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* Context.--Whole-slide imaging has ushered in a new era of technology that has fostered the use of computational image analysis for diagnostic support and has begun to transfer the act of analyzing a slide to computer monitors. Due to the overwhelming amount of detail available in whole-slide images, analytic procedures--whether computational or visual--often operate at magnifications lower than the magnification at which the image was acquired. As a result, a corresponding reduction in image resolution occurs. It is unclear how much information is lost when magnification is reduced, and whether the rich color attributes of histologic slides can aid in reconstructing some of that information.Objective.--To examine the correspondence between the color and spatial properties of whole-slide images to elucidate the impact of resolution reduction on the histologic attributes of the slide.Design.--We simulated image resolution reduction and modeled its effect on classification of the underlying histologic structure. By harnessing measured histologic features and the intrinsic spatial relationships between histologic structures, we developed a predictive model to estimate the histologic composition of tissue in a manner that exceeds the resolution of the image.Results.--Reduction in resolution resulted in a significant loss of the ability to accurately characterize histologic components at magnifications less than X10. By utilizing pixel color, this ability was improved at all magnifications.Conclusions.--Multiscale analysis of histologic images requires an adequate understanding of the limitations imposed by image resolution. Our findings suggest that some of these limitations may be overcome with computational modeling.(Arch Pathol Lab Med. 2018;142:1394-1402; doi: 10.5858/arpa.2017-0380-OA), The analysis of a slide is often performed across a wide range of magnifications subject to the dynamic tradeoff between field of view and the amount of detail desired. The [...]

We describe a macrocantilever-based method for detecting a prostate cancer biomarker ([alpha]-methylacyl-CoA racemase; AMACR) directly in patient urine without a sample preparation step and without the use of labeled reagents. Clean catch voided urine specimens were prospectively collected from five confirmed prostate cancer patients 3 weeks postbiopsy. The presence of AMACR was measured in a blinded manner by exposing 3 mL of urine to the anti-AMACR-immobilized piezoelectric-excited millimeter-sized (PEMC) sensor. The resonance frequency of PEMC decreases as AMACR from sample binds to the antibody on the sensor. The resonance frequency changes for the five patients tested were 4,314 [+ or -] 35 (n = 2), 269 [+ or -] 17 (n = 2), 977 [+ or -] 64 (n = 3), 600 [+ or -] 31 (n = 2), and 801 [+ or -] 81 (n = 2) Hz, respectively. Positive detection was observed within ~15 min. The responses to positive, negative, and buffer controls were -9 [+ or -] 13, -34 [+ or -] 18, and -6 [+ or -] 18 Hz, respectively. Positive verification of AMACR attachment was confirmed by low-pH buffer release. The sensor response was quantitatively related to AMACR concentration in control urine, and the relationship was used in developing an in situ calibration method for quantifying AMACR in patient urine. Estimated concentrations of 42, 2, and 3 fg/mL AMACR were calculated for the three patients' urine, while absence of AMAC Rwas confirmed in control urine (n = 13). Because of simplicity of measurement combined with high sensitivity and specificity, the method may be a useful adjunct in a point-of-care setting to identify men at increased risk for prostate cancer.

Breast tumors are typically heterogeneous and contain diverse subpopulations of tumor cells with differing phenotypic properties. Planar cultures of cancer cell lines are not viable models of investigation of cell-cell [...]

* Cholesterol granuloma is usually associated with chronic middle ear disease and is common in the mastoid antrum and air cells of the temporal bone. It has also been reported in other parts of the skull, such as the frontal and maxillary sinuses and orbit. Cholesterol granuloma is rare in the paranasal sinuses. We report a new case of cholesterol granuloma in the maxillary sinus of a 38-year-old man who underwent surgical excision. We also review the literature and discuss the mechanism of development for this lesion. The resected specimen showed fragments of respiratory mucosa with cholesterol clefts surrounded by multinucleated foreign-body giant cells. Some multinucleated foreign-body giant cells showed asteroid bodies. Hemorrhagic areas, hemosiderin-laden macrophages, chronic inflammatory cells, and dilated lymphatics vessels were seen as well. Increased intrasinus pressure due to drainage obstruction may affect venous and lymphatic drainage from the sinus cavity, leading to venule microhemorrhages while still allowing arterial blood into the sinus mucosa and further contributing to a large localized hemorrhage. Lymphatic drainage may be insufficient to completely remove the lipid components of the red blood cells, and the lipid accumulation may contribute to the formation of cholesterol crystals and their esters., Cholesterol granuloma is a histopathologic term describing a large number of clefts present after cholesterol crystals have dissolved during processing, with surrounding foreign-body giant cells, foam cells, and macrophages filled [...]

Abstract Background Tumor classification is inexact and largely dependent on the qualitative pathological examination of the images of the tumor tissue slides. In this study, our aim was to develop an automated computational method to classify Hematoxylin and Eosin (H&E) stained tissue sections based on cancer tissue texture features. Methods Image processing of histology slide images was used to detect and identify adipose tissue, extracellular matrix, morphologically distinct cell nuclei types, and the tubular architecture. The texture parameters derived from image analysis were then applied to classify images in a supervised classification scheme using histologic grade of a testing set as guidance. Results The histologic grade assigned by pathologists to invasive breast carcinoma images strongly correlated with both the presence and extent of cell nuclei with dispersed chromatin and the architecture, specifically the extent of presence of tubular cross sections. The two parameters that differentiated tumor grade found in this study were (1) the number density of cell nuclei with dispersed chromatin and (2) the number density of tubular cross sections identified through image processing as white blobs that were surrounded by a continuous string of cell nuclei. Classification based on subdivisions of a whole slide image containing a high concentration of cancer cell nuclei consistently agreed with the grade classification of the entire slide. Conclusion The automated image analysis and classification presented in this study demonstrate the feasibility of developing clinically relevant classification of histology images based on micro- texture. This method provides pathologists an invaluable quantitative tool for evaluation of the components of the Nottingham system for breast tumor grading and avoid intra-observer variability thus increasing the consistency of the decision-making process.

To the Editor.--We read with interest the article on lipochrome pigment granules (LPGs) in the differential diagnosis of prostatic adenocarcinoma versus seminal vesicle-ejaculatory duct epithelium by Shidham and colleagues.[1] The [...]

Abstract: The increasing availability of next‐generation sequencing for clinical research dramatically improved our understanding of breast cancer genetics and resulted in detection of new mutation variants. Cancer risk data relating to some of these variants are insufficient, prompting the designation of variants of uncertain significance (VUS). The histopathologic characteristics of these variants have not been previously described. We propose to depict these characteristics and determine if invasive carcinomas with similar VUS genes share similar histomorphologic features. In total, 28 invasive breast cancers with VUS were retrospectively identified. Tumor sections were reviewed and a predefined set of histopathologic characteristics were documented and compared. Nine of the 28 cases were variants in the ATM gene and were found to share similar histologic characteristics; all had tumor cells with low nuclear grade, absent tumor infiltrating lymphocytes, as well as a marked desmoplastic response. A subset of the above findings were identified in variants of other genes but none had all findings collectively. Furthermore, variants of ATM gene had smaller tumor size, lower pathologic T stage at presentation, and more favorable surrogate molecular subtype compared to variants of other genes. These findings could potentially be used to reclassify VUS and predict which patients may harbor ATM mutations, and hence could have implications in triaging toward ATM variant identification for potential future targeted therapy. [ABSTRACT FROM AUTHOR]