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Abstract Objective Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA). Context Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals. Patients and Methods Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists. Results Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists. Conclusion The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.

Classification schemes for reporting thyroid cytology of fine needle aspiration (FNA) of thyroid nodules are largely used in clinical practice, but the level of inter-observer agreement among cytopathologists is poorly acknowledged. The present study aimed to explore the inter-observer agreement among the experienced authors of the 2014 Italian Consensus for Classification and Reporting of Thyroid Cytology (ICCRTC). A stratified randomization was performed in order to obtain a sample homogeneously distributed and representative of all ICCRTC classes. Four high-experience raters were randomly selected among the extensors of the Italian consensus. They independently reviewed 60 FNA samples blindly of the initial cytological report and clinical features. Their overall agreement was evaluated according to Fleiss’ kappa. The overall inter-observer agreement was moderate (κ 0.46). Specifically, a good agreement was found when the samples were consistent for malignancy (TIR5) or were not adequate for diagnosis (TIR1) (κ 0.67 and κ 0.73, respectively). A moderate agreement was present for suspicious-for-malignant category (TIR4), and a fair agreement was recorded in the two intermediate ones (TIR3A and TIR3B) (κ 0.36 and κ 0.35, respectively). For clinical purposes, the agreement was good (κ 0.74) in differentiating cases with surgical indication (TIR4/TIR5) from those in which surgery is not essential or requires limited extension (TIR3B/TIR3A/TIR2). In conclusion, the present study confirms the reliability of ICCRTC. These data represent a reference for cytopathologists using this system and are useful for the practice of clinicians and surgeons.

Vaginal self-sampling for human papillomavirus (HPV) DNA testing could increase rates of screening participation. In clinic-based settings, vaginal HPV testing is at least as sensitive as cytology for detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse; however, effectiveness in home settings is unknown. We aimed to establish the relative sensitivity and positive predictive value for HPV screening of vaginal samples self-collected at home as compared with clinic-based cervical cytology. We did a community-based, randomised equivalence trial in Mexican women of low socioeconomic status aged 25–65 years. Participants came from 540 medically underserved, predominantly rural communities in Morelos, Guerrero, and the state of Mexico. Our primary endpoint was CIN 2 or worse, detected by colposcopy. We used a computer-generated randomisation sequence to randomly allocate patients to HPV screening or cervical cytology. Eight community nurses who were masked to patient allocation received daily lists of the women's names and addresses, and did the assigned home visits. We referred women with positive results in either test to colposcopy. We did per-protocol and intention-to-screen analyses. This trial was registered with the Instituto Nacional de Salud Pública, Mexico, INSP number 590. 12 330 women were randomly allocated to HPV screening and 12 731 to cervical cytology; 9202 women in the HPV screening group adhered to the protocol, as did 11 054 in the cervical cytology group. HPV prevalence was 9·8% (95% CI 9·1–10·4) and abnormal cytology rate was 0·38% (0·23–0·45). HPV testing identified 117·4 women with CIN 2 or worse per 10 000 (95·2–139·5) compared with 34·4 women with CIN 2 or worse per 10 000 (23·4–45·3) identified by cytology; the relative sensitivity of HPV testing was 3·4 times greater (2·4–4·9). Similarly, HPV testing detected 4·2 times (1·9–9·2) more invasive cancers than did cytology (30·4 per 10 000 [19·1–41·7] vs 7·2 per 10 000 [2·2–12·3]). The positive predictive value of HPV testing for CIN 2 or worse was 12·2% (9·9–14·5) compared with 90·5% (61·7–100) for cytology. Despite the much lower positive predictive value for HPV testing of self-collected vaginal specimens compared with cytology, such testing might be preferred for detecting CIN 2 or worse in low-resource settings where restricted infrastructure reduces the effectiveness of cytology screening programmes. Because women at these sites will be screened only a few times in their lives, the high sensitivity of a HPV screen is of paramount importance. Instituto Nacional de Salud Pública, the Health Ministry of Mexico, QiAGEN Corp

Lung cancer is a leading cause of death worldwide. Currently, in differential diagnosis of lung cancer, accurate classification of cancer types (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma) is required. However, improving the accuracy and stability of diagnosis is challenging. In this study, we developed an automated classification scheme for lung cancers presented in microscopic images using a deep convolutional neural network (DCNN), which is a major deep learning technique. The DCNN used for classification consists of three convolutional layers, three pooling layers, and two fully connected layers. In evaluation experiments conducted, the DCNN was trained using our original database with a graphics processing unit. Microscopic images were first cropped and resampled to obtain images with resolution of 256 × 256 pixels and, to prevent overfitting, collected images were augmented via rotation, flipping, and filtering. The probabilities of three types of cancers were estimated using the developed scheme and its classification accuracy was evaluated using threefold cross validation. In the results obtained, approximately 71% of the images were classified correctly, which is on par with the accuracy of cytotechnologists and pathologists. Thus, the developed scheme is useful for classification of lung cancers from microscopic images.

Cervical microbiota (CM) are considered an important factor affecting the progression of cervical intraepithelial neoplasia (CIN) and are implicated in the persistence of human papillomavirus (HPV). Collection of liquid-based cytology (LBC) samples is routine for cervical cancer screening and HPV genotyping and can be used for long-term cytological biobanking. We sought to determine whether it is possible to access microbial DNA from LBC specimens, and compared the performance of four different extraction protocols: (ZymoBIOMICS DNA Miniprep Kit; QIAamp PowerFecal Pro DNA Kit; QIAamp DNA Mini Kit; and IndiSpin Pathogen Kit) and their ability to capture the diversity of CM from LBC specimens. LBC specimens from 20 patients (stored for 716 ± 105 days) with CIN values of 2 or 3 were each aliquoted for each of the four kits. Loss of microbial diversity due to long-term LBC storage could not be assessed due to lack of fresh LBC samples. Comparisons with other types of cervical sampling were not performed. We observed that all DNA extraction kits provided equivalent accessibility to the cervical microbial DNA within stored LBC samples. Approximately 80% microbial genera were shared among all DNA extraction protocols. Potential kit contaminants were observed as well. Variation between individuals was a significantly greater influence on the observed microbial composition than was the method of DNA extraction. We also observed that HPV16 was significantly associated with community types that were not dominated by Lactobacillus iners .

Organ-specific Parasites in Cattle explores parasitic diseases affecting various organs in cattle, offering a deep dive into their diagnosis, treatment, and prevention. The book provides valuable insights into the etiology, symptoms, and pathophysiology of parasitic infections across critical organ systems, including the gastrointestinal tract, urogenital system, circulatory system, and more. With an emphasis on the latest research, it highlights advanced diagnostics, histopathological techniques, and the development of antiparasitic drugs and vaccines. Readers will gain a thorough understanding of host-parasite interactions, resistance mechanisms, and effective control strategies, all presented with detailed explanations and visual aids. Designed to serve as a key reference, this book is essential for students, researchers, veterinary practitioners, and academicians aiming to deepen their knowledge in parasitology and animal health. Key Features: - Comprehensive coverage of organ-specific parasitic diseases in cattle - Detailed focus on diagnosis, treatment, and preventive strategies - Latest advancements in anti-parasitic drugs and vaccines Readership: Ideal for graduate and postgraduate students, researchers, and veterinarians

- Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. - To provide updated, practical guidelines for the pathologic diagnosis of MM. - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.

The adoption of digital capture of pathology slides as whole slide images (WSI) for educational and research applications has proven utility. To compare pathologists' primary diagnoses derived from WSI versus the standard microscope. Because WSIs differ in format and method of observation compared with the current standard glass slide microscopy, this study is critical to potential clinical adoption of digital pathology. The study enrolled a total of 2045 cases enriched for more difficult diagnostic categories and represented as 5849 slides were curated and provided for diagnosis by a team of 19 reading pathologists separately as WSI or as glass slides viewed by light microscope. Cases were reviewed by each pathologist in both modalities in randomized order with a minimum 31-day washout between modality reads for each case. Each diagnosis was compared with the original clinical reference diagnosis by an independent central adjudication review. The overall major discrepancy rates were 3.64% for WSI review and 3.20% for manual slide review diagnosis methods, a difference of 0.44% (95% CI, -0.15 to 1.03). The time to review a case averaged 5.20 minutes for WSI and 4.95 minutes for glass slides. There was no specific subset of diagnostic category that showed higher rates of modality-specific discrepancy, though some categories showed greater discrepancy than others in both modalities. WSIs are noninferior to traditional glass slides for primary diagnosis in anatomic pathology.