Molecular Pathological Diagnosis of Thyroid Tumors Using Spatially Resolved Metabolomics.

The pathological diagnosis of benign and malignant follicular thyroid tumors remains a major challenge using the current histopathological technique. To improve diagnosis accuracy, spatially resolved metabolomics analysis based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique was used to establish a molecular diagnostic strategy for discriminating four pathological types of thyroid tumor. Without any specific labels, numerous metabolite features with their spatial distribution information can be acquired by AFADESI-MSI. The underlying metabolic heterogeneity can be visualized in line with the cellular heterogeneity in native tumor tissue. Through micro-regional feature extraction and in situ metabolomics analysis, three sets of metabolic biomarkers for the visual discrimination of benign follicular adenoma and differentiated thyroid carcinomas were discovered. Additionally, the automated prediction of tumor foci was supported by a diagnostic model based on the metabolic profile of 65 thyroid nodules. The model prediction accuracy was 83.3% when a test set of 12 independent samples was used. This diagnostic strategy presents a new way of performing in situ pathological examinations using small molecular biomarkers and provides a model diagnosis for clinically indeterminate thyroid tumor cases.

Possibilities of Automated Diagnostics of Odontogenic Sinusitis According to the Computer Tomography Data.

Individual anatomical features of the paranasal sinuses and dentoalveolar system, the complexity of physiological and pathophysiological processes in this area, and the absence of actual standards of the norm and typical pathologies lead to the fact that differential diagnosis and assessment of the severity of the course of odontogenic sinusitis significantly depend on the measurement methods of significant indicators and have significant variability. Therefore, an urgent task is to expand the diagnostic capabilities of existing research methods, study the significance of the measured indicators, and substantiate the expediency of their use in the diagnosis of specific pathologies in an automated mode. Methods of digital filtering, image segmentation and analysis, fluid dynamics, and statistical and discriminant analysis were used. Preliminary differential diagnosis of odontogenic sinusitis can be performed by densitemetric analysis of tomographic images of the maxillary sinuses, performed using frontal multiplanar reconstructions according to a given algorithm. The very manifestation of the characteristic changes in the densitography of the maxillary sinus allows for the initiation of certain pathological processes and permits the development of the effectiveness of the diagnosis of the pathology of the sinus sinuses, which can be realized automatically in real life.

Hodgkin's lymphoma and its association with EBV and HIV infection.

Hodgkin's lymphoma (HL) constitutes a clonal expansion of what appears to be malignant B cells. Viruses are involved in its pathogenesis, such as the Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Since these viral infections have been shown to play key roles in the pathogenesis of HL, countries with a prevalence of HIV and EBV represent interesting population targets to study the pathogenesis of HL, linking the evolution of the disease with viral infections. Usually, patients present with late stage disease often involving the bone marrow at the time of diagnosis. The present paper discusses the role of viral infection in African countries, as HL is considered to be a malignant disease characterized by an inflammatory reaction to an aberrant B cell clone that is well known as the Reed-Sternberg cell (HRS).

Any value in a specialist review of liver biopsies? Conclusions of a 4-year review.

AIMS: Liver pathology is a challenging subspeciality, with histopathologists frequently seeking specialist opinions. This study aims to determine the impact of specialist reviews on the final diagnosis and patient management. METHODS AND RESULTS: Agreement with the initial reporting centre in the histopathological diagnosis of 1265 liver biopsies was determined. The nature of differences was explored in more depth for 103 discrepant cases. Differences in the histopathological interpretation were present in 749 of 1265 (59%) biopsies, of which 505 of 749 (67%) were predicted at the time of reporting to impact upon patient management. Agreement was good in cases with chronic viral hepatitis, fatty liver disease, malignancy and minimal pathological changes, while diagnostic differences occurred in more than 70% with biliary disease, autoimmune hepatitis or vascular/architectural changes. A clinical review of a subset of reports with histopathological differences predicted changes in patient management in 63 of 103 (61%). CONCLUSIONS: Clinically significant differences in liver biopsy interpretation between local pathologists and subspecialists are common. Diagnoses with frequent discrepancies, such as biliary disease, may benefit from a specialist review as standard when diagnosed initially, while cases requiring specialist advice from disease subgroups where discrepancies are less common, such as chronic viral hepatitis, could be selected during the clinicopathological conference process.

Combined ultrasound endoscopy-guided fine-needle aspiration with DNA methylation of SHOX2 and RASSF1A genes to enhance the auxiliary diagnostic precision of pancreatic cancer.

The purpose of this study was to assess the influence and the clinical effectiveness of the short stature homeobox 2 (SHOX2) and ras association domain family 1A (RASSF1A) genes by tissue sampling through ultrasound endoscopy-guided fine-needle aspiration (EUS-FNA) as auxiliary diagnostic tools for pancreatic cancer (PC). Methylation markers were detected in 96 patients using real-time fluorescence quantitative PCR (qPCR), and the performance of this diagnostic assay was compared with CA19-9, CEA, and puncture fluid-based exfoliative cytology using receiver operating characteristic curve (ROC) analysis. The PC group exhibited higher methylation rates for SHOX2, RASSF1A, and the combined assay of both genes compared to the control group (95.7 % vs. 54.0 %, 78.3 % vs. 36.0 %, and 73.9 % vs. 16.0 %, P < 0.05). The areas under the ROC curve (AUC) for CA19-9, CEA, liquid-based exfoliative cytology, SHOX2, RASSF1A, the combination of SHOX2 and RASSF1A, the combination assay with CEA, CA19-9, and liquid-based exfoliative cytology were 0.827, 0.692, 0.767, 0.770, 0.732, 0.870, 0.870, 0.933, and 0.900, respectively. Therefore, the methylation assay based on the combined SHOX2 and RASSF1A genes in EUS-FNA puncture fluid is more effective than using a single gene, liquid-based exfoliative cytology, or intravenous tumor markers for diagnosing PC. Combining the conventional marker CA19-9 enhances the diagnostic value, making it a promising approach to complement histology and cytology.

Amplifying pathological detection in EEG signaling pathways through cross-dataset transfer learning.

Pathology diagnosis based on EEG signals and decoding brain activity holds immense importance in understanding neurological disorders. With the advancement of artificial intelligence methods and machine learning techniques, the potential for accurate data-driven diagnoses and effective treatments has grown significantly. However, applying machine learning algorithms to real-world datasets presents diverse challenges at multiple levels. The scarcity of labeled data, especially in low regime scenarios with limited availability of real patient cohorts due to high costs of recruitment, underscores the vital deployment of scaling and transfer learning techniques. In this study, we explore a real-world pathology classification task to highlight the effectiveness of data and model scaling and cross-dataset knowledge transfer. As such, we observe varying performance improvements through data scaling, indicating the need for careful evaluation and labeling. Additionally, we identify the challenges of possible negative transfer and emphasize the significance of some key components to overcome distribution shifts and potential spurious correlations and achieve positive transfer. We see improvement in the performance of the target model on the target (NMT) datasets by using the knowledge from the source dataset (TUAB) when a low amount of labeled data was available. Our findings demonstrated that a small and generic model (e.g. ShallowNet) performs well on a single dataset, however, a larger model (e.g. TCN) performs better in transfer learning when leveraging a larger and more diverse dataset.

The tauopathies.

Tauopathies are a clinically and neuropathologically heterogeneous group of neurodegenerative disorders, characterized by abnormal tau aggregates. Tau, a microtubule-associated protein, is important for cytoskeletal structure and intracellular transport. Aberrant posttranslational modification of tau results in abnormal tau aggregates causing neurodegeneration. Tauopathies may be primary, or secondary, where a second protein, such as Aß, is necessary for pathology, for example, in Alzheimer's disease, the most common tauopathy. Primary tauopathies are classified based on tau isoform and cell types where pathology predominates. Primary tauopathies include Pick disease, corticobasal degeneration, progressive supranuclear palsy, and argyrophilic grain disease. Environmental tauopathies include chronic traumatic encephalopathy and geographically isolated tauopathies such as the Guam-Parkinsonian-dementia complex. The clinical presentation of tauopathies varies based on the brain areas affected, generally presenting with a combination of cognitive and motor symptoms either earlier or later in the disease course. As symptoms overlap and tauopathies such as Alzheimer's disease and argyrophilic grain disease often coexist, accurate clinical diagnosis is challenging when biomarkers are unavailable. Available treatments target cognitive, motor, and behavioral symptoms. Disease-modifying therapies have been the focus of drug development, particularly agents targeting Aß and tau pathology in Alzheimer's disease, although most of these trials have failed.

Colorectal cancer metastasis to the thyroid: A case report and review of the literature.

Metastatic thyroid cancer is rare. Here, the case of a patient with colon cancer that metastasized to the thyroid is described. The patient underwent radical rectal cancer surgery in August 2017 and received six cycles of chemotherapy with oxaliplatin and capecitabine postoperatively. On August 4, 2018, the patient was admitted to the hospital due to the discovery of thyroid nodules on ultrasound and carcinoembryonic antigen levels within the normal range. The biopsy from the fine needle aspiration suggested a malignant tumor. The patient underwent radical thyroid cancer surgery. Using intraoperative rapid frozen pathology, medullary carcinoma was diagnosed. Using postoperative routine pathology combined with immunohistochemistry results, thyroid metastasis from colorectal adenocarcinoma was diagnosed. After surgery, the patient regularly visited the outpatient clinic for chemotherapy with capecitabine. As of May 2023, the patient is still alive with no recurrence.

A hyperspectral dataset of precancerous lesions in gastric cancer and benchmarks for pathological diagnosis.

Gastric cancer (GC) is one of the most common cancers worldwide. A lot of studies have found that early GC has good prognosis. Unfortunately, the diagnosis rate of early GC is suboptimal due to inadequate disease screening and the insidious nature of early lesions. Pathological diagnosis is usually regarded as the "gold standard" for the diagnosis of GC. However, traditional pathological diagnosis is tedious and time-consuming. With the development of deep learning, computer-aided diagnosis is widely used to assist pathologists for diagnosis. As conventional pathology, diagnosis is based on color images, it is not as informative as hyperspectral imaging, which introduces spectroscopy into imaging techniques. This article combines microscopic hyperspectral image (HSI) with deep learning networks to assist in the diagnosis of precancerous lesions in gastric cancer (PLGC). A large scale microscopic hyperspectral PLGC dataset with 924 effective scenes is built and self-supervised learning is adopted to provide pretrained models for HSI. These pretrained models effectively improve the performance of downstream classification tasks. Furthermore, a symmetrically deep connected network is proposed to train with images from different imaging modalities and improve the diagnostic accuracy to 96.59%.

Diagnosis of vertebral column pathologies using concatenated resampling with machine learning algorithms.

Medical diagnosis through the classification of biomedical attributes is one of the exponentially growing fields in bioinformatics. Although a large number of approaches have been presented in the past, wide use and superior performance of the machine learning (ML) methods in medical diagnosis necessitates significant consideration for automatic diagnostic methods. This study proposes a novel approach called concatenated resampling (CR) to increase the efficacy of traditional ML algorithms. The performance is analyzed leveraging four ML approaches like tree-based ensemble approaches, and linear machine learning approach for automatic diagnosis of inter-vertebral pathologies with increased. Besides, undersampling, over-sampling, and proposed CR techniques have been applied to unbalanced training dataset to analyze the impact of these techniques on the accuracy of each of the classification model. Extensive experiments have been conducted to make comparisons among different classification models using several metrics including accuracy, precision, recall, and F 1 score. Comparative analysis has been performed on the experimental results to identify the best performing classifier along with the application of the re-sampling technique. The results show that the extra tree classifier achieves an accuracy of 0.99 in association with the proposed CR technique.

Pseudosarcomatous Vaginal Polyp.

BACKGROUND: Although rare, pregnant women can present with fibroepithelial polyps of the vagina. Most likely hormonally related, these polyps have been described in various locations of the lower female genital tract. They can be mistaken for malignant lesions due to hypercellularity and cytologic atypia. CASE: We describe the case of a 31-year-old woman who presented with a polyp of the vagina during a postpartum visit. RESULTS: Atypical cells were seen in hypercellular areas of the stroma of the polyp. CONCLUSION: A pitfall to avoid is classifying these benign lesions as malignant based on atypical histopathology.

Diffuse-Type Hepatoma: A Grave Prognostic Marker.

BACKGROUND: Data on diffuse-type hepatocellular carcinoma (HCC) are rare. HCC in Sri Lanka is rising, and the majority is related to nonalcoholic fatty liver disease. This study was planned to compare nodular- and diffuse-type HCC in this cohort. METHODS: CT scans of 227 patients with HCC negative for infective hepatitis were analyzed and grouped as nodular and diffuse from July 2011 to July 2014. Diffuse-type cancer was defined as a tumor without convex/distinct margin, diffusely infiltrating the hepatic parenchyma. There were 45 (20%) cases. The baseline liver functions, etiology, treatment, and the outcome were compared with nodular-type cancers. Stage III diffuse cancers were matched with 2 stage III nodular cancers looking at the T stage and background liver. RESULTS: There was no difference in the age (63 vs. 62 years, p = 0.937) and gender. Diffuse cancers had a low BMI (24 vs. 22, p = 0.009), a higher alpha fetoprotein (AFP) level (p < 0.001), a higher incidence of major vascular invasion (14 vs. 80%, p < 0.001), and a history of significant alcohol consumption (39 vs. 67%, p = 0.001). The baseline liver functions were similar in diffuse and nodular cancers. A large proportion (27 vs.77%, p < 0.001) of diffuse cancers were not candidates for active treatment. Overall survival was poor in the diffuse type (4.7 vs. 25 months, p < 0.001). Diffuse-type stage III cancers had a poor survival compared to matched nodular cancers (2.5 vs. 15.8 months, p = 0.001). CONCLUSION: HCC without a background of infective hepatitis were common in our cohort. These tumors are associated with high AFP levels, major vascular invasion, and a poor prognosis.

PathEdEx - Uncovering High-explanatory Visual Diagnostics Heuristics Using Digital Pathology and Multiscale Gaze Data.

BACKGROUND: Visual heuristics of pathology diagnosis is a largely unexplored area where reported studies only provided a qualitative insight into the subject. Uncovering and quantifying pathology visual and nonvisual diagnostic patterns have great potential to improve clinical outcomes and avoid diagnostic pitfalls. METHODS: Here, we present PathEdEx, an informatics computational framework that incorporates whole-slide digital pathology imaging with multiscale gaze-tracking technology to create web-based interactive pathology educational atlases and to datamine visual and nonvisual diagnostic heuristics. RESULTS: We demonstrate the capabilities of PathEdEx for mining visual and nonvisual diagnostic heuristics using the first PathEdEx volume of a hematopathology atlas. We conducted a quantitative study on the time dynamics of zooming and panning operations utilized by experts and novices to come to the correct diagnosis. We then performed association rule mining to determine sets of diagnostic factors that consistently result in a correct diagnosis, and studied differences in diagnostic strategies across different levels of pathology expertise using Markov chain (MC) modeling and MC Monte Carlo simulations. To perform these studies, we translated raw gaze points to high-explanatory semantic labels that represent pathology diagnostic clues. Therefore, the outcome of these studies is readily transformed into narrative descriptors for direct use in pathology education and practice. CONCLUSION: PathEdEx framework can be used to capture best practices of pathology visual and nonvisual diagnostic heuristics that can be passed over to the next generation of pathologists and have potential to streamline implementation of precision diagnostics in precision medicine settings.

The surgical pathology laboratory in Mwanza, Tanzania: a survey on the reproducibility of diagnoses after the first years of autonomous activity.

BACKGROUND: In 2000, an Italian non-governmental organisation (NGO) began a 9-year project to establish a surgical pathology laboratory at the Bugando Medical Centre (BMC) in Mwanza, Tanzania, a country with a low Human Development Index (HDI), and as of 2009, the laboratory was operating autonomously. The present survey aims to evaluate the reproducibility of histological and cytological diagnoses assigned in the laboratory's early years of autonomous activity. We selected a random sample of 196 histological and cytological diagnoses issued in 2010-2011 at the BMC surgical pathology laboratory. The corresponding samples were sent to Italy for review by Italian senior pathologists, who were blinded to the local results. Samples were classified into four diagnostic categories: malignant, benign, inflammatory, and suspicious. The two-observer kappa-statistic for categorised (qualitative) data was then calculated to measure diagnostic concordance between the local Tanzanian pathologists and Italian senior pathologists. The k-Cohen was calculated for concordance in the overall study sample. Concordance and discordance rates were also stratified by subset: general adult, paediatric/adolescent, and lymphoproliferative histopathological diagnoses; fluid and fine needle aspiration (FNA) cytological diagnoses; and PAP tests. Discordance was also categorised by the corresponding hypothetical clinical implications: high, intermediate, and not significant. RESULTS: Overall concordance was 85.2% (167 of 196 diagnoses), with a k-Cohen of 0.7691 (P = 0.0000). Very high concordance was observed in the subsets of adult general pathological diagnoses (90%) and paediatric/adolescent pathological diagnoses (91.18%). Concordance in the subset of PAP tests was 75%, and for fluid/FNA cytological diagnoses it was 56.52%. Concordance among 12 histological subtypes of lymphoma was 75.86%, with substantial discordance observed in the diagnosis of Burkitt lymphoma (five cases diagnosed by Italian pathologists versus 2 by local pathologists). The overall proportion of discordance with high hypothetical clinical implications was 6.1% (12 diagnoses). CONCLUSION: This blind review of diagnoses assigned in Tanzania, a country with low HDI, and in Italy, a country with a very high HDI, seemed to be a sensitive and effective method to identify areas of potential error and may represent a reference point for future, more detailed quality control processes or audits of surgical pathology services located in limited-resource regions.

Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis.

Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management.

Evaluación de nódulos tiroideos con interpretación citológica rápida en el sitio (ROSE) / Evaluation of thyroid nodules with Rapid On-Site Evaluation (ROSE)

La aspiración con aguja fina (ACAF) es una técnica ampliamente utilizada por su alta seguridad y fácil uso. Sin embargo, al usarse en conjunto con la evaluación rápida de la muestra en el sitio de la toma (ROSE, del inglés, Rapid On- Site Evaluation), disminuyen los tiempos necesarios para la evaluación y el diagnóstico, mejora la calidad de la muestra, disminuye el número de punciones por procedimiento y limita la necesidad de repetir la prueba, lo que hace que el uso combinado de ambas técnicas sea de gran utilidad y cada vez más solicitado en los servicios de imágenes diagnósticas y patología. ROSE, además, permite una clasificación adecuada del material recolectado para cultivos, estudios de citometría de flujo y pruebas moleculares. Particularmente, en los pacientes con nódulos tiroideos, la realización de ROSE durante el procedimiento de evaluación ecográfica y punción, puede garantizar que la muestra extraída sea suficiente y adecuada para el diagnóstico, y, así mismo, permite evaluar la necesidad de estudios complementarios de manera inmediata, brindando un diagnóstico rápido y preciso, disminuyendo los costos relacionados con la repetición del procedimiento y la morbilidad asociada a complicaciones por punciones múltiples

Fine needle aspiration (FNA) is a widely used technique due to its high safety and ease of use. However, when used in combination with Rapid On-Site Evaluation (ROSE), there is a reduction in the time required for evaluation and diagnosis, as well as an improvement in the sample quality, a reduction in the number of needle passes and the need to repeat the test, which makes the combined use of both techniques very useful and increasingly requested in the diagnostic imaging and pathology services. ROSE also allows a proper classification of the collected material for cultures, flow cytometry studies and molecular tests. Particularly in patients with thyroid nodules, the performance of ROSE during the ultrasound evaluation and biopsy procedure can guarantee that the sample extracted is sufficient and adequate for the diagnosis, and, likewise, an immediate evaluation for the need for complementary studies can be achieved, providing a fast and accurate diagnosis, reducing the costs related to repeating the procedure, and the morbidity associated with complications from multiple biopsies

Ossifying parosteal lipoma of the thoracic spine: a case report and review of literature.

INTRODUCTION: Lipomas are derived from the mesodermal germ layer and are frequently encountered in adults, and account for almost 50% of all soft tissue tumors. Lipomas are classified based on their component tissues and location. A rare subtype, ossifying parosteal lipoma, accounts for 0.3% of all lipomas and occurs with intimate association with the underlying periosteum of the adjacent bone. Though lipomas are considered to be benign tumors, ossifying parosteal lipomas can manifest symptoms due to their location and relationship to nearby skeletal tissues. We herewith report the first known case of ossifying parosteal lipoma presenting in the region of the thoracic spine. CASE PRESENTATION: An otherwise healthy adolescent boy presented with a 3-year history of a slowly enlarging painless thoracic mass. A general physical examination was normal, aside from a painless 10 cm mobile, hard mass along the posterior spine in the region of T4 through T6. Musculoskeletal and neurovascular examinations were normal. An ultrasound suggested a solid, cylindrically shaped mass with diffuse ossification. The mass was resected, and the pathology revealed ossifying parosteal lipoma without evidence of malignancy. CONCLUSION: Ossifying parosteal lipomas are rare, benign soft tissue tumors that should be added to the differential diagnosis of thoracic masses.

A pathologist-in-the-loop IHC antibody test selection using the entropy-based probabilistic method.

BACKGROUND: Immunohistochemistry (IHC) is an important tool to identify and quantify expression of certain proteins (antigens) to gain insights into the molecular processes in a diseased tissue. However, it is a challenge for pathologists to remember the discriminative characteristics of the growing number of such antigens across multiple diseases. The complexity of their expression patterns, fueled by continuous discoveries in molecular pathology, gives rise to a combinatorial explosion that places an unprecedented burden on a practicing pathologist and therefore increases cost and variability of IHC studies. MATERIALS AND METHODS: To tackle these issues, we have developed antibody test optimized selection method, a novel informatics tool to help pathologists in improving the IHC antibody selection process. The method uses extensions of Shannon's information entropies and Bayesian probabilities to dynamically build an efficient diagnostic tree. RESULTS: A comparative analysis of our method with the expert and World Health Organization classification guidelines showed that the proposed method brings threefold reduction in number of antibody tests required to reach a diagnostic conclusion. CONCLUSION: The developed method can significantly streamline the antibody test selection process, decrease associated costs and reduce inter- and intrapathologist variability in IHC decision-making.