Primary Thyroid Gland Alveolar Soft Part Sarcoma

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor of unknown histogenesis generally characterized by the der(17)t(X;17)(p11.2;q25) translocation which results in the ASPSCR1-TFE3 gene fusion. Primary ASPS of the thyroid gland has not yet been reported. During oncology follow-up for breast cancer, a pulmonary nodule and thyroid gland mass were identified in a 71-year-old Korean male. Thyroid ultrasound showed a 5.7 cm left thyroid gland mass. After several fine needle aspirations, a thyroid gland lobectomy was performed after documenting only non-caseating granulomatous inflammation in a biopsy of the lung nodule. A 7.6 cm bulging nodular thyroid gland mass was identified, showing significant destructive invasion. Alveolar nests of large polygonal, eosinophilic, granular neoplastic cells were separated by vascularized stroma. Colloid was absent. Tumor necrosis and increased mitoses were identified. The neoplastic cells were positive with TFE3 and CD68, but negative with pancytokeratin, thyroglobulin, TTF-1, napsin-A, calcitonin, PAX8, CAIX, S100 protein, HMB45, SMA, and desmin. FISH confirmed a TFE3 gene rearrangement. The differential includes several primary thyroid gland epithelial neoplasms, paraganglioma, PEComa, melanoma, crystal storage disease, and metastatic carcinomas, especially Xp11 translocation renal cell carcinoma. The patient has refused additional therapy, but is alive without tumor identified (primary or metastatic)

Machine learning methods for automated classification of tumors with papillary thyroid carcinoma-like nuclei : A quantitative analysis

When approaching thyroid gland tumor classification, the differentiation between samples with and without “papillary thyroid carcinoma-like” nuclei is a daunting task with high inter-observer variability among pathologists. Thus, there is increasing interest in the use of machine learning approaches to provide pathologists real-time decision support. In this paper, we optimize and quantitatively compare two automated machine learning methods for thyroid gland tumor classification on two datasets to assist pathologists in decision-making regarding these methods and their parameters. The first method is a feature-based classification originating from common image processing and consists of cell nucleus segmentation, feature extraction, and subsequent thyroid gland tumor classification utilizing different classifiers. The second method is a deep learning-based classification which directly classifies the input images with a convolutional neural network without the need for cell nucleus segmentation. On the Tharun and Thompson dataset, the feature-based classification achieves an accuracy of 89.7% (Cohen’s Kappa 0.79), compared to the deep learning-based classification of 89.1% (Cohen’s Kappa 0.78). On the Nikiforov dataset, the feature-based classification achieves an accuracy of 83.5% (Cohen’s Kappa 0.46) compared to the deep learning-based classification 77.4% (Cohen’s Kappa 0.35). Thus, both automated thyroid tumor classification methods can reach the classification level of an expert pathologist. To our knowledge, this is the first study comparing feature-based and deep learning-based classification regarding their ability to classify samples with and without papillary thyroid carcinoma-like nuclei on two large-scale datasets

An Unusual Migration of A Stent: A Case Report

Stent dislodgment and embolization is a rare complication of coronary stenting. There are reports of intra-coronary stent entrapment, stripping, and dislodgement during percutaneous coronary interventions causing potentially life threatening complications, including intra-coronary or systemic embolization. Reports of dislodgment and migration of previously placed drug eluting intra-coronary stent several months after deployment are very limited in the literature. We describe a drug eluting stent dislodgment and migration in an 88 year-old male 10 months after its deployment

Lymphoepithelial Carcinoma of Salivary Gland EBV-association in Endemic versus Non-Endemic Patients: A Report of 16 Cases

Lymphoepithelial carcinoma of salivary glands (LECSG) are rare neoplasms, reported in endemic populations (southeastern Chinese) with a strong Epstein-Barr virus (EBV) association. A retrospective series comparing EBV status within an ethnically diverse population (endemic vs. non-endemic patients) has not been reported. Sixteen LECSG were equally distributed between males (n = 8) and females (n = 8) with a median age of 54 years (range 18 to 85 years) at initial diagnosis. Ten patients were white, 4 Asian, and 2 black. The patients typically presented with swelling or mass for an average of 11.6 months. Tumors affected only major salivary glands: parotid (n = 13); submandibular (n = 3). Tumors were an average of 2.9 cm (range 1.5 to 5.8 cm). Nine of 16 (56%) patients had cervical lymph node metastases at presentation. No patients had nasopharyngeal or oropharyngeal tumors. Microscopically, the tumors were widely infiltrative, characterized by large polygonal to spindled cells arranged in a syncytial, lattice-like network in a background of lymphoplasmacytic cells. The neoplastic cells showed an open-vesicular nuclear chromatin to a more basaloid-morphology, the latter showing hyperchromatic nuclei and less cytoplasm, while nearly all of the cases had associated lymphoepithelial lesions/sialadenitis. By in situ hybridization, 8 of 16 cases had a strong, diffuse EBER expression (4 of 4 Asians; 4 of 12 non-Asians), while with immunohistochemistry all cases tested were pan-cytokeratin, CK5/6 and p63 reactive; none of the cases tested were p16 reactive. All patients were managed with wide or radical excision, 4 with concurrent chemoradiation, and 6 with radiation alone. Distant metastasis (lung, brain, and bone) developed in 2 patients. Overall follow-up (mean 3.8 years) revealed 12 patients alive and 2 dead, none with evidence of disease (mean 4.3 years); one white male alive with disease at 1.9 years, and one Asian female dead of disease at 4.2 years; both of these latter patients had Group IV stage disease. High stage (Group IV) patients had a shorter mean survival than lower stage patients: 3.1 versus 4.8 years, respectively. In conclusion, LECSG are uncommon primary neoplasms. Concurrent lymphoepithelial lesions may help suggest a primary tumor. The tumors, irrespective of race or ethnicity, may express EBER. There is an overall good survival, perhaps better for EBV-negative patients and for those with lower stage disease

Developing Classifications of Laryngeal Dysplasia: The Historical Basis

During the last 60 years numerous significant attempts have been made to achieve a widely acceptable terminology and histological grading for laryngeal squamous intraepithelial lesions. While dysplasia was included in the pathology of the uterine cervix already in 1953, the term dysplasia was accepted in laryngeal pathology first after the Toronto Centennial Conference on Laryngeal Cancer in 1974. In 1963 Kleinsasser proposed a three-tier classification, and in 1971 Kambic and Lenart proposed a four-tier classification. Since then, four editions of the World Health Organisation (WHO) classification have been proposed (1978, 1991, 2005 and 2017). Several terms such as squamous intraepithelial neoplasia (SIN) and laryngeal intraepithelial neoplasia (LIN) are now being abandoned and replaced by squamous intraepithelial lesions (SIL). The essential change between the 2005 and 2017 WHO classifications is the attempt to induce a simplification from a four- to a two-tier system. The current WHO classification (2017) thus recommends the use of a two-tier system with reasonably clear histopathological criteria for the two groups: low-grade and high-grade dysplasia. Problems with interobserver variability apart, subjectivities and uncertainties remain, but to a lesser degree. Ongoing and additional molecular studies may help to clarify underlying events that will increase our understanding and possibly can facilitate our attempts to obtain an even better classification. The classification needs to be easier for the general pathologist to perform and easier for the clinician to interpret. These two objectives are equally important to provide each patient the best personalised treatment available for squamous intraepithelial lesions.Peer reviewe

Evaluation of Sample Design and Estimation Methods for Great Lakes Angler Surveys

The waters of the Great Lakes support outstanding recreational fishing opportunities. Total catch and effort estimates obtained from on‐site angler surveys are essential for the management of the recreational fisheries. However, quality of angler survey estimates can be greatly affected by the survey design and estimation approaches used. Using Monte Carlo simulation techniques, we evaluated the effects of two potential sources of bias (disproportional sampling of angler trips and subsampling of the fishing day) on two catch estimators: (1) a multiple‐day estimator that ignores day effects and pools the angler trip data over a multiple‐day period, and (2) a daily estimator that treats the trip data in each day separately. When catch rates are constant among different time periods of the fishing day, the daily estimator produces total catch estimates with little bias, whereas the multiple‐day estimator is prone to bias caused by disproportional sampling of angler trips. When catch rates vary among different periods of a fishing day, the daily estimator produces biased estimates of total catch when the fishing day is subsampled, whereas the multiple‐day estimator is less affected by the variation in daily time‐period catch rates and subsampling of fishing days. Quality of total catch and effort estimates, in terms of root mean square error and coverage probability of confidence intervals, is poor when the number of days sampled each month is low and fishing days are subsampled.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141929/1/tafs0234.pd

Spectrophotometric Distances to Galactic H\,{\sc{ii}} Regions

We present a near infrared study of the stellar content of 35 H\,{\sc{ii}} regions in the Galactic plane. In this work, we have used the near infrared domain $J-$, $H-$ and $K_{s}-$ band color images to visually inspect the sample. Also, color-color and color-magnitude diagrams were used to indicate ionizing star candidates, as well as, the presence of young stellar objects such as classical TTauri Stars (CTTS) and massive young stellar objects (MYSOs). We have obtained {\it Spitzer} IRAC images for each region to help further characterize them. {\it Spitzer} and near infrared morphology to place each cluster in an evolutionary phase of development. {\it Spitzer} photometry was also used to classify the MYSOs. Comparison of the main sequence in color-magnitude diagrams to each observed cluster was used to infer whether or not the cluster kinematic distance is consistent with brightnesses of the stellar sources. We find qualitative agreement for a dozen of the regions, but about half the regions have near infrared photometry that suggests they may be closer than the kinematic distance. A significant fraction of these already have spectrophotometric parallaxes which support smaller distances. These discrepancies between kinematic and spectrophotometric distances are not due to the spectrophotometric methodologies, since independent non-kinematic measurements are in agreement with the spectrophotometric results. For instance, trigonometric parallaxes of star-forming regions were collected from the literature and show the same effect of smaller distances when compared to the kinematic results. In our sample of H\,{\sc{ii}} regions, most of the clusters are evident in the near infrared images. Finally, it is possible to distinguish among qualitative evolutionary stages for these objects.Comment: 59 pages, 146 figures and 4 tables. MNRAS accepte

A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.Comment: Accepted by Physical Biology; includes a supplement and a supplementary mpeg movie can be found at http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp

Resolved 24.5 micron emission from massive young stellar objects

Massive young stellar objects (MYSO) are surrounded by massive dusty envelopes. Our aim is to establish their density structure on scales of ~1000 AU, i.e. a factor 10 increase in angular resolution compared to similar studies performed in the (sub)mm. We have obtained diffraction-limited (0.6") 24.5 micron images of 14 well-known massive star formation regions with Subaru/COMICS. The images reveal the presence of discrete MYSO sources which are resolved on arcsecond scales. For many sources, radiative transfer models are capable of satisfactorily reproducing the observations. They are described by density powerlaw distributions (n(r) ~ r^(-p)) with p = 1.0 +/-0.25. Such distributions are shallower than those found on larger scales probed with single-dish (sub)mm studies. Other sources have density laws that are shallower/steeper than p = 1.0 and there is evidence that these MYSOs are viewed near edge-on or near face-on, respectively. The images also reveal a diffuse component tracing somewhat larger scale structures, particularly visible in the regions S140, AFGL 2136, IRAS 20126+4104, Mon R2, and Cep A. We thus find a flattening of the MYSO envelope density law going from ~10 000 AU down to scales of ~1000 AU. We propose that this may be evidence of rotational support of the envelope (abridged).Comment: 21 pages, accepted for A&