Diagnostic Pathology Research Articles

Molecular underpinnings of dedifferentiation and aggressiveness in chromophobe renal cell carcinoma.

Sarcomatoid dedifferentiation is common to multiple renal cell carcinoma (RCC) subtypes, including chromophobe RCC (ChRCC), and is associated with increased aggressiveness, resistance to targeted therapies, and heightened sensitivity to immunotherapy. To study ChRCC dedifferentiation, we performed multiregion integrated paired pathological and genomic analyses. Interestingly, ChRCC dedifferentiates not only into sarcomatoid but also into anaplastic and glandular subtypes, which are similarly associated with increased aggressiveness and metastases. Dedifferentiated ChRCC shows loss of epithelial markers, convergent gene expression, and whole genome duplication from a hypodiploid state characteristic of classic ChRCC. We identified an intermediate state with atypia and increased mitosis but preserved epithelial markers. Our data suggest that dedifferentiation is initiated by hemizygous mutation of TP53, which can be observed in differentiated areas, as well as mutation of PTEN. Notably, these mutations become homozygous with duplication of preexisting monosomes (i.e., chromosomes 17 and 10), which characterizes the transition to dedifferentiated ChRCC. Serving as potential biomarkers, dedifferentiated areas become accentuated by mTORC1 activation (phospho-S6) and p53 stabilization. Notably, dedifferentiated ChRCC share gene enrichment and pathway activation features with other sarcomatoid RCC, suggesting convergent evolutionary trajectories. This study expands our understanding of aggressive ChRCC, provides insight into molecular mechanisms of tumor progression, and informs pathologic classification and diagnostics.

A Continuum of Nerve Biopsies in Peripheral Neuropathy: A Clinicopathological Insight

Background: Peripheral neuropathy is a common neurological disease faced by the neurologists these days. The role of nerve biopsy is ambiguous and the dilemma to identify the underling etiology further adds to the uncertainty. However, ruling out certain etiological causes and confirming specific diagnosis still mandates the procedure. Aim: The aim of the study is to evaluate the contribution of nerve biopsy in peripheral neuropathies and study the histomorphological spectrum of these biopsies. Material and methods: A retrospective 2-year review of 54 nerve biopsies received in the Department of Pathology was performed at a tertiary care centre. Results: A total of 54 nerve biopsies were reviewed during the study period, of which, 6 biopsies (11%) were considered inadequate. Biopsies were broadly divided as biopsies supportive for patient management and biopsies essential for patient management. Biopsies essential for patient management (n=16) comprise vasculitic neuropathy (n=9), lepromatous neuropathy (n=4), hereditary motor sensory neuropathy (n=1) and CIDP (n=2). Biopsies supportive for patient management (n=14) comprise axonal neuropathies (n=6), demyelinating neuropathies (n=5) and mixed neuropathies (predominantly Axonal with secondary demyelinating features, n=3). No diagnostic pathology was identified in 13 cases (24%). Conclusion: With the advent of molecular tests and electrophysiologic examinations, nerve biopsy is losing its charm. However, its contribution still hold grounds in specific etiologies like Vasculitic neuropathy, lepromatous neuropathy and to some extent in management of CIDP. Increase in awareness among the pathologists of the histomorphology is essential to aid the physicians managing these patients. Keywords: Nerve biopsies, Axonal neuropathy, Demyelinating neuropathy, CIDP

Molecular pathological analysis through the ages

Molecular pathological examinations of tumor samples encompass awide range of diagnostic analyses. Especially in recent years, numerous new biomarkers have come to the forefront-the analysis of which is crucial for therapy decisions. Within the field of molecular pathology, the demands of next generation sequencing (NGS)-based requirements have experienced massive growth in recent years. To meet this demand, methods are constantly being adapted and further developed. The following sections aim to illuminate how this trend arises and which analyses are gaining importance. The article provides an overview of the essential nucleic acid-based analysis techniques in the field of massive parallel sequencing. Terms such as DNA- and RNA-based techniques, as well as the associated analysis methods, are described, particularly with regard to their use in routine molecular pathological diagnostics. The breadth of genomic sequencing has been steadily growing in recent years, particularly due to the increasing relevance of personalized medicine, along with the rising approvals of targeted therapeutics. This necessitates, among other things, the analysis of new biomarkers. The diagnostics as part of interdisciplinary molecular tumor boards (MTB) are now based on large gene panels (> 1 megabase). Furthermore, through the "Modellvorhaben Genomsequenzierung" §64e, whole exome or whole genome sequencing has been made available for oncological patients. Given these developments, it is evident that future analyses will require the integration of additional omics fields, such as whole transcriptome analysis, epigenomics, and proteomics. The challenges of personalized medicine along with the necessity of simultaneously assessing numerous new biomarkers require the implementation and execution of new techniques in molecular pathology whose complexity is steadily increasing.

The digital revolution in pathology: Towards a smarter approach to research and treatment.

Artificial intelligence (AI) applications in oncology are at the forefront of transforming healthcare during the Fourth Industrial Revolution, driven by the digital data explosion. This review provides an accessible introduction to the field of AI, presenting a concise yet structured overview of the foundations of AI, including expert systems, classical machine learning, and deep learning, along with their contextual application in clinical research and healthcare. We delve into the current applications of AI in oncology, with a particular focus on diagnostic imaging and pathology. Numerous AI tools have already received regulatory approval, and more are under active development, bringing clear benefits but not without challenges. We discuss the importance of data security, the need for transparent and interpretable models, and the ethical considerations that must guide AI development in healthcare. By providing a perspective on the opportunities and challenges, this review aims to inform and guide researchers, clinicians, and policymakers in the adoption of AI in oncology.

Artificial intelligence in kidney transplant pathology

Artificial intelligence (AI) systems have showed promising results in digital pathology, including digital nephropathology and specifically also kidney transplant pathology. Summarize the current state of research and limitations in the field of AI in kidney transplant pathology diagnostics and provide afuture outlook. Literature search in PubMed and Web of Science using the search terms "deep learning", "transplant", and "kidney". Based on these results and studies cited in the identified literature, aselection was made of studies that have ahistopathological focus and use AI to improve kidney transplant diagnostics. Many studies have already made important contributions, particularly to the automation of the quantification of some histopathological lesions in nephropathology. This likely can be extended to automatically quantify all relevant lesions for akidney transplant, such as Banff lesions. Important limitations and challenges exist in the collection of representative data sets and the updates of Banff classification, making large-scale studies challenging. The already positive study results make future AI support in kidney transplant pathology appear likely.

SONOGRAPHIC PARAMETERS IN THE DIAGNOSIS OF CHRONIC CERVICITIS

Introduction. Inflammatory diseases of the pelvic organs (IDPO) remain the most relevant issue in contemporary gynecology. In modern diagnostics of reproductive organ pathologies, a highly effective and accessible method is ultrasound examination. Recent studies in this field, conducted using high-frequency digital transvaginal echography, have significantly contributed to reevaluating the potential of ultrasonographic diagnosis of the cervix; however, further research is warranted.
 The aim of this research is to enhance the diagnosis of cervical changes in cervicitis.
 Materials and methods. The study included 68 women with chronic cervicitis. The diagnosis was established based on clinical, colposcopy, and bacterioscopist examinations. During transvaginal ultrasound examinations, the cervix was visualized in both longitudinal and transverse projections for all patients. The patients with chronic cervicitis were divided into two groups: Group I consisted of 37 patients with visual changes in the cervix, while Group II comprised 31 women without any changes. A comparison group included 35 healthy women.
 Results. Chronic cervicitis is characterized by an increase in the thickness and volume of the cervix, as well as the heterogeneity of the stroma due to cystic cavities, with elevated ratios of cervix thickness to length and endocervix thickness to cervix thickness. Significant sonographic signs of the inflammatory process in the endocervix also include certain structural features, such as indistinct contours, increased echogenicity, small cysts, and multiple microcalcifications in the endocervix, uneven dilation of the cervical canal, and an area of reduced echogenicity.
 Conclusions. Therefore, a thorough ultrasound examination to determine the condition of the cervix, thickness, and structure of the endocervix can be a valuable adjunct non-invasive tool in the diagnosis of chronic cervicitis and can assist clinicians in diagnosing this pathology even in cases where there are no visual changes in the cervix during an examination.

AUTOTRANSPLANTATION WITH EXTRACORPORAL RECONSTRUCTION OF RENAL VESSELS: A CLINICAL CASE OF “THE NUTCRACKER SYNDROME” AND LEFT RENAL ARTERIES HYPOPLASIA COMBINATION

Ex vivo kidney autotransplantation with renal artery reconstruction is an effective method of surgical correction of vascular abnormalities (fibromuscular dysplasia, hypoplasia, and renal artery aneurysms) showing good long-term results. The combination of renal artery abnormalities with aorto-mesenteric compression syndrome (“the nutcracker” syndrome) is extremely rare and complicates the diagnosis making greatly. Renal artery hypoplasia is an abnormality that is rarely diagnosed and may not manifest clinically in the absence of contralateral kidney pathology as well as its vascular structures. Renal hypoplasia may be caused by mutations in the kidney development genes (HNF1B, PAX2, PBX1) and/or several environmental factors such as intrauterine growth retardation, maternal diseases (diabetes, hypertension), medication taken by the mother (renin-angiotensin system inhibitors or nonsteroidal anti-inflammatory drugs) and intoxication (smoking and alcohol). Premature delivery (before the 36th week) is also a risk factor due to incomplete nephrogenesis. Renal arteries hypoplasia is associated with fibromuscular dysplasia in most cases. The disease is characterized by non-inflammatory non-uniform focal hyperplasia of the renal artery wall with damage to small and medium arteries. Simultaneous damage to two or more vascular segments is detected in 25% of patients.
 A clinical case of successful treatment of “the nutcracker” syndrome (annular renal vein) combined with hypoplasia of the left main and accessory renal arteries associated with fibromuscular dysplasia is described. A 27-year-old female was admitted to the Department of Vascular Surgery of Municipal Noncommercial Enterprise of the Lviv Regional Council “Lviv Regional Clinical Hospital” on October 4, 2021, with complaints of pain in the left lumbar region and the left half of the abdomen, hematuria, proteinuria, a persistent increase in blood pressure. Ultrasound of the renal veins: the left renal vein in the aorto-mesenteric segment was not visualized, the posterior portion of the left renal vein was determined. Peak systolic velocity was up to 230 cm/s at the point of confluence with the inferior vena cava and 28 cm/s more distally. The vein was up to 12.0 mm in the renal hilum and up to 11.0 mm in the middle third. MSCT of the abdominal cavity, retroperitoneal space and pelvic organs: CT signs of pyelonephritis of the left kidney. Hypoplasia of the left kidney. Reactive para-aortic lymphadenopathy on the left. Hypoplastic left renal artery (3,8 mm) and presense of accessory ones, annular left renal vein. Angiomyolipoma of the right kidney (2,6 cm). Varicose veins of the small pelvis on the left. The patient underwent surgical treatment, namely ex vivo autovenous prosthetic repair of the left renal artery with autotransplantation of the left kidney. The course of the postoperative period was without complications, the reconstruction was functioning. Ultrasound of the renal vessels (1 week after the surgery): the blood flow was located in the renal hilum in the course of Doppler sonography of intrarenal branches. Venous outflow was unobstructed. Corticomedullary differentiation was marked satisfactorily.
 The study presented by us demonstrates the effectiveness of kidney autotransplantation for the correction of renal vascular abnormalities.
 Though of a solitary nature, the combination of renal vessels abnormalities complicates significantly the course of the disease and the possibilities of this pathology diagnostics.

Enhancing Specific Fluorescence In Situ Hybridization with Quantum Dots for Single-Molecule RNA Imaging in Formalin-Fixed Paraffin-Embedded Tumor Tissues.

Single-molecule fluorescence in situ hybridization (smFISH) represents a promising approach for the quantitative analysis of nucleic acid biomarkers in clinical tissue samples. However, low signal intensity and high background noise are complications that arise from diagnostic pathology when performed with smFISH-based RNA imaging in formalin-fixed paraffin-embedded (FFPE) tissue specimens. Moreover, the associated complex procedures can produce uncertain results and poor image quality. Herein, by combining the high specificity of split DNA probes with the high signal readout of ZnCdSe/ZnS quantum dot (QD) labeling, we introduce QD split-FISH, a high-brightness smFISH technology, to quantify the expression of mRNA in both cell lines and clinical FFPE tissue samples of breast cancer and lung squamous carcinoma. Owing to its high signal-to-noise ratio, QD split-FISH is a fast, inexpensive, and sensitive method for quantifying mRNA expression in FFPE tumor tissues, making it suitable for biomarker imaging and diagnostic pathology.

Natural Infection with H5N1 Highly Pathogenic Influenza (HPAI) Virus in 5- and 10-Day-Old Commercial Pekin Ducklings (Anas platyrhynchos domesticus).

Highly pathogenic avian influenza (HPAI) has resulted in catastrophic economic losses globally in poultry. This case report describes the diagnostic detection and pathology of HPAI H5N1 in 5-day-old commercial ducklings, which is an atypical age for detection of natural infection of HPAI in poultry. The pathology observed at 5 days of age was also compared to lesions observed in ducklings from the same flock evaluated at 10 days of age before depopulation. The California Animal Health and Food Safety (CAHFS) Laboratory, Tulare, received ten 5-day-old Pekin duckling (Anas platyrhynchos domesticus) carcasses for diagnostic evaluation due to mortality that started increasing at 3 days of age. The most common gross findings included bilateral pulmonary edema with congestion and enlarged, mottled livers and spleens. Microscopically, cerebral neuronophagia, pancreatic necrosis, and interstitial pneumonia with pulmonary edema were observed in the 5-day-old ducklings. Oropharyngeal and cloacal swabs were positive for avian influenza virus (AIV) by real-time reverse transcriptase PCR. The AIV was typed as HPAI, EA/AM 2.3.4.4b H5N1 goose/Guangdong clade lineage by the National Veterinary Services Laboratory. Ducks at the affected premises were depopulated 4 days after the 5-day-old ducklings were submitted to the CAHFS lab, at which time additional tissue samples were collected for comparison to 10-day-old ducklings on the same premises. Differences in microscopic lesions and AIV tissue distribution were observed between the 5-day and 10-day tissues collected. Notably, microscopic lesions were more severe in the brain and pancreas at 10 days of age. Findings in 10-day-old ducklings included cerebral lymphoplasmacytic perivascular cuffing, gliosis, neuronal degeneration, and pancreatic necrosis. AIV antigen distribution and intensity was greatest in the cerebral tissue of the brains at 10 days and in the lungs at 5 days of age. To the authors' knowledge, published studies are limited on AIV natural infection in domestic ducks less than 9 days of age.

Application and fallibility of Artificial Intelligence and machine learning in Diagnostic Pathology

Artificial intelligence (AI) refers to the use of technology and computers to replicate behavioral intelligence and analytical reasoning that is equivalent to that of a human being. The medical sciences make substantial use of computer systems with artificial intelligence which primarily include remote patient treatment, prescription recording, increasing doctor-patient interaction, medication discovery and patient diagnosis. Its application in health care industry is mainly because of increased job demands, difficult tasks, and probable doctor weariness all have the potential to impair diagnostic performance. In this review we have enlightened the various roles of AI such as automated diagnosis, predictive analysis, image analysis, precision medicine and the biomarker development. The use of AI tools in pathology has grown significantly in recent years, and it is predicted that they will revolutionize the field in the years to come. AI tools can change how pathology functions while rendering it more efficient at meeting the demands of the modern era of precision medicine. Bangladesh Journal of Medical Science Vol.23 (Special Issue) 2024 p.S32-S37

Pros and cons of artificial intelligence implementation in diagnostic pathology.

The rapid introduction of digital pathology has greatly facilitated development of artificial intelligence (AI) models in pathology that have shown great promise in assisting morphological diagnostics and quantitation of therapeutic targets. We are now at a tipping point where companies have started to bring algorithms to the market, and questions arise whether the pathology community is ready to implement AI in routine workflow. However, concerns also arise about the use of AI in pathology. This article reviews the pros and cons of introducing AI in diagnostic pathology.

Assessment of the risk of developing cardiovascular pathology in medical university students

Diseases of the cardiovascular system (hypertension, coronary heart disease, and heart failure) occupy leading places in the overall pathology structure. A specific feature is a growing share of young people who suffer from cardiovascular diseases (CVDs) in the total population. This is facilitated by physical inactivity, unhealthy diets, elevated stress levels as well as genetic predisposition. Identification of leading risk factors at the latent stage can make for timely diagnostics of cardiovascular pathology in young people. This, in its turn, allows implementing relevant prevention as well as adjusting therapies thereby improving quality of life of each individual patient. Given that, the aim of this study was to assess risk factors causing CVDs in medical university students; to determine severity of existing cardiovascular disorders as well as their relationships with factors that may have caused them. Eight hundred and seventeen students participated in the study. They all took part in a survey to identify risks of developing CVDs with certain adjustments made to an applied questionnaire to adapt it for use among students. Also, the study involved assessing basic anthropometric parameters (height, weight, and body mass index (BMI)), hypertension in family case history, physical activity, time spent with gadgets (use of smartphone), and alcohol consumption. The study revealed that 30 % of the examined people had overweight; more than 54 % abused alcohol; 53 % of the respondents mentioned elevated stress levels. All this creates significantly elevated risks of cardiovascular diseases as well as their complications for young and middle-aged people. The study results clearly indicate elevated risks of cardiovascular pathology and this requires correction of risk factors at an early stage.

Оценка риска развития сердечно-сосудистой патологии у студентов медицинского вуза

Diseases of the cardiovascular system (hypertension, coronary heart disease, and heart failure) occupy leading places in the overall pathology structure. A specific feature is a growing share of young people who suffer from cardiovascular diseases (CVDs) in the total population. This is facilitated by physical inactivity, unhealthy diets, elevated stress levels as well as genetic predisposition. Identification of leading risk factors at the latent stage can make for timely diagnostics of cardiovascular pathology in young people. This, in its turn, allows implementing relevant prevention as well as adjusting therapies thereby improving quality of life of each individual patient. Given that, the aim of this study was to assess risk factors causing CVDs in medical university students; to determine severity of existing cardiovascular disorders as well as their relationships with factors that may have caused them. Eight hundred and seventeen students participated in the study. They all took part in a survey to identify risks of developing CVDs with certain adjustments made to an applied questionnaire to adapt it for use among students. Also, the study involved assessing basic anthropometric parameters (height, weight, and body mass index (BMI)), hypertension in family case history, physical activity, time spent with gadgets (use of smartphone), and alcohol consumption. The study revealed that 30 % of the examined people had overweight; more than 54 % abused alcohol; 53 % of the respondents mentioned elevated stress levels. All this creates significantly elevated risks of cardiovascular diseases as well as their complications for young and middle-aged people. The study results clearly indicate elevated risks of cardiovascular pathology and this requires correction of risk factors at an early stage.

Digital Pathology in the Detection of Infectious Microorganisms: An Evaluation of Its Strengths and Weaknesses Across a Panel of Immunohistochemical and Histochemical Stains Routinely Used in Diagnostic Surgical Pathology.

The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of microorganism detection from digital images must be delineated. To assess the reliability of microorganism detection from digitized images of histochemical and immunohistochemical stains commonly used in pathology. Original glass slides from 620 surgical pathology cases evaluated for the presence of infectious microorganisms were digitized. Immunohistochemical stains included those for herpes simplex virus (n = 100), cytomegalovirus (n = 100), Helicobacter pylori (n = 100), and spirochetes (n = 80). Histochemical stains included mucicarmine for Cryptococcus spp (n = 20), Grocott methenamine silver for fungi (n = 100), Giemsa for H pylori (n = 100), and Ziehl-Neelsen for acid-fast bacilli (n = 20). The original diagnosis based on the glass slides was regarded as the reference standard. Six pathologists reviewed the digital images. Digital review was generally associated with high (ie, ≥90%) specificity and positive predictive value owing to a low percentage of false positive reads, whereas a high percentage of false negatives contributed to low sensitivity and negative predictive value for many stains. Fleiss κ showed substantial interobserver agreement in the interpretation of Grocott methenamine silver and immunostains for herpes simplex virus, H pylori, and cytomegalovirus; moderate agreement for spirochete, Ziehl-Neelsen, and mucicarmine; and poor agreement for Giemsa. Digital immunohistochemistry generally outperforms histochemical stains for microorganism detection. Digital interpretation of Ziehl-Neelsen and mucicarmine stains is associated with low scores for interrater reliability, accuracy, sensitivity, and negative predictive value such that it should not substitute for conventional review of glass slides.

Embodied cognition and the imaging of bio-pathologies: the question of experiential primacy in detecting diagnostic phenomena.

This article investigates the origins of the experiences involved in the diagnostics (detection and normative evaluation) of biological entities in image-based medical praxis. Our specific research aim presupposes a vast discussion regarding the origins of knowledge in general, but is narrowed down to the alternatives of anthropomorphism and biomorphism. Accordingly, in the subsequent chapters we will make an attempt to investigate and illustrate what holds the diagnostic experiential situation together-biological regularities, manifestation via movement, conscious synthesis, causal categories, or something else. We argue that as long as knowledge originates out of practices, a promising way forward is to oscillate between the prominent although controversial ideas of the history of philosophy and observations of concrete human practices, such as, in our chosen example, image-based medical diagnostics of biological pathologies. Although a number of thinkers are involved in the discussion, Aristotle and Husserl are most important here as the representatives of historical paradigms on the matter. The body in this research was not taken solely as the physical entity (Körper) but rather as a transcendental, constitutive structure where diagnostic and biological processes synchronize in teleological movement (Leib). However, philosophical speculations are illustrated by actual radiograms, the interpretation of which brings us back to the aforementioned question of primacy regarding cognition.

A snapshot of the landscape of endometrial cancer in Kenya: Implications of recent updates in pathological classification

Background: The incidence of endometrial carcinoma is rising worldwide, partly due to the risingprevalence of obesity. From a diagnostic pathology perspective, it is a heterogeneous disease with avaried range of histomorphological features and is prone to poor interobserver reproducibility. This oftenhas downstream effects on treatment protocols and patient outcomes. The current WHO Classification ofTumors of the Female Genital Tract recommends the incorporation of histology, immunohistochemistry,and molecular testing where possible in the classification of endometrial carcinoma into clinically relevantsubtypes. In Kenya, access to ancillary testing is limited and prohibitively expensive, negatively affectingaccurate tumor classification. In addition, there are limited local data on the various histologic subtypes ofendometrial carcinoma and their respective clinical outcomes.Objectives: To review the classification of endometrial carcinoma as defined by the current WHOClassification contextualized with local clinical, demographic, pathology, and outcome data from twotertiary referral centers in Kenya.Methods: Formalin-fixed paraffin-embedded blocks (FFPE) of 123 cases of endometrial carcinomasbetween 2012 and 2020 were retrieved from the Aga Khan University and Moi Teaching and ReferralHospitals. The clinical history and follow-up data were abstracted. Hematoxylin and eosin sections werereviewed and 11 immunohistochemical markers (MLH1, MSH2, MSH6, PMS2, ER, PR, ARID1A, P16,PTEN, napsin A, and p53) were determined, and analyzed to arrive at a consensus diagnosis.Results: Six endometrial carcinoma subtypes: endometrioid (68 cases, 55%), serous (32 cases, 26%),carcinosarcoma (15 cases, 12%), clear cell (5 cases, 4%), mixed carcinoma (2 cases, 1.5%), anddedifferentiated carcinoma (1 case, <1%) were reported. The median age of presentation was 63 years(range of 34-90 years) and the median body mass index (BMI) was 27.4 kg/m2. Staging data wereavailable in 95 cases, of which 64 (67%) were in the early stage at presentation. Follow-up data wereavailable in 70 patients with a median follow-up time of 18 months. Recurrences were reported in 11cases, 5 of which were of the serous subtype. Of the 26 patients whose status was known at the time ofthe conclusion of the study, 7 died of the disease.Conclusion: To our knowledge, this is the first comprehensive review of the clinical and pathologicalprofiles of various subtypes of endometrial cancer in Kenya with follow-up and outcome data using awide array of immunohistochemical markers for accurate classification as per the WHO classification.

Creating Efficient Workflows for Electron Microscopy Laboratories with Automated Specimen Preparation

Abstract Electron microscopy (EM) is essential to the biological and biomedical sciences and clinical diagnostic pathology. Electron microscopy specimen preparation is laborious and time-consuming, with transmission EM (TEM) chemical preparation typically requiring 1–3 days, while volume electron microscopy (vEM) takes 3–5 days of tedious manual reagent exchanges every few minutes or hours. This places a considerable burden on laboratory scientists with the ongoing demand for TEM, and the rapidly growing demand for vEM due to its potential to revolutionize structural biology, connectomics, and related fields. This burden is exacerbated by a shortage of trained electron microscopy scientists as current staff retire, and few enter the workforce. This report provides four case studies to illustrate how automated and faster specimen preparation workflows using mPrep™ Automated Specimen Processors (ASP-1000™ and ASP-2000™, Microscopy Innovations, LLC) free electron microscopy staff in academic and pre-clinical research labs and a clinical pathology laboratory.

Explainable artificial intelligence in pathology

With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of histomorphological and molecular pathological data. Great hopes are placed in artificial intelligence (AI) methods, which have demonstrated the ability to analyze complex clinical, histological, and molecular data for disease classification, biomarker quantification, and prognosis estimation. This paper provides an overview of the latest developments in pathology AI, discusses the limitations, particularly concerning the black box character of AI, and describes solutions to make decision processes more transparent using methods of so-called explainable AI (XAI).

Fibre-based fluorescence-lifetime imaging microscopy: a real-time biopsy guidance tool for suspected lung cancer.

Lung cancer is the most common cause of cancer-related deaths worldwide. Early detection improves outcomes, however, existing sampling techniques are associated with suboptimal diagnostic yield and procedure-related complications. Autofluorescence-based fluorescence-lifetime imaging microscopy (FLIM), a technique which measures endogenous fluorophore decay rates, may aid identification of optimal biopsy sites in suspected lung cancer. Our fibre-based fluorescence-lifetime imaging system, utilising 488 nm excitation, which is deliverable via existing diagnostic platforms, enables real-time visualisation and lifetime analysis of distal alveolar lung structure. We evaluated the diagnostic accuracy of the fibre-based fluorescence-lifetime imaging system to detect changes in fluorescence lifetime in freshly resected ex vivo lung cancer and adjacent healthy tissue as a first step towards future translation. The study compares paired non-small cell lung cancer (NSCLC) and non-cancerous tissues with gold standard diagnostic pathology to assess the performance of the technique. Paired NSCLC and non-cancerous lung tissues were obtained from thoracic resection patients (N=21). A clinically compatible 488 nm fluorescence-lifetime endomicroscopy platform was used to acquire simultaneous fluorescence intensity and lifetime images. Fluorescence lifetimes were calculated using a computationally-lightweight, rapid lifetime determination method. Fluorescence lifetime was significantly reduced in ex vivo lung cancer, compared with non-cancerous lung tissue [mean ± standard deviation (SD), 1.79±0.40 vs. 2.15±0.26 ns, P<0.0001], and fluorescence intensity images demonstrated distortion of alveolar elastin autofluorescence structure. Fibre-based fluorescence-lifetime imaging demonstrated good performance characteristics for distinguishing lung cancer, from adjacent non-cancerous tissue, with 81.0% sensitivity and 71.4% specificity. Our novel fibre-based fluorescence-lifetime imaging system, which enables label-free imaging and quantitative lifetime analysis, discriminates ex vivo lung cancer from adjacent healthy tissue. This minimally invasive technique has potential to be translated as a real-time biopsy guidance tool, capable of optimising diagnostic accuracy in lung cancer.

PATHOLOGICAL DIAGNOSIS IN MALIGNANT SKIN TUMORS

Skin cancer is a disease characterized by the uncontrolled growth of cells in the skin. There are two distinct types of skin cancer: nonmelanoma and melanoma. Melanoma is cancer of pigmented cells and is far more dangerous than nonmelanoma, which is the most common cancer in the United States. This article discusses the pathology of nonmelanoma skin cancers in depth, focusing on the two most common types of carcinoma. Squamous cell carcinoma develops from the surface of the epidermis and accounts for about one-fourth of nonmelanoma cases. Basal cell carcinoma is believed to derive from the basal layer of the epidermis or follicular epithelium, accounting for roughly three-fourths of cases. Immunohistochemistry is an extremely valuable adjunct to the standard morphologic diagnosis in diagnostic pathology. The diagnosis of epithelial tumors depends significantly on morphological features, but in rare cases, immunohistochemical stains are needed for a definitive diagnosis. Received 28 June 2023Revised 26 September 2023Accepted 29 November 2023