Search

Context.--Tissue contaminants on histology slides represent a serious risk of diagnostic error. Despite their pervasive presence, published peer-reviewed criteria defining contaminants are lacking. The absence of a standardized diagnostic workup algorithm for contaminants contributes to variation in management, including investigation and reporting by pathologists. Objective.--To study the frequency and type of tissue contaminants on microscopic slides using standardized criteria. Using these data, we propose a taxonomy and algorithm for pathologists on "floater" management, including identification, workup, and reporting, with an eye on patient safety. Design.--A retrospective study arm of 1574 histologic glass slides as well as a prospective study arm of 50 slide contamination events was performed. Using these data we propose a structured classification taxonomy and guidelines for the workup and resolution of tissue contamination events. Results.--In the retrospective arm of the study, we identified reasonably sized benign tissue contaminants on 52 of 1574 slides (3.3%). We found size to be an important parameter for evaluation, among other visual features including location on the slide, folding, ink, and tissue of origin. The prospective arm of the study suggested that overall, pathologists tend to use similar features when determining management of potentially actionable contaminants. We also report successfully used case-based ancillary testing strategies, including fluorescence in situ hybridization analysis of chromosomes and DNA finger-printing. Conclusions.--Tissue contamination events are underreported and represent a patient safety risk. Use of a reproducible classification taxonomy and a standardized algorithm for contaminant workup, management, and reporting may aid pathologists in understanding and reducing risk. [ABSTRACT FROM AUTHOR]

Simple Summary: This study introduces a deep learning model designed to predict the 5-year recurrence risk of lung adenocarcinoma based on histopathology images. Using a dataset of 189 patients with 455 histopathology slides, our model demonstrated superior performance in risk stratification, achieving a hazard ratio of 2.29 (95% CI: 1.69–3.09, p < 0.005). This outperforms several existing deep learning methods, showcasing the potential of deep learning in automatically predicting lung adenocarcinoma recurrence risk. The superior performance of this model underscores the potential for deep learning models to be integrated into clinical workflows for more accurate and automated risk assessment in lung adenocarcinoma. This could lead to more personalized treatment strategies and better patient outcomes. Lung cancer is the leading cause of cancer-related death in the United States. Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer that can be treated with resection. While resection can be curative, there is a significant risk of recurrence, which necessitates close monitoring and additional treatment planning. Traditionally, microscopic evaluation of tumor grading in resected specimens is a standard pathologic practice that informs subsequent therapy and patient management. However, this approach is labor-intensive and subject to inter-observer variability. To address the challenge of accurately predicting recurrence, we propose a deep learning-based model to predict the 5-year recurrence of LUAD in patients following surgical resection. In our model, we introduce an innovative dual-attention architecture that significantly enhances computational efficiency. Our model demonstrates excellent performance in recurrent risk stratification, achieving a hazard ratio of 2.29 (95% CI: 1.69–3.09, p < 0.005), which outperforms several existing deep learning methods. This study contributes to ongoing efforts to use deep learning models for automatically learning histologic patterns from whole slide images (WSIs) and predicting LUAD recurrence risk, thereby improving the accuracy and efficiency of treatment decision making. [ABSTRACT FROM AUTHOR]

Simple Summary: In the context of endometrial cancer, molecular classification is becoming increasingly significant as the molecular class determines appropriate treatments and the prognosis. However, performing clinical testing for molecular classification in a large number of patients entails significant financial and time costs. Therefore, there is a need to develop a substantial molecular profile screening method for endometrial cancers. The objective of this study was to explore whether the molecular classification of endometrial cancer could be predicted from digital images of hematoxylin and eosin (H&E)-stained slides using deep learning as a screening tool. After making adjustments to the training data set and hyperparameters, we confirmed the feasibility of estimating the mismatch repair status from histological digital images of endometrial cancer. Deep learning was found to be effective for predicting one aspect of the molecular classification from H&E-stained histological digital images. The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly for gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests. [ABSTRACT FROM AUTHOR]

Background: Histopathology by pathologists is essential in the diagnosis of non‐small cell lung cancer (NSCLC). However, auxiliary diagnostic procedures for malignant tumor have continued to evolve. Despite the poor prognosis of patients with NSCLC, the application of the latest procedures and technologies to the field of lung cancer has lagged. Mass spectrometry was used to detect trace amounts of peptides in human tissue with high accuracy. The aim of this study was to establish a method for diagnostic mass spectrometry to identify lymph node metastasis by detecting cytokeratin (CK)19, a useful biomarker in lung cancer. Methods: We collected 81 lymph nodes with positive expression of CK19 in patients who underwent radical surgical resection in the Department of Thoracic Surgery at Iwate Medical University between May 2020 and December 2022. An X500R instrument was used for sample analysis. A positive result for lymph node metastasis as the detection at least two product ions (FGPGVAFR and ILGATIENSR) from CK19 was defined. Results: Our study indicated a high diagnostic efficiency for mass spectrometry, with 87.5% sensitivity and 91.2% specificity. The mutual concordance of mass spectrometry methods and histopathological diagnosis was 90.1%. Conclusions: Mass spectrometry offers high diagnostic accuracy and can be clinically applied to auxiliary diagnostic procedures for lymph node metastasis from NSCLC. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the demographic characteristics of patients diagnosed with Spitz nevus and to investigate potential distinctions in clinicopathological findings of Spitz nevi in relation to age and location of the lesion. Materials and Methods: Clinical and histopathological findings of 32 patients who were diagnosed with Spitz nevus from our archives between 2010 and 2020 were obtained and evaluated retrospectively. Results: A total of 32 patients were included, of whom 19 (59.4%) were female and 15 (40.6%) were under the age of 18 years. Most of the lesions (14, 43.7%) were located on the upper extremity, followed by the lower extremity and the head and neck. The most common histological subtype was the compound variant. In the pediatric age group, the majority of the lesions were located on the upper extremity, and the most common histological subtypes were pigmented and compound variant. In adults, the lesions were chiefly located on the lower extremitiy and the most common histological subtype was the desmoplastic variant. Conclusion: In this study, it was found that the location of the lesions and histopathological subtypes of Spitz nevi may differ in children and adults. Further studies incorporating genetic data and involving larger cohorts of patients are needed in order to determine these differences between age groups more clearly. The small sample size is the main limitation of this study. [ABSTRACT FROM AUTHOR]

Context.--Tissue contaminants on histology slides represent a serious risk of diagnostic error. Despite their pervasive presence, published peer-reviewed criteria defining contaminants are lacking. The absence of a standardized diagnostic workup algorithm for contaminants contributes to variation in management, including investigation and reporting by pathologists. Objective.--To study the frequency and type of tissue contaminants on microscopic slides using standardized criteria. Using these data, we propose a taxonomy and algorithm for pathologists on ''floater'' management, including identification, workup, and reporting, with an eye on patient safety. Design.--A retrospective study arm of 1574 histologic glass slides as well as a prospective study arm of 50 slide contamination events was performed. Using these data we propose a structured classification taxonomy and guidelines for the workup and resolution of tissue contamination events. Results.--In the retrospective arm of the study, we identified reasonably sized benign tissue contaminants on 52 of 1574 slides (3.3%). We found size to be an important parameter for evaluation, among other visual features including location on the slide, folding, ink, and tissue of origin. The prospective arm of the study suggested that overall, pathologists tend to use similar features when determining management of potentially actionable contaminants. We also report successfully used case-based ancillary testing strategies, including fluorescence in situ hybridization analysis of chromosomes and DNA fingerprinting. Conclusions.--Tissue contamination events are underreported and represent a patient safety risk. Use of a reproducible classification taxonomy and a standardized algorithm for contaminant workup, management, and reporting may aid pathologists in understanding and reducing risk. [ABSTRACT FROM AUTHOR]

Papillary renal neoplasm with reverse nuclear polarity (PRNRP) is an emerging oncocytic renal tumor. Cytomorphologic features of this tumor have not been described in the literature before. Thee objective of this study was to review the cytomorphology of a case PRNRP and compare with cytomorphologic features of papillary renal cell carcinomas (pRCCs) reported in the literature. 1 case of core needle biopsy (CNB) with touch preparation (TP) of a renal mass diagnosed as PRNRP was reviewed retrospectively. Clinical presentation, cytomorphologic features, ancillary tests and histopathology results were analyzed. The touch preparation was cellular and showed tight 3-D clusters of cuboidal epithelial cells with variable presence of fibrovascular cores (FC), granular eosinophilic cytoplasm, round apically located grade 1 nuclei compared to cases of pRCC that consistently showed presence of FCs lined by cuboidal to columnar epithelial cells with variable degree of cytologic atypia. Features characteristic of pRCC like foamy macrophages, hemosiderin laden macrophages, nuclear grooves or psammoma bodies were not present. No necrosis or mitosis were identified. By immunohistochemistry (IHC) the tumor cells were positive for cytokeratin 7, GATA-3 and AMACR (focal) and negative for CA-IX, CD117 and vimentin. Cytomorphologic features of PRNRP are unique and characterized by tight 3-D clusters (with or without FCs) of cuboidal cells with small round apically located nuclei and finely granular oncocytic cytoplasm. Specific diagnosis of PRNRP on cytology or CNB is feasible along with use of ancillary tests IHC and /or molecular tests. [ABSTRACT FROM AUTHOR]

* Context.--Pancreatic ductal adenocarcinoma has some of the worst prognostic outcomes among various cancer types. Detection of histologic patterns of pancreatic tumors is essential to predict prognosis and decide the treatment for patients. This histologic classification can have a large degree of variability even among expert pathologists. Objective.--To detect aggressive adenocarcinoma and less aggressive pancreatic tumors from nonneoplasm cases using a graph convolutional network--based deep learning model. Design.--Our model uses a convolutional neural network to extract detailed information from every small region in a whole slide image. Then, we use a graph architecture to aggregate the extracted features from these regions and their positional information to capture the whole slide--level structure and make the final prediction. Results.--We evaluated our model on an independent test set and achieved an F1 score of 0.85 for detecting neoplastic cells and ductal adenocarcinoma, significantly outperforming other baseline methods. Conclusions.--If validated in prospective studies, this approach has a great potential to assist pathologists in identifying adenocarcinoma and other types of pancreatic tumors in clinical settings. [ABSTRACT FROM AUTHOR]

Copyright of Comparative Literature / Primerjalna Književnost is the property of Slovenian Comparative Literature Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The research relevance is determined by an insufficient study of morphological changes in the mesentery of cats with infectious peritonitis, even though their understanding is necessary to explain the mechanism of development of the main symptom of the disease – the effusion of fluid into the abdominal cavity. The research aims to establish gross and microscopic changes in the mesentery of the small intestine of cats with infectious peritonitis. The research employs gross and histological examination of the mesentery of the small intestine of cats at the infectious peritonitis. Slides of the mesentery were stained with haematoxylin and eosin. At dry and mixed forms of infectious peritonitis, gross and microscopic changes in the mesentery of the small intestine of cats are similar. In the mesentery grossly, small white spots were found, which protruded above the general surface and had a homogeneous appearance on the section. Microscopic changes in the mesentery of the small intestine of cats with dry and mixed forms of infectious peritonitis were also similar. When conducting histological studies, it was established that the mesothelium on the surface of the mesentery was necrotized or absent. The submesothelial layer of collagen fibres was necrotized or contained partially lysed and fragmented fibres. The loose fibrous connective tissue of the mesentery was swollen, necrotized in places, and infiltrated by lymphocytes, monocytes, and macrophages. Eosinophilic inclusion bodies were detected in the cytoplasm of some monocytes and macrophages. Foci of adipose tissue in the mesentery of the small intestine were infiltrated by lymphocytes and monocytes. Necrosis and destruction of their walls were found in blood vessels and destruction of endothelial cells in lymphatic vessels. Perivascular lymphoid nodules were markedly enlarged due to their swelling and an increase in the number of cells in them. In perivascular lymphoid nodules, expansion of lymphatic vessels and destruction of part of their endothelium cells were also established. Some of the lymphatic vessels of the mesentery were expanded and filled with lymph, which contained a significant number of lymphocytes, monocytes, and single neutrophils. The materials presented in the article are of practical value for anatomists, histologists and pathomorphologists, as well as for scientists who study the pathogenesis of infectious peritonitis in cats [ABSTRACT FROM AUTHOR]

Context.--More people receive a diagnosis of skin cancer each year in the United States than all other cancers combined. Many patients around the globe do not have access to highly trained dermatopathologists, whereas some biopsy diagnoses of patients who do have access result in disagreements between such specialists. Mechanomind has developed software based on a deep-learning algorithm to classify 40 different diagnostic dermatopathology entities to improve diagnostic accuracy and to enable improvements in turnaround times and effort allocation. Objective.--To assess the value of machine learning for microscopic tissue evaluation in dermatopathology. Design.--A retrospective study comparing diagnoses of hematoxylin and eosin--stained glass slides rendered by 2 senior board-certified pathologists not involved in algorithm creation with the machine learning algorithm's classification was conducted. A total of 300 glass slides (1 slide per patient's case) from 4 hospitals in the United States and Africa with common variations in tissue preparation, staining, and scanning methods were included in the study. Results.--The automated algorithm demonstrated sensitivity of 89 of 91 (97.8%), 107 of 107 (100%), and 101 of 102 (99%), as well as specificity of 204 of 209 (97.6%), 189 of 193 (97.9%), and 198 of 198 (100%) while identifying melanoma, nevi, and basal cell carcinoma in whole slide images, respectively. Conclusions.--Appropriately trained deep learning image analysis algorithms demonstrate high specificity and high sensitivity sufficient for use in screening, quality assurance, and workload distribution in anatomic pathology. [ABSTRACT FROM AUTHOR]

Context: Quality assurance in cervical cytology is based on the cyto-histological correlation that is performed in several countries even without standardized protocols. Aims: To evaluate the quality of the Pap smear with the Clinical and Laboratory Standards Institute (CLSI) EP12-A2 guideline in a Peruvian hospital. Settings and design: This prospective study was carried out at tertiary care national hospital. Methods and material: The 156 cyto-histological results were collected and coded according to the Bethesda 2014 and FIGO system. The evaluation with the CLSI EP12-A2 guide allowed estimating the performance and quality of the test. Statistical analysis used: We performed a descriptive analysis of the cytological and histological data and correlation with the weight Kappa test. From the calculation of the likelihood ratios, the post-test probability was estimated using Bayes' theorem. Results: In cytology, 57 (36.5%) were undetermined abnormalities, 34 (21.8%) low-grade squamous intraepithelial lesion (SIL), and 42 (26.9%) high-grade SIL. Of the total biopsies, 56 (36.9%) were cervical intraepithelial neoplasia (CIN) grade 1, 23 (14.7%) were both CIN grade 2 and 3. We determined sensitivity, specificity, a positive and negative predictive value of 94%, 74.6%, 58%, and 97.1%, respectively. We determined a moderate cyto-histological agreement (k = 0.57). Atypical squamous cells of undetermined significance (40%), and cannot exclude high-grade squamous intraepithelial lesions (42.1%) that showed higher overdiagnosis results. Conclusions: The quality and performance of the Papanicolaou test show high sensitivity and moderate specificity. The concordance found was moderate and the proportion of underdiagnosis was higher in abnormalities of undetermined significance. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare multisystem disorder with a common histopathological finding of Langerhans-type cell proliferation mixed with a milieu of inflammatory cells. Bone involvement is a common presentation occurring in children and young adults. Recent studies using cell-specific gene expression profiling suggest that LCH arises from bone marrow-derived immature myeloid dendritic cells. We present a case of solitary LCH of cervical vertebrae in a young adult with pain and numbness in the shoulder diagnosed on fine-needle aspiration and confirmed on histopathology and immunohistochemistry. It was treated with tumor resection and stabilization of the vertebrae. [ABSTRACT FROM AUTHOR]

The impressive list of achievements of Dr. G. N. Papanicolaou and his tedious journey from normal to abnormal human cell includes the importance of wet fixation of cells and the development of the unique polychromatic Pap stain. The 5-dye Pap stain method evolved through 2 salient phases. The first being the development of wet fixation using alcohol-ether to enhance cellular transparency and the second phase saw the introduction of various cytoplasmic counterstaining methods using orange G and EA (light green, Bismarck brown, eosin) and phosphotungstic acid, facilitating the distinction of cell types. The specific characteristics of the staining method is, the cellular transparency combined with crisp nuclear staining, achieved through tailored cellular fixation and cytoplasmic staining using variable dye and pH combinations. With little modifications if any the Pap stain continues to be applied uniformly globally. However, institutional supply of dyes and chemicals from different companies make minor modifications, that remain consistent, an essential part of the staining protocol. This chapter describes the preparation and principles of various components of the stain that are being currently used in our department. [ABSTRACT FROM AUTHOR]

Background. Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35. Methods. MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins. Results. We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent. Conclusion. The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo. [ABSTRACT FROM AUTHOR]

Invasive fungal sinusitis is a morbid pathology that typically affects immunocompromised patients and may quickly progress to fulminant disease. The purpose of this study was to measure the sensitivity and specificity of touch preparation of nasal debridement specimens as a rapid diagnostic tool for invasive fungal sinusitis. A retrospective chart review was performed of 22 patients undergoing nasal debridement due to suspicion for invasive fungal sinusitis over a 10-year period. Thirteen patients had touch preparation of nasal specimens followed by routine histologic processing; two of these patients underwent 2, and 1 patient had 3 separate debridements, for a total of 17 touch preparations performed. The sensitivity and specificity of touch preparation were calculated by correlating the initial results with the presence of fungal invasion on final pathologic analysis. The sensitivity of touch preparation was 56% (95% confidence interval [CI]: 0.23-0.85), specificity was 100% (95% CI: 0.60-1.00), positive predictive value was 100% (95% CI: 0.46-1.00), and negative predictive value was 67% (95% CI: 0.35-0.89). This procedure may be a useful adjunct in situations requiring rapid diagnosis of invasive fungal sinusitis but should not be used as the sole criteria for determining the need for surgical intervention. [ABSTRACT FROM AUTHOR]

Introduction. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a significant step to standardize the reporting of thyroid fine needle aspiration (FNA). It has high predictive value, reproducibility, and improved clinical significance. Aim. The study was aimed to evaluate the diagnostic utility and reproducibility of "TBSRTC" at our institute. Methods and Material. The study included 646 thyroid FNAs which were reviewed by three pathologists and classified according to TBSRTC. Cytohistological correlation was done for 100 cases with surgical follow-up and the sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and risk of malignancy (ROM) were calculated. The interobserver variation among three pathologists was also assessed. Results. The distribution of cases in various TBSRTC categories is as follows: I—nondiagnostic 13.8%, II—benign 75.9%, III—atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) 1.2%, IV—follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN) 3.7%, V—suspicious for malignancy (SM) 2.6%, and VI—malignant 2.8%. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy are 72.4%, 94.3%, 84%, 89.2%, and 87.9%, respectively. The ROM of various TBSRTC categories were II—8.5%; III—66.7%; IV—63.6%; and V and VI—100%. Cohen's Weighted Kappa score was 0.99 which indicates almost perfect agreement among the three pathologists. Conclusions. Our study substantiates greater reproducibility among pathologists using TBSRTC to arrive at a precise diagnosis with an added advantage of predicting the risk of malignancy which enables the clinician to plan for follow-up or surgery and also the extent of surgery. [ABSTRACT FROM AUTHOR]

Background: Liquid-based cytology (LBC) for cervical cancer screening offers several advantages over conventional cytology. However, the extremely high cost of the current approved devices precludes widespread application of LBC technique in resource-constrained countries. This study aimed to evaluate the performance of an indigenous low-cost LBC technique, EziPREP™ (EP), against conventional preparations (CPs) for cervical cancer screening. Materials and Methods: A cross-sectional split-sample study with consecutive cervical sampling was conducted on 515 women attending the clinic at our institute. CP smears were prepared as per the standard technique using spatula and endocervical brush followed by detaching the head of brush into the fixative vial of EP. The EP samples were processed as per the manufacturer's protocol. Both CP and EP smears were stained using standard Papanicolaou stain protocol. Both sets of smears were evaluated for staining quality, morphologic details, and cytologic diagnoses. Cytologic diagnoses were correlated with cervical biopsy findings, wherever available. Performance characteristics of the two techniques were calculated. Results: The unsatisfactory rate for CP was 1.0%, while on EP, 1.3% smears had inadequate cellular material. The staining quality and morphological details were comparable in both sets of smears. The detection of infections and epithelial cell abnormality was more, though not statistically significant in EP smears. There was a 98% concordance in cytologic diagnosis between CP and EP smears. Cytohistologic concordance was observed in 96% of cases for both CP and EP smears. Although the time taken for processing and staining of smears was higher for EP (2.5 min for EP per smear and 1.6 min for CP per smear), the screening time reduced from 6.5 min per smear for CP to 2.2 min in EP smears. Conclusion: EP provides monolayered cervical smears with vivid morphological details, leading to reduced screening time and relatively higher pick-up of infections and low-grade cervical lesions as compared to conventional smears. The availability of such low-cost devices may enable wider application of cytology-based cervical cancer screening in low-resource countries. [ABSTRACT FROM AUTHOR]

Background: The Bethesda system of reporting thyroid cytopathology (BSRTC) was introduced in 2007. The third category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) poses difficulties for the pathologist, and different papers have been published varying the risks of malignancy. Aims: (1) Evaluation of the cytological features of thyroid lesions according to BSRTC. (2) After resection, correlation with histopathological report to evaluate the risk of malignancy (ROM) and the risk of neoplasm (RON). (3) Division of category III into six subgroups based on cytological findings and assessment of ROM and RON. Materials and Methods: A total of 282 patients with diagnosed thyroid lesions underwent fine-needle sampling under ultrasound guidance. Smears were prepared and stained with May--Grunwald--Giemsa stain and Papanicolaou stain. Results: Of 282 cases, there were 9 cases (3.1%) of category I, 157 cases (55.8%) of category II, 24 cases (8.5%) of category III, 20 cases (7.1%) of category IV, 14 cases (4.8%) of category V, and 58 cases (20.7%) of category VI. The RON was 60, 17.1, 63.1, 77.7, 91.7, and 98.2% and the ROM was 60, 14.3, 26.3, 38.9, 91.7, and 96.3% in categories I, II, III, IV, V, and VI, respectively. The RON was 0, 75, 50, 100, 66.6, and 100% and the ROM was 0, 25, 50, 100, 16.6, and 0% in subgroups 1, 2, 3, 4, 5, and 6, respectively. We have proposed a system of subgrouping AUS/FLUS that may help to dispel the confusion generated by an AUS/FLUS report, and provide with a more exact and reproducible diagnostic and prognostic tool. [ABSTRACT FROM AUTHOR]

Background: Although corrosion casting has been implemented for almost five centuries, the choice of resin has a strong influence on the effectiveness of casting vessel formations. Our aim was to compare quality and quantity features of two groups of corrosion casts made using two kits: Plastogen G resin and Batson no. 17 resin.Materials and Methods: Thirty corrosion casts were made of testicular arterial vessels (15 made using Plastogen G and 15 made using Batson no. 17) and their shape, colour, fragility and flexibility were evaluated. The following parameters were measured: maximal width of corrosion cast of testis, maximal length of centripetal and centrifugal arteries, diameter of testicular artery and its terminal branches. Based on these measurements, five indexes were calculated (Iq1-Iq5).Results: Generally both groups of corrosion casts demonstrated similar attributes. Only the rami tunicales minores displayed higher fragility and lower flexibility in the Plastogen G group than the Batson no. 17 group. The only observed quantitative difference was that Iq3 was significantly lower in the Plastogen G group (0.71 ± 0.01) than in Batson no. 17 group (0.79 ± 0.01; p = 0.0092).Conclusions: The two corrosion cast groups displayed similar qualitative and quantitative attributes. Batson no. 17 appears to be a good resin for three-dimensional visualisation of extra- and intratesticular arterial vessels. [ABSTRACT FROM AUTHOR]

Background: Cytologic examination of body fluids commonly involves the use of direct or sediment smears, cytocentrifuge preparations, membrane filter preparations, or cell block sections. Cytospin and cell block techniques are extremely useful in improving cell yield of thin serous effusions and urine samples, and ensure high diagnostic efficacy. Materials and Methods: We studied cytospin preparations and cell block sections prepared from 180 samples of body fluids and urine samples to compare the relative efficiency of cell retrieval, preservation of cell morphology, ease of application of special stains, and diagnostic efficacy. Samples were collected and processed to prepare cytospin smears and cell block sections. Results: We observed that overall, cell yield and preservation of individual cell morphology were better in cytospin preparations as compared to cell blocks, while preservation of architectural pattern was better in cell block sections. The number of suspicious cases also decreased on cell block sections, with increased detection of malignancy. It was difficult to prepare cell blocks from urine samples due to low cellularity. Conclusions: Cytospin technology is a quick, efficient, and cost-effective method of increasing cell yield in hypocellular samples, with better preservation of cell morphology. Cell blocks are better prepared from high cellularity fluids; however, tissue architecture is better studied, with improved rate of diagnosis and decrease in ambiguous results. Numerous sections can be prepared from a small amount of material. Special stains and immunochemical stains can be easily applied to cell blocks. It also provides a source of archival material. [ABSTRACT FROM AUTHOR]

Purpose. To investigate whether the SNARE protein vesicle-associated membrane protein 8 (VAMP8) was implicated in the development of chronic ocular graft-versus-host disease (GVHD). Methods. Firstly, the chronic GVHD (cGVHD) and Sjögren’s syndrome (SS)-impaired lacrimal gland (LG) tissue sections from humans for diagnostic purpose were evaluated for VAMP8 expression by histopathology and immunohistochemistry. Next, serial changes of tear secretion and VAMP8 expression at both protein and mRNA level of LG in an animal cGVHD model compared with the syngeneic control. Results. Decreased VAMP 8 expression in the cGVHD-affected human LG was detected in comparison with SS-affected LG. Tear secretion in the murine cGVHD model was significantly reduced compared with that in the syngeneic controls 8 weeks after BMT. Protein expression of VAMP8 in the cGVHD-affected LG in murine cGVHD was decreased in comparison with that in the controls. Gene expression of VAMP8 in the cGVHD-affected murine LG was significantly less than that in the syngeneic control 3 weeks after BMT. Conclusions. Our results suggested that expression of VAMP8 in the cGVHD-affected LG was decreased and accordingly tear secretion in cGVHD was reduced. Collectively, the reduction of VAMP8 expression in the cGVHD-affected LG can be involved in the pathogenic processes of cGVHD-induced dry eye disease. [ABSTRACT FROM AUTHOR]

Tumors of the pituitary gland and sellar region represent approximately 10-15% of all brain tumors. Pituitary adenoma (PA), the most common pathology of the pituitary gland, can be effectively subclassified only with the help of immunohistochemistry (IHC). This is important and needed for individual patient management.~Background~Background~The objective of the study was to analyze the importance of intraoperative imprint smear cytology and correlating with final histopathological diagnosis. Furthermore, to classify the different types of PA with the help of IHC, prolactin (PRL), adrenocorticotropic hormone (ACTH), and growth hormone (GH) and to predict the benign, atypical, or malignant nature of the tumor with the help of prognostic marker Ki-67.~Aims and Objectives~Objective~A prospective study was done in 34 cases. The patients whose pituitary gland samples are referred from the endocrine and the neurosurgery department to the pathology department for histopathological examinations were selected. We have studied the clinical features, radiology and touch imprint cytology, histopathology, and IHC with the help of PRL, ACTH, GH, and Ki-67 of PA over 2 years.~Materials and Methods~Methods~In our study, we had 32 cases of PA of 34 cases over a span of 2 years. We have seen that there is a correlation between cytological and histological diagnosis of the subtypes of PA in 62% cases, and the Kappa statistics show a moderate extent of agreement (Kappa - 0.320, 95% confidence interval = 0.031-0.609). Ki-67 when compared to the radiological grading showed a high degree of comparability (Chi-square test: P < 0.001). All cases with invasion had a higher Ki-67. On using the Fisher's exact test, we found that the Ki-67 expression with GH-producing adenomas and ACTH-producing adenomas was comparable (P = 1.000) while in PRL-producing adenomas too this was not significant (P = 0.269).~Results~Results~PA can be effectively classified with the help of IHC. Intraoperative cytology is important in diagnosing PA, but histopathology remains the gold standard in diagnosing and differentiating PA from other pathologies of the pituitary gland. The radiological grading together with immunological classification and the prognostic markers of Ki-67 is important in deciding the benign or atypical nature of the adenomas thus helping in better patient management.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]

Tensorial logic is a primitive logic of tensor and negation which refines linear logic by relaxing the hypothesis that linear negation is involutive. Thanks to this mild modification, tensorial logic provides a type-theoretic account of game semantics where innocent strategies are portrayed as temporal refinements of traditional proof-nets in linear logic. In this paper, we study the algebraic and combinatorial structure of negation in a non-commutative variant of tensorial logic. The analysis is based on a 2-categorical account of dialogue categories, which unifies tensorial logic with linear logic, and discloses a primitive symmetry between proofs and anti-proofs. The micrological analysis of tensorial negation reveals that it can be decomposed into a series of more elementary components: an adjunction L ⊣ R between the left and right negation functors L and R ; a pair of linear distributivity laws κ and κ which refines the linear distributivity law between ⊗ and ⅋ in linear logic, and generates the Opponent and Proponent views of innocent strategies between dialogue games; a pair of axiom and cut combinators adapted from linear logic; an involutive change of frame ( − ) ⁎ reversing the point of view of Prover and of Denier on the logical dispute, and reversing the polarity of moves in the dialogue game associated to the tensorial formula. [ABSTRACT FROM AUTHOR]

Aim. In routine histopathology, decalcification is an essential step for mineralized tissues. The purpose of this study is to evaluate the effects of different decalcification solutions on the morphological and antigenicity preservation in Sprague Dawley (SD) rat femurs. Materials and Methods. Four different decalcification solutions were employed to remove the mineral substances from rat femurs, including 10% neutral buffered EDTA, 3% nitric acid, 5% nitric acid, and 8% hydrochloric acid/formic acid. Shaking and low temperature were used to process the samples. The stainings of hematoxylin-eosin (HE) and immunohistochemical (IHC) were employed to evaluate the bone morphology and antigenicity. Key Findings. Different decalcification solutions may affect the quality of morphology and the staining of paraffin-embedded sections in pathological examinations. Among four decalcifying solutions, 3% nitric acid is the best decalcifying agent for HE staining. 10% neutral buffered EDTA and 5% nitric acid are the preferred decalcifying agents for IHC staining. Significance. The current study investigated the effects of different decalcifying agents on the preservation of the bone structure and antigenicity, which will help to develop suitable protocols for the analyses of the bony tissue. [ABSTRACT FROM AUTHOR]

* Context.--In an era in which testing of patient tumor material for molecular and other ancillary studies is of increasing clinical importance for selection of therapy, the ability to test on small samplings becomes critical. Often, small samplings are rapidly depleted in the diagnostic workup or are insufficient for multiple ancillary testing approaches. Objective.--To describe technical methodologies that can be implemented to preserve and maximize tissue for molecular and other ancillary testing. Data Sources.--Retrospective analysis of a case cohort from the University of Colorado, description of techniques used at the University of Colorado, and published literature. Conclusions.--Numerous techniques can be deployed to maximize molecular and other ancillary testing, even when specimens are from small samplings. A dedicated process for molecular prioritization has a high success rate, but also increases workload, which must be factored into establishing such a process. Additionally, establishing high- fidelity communication strings is critical for success of dedicated molecular prioritization of samples. Numerous approaches can be deployed for alternative specimen types, and several technical approaches can also aid in maximizing small specimens. [ABSTRACT FROM AUTHOR]

* Context.--As our understanding of genomic alterations underlying solid tumor malignancies continues to evolve, molecular testing of tumor samples is increasingly used to guide therapeutic management. Next-generation sequencing (NGS) provides a novel platform for the simultaneous screening of multiple genes using small amounts of DNA. Several recent studies have described NGS mutational analysis using cytologic specimens. The cytopathologist's role in specimen assessment and triaging is critical to effectively implementing NGS in routine cytology practice. Objectives.--To review the NGS experience and a variety of preanalytic factors that affect NGS success rates of cytologic specimens at our institution. Data Sources.--To evaluate cytology specimen adequacy rates for NGS, we reviewed a 14-month period of image-guided fine-needle aspiration and core needle biopsies used for testing. In addition, we reviewed data from our previously published studies to evaluate preanalytic factors affecting NGS success in these specimens. Conclusions.--Identifying factors that affect NGS success rates in cytology specimens is crucial for a better understanding of specimen adequacy requirements and for proper use of limited-volume tissue samples. In our practice, which uses direct smears as well as cell block sections, NGS success rates in core needle biopsy and fine-needle aspiration samples are comparable. The chance of successful testing is further increased by procuring concurrent fine-needle aspiration and core needle biopsy samples. The type of glass slides used for direct smears and the method of tissue extraction affect our DNA yield. Validating a DNA input for cytology samples that is lower than that recommended by the manufacturer has significantly increased our NGS success rate. [ABSTRACT FROM AUTHOR]

* The value and suitability of cytology specimens for molecular diagnosis has been demonstrated by numerous studies. In practice, however, the success rates vary widely across institutions depending on the disease setting, institutional practices of acquisition, handling/processing, and testing methodologies. As the number of clinically relevant biomarkers continues to increase, more laboratories are turning to next-generation sequencing platforms for testing. Although amplicon-based next-generation sequencing assays, interrogating a limited genomic territory, can be performed with minimal input material, broader-based next-generation sequencing assays have higher DNA input requirements that may not be met if the small tissue samples are not acquired and handled appropriately. We briefly describe some of the process changes we have instituted in our laboratories when handling cytologic material to maximize the tissue available for broad hybrid-capture--based next-generation sequencing assays. Among the key changes established were the consolidation and preservation of previously discarded supernatant material in cytologic samples, the introduction of mineral oil for deparaffinization of cell blocks, and adjustments in the molecular laboratory process and bioinformatics pipelines. We emphasize that even minimal changes can have broad implications for test performance, highlighting the importance of a cohesive group-based approach among clinical, cytopathology, surgical pathology, molecular, and bioinformatics teams. [ABSTRACT FROM AUTHOR]

* The advent of targeted therapy in lung cancer has heralded a paradigm shift in the practice of cytopathology with the need for accurately subtyping lung carcinoma, as well as providing adequate material for molecular studies, to help guide clinical and therapeutic decisions. The variety and versatility of cytologic-specimen preparations offer significant advantages to molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is critical, not only from a lung cancer diagnosis standpoint but also for the myriad ancillary studies that are necessary to provide appropriate clinical management. A large fraction of lung cancers are diagnosed by aspiration or exfoliative cytology specimens, and thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. This review focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era. [ABSTRACT FROM AUTHOR]

Background: The role of fine-needle aspiration cytology (FNAC) in thyroid nodules has been well-studied but there is a paucity of studies solely involving papillary thyroid carcinoma (PTC). The diagnostic criteria for PTC are established but still there is a worrisome possibility of false positive and false-negative results, which can have a serious impact on patient care. This article correlates the cytological and histological diagnosis of PTC with an eventual aim of analyzing the cause of false positive and false negative results in order to prevent misdiagnosis. An increase in the incidence of PTC in the younger population has been noted. Aims: To analyze the epidemiological trends and cytohistological correlation of PTC and evaluate the discordant cases and pitfalls of FNAC. Materials and Methods: Seventy-two cases who had undergone both FNAC and histopathological examination (HPE) of the thyroid gland were selected. Age and sex distribution as well as cytohistological correlation were done for all the cases. Results: Cytohistological correlation was 81.94%. False positives were 5.56% and the false negative rate was 13.2%. Sensitivity was 86.7% and the positive predictive value was 93.6%. The peak age was 31-40 years among females and 41 -60 years among males. Seven of our patients were <20 years of age (10%). Conclusion: FNAC is an indispensible tool for the early diagnosis of PTC. However, certain conditions of the thyroid gland can cause diagnostic dilemma. Awareness of pathologists regarding these pitfalls can prevent misdiagnosis and provide better patient care. Increasing the incidence of PTC with a more striking increase in the younger population makes early diagnosis all the more important owing to better prognosis in this age group. [ABSTRACT FROM AUTHOR]

The 5-HT2A receptor is highly involved in aspects of cognition and executive function and seen to be affected in neurodegenerative diseases like Alzheimer’s disease and related to the disease pathology. Even though Parkinson’s disease (PD) is primarily a motor disorder, reports of impaired executive function are also steadily being associated with this disease. Not much is known about the pathophysiology behind this. The aim of this study was thereby twofold: (1) to investigate 5-HT2A receptor binding levels in Parkinson’s brains and (2) to investigate whether PD associated pathology, alpha-synuclein (AS) overexpression, could be associated with 5-HT2A alterations. Binding density for the 5-HT2A-specific radioligand [3H]-MDL 100.907 was measured in membrane suspensions of frontal cortex tissue from PD patients. Protein levels of AS were further measured using western blotting. Results showed higher AS levels accompanied by increased 5-HT2A receptor binding in PD brains. In a separate study, we looked for changes in 5-HT2A receptors in the prefrontal cortex in 52-week-old transgenic mice overexpressing human AS. We performed region-specific 5-HT2A receptor binding measurements followed by gene expression analysis. The transgenic mice showed lower 5-HT2A binding in the frontal association cortex that was not accompanied by changes in gene expression levels. This study is one of the first to look at differences in serotonin receptor levels in PD and in relation to AS overexpression. [ABSTRACT FROM AUTHOR]

Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs) isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia. [ABSTRACT FROM AUTHOR]

Background: Pigs are frequently used as animal models in experimental medicine. To identify processes of vascular development or regression, vascular elements must be recognised and quantified in a three-dimensional (3D) arrangement. Vascular corrosion casts enable the creation of 3D replicas of vascular trees. The aim of our study was to identify suitable casting media and optimise the protocol for porcine liver vascular corrosion casting.Materials and Methods: Mercox II® (Ladd Research, Williston, Vermont, USA) and Biodur E20® Plus (Biodur Products, Heidelberg, Germany) were tested in 4 porcine livers. The resins (volume approximately 700 mL) were injected via the portal vein. Corrosion casts were examined by macro-computed tomography, micro-computed tomography and scanning electron microscopy.Results: For hepatectomies, the operating protocol was optimised to avoid gas or blood clot embolisation. We present a protocol for porcine liver vascular bed casting based on corrosion specimens prepared using Biodur E20® epoxy resin.Conclusions: Only Biodur E20®Plus appeared to be suitable for high-volume vascular corrosion casting due to its optimal permeability, sufficient processing time and minimum fragility. Biodur E20® Plus is slightly elastic, radio-opaque and alcohol-resistant. These properties make this acrylic resin suitable for not only vascular research but also teaching purposes. [ABSTRACT FROM AUTHOR]

Stem cells have infinite potential for regenerative therapy thanks to their advantageous ability which is differentiable to requisite cell types for recovery and self-renewal. The microsystem has been proved to be more helpful to stem cell studies compared to the traditional methods, relying on its advantageous feature of mimicking in vivo cellular environments as well as other profitable features such as minimum sample consumption for analysis and multiprocedures. A wide variety of microsystems were developed for stem cell studies; however, regenerative therapy-targeted applications of microtechnology should be more emphasized and gain more attractions since the regenerative therapy is one of ultimate goals of biologists and bioengineers. In this review, we introduce stem cell researches harnessing well-known microtechniques (microwell, micropattern, and microfluidic channel) in view point of physical principles and how these systems and principles have been implemented appropriately for characterizing stem cells and finding possible regenerative therapies. Biologists may gain information on the principles of microsystems to apply them to find solutions for their current challenges, and engineers may understand limitations of the conventional microsystems and find new chances for further developing practical microsystems. Through the well combination of engineers and biologists, the regenerative therapy-targeted stem cell researches harnessing microtechnology will find better suitable treatments for human disorders. [ABSTRACT FROM AUTHOR]

Automated DNA isolation can decrease hands-on time in routine pathology. Our aim was to apply automated DNA isolation and perform DNA methylation analyses. DNA isolation was performed manually from fresh frozen (CRC = 10, normal = 10) specimens and colonic biopsies (CRC = 10, healthy = 10) with QIAamp DNA Mini Kit and from FFPE blocks (CRC = 10, normal = 10) with QIAamp DNA FFPET Kit. Automated DNA isolation was performed with MagNA Pure DNA and Viral NA SV kit on MagNA Pure 96 system. DNA methylation of MAL, SFRP1, and SFRP2 were analyzed with methylation-specific high-resolution melting analysis. Yield of automatically isolated samples was equal in fresh frozens and significantly lower compared to manually isolated biopsy and FFPE samples. OD260/280 of fresh frozen and biopsy samples were similar after both isolations, automated isolation resulted in lower purity in FFPE samples. Both protocols resulted in similar OD260/230 from fresh frozens, automated isolation method was superior in biopsies and manual protocol in FFPE samples. DNA methylation of biopsies, fresh frozen samples were highly similar after both methods, results of automatically and manually isolated FFPE samples were different. Automated DNA isolation from fresh frozen samples can be suitable for high-throughput laboratories. [ABSTRACT FROM AUTHOR]

Context.--Esophageal cancer continues to be one of the most lethal of all gastrointestinal malignancies. Its prognostic parameters are based on the gross and histopathologic examination of resected specimens by pathologists. Objective.--To describe the implications of appropriate handling and examination of endomucosal resection and esophagectomy specimens from patients with esophageal carcinoma while considering the implications of the surgical techniques used to obtain such specimens. Parameters include histopathologic findings necessary for accurate staging, differences in the assessment of margins, residual malignancy, and criteria to evaluate for tumor regression after chemoradiation therapy as well as the role of immunohistochemistry and the judicious use of frozen sections. Data Sources.--Sources were a review of the literature and the authors' experience handling these types of specimens. Conclusions.--Examining surgical specimens of the esophagus is critical in the management of patients with esophageal carcinoma, and it requires careful consideration of the diagnostic pitfalls, staging-related parameters, and results of molecular tests. [ABSTRACT FROM AUTHOR]

Background. Cast immobilization induces mechanical hypersensitivity, which disturbs rehabilitation. Although vibration therapy can reduce various types of pain, whether vibration reduces immobilization-induced hypersensitivity remains unclear. Objective. The purpose of this study was to investigate the preventive and therapeutic effects of vibration therapy on immobilization-induced hypersensitivity. Design. The experimental design of the study involved conducting behavioral, histological, and immunohistochemical studies in model rats. Methods. Thirty-five Wistar rats (8 weeks old, all male) were used. The right ankle joints of 30 rats were immobilized by plaster cast for 8 weeks, and 5 rats were used as controls. The immobilized rats were divided randomly into the following 3 groups: (1) immobilization-only group (Im, n=10); (2) vibration therapy group 1, for which vibration therapy was initiated immediately after the onset of immobilization (Im+Vib1, n=10); and (3) vibration therapy group 2, for which vibration therapy was initiated 4 weeks after the onset of immobilization (Im+Vib2, n=10). Vibration was applied to the hind paw. The mechanical hypersensitivity and epidermal thickness of the hind paw skin were measured. To investigate central sensitization, calcitonin gene-related peptide (CGRP) expression in the spinal cord and dorsal root ganglion (DRG) was analyzed. Results. Immobilization-induced hypersensitivity was inhibited in the Im+Vib1 group but not in the Im+Vib2 group. Central sensitization, which was indicated by increases in CGRP expression in the spinal cord and the size of the area of CGRP-positive neurons in the DRG, was inhibited in only the Im+Vib1 group. Epidermal thickness was not affected by vibration stimulation. Limitations. A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans. Conclusions. The data suggest that initiation of vibration therapy in the early phase of immobilization may inhibit the development of immobilization-induced hypersensitivity. [ABSTRACT FROM AUTHOR]

Context.—Genomic medicine requires the identification of biomarkers and therapeutic targets, which in turn, requires high-quality biospecimens. Achieving high-quality biospecimens requires implementing standard operating procedures to control the variations of preanalytic variables in biobanking. Currently, most biobanks do not control the variations of preanalytic variables when collecting, processing, and storing their biospecimens. However, those variations have been shown to affect the quality of biospecimens and gene expression profiling. Objective.—To identify evidence-based preanalytic parameters that can be applied and those parameters that need further study. Data Sources.—We searched the Biospecimen Research and PubMed databases using defined key words. We retrieved and reviewed 212 articles obtained through those searches. We included 58 articles (27%) according to our inclusion and exclusion criteria for this review. Conclusion.—Preanalytic variables in biobanking can degrade the quality of biospecimens and alter gene expression profiling. Variables that require further study include the effect of surgical manipulation; the effect of warm ischemia; the allowable duration of delayed specimen processing; the optimal type, duration, and temperature of preservation and fixation; and the optimal storage duration of formalin-fixed, paraffin embedded specimens in a fit-for-purpose approach. [ABSTRACT FROM AUTHOR]

Objective Definitive diagnosis of the central nervous system (CNS) lesions is unknown prior to histopathological examination. To determine the method and the endpoint for surgery, intraoperative evaluation of the lesion helps the surgeon. In this study, the diagnostic accuracy and pitfalls of using frozen section (FS) of CNS lesions is determined. Materials & Methods In this retrospective study, we analyzed the results of FS and permanent diagnoses of all CNS lesions by reviewing reports from 3 general hospitals between March 2001 and March 2011. Results 273 cases were reviewed and patients with an age range from 3 to 77 years of age were considered. 166 (60.4%) had complete concordance between FS and permanent section diagnosis, 83 (30.2%) had partial concordance, and 24 cases (9.5%) were discordant. Considering the concordant and partially concordant cases, the accuracy rate was 99.5%, sensitivity was 91.4%, specificity was 99.7%, and positive and negative predictive values were 88.4% and 99.8%, respectively. Conclusion Our results show high sensitivity and specificity of FS diagnosis in the evaluation of CNS lesions. A Kappa agreement score of 0.88 shows high concordance for FS results with permanent section. Pathologist's misinterpretation, small biopsy samples (not representative of the entire tumor), suboptimal slides, and inadequate information about tumor location and radiologic findings appear to be the major causes for these discrepancies indicated from our study. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to evaluate the feasibility and accuracy of sentinel lymph node (SLN) detection using preoperative lymphoscintigraphy and intra-operative gamma probe/blue dye for endometrial cancer patients. MATERIAL AND METHODS: Twenty four consecutive patients with endometrial cancer were recruited. All patients underwent lymphatic mapping and sentinel node biopsy using combined intracervical radiotracer and blue dye injections. Pelvic lymph node dissection was performed for all patients. Para-aortic lymphadenectomy was done in high risk patients. All SLNs were examined by frozen section and Hematoxylin and Eosin (H&E) permanent sections. RESULTS: Pre-operative lymphoscintigraphy showed at least one SLN in 21/24 patients. Intra-operatively, at least one SLN could be harvested by gamma probe and/or blue dye methods. A total of 95 SLNs were detected. Four SLNs were detected only by blue dye, 42 only by radiotracer, and 49 were hot/blue. Median number of SLN per patient was 3. Three patients had positive pelvic lymph nodes. All of them had positive SLN (no false negative case). Frozen section could identify SLN involve- ment in two of three patients with positive pathology. CONCLUSION: Lymphatic mapping and sentinel node biopsy is feasible and accurate in endometrial cancer patients using combined radiotracer and blue dye methods. Frozen section accuracy was lower and underscores the importance of expert pathologists for SLN mapping technique. [ABSTRACT FROM AUTHOR]

Context.—The use of a touch preparation for intraoperative sentinel lymph node diagnosis has become a preferred method of many pathologists because of its reported high sensitivity and rapid turnaround time. However, after neoadjuvant chemotherapy many lymph nodes have significant treatment-related changes that may affect the diagnostic accuracy of the intraoperative evaluation. Objective.—To determine the accuracy of touch preparation for the intraoperative diagnosis of metastatic breast carcinoma in the neoadjuvant setting. Design.—We reviewed retrospectively the results of intraoperative evaluations for 148 different sentinel lymph nodes from 63 patients who had undergone neoadjuvant chemotherapy for invasive breast cancer at our institution. The intraoperative touch preparation results were compared with the final pathology reports in conjunction with relevant clinical data. Results.—Use of touch preparation for the evaluation of sentinel lymph nodes intraoperatively after neoadjuvant therapy was associated with a low sensitivity of 38.6% (95% confidence interval [CI], 24.4–54.5) but high specificity of 100% (95% CI, 96.5–100). There was no difference in sensitivity rates between cytopathologists and noncytopathologists in this cohort (P = .40). Patients with invasive lobular carcinoma and those who had a clinically positive axilla before the initiation of neoadjuvant therapy were the most likely to have a false-negative result at surgery. Conclusions.—Intraoperative touch preparations should not be used alone for the evaluation of sentinel lymph nodes in the setting of neoadjuvant therapy for breast cancer because of low overall sensitivity. [ABSTRACT FROM AUTHOR]

Context.-Despite continuing advances in tissue processing automation, traditional embedding, cutting, and staining methods limit our ability for rapid, comprehensive visual examination. These limitations are particularly relevant to biopsies for which immediate therapeutic decisions are most necessary, faster feedback to the patient is desired, and preservation of tissue for ancillary studies is most important. The recent development of improved tissue clearing techniques has made it possible to consider use of multiphoton microscopy (MPM) tools in clinical settings, which could address difficulties of established methods. Objective.-To demonstrate the potential of MPM of cleared tissue for the evaluation of unembedded and uncut pathology samples. Design.-Human prostate, liver, breast, and kidney specimens were fixed and dehydrated by using traditional histologic techniques, with or without incorporation of nucleic acid fluorescent stains into dehydration steps. A benzyl alcohol/benzyl benzoate clearing protocol was substituted for xylene. Multiphoton microscopy was performed on a home-built system. Results.-Excellent morphologic detail was achievable with MPM at depths greater than 500 μm. Pseudocoloring produced images analogous to hematoxylin-eosin-stained images. Concurrent second-harmonic generation detection allowed mapping of collagen. Subsequent traditional section staining with hematoxylin-eosin did not reveal any detrimental morphologic effects. Sample immunostains on renal tissue showed preservation of normal reactivity. Complete reconstructions of 1-mm cubic samples elucidated 3-dimensional architectural organization. Conclusions.-Multiphoton microscopy on cleared, unembedded, uncut biopsy specimens shows potential as a practical clinical tool with significant advantages over traditional histology while maintaining compatibility with gold standard techniques. Further investigation to address remaining implementation barriers is warranted. [ABSTRACT FROM AUTHOR]