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Introduction: The International System for Serous Fluid Cytopathology (TIS) has gained acceptance and has led to literature validating original concepts and suggesting refinements. In preparation for the second edition of TIS, editors generated a survey to solicit experience with and opinions about TIS., Materials and Methods: An online survey available from March 8 to June 15, 2024, included 56 questions, offered in 7 languages, related to the practice of serous fluid cytopathology., Results: A total of 598 respondents accessed the survey. Information was collected regarding certification, work setting, work volume and years in practice. In the respondent group, 78% (401 of 513) were pathologists, 18% (92 of 513) cytologists of cytotechnologists, 2% (10 of 513) trainees, and 2% (10 of 513) medical scientists. A total of 23% of participants came from academia. Also, 59% of respondents were (280 of 474) from Asia, 17% Europe, 12% North America, and 10% South America. In all, 61% (287 of 474) have adopted TIS. Over 50% issue a preliminary report awaiting ancillary test results. Another 20% issue such a report depending on circumstance. The most frequent request for refinement of criteria centered around Atypia of Uncertain Significance (AUS). Only small numbers of participants provided data on diagnostic category percentage and risk of malignancy (ROM); however, those that did reported a decrease in nondiagnostic and atypical results with corresponding decreases in ROM for those categories. Variable use of cytochemical and immunocytochemical stains for resolving mesothelial proliferations was reported. Respondents indicated a desire for incorporation of recommendations on clinical management and extension of TIS into body fluid types beyond pleural, pericardial, and peritoneal., Conclusions: This survey examines acceptance of TIS and advice for future directions., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm 2 area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Aortic root involvement during acute type A aortic dissection (ATAAD) may depend on ascending aortic wall degeneration. Surgical decision-making for extended resection of the aortic root is clinically made without histopathology. The aim of the study was to investigate whether the degree of degeneration of the ascending aortic wall found in patients with ATAAD is associated with the aortic root involvement., Methods: Collectively, 141 consecutive patients undergoing ATAAD surgery at Tampere University Heart Hospital were investigated. The ascending aortic wall resected in surgery was processed for 11 different variables that describe medial and adventitial degeneration. In addition, atherosclerosis and inflammation were separately evaluated. Patients undergoing aortic root replacement were compared with those with supracoronary reconstruction of the ascending aorta with/without aortic valve surgery (root-sparing surgery) during a mean 4.9-year follow-up., Results: Aortic root replacement together with the ascending aortic replacement was performed in 39% of the patients (n=55). The mean age for all patients was 65 years [standard deviation (SD 13)]. Many patients with aortic root replacement had moderate to severe aortic valve regurgitation (85.5%). Most of the patients with aortic root-sparing surgery included a supracoronary tube prosthesis (89.5%), while nine patients also had aortic valve replacement. The degree of mucoid extracellular matrix accumulation was more prominent in patients with aortic root replacement compared to patients with root-sparing surgery (2.1 SD 0.4 vs. 1.9 SD 0.4, P=0.04, respectively). During follow-up, there were 52 deaths among patients (log rank P=0.79)., Conclusions: Histopathology of the ascending aorta during ATAAD reveals distinctive aortic wall degeneration in patients with aortic root involvement vs. not. The degree of mucoid extracellular matrix accumulation assessed postoperatively is associated with the choice of surgical procedure in many patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-206/coif). All authors report that this work was supported by research funding from the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital, Tuberculosis Foundation, The Finnish Heart Association, Aarne Koskelo Foundation, The Finnish Cultural Foundation. T.C. reports a travel award to attend the 10th Biennial Meeting of the Association for European Cardiovascular Pathology. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: There are numerous methods and procedures described for the preparation of cell blocks (CBs) from cytological samples. The objective of this study was to determine current practices and issues with CBs in European laboratories., Methods: A link to an online survey, with 11 questions about CB practices, was distributed to cytology laboratories via participants of United Kingdom National External Quality Assurance Service for Cellular Pathology Techniques and national representatives in the European Federation of Cytology Societies., Results: A total of 402 laboratories responded completely (337/402, 84%) or partially (65/402, 16%) to the survey by February 4, 2022. The most common CB practice is embedding cell pellets using plasma and thrombin (23.3%), agar (17.1%), Shandon/Epredia Cytoblock (11.4%), HistoGel (7.9%), and Cellient (3.5%). Other methods such as CytoFoam, albumin, gelatin, Cytomatrix, and collodion bags are rarely used (1.0%, 0.7%, 0.7%, 0.3%, and 0.2%, respectively). CBs are also prepared from naturally occurring clots or tissue fragments (29.5%) and cells scraped from unstained or prestained smears (4.4%). The most frequent issues with the CBs in a daily cytology practice are low cellularity (248/402, 62%) and dispersed cells (89/402, 22%), regardless of the CBs preparation method or how the samples for embedding were selected., Conclusions: There is a great variability in CB practices in European laboratories with low cellular CBs as the main issue. Additional studies are mandatory to evaluate and improve performance and cellular yield of CBs., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Progression of proximal or distal aortic dilatation is defined as reverse aortic remodeling after surgery for acute type A aortic dissection (ATAAD) that may be dependent on aortic wall degeneration., Methods: We investigated whether aortic wall degeneration is associated with reverse aortic remodeling leading to aortic reoperation after surgery for ATAAD. Altogether, 141 consecutive patients undergoing surgery for ATAAD at Tampere were evaluated. The resected ascending aortic wall at surgery was processed for 42 degenerative, atherosclerotic and inflammatory histological variables. Patients undergoing aortic reoperations (Redos) were compared with those without aortic reoperations (Controls) during a mean 4.9-year follow-up., Results: Redos were younger than Controls (56 and 66 years, respectively, P < 0.001), and had less frequently previous cardiac surgery prior to ATAAD. Initial surgery encompassed replacement of the ascending aorta in the majority. There were 21 Redos in which one patient died during follow-up as compared with 51 deaths in Controls (log Rank P = 0.002). Histology of the aortic wall revealed increased elastic fiber fragmentation, loss, and disorganization in Redos as compared with Controls (2.1 ± 0.5 vs. 1.9 ± 0.5, Point score unit (PSU), P = 0.043 and 1.7 ± 0.8 vs. 1.2 ± 0.8, PSU, P = 0.016, respectively). Moderate atherosclerosis occurred less often in Redos vs. Controls (9.5% vs. 33%, PSU, P = 0.037, respectively)., Conclusions: According to this exploratory study, histopathology reveals distinctive aortic wall degeneration during ATAAD. Reverse aortic remodeling after ATAAD is associated with the presence of ascending aortic wall elastic fiber fragmentation, loss and disorganization during ATAAD., (© 2024. The Author(s).)

Background: The extent of aortic valve inflammation in patients undergoing aortic valve replacement (AVR) is unsettled. The significance of aortic valve histopathology in patients undergoing AVR is undetermined., Methods: A total of 145 resected aortic valves of consecutive patients undergoing surgery for a local aortic valve disease with or without ascending aorta were investigated for histopathology. The extent of inflammation and degeneration were investigated. Unadjusted survival was evaluated by Kaplan-Meier analysis. Median follow-up was 2.7 years (interquartile range 1.5-3.9)., Results: Mean patient age was 69 (SD 11) years. Though endocarditis was apparent in only six patients preoperatively, severe aortic valve inflammation was diagnosed histologically in 32 patients of whom 12 patients had acute, subacute or chronic endocarditis. Despite complete aortic valve resection, survival was decreased in patients with severe aortic valve inflammation as opposed to those without (log rank, P = 0.044), even after exclusion of patients with endocarditis, emergency and aortic surgery., Conclusions: Aortic valve tissue analysis reveals severe inflammation that may require postoperative treatment. The association of severe but local aortic valve inflammation with patient outcome after aortic valve surgery merits further investigation., (© 2024. The Author(s).)

Background: Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine-needle aspiration (FNA) cases., Methods: FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles., Results: In total, 40 SCs were identified (male-to-female ratio, 14:26) in patients with a mean age of 52 years (age range, 13-80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round-to-oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA-3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6-NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next-generation sequencing (n = 1)., Conclusions: Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy., (© 2022 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The magnitude of ascending aortic degeneration in patients with bicuspid aortic valves (BAV) is controversial., Methods: The aim of this study was to investigate ascending aortic wall degeneration in patients with BAV as compared with tricuspid aortic valves (TAV). The ascending aortic wall of 67 consecutive patients was processed for histology and immunohistochemistry. The extent of surgery and wall degeneration were investigated. Unadjusted survival was evaluated by Kaplan-Meier analysis. Median follow-up for patients with BAV and TAV was 3.8 years (interquartile range [IQR] 3.5-4.1) and 3.7 years (IQR 3.4-3.9), respectively., Results: There were 33 patients with BAV and 34 with TAV. Mid-ascending aorta diameter was 54 mm (IQR 50-60). Replacement of the aortic valve, together with an ascending aortic prosthesis, was more frequent in BAV vs TAV patients (24% vs. 3%, P = 0.013). However, medial fibrosis, elastic fiber thinning, incremental medial degeneration and smooth muscle cell nuclei loss were less prominent in BAV vs TAV patients (0.1 ± 0.4 vs. 0.8 ± 1.4, P = 0.016; 0.6 ± 1.4 vs. 1.6 ± 2.0, P = 0.027; 1.7 ± 0.7 vs. 2.2 ± 0.8, P = 0.045 and 2.3 ± 1.5 vs. 3.2 ± 1.3, P = 0.026, respectively)., Conclusions: Since degeneration of the ascending aortic wall was seldom prominent, histopathology alone may not support the need for surgery of the dilated ascending aorta in BAV patients as compared with TAV patients., (© 2022. The Author(s).)

Background: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020)., Methods: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses., Results: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001)., Conclusions: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality., (© 2022 American Cancer Society.)

In sudden cardiac death, an autopsy is an essential step in establishing a diagnosis of inherited cardiac disease and identifying families that require cardiac screening. To evaluate aspects of post-mortem practice in Europe, a questionnaire was designed and circulated to both clinical and forensic pathologists. There was a 48% response rate and information was obtained from 17 countries. The results showed a wide variety in the management of sudden cardiac death, with a general tendency towards a lack of thorough investigation. In up to 40% of cases, autopsies were not performed in subjects less than 50 years who may have died from cardiac disease. Reasons for this were lack of finance and lack of interest from police, legal authorities, and doctors. Only 50% of pathologists seem to follow a standard protocol for autopsy examination, apparently due to lack of expertise and/or training. When autopsies were performed, histology and toxicology were almost always taken, genetic studies were generally available and retention of the heart for specialist study was usually permitted. Our results suggest that although the standard of practice is appropriate in many centres, many more cases should have autopsies, especially in sudden deaths in subjects less than 50 years.

Purpose: The treatment strategy of parotid gland tumours depends mainly on the histopathological type of the lesion. Fine-needle aspiration biopsy (FNAB) is recommended in preoperative diagnostics. The aim of the study was to evaluate the FNAB standing in the diagnostic algorithm of parotid gland lesions and to correlate FNAB results in relation to the definitive histopathological diagnosis., Material and Methods: The retrospective analyses of 651 examined and consequently surgically treated parotid gland lesions at the Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague between 2006 and 2016 were used. Preoperative cytological results were consequently evaluated in relation to the definitive histopathological diagnosis., Results: The cohort consisted of 367 women and 284 men (average age 58 years). FNAB was diagnostic in 604 (92.8%) patients and non-diagnostic in 47 (7.2%) patients. The result of FNAB was positive (suspicious for malignant tumour) in 89 (14.7%) patients and negative (benign) in 515 (85.3%) patients. Sensitivity of the examination was 80.00%, specificity was 93.82%, PPV 62.92%, NPV 97.28%, and LR + and LR- were 12.95 and 0.21, respectively, with an accuracy of 92.22%., Conclusion: Our results confirm the significant role of FNAB in the diagnostic algorithm of parotid gland lesions.

Background/aim: The aim of this study was to examine clonal heterogeneity, to test the utility of liquid biopsy in monitoring disease progression and to evaluate the usefulness of ex vivo drug screening in a BRAF L597Q-mutated colorectal cancer (CRC) patient developing metastases during adjuvant therapy., Materials and Methods: Next generation sequencing (NGS) and droplet digital PCR (ddPCR) were performed in samples from tumor tissues and liquid biopsies. Live cancer cells from a metastatic lesion were used in ex vivo drug sensitivity assays., Results: We found evidence of continued dependence of MEK/MAPK pathway activation, but different activating mutations in primary tumor and metastases. Liquid biopsy based BRAF L597Q ddPCR testing was a sensitive personalized biomarker predicting the rise of clinically aggressive metastatic disease. Ex vivo drug sensitivity assays with BRAF L597Q mutated cells showed response to MEK/MAPK targeted therapies., Conclusion: The rare BRAF L597Q mutation may be associated with aggressive tumor behavior in CRC. Liquid biopsy can be used to capture clinically relevant tumor features., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We evaluated the diagnostic accuracy (DA), risk of neoplasm (RON), and risk of malignancy (ROM) for the commonly encountered malignant salivary gland tumors mucoepidermoid carcinoma (MECa), acinic cell carcinoma (ACCa), and adenoid cystic carcinoma (ADCa) applying The Milan System for Reporting Salivary Gland Cytology (MSRSGC)., Materials and Methods: The cytology archives from 2007 to 2017 of 9 academic institutions were searched for salivary gland FNAs for the following key words mentioned either in the principal and/or differential diagnosis: MEC, ACCa, and ADCa. The original cytology diagnosis was retrospectively classified according to the MSRSGC. Patient demographics, biopsy site, and available surgical follow-up were recorded. The final analysis included only cases with surgical follow-up., Results: A total of 212 salivary gland FNAs were included. Based on retrospective reclassification according to MSRSGC, 97 of 212 (46%) FNA cases carried a diagnosis of malignancy specific for either MECa, ACCa, or ADCa. In the remaining 115 cases, 24 of 212 (11%) were reclassified as suspicious for malignancy (SM) and 91 of 212 (43%) as salivary gland neoplasm of uncertain malignant potential (SUMP). The DA for MECa, ACCa, and ADCa was 78.7%, 75% and 89%, respectively. The RON was 100% for all 3 tumors and the ROM was 93.6% for MECa, 96.8% for ACCa, and 94.4% for ADCa., Conclusions: The DA of 78.7% for MECa, 75% for ACCa, and 89% for ADCa is reasonable in FNA specimens. Although the management of definitive cases of malignancy remains unchanged, the MSRSGC provides a ROM for SM and SUMP categories, which can improve patient management., (Copyright © 2019 American Society of Cytopathology. All rights reserved.)

Background/aim: The aim of this study was to analyze the pretreatment cytokeratin serum levels in head and neck squamous cell carcinoma (HNSCC) by three assays in relation to selected clinicopathological characteristics in an effort to find diagnostic/prognostic biomarkers for HNSCC and determine the best assay., Patients and Methods: In total, 46 patients with HNSCC with different subsite (oropharyngeal-21 cases, hypopharyngeal-4 and laryngeal-21) were included in this prospective study. MonoTotal, Cyfra 21-1, and TPS radioimmunoassay kits were used to analyze cytokeratin fragments serum levels., Results: Statistically significant differences in serum levels of TPS and Cyfra 21-1 were found between low (stage I-II)- and high-stage (stage III-IV) tumors (p=0.0057; p=0.0138 respectively). Cyfra21-1 assay showed significant differences between tumors of different sites with prominent elevation being found in oropharyngeal carcinomas and between patients with p16 positive and p16 negative HNSCC (p=0.0242), being elevated in p16 positive tumors., Conclusion: The present study is the first to compare cytokeratin serum levels between various subgroups of HNSCC using three different assays. Cyfra 21-1 seems to be the most useful for clinical practice. The relation between elevated Cyfra 21-1 serum levels and p16 expression requires further investigation., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Neovascularization of the aortic wall may be associated with aortic dissection (AD). Aortic wall endothelial CD31 deposition together with chronic inflammation indicates angiogenesis that may lead to tissue disruption. We studied the presence of neovascularization of the ascending aortic wall by characterizing CD31 positive endothelial cells., Methods: Aortic wall routine histology and immunohistochemistry for CD31, T- and B-lymphocytes, plasma cells, macrophages, endothelial cells, smooth muscle cells, and cell proliferation were performed on 35 selected patients who underwent surgery for the ascending aorta, and the samples were grouped according to the presence of AD., Results: Three subjects with Marfan syndrome were excluded from the study. A total of 14 out of 32 patients had AD. A total of 18 patients were operated on due to dilatation only. Chronic inflammation of the adventitia (p=0.003), media (p=0.001), and intima (p=0.005) was increased in AD. Neovascularization was predominant in the outer third medial layer in AD (p=0.037), corresponding to the site of aortic wall disruption. A receiver operating characteristic curve analysis showed that neovascularization was associated with AD (AUC 0.750; SE 0.092; p=0.022; 95% CI 0.570-0.930)., Conclusion: Endothelial immunohistochemistry confirms neovascularization of the outer third medial layer during AD. Aortic wall remodeling including neovascularization characterizes AD. Chronic inflammation and neovascularization of the dilated ascending aorta suggest susceptibility for AD.

α-melanocyte-stimulating hormone (α-MSH) is processed from pro-opiomelanocortin (POMC) and mediates anti-inflammatory actions in leukocytes. α-MSH also promotes macrophage reverse cholesterol transport by inducing ATP-binding cassette transporters ABCA1 and ABCG1. Here we investigated the regulation of POMC and α-MSH expression in atherosclerosis. First, transcript levels of POMC and its processing enzymes were analyzed in human arterial plaques (n = 68) and non-atherosclerotic controls (n = 24) as well as in whole blood samples from coronary artery disease patients (n = 55) and controls (n = 45) by microarray. POMC expression was increased in femoral plaques compared to control samples as well as in unstable advanced plaques. α-MSH-producing enzyme, carboxypeptidase E, was down-regulated, whereas prolylcarboxypeptidase, an enzyme inactivating α-MSH, was up-regulated in unstable plaques compared to stable plaques, suggesting a possible reduction in intraplaque α-MSH levels. Second, immunohistochemical analyses revealed the presence of α-MSH in atherosclerotic plaques and its localization in macrophages and other cell types. Lastly, supporting the role of α-MSH in reverse cholesterol transport, POMC expression correlated with ABCA1 and ABCG1 in human plaque and whole blood samples. In conclusion, α-MSH is expressed in atherosclerotic plaques and its processing enzymes associate with plaque stability, suggesting that measures to enhance the local bioavailability of α-MSH might protect against atherosclerosis.

Objectives/hypothesis: To study the pathology of upper airway mucosa, as well as valuate and compare changes in pathology after the treatment of chronic rhinosinusitis (CRS) patients with balloon sinuplasty versus uncinectomy., Methods: A prospective randomized controlled trial in patients with CRS of the maxillary sinuses without severe pathology of other sinuses. Patients were randomized into two groups: uncinectomy and balloon sinuplasty. The main variables in our study are histopathology of nasal mucosa and expression of metalloproteinase-9 protein. These parameters were analyzed preoperatively and at 3 months, 6 months, and 12 months postoperatively., Results: Thickened epithelium, absence of cilia, metaplasia of epithelium, hyperplasia of mucosal glands, angiogenesis, and increased inflammatory cells were observed in the majority of preoperative samples. History of allergy was associated with a higher number of goblet cells, and shedding of epithelium was associated with worse quality of life. A higher number of inflammatory cells were associated with an increased number of goblet cells preoperatively, as well as after treatment. Both treatments resulted in a decrease of inflammation in the mucosa and epithelium. Hypertrophy of the mucosal glands, hyperplasia of blood vessels, and mucosal edema decreased after treatment. These changes were more noticeable in uncinectomy group. Balloon sinuplasty was associated with a higher number of inflammatory cells at 6 months after treatment (P = 0.05)., Level of Evidence: 1b. Laryngoscope, 126:2652-2658, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys-Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behçet's disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Kindlins (FERMT) are cytoplasmic proteins required for integrin (ITG) activation, leukocyte transmigration, platelet aggregation and thrombosis. Characterization of kindlins and their association with atherosclerotic plaques in human(s) is lacking., Methods and Results: Exploratory microarray (MA) was first performed followed by selective quantitative validation of robustly expressed genes with qRT-PCR low-density array (LDA). In LDA, ITGA1 (1.30-fold, p = 0.041) and ITGB3 (1.37-fold, p = 0.036) were upregulated in whole blood samples of patients with coronary artery disease (CAD) compared to healthy controls. In arterial plaques, both robustly expressed transcript variants of FERMT3 (MA: 5.90- and 3.4-fold; LDA: 3.99-fold, p < 0.0001 for all) and ITGB2 (MA: 4.81- and 4.92-fold; LDA: 5.29-fold, p < 0.0001 for all) were upregulated while FERMT2 was downregulated (MA: -1.61-fold; LDA: -2.88-fold, p < 0.0001 for both). The other integrins (ITGA1, ITGAV, ITGB3, ITGB5) were downregulated. All these results were replicated in at least one arterial bed. The latter FERMT3 transcript variant associated with unstable plaques (p = 0.0004). FERMT3 correlated with M2 macrophage markers and in hierarchical cluster analysis clustered with inflammatory and macrophage markers, while FERMT2 correlated with SMC-rich plaque markers and clustered with SMC markers. In confocal immunofluorescence analysis, FERMT3 protein colocalized with abundant CD68-positive cells of monocytic origin in the atherosclerotic plaques, while co-localization of FERMT3 with HHF35 indicative of smooth muscle cells was low., Conclusions: Kindlin-3 (FERMT3) is upregulated in atherosclerotic, especially unstable plaques, mainly in cells of monocytic origin and of M2 type. Simultaneous upregulation of ITGB2 suggests a synergistic effect on leukocyte adherence and transmigration into the vessel wall., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)