologies. As described by the WHO, invasive carcinomas with micropapillary features have small, hollow, or morula-like clusters of cells surrounded by clear stromal spaces. All cases had HER2 immunohistochemistry and fluorescence in situ hybridization performed, and for cases with equivocal fluorescence in situ hybridization results, an alternative Chromosome 17 probe (RAI1) was employed. All assays were scored according to the 2013 ASCO/CAP guidelines. Specifically for this study, immunohistochemistry was scored irrespective of the presence of micropapillary features. Overall, we identified HER2 amplification in 21 (47%) of the cases assayed, with the corresponding immunohistochemistry being 1+ (n=9), 2+ (n=11), and 3+ (n=1). The ASCO/CAP recommendation that this morphology may deviate from the typical staining pattern is highlighted, as we found that 43% of cases with micropapillary features and HER2 staining that would otherwise be scored as 1+ were HER2-amplified by fluorescence in situ hybridization. This study supports the ASCO/CAP recommendation that pathologists should consider reporting immunohistochemistry in this morphology as equivocal and perform reflex testing using in situ hybridization.

Liver function testing on the Abaxis Piccolo Xpress: Use in Ebola virus disease protocols.

BACKGROUND: Laboratories that choose a point-of-care approach for liver function testing in patients undergoing evaluation for Ebola virus disease (EVD) have few options to choose from. The primary objective of this study was to conduct a performance characterization of a Clinical Laboratory Improvement Amendments (CLIA)-waived liver function panel on the Abaxis Piccolo® Xpress chemistry analyzer. The secondary objectives were to evaluate multiple specimen types, characterize whole blood specimen stability, and validate disposable exact transfer pipettes. Our final objective was to assess instrument airflow from a biosafety perspective. METHODS: An instrument performance characterization, including precision, linearity, accuracy, reference interval verification, and specimen type evaluation was conducted using Liver Panel Plus reagent discs on the Piccolo® Xpress. RESULTS: All assays demonstrated acceptable linearity (slopes, 0.938-1.061; observed error, 0.8-6.3%). Assay precision was 0.0-3.6% (%CV; within-day studies) and 0.9-5.6% (between-day studies). Method comparison experiments (versus Roche cobas c502/c702 chemistry analyzers) showed excellent correlation for most assays, although a few notable differences were observed (Piccolo versus Roche): alkaline phosphatase, -18.6%; amylase, -29.0%; total bilirubin, +0.3mg/dl. Pre-programmed reference intervals were verified except for the alkaline phosphatase (male and female) and alanine aminotransferase (female), which had greater than 10% of results fall below the programmed ranges. Piccolo instrument results were largely consistent across specimen types tested (lithium-heparin whole blood, lithium-heparin plasma, and serum), although some statistical differences were observed for aspartate aminotransferase, gamma glutamyltransferase, and total protein. Whole blood time course studies demonstrated that some analytes (albumin, amylase, and total protein) showed remarkable stability, while others (such as aspartate aminotransferase) showed a slight trend toward decreased activity over time. Exact volume transfer pipettes provided an effective disposable option for disc loading. Finally, airflow studies suggested that, in the context of EVD protocols, instrument placement in a biosafety level (BSL) 2 cabinet or greater is justified. CONCLUSIONS: Given its analytical performance and ease of operation, the Piccolo Xpress was transferred to a BSL-2 cabinet in our BSL-3 suite for use in our hospital's diagnostic protocol for providing liver function testing in patients undergoing evaluation for EVD.

Severely depressed interleukin-17 production by human neonatal mononuclear cells.

BACKGROUND: The role of T-helper 17 cells (Th17) in neonatal host defense remains to be fully elucidated. Interleukin (IL)-17 plays an important role in the immune response to bacterial and fungal pathogens by promoting inflammation. METHODS: We examined neonatal production of IL-17 in mixed mononuclear cells (MMCs) isolated from umbilical cord blood for comparison with adult peripheral blood mononuclear cell controls. RESULTS: IL-17 production was profoundly diminished in MMCs isolated from cord blood when compared with MMCs from adult blood. This was associated with a marked reduction in the population of CCR6+ IL-17(+) T-cells in the neonatal cord blood. We also found diminished intracellular formation of IL-17, and diminished IL-17 responses to both group B streptococci (GBS) and Escherichia coli. Neonatal mononuclear cells were found to adequately phosphorylate signal transducer and activator of transcription 3, pY705, and pS727. We and others have reported markedly reduced interferon-γ production by neonate mononuclear cells exposed to GBS. Here, we correct that profound abnormality with added IL-17. CONCLUSION: Our results suggest that profound deficiency of IL-17 production associated with a marked decrease in Th17 cells likely contributes significantly to the increased susceptibility of human neonates to invasive bacterial and fungal infections.

Multiplex analysis of toll-like receptor-stimulated neonatal cytokine response.

BACKGROUND: The human neonate's increased susceptibility to bacterial infections is not completely understood. Toll-like receptors (TLRs) have been recognized as pattern-recognition receptors critical to the innate immune response. TLR function in neonates, however, remains incompletely defined. OBJECTIVE: To examine regulatory and proinflammatory cytokine responses to TLR-1-6 stimulation of cord blood compared to adult blood. METHODS: We stimulated cord blood with ligands for each of TLRs 1-6 and compared these responses to adult controls. The following TLR ligands were utilized: Pam3CSK4 (TLR-1 and 2), zymosan (TLR-2 and 6), poly I:C (TLR-3), LPS (TLR-4), and flagellin (TLR-5). Cytokine production was measured with an assay developed in-house utilizing multi-analyte technology. RESULTS: TLR-1-6 stimulation produced higher concentrations of proinflammatory cytokines (IL-1beta, IL-6, and IL-8) in cord blood compared to adult blood, with the exception of TLR-4-stimulated TNF-alpha production, which was significantly lower in cord blood (319 pg/ml) compared to adult blood (645 pg/ml; p = 0.027). In contrast, TLR-1-6 stimulation resulted in decreased concentrations of Th1 and Th2 cytokines in cord blood compared to adult blood, with significantly diminished production of IL-12 (TLRs 1/2, 2/6, 3 and 4), IL-13 (TLR-1-6), and IL-10 (TLR-4). CONCLUSION: Cord blood production of regulatory Th1 and Th2 cytokines following TLR stimulation is decreased compared to that of adult blood. In contrast, TLR-stimulated proinflammatory cytokine production was markedly higher in neonates than in adults, with the exception of TLR-4-induced TNF-alpha production. The human neonate's increased susceptibility to bacterial infections may be related to abnormal TLR responsiveness, with enhanced proinflammatory and decreased regulatory cytokine production.