Histological Classification Research Articles

Digital pathology and artificial intelligence in renal cell carcinoma focusing on feature extraction: a literature review

The integrated application of artificial intelligence (AI) and digital pathology (DP) technology has opened new avenues for advancements in oncology and molecular pathology. Consequently, studies in renal cell carcinoma (RCC) have emerged, highlighting potential in histological subtype classification, molecular aberration identification, and outcome prediction by extracting high-throughput features. However, reviews of these studies are still rare. To address this gap, we conducted a thorough literature review on DP and AI applications in RCC through database searches. Notably, we found that AI models based on deep learning achieved area under the curve (AUC) of over 0.93 in subtype classification, 0.89-0.96 in grading of clear cell RCC, 0.70-0,89 in molecular prediction, and over 0.78 in survival prediction. This review finally discussed the current state of researches and potential future directions.

PET radiomics for histologic subtype classification of non-small cell lung cancer: a systematic review and meta-analysis.

To systematically review the literature and perform a meta-analysis of PET radiomics for histologic subtype classification in non-small cell lung cancer (NSCLC). PubMed, Embase, Scopus, and Web of Science databases were systematically searched in English on human subjects for studies on distinguishing adenocarcinoma (ADC) from squamous cell carcinoma (SCC) using PET radiomics published from inception until November 2024. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and the Radiomics Quality Score (RQS) were utilized to assess the methodological quality of the included studies. The area under the receiver operating characteristic curves (AUC) was pooled to estimate predictive performance. An overall effect size was estimated using a random-effects model. Statistical heterogeneity was evaluated by the I2 value. Subgroup analyses were conducted to explore sources of heterogeneity. Twelve studies were included in the analysis, yielding a pooled AUC of 0.92 (95% confidence interval [CI]: 0.89-0.94). Despite this promising result, the studies showed limitations in both study design and methodological quality, as evidenced by a median RQS of 11/36. A significant degree of heterogeneity was observed among the studies, with an I2 of 92.20% (95% CI: 89.01-95.39) for sensitivity and 89.29% (95% CI: 84.48-94.10) for specificity. This meta-analysis highlights the potential utility of PET radiomics in distinguishing ADC from SCC. However, the observed high heterogeneity indicates substantial methodological variability across the included studies. Future research should focus on standardization, transparency, and multicenter collaborations to improve the reliability and clinical applicability of PET radiomics for histologic subtype classification in NSCLC.

Long-term epidemiological trends in (primary) pediatric central nervous system tumors: a 25-year cohort analysis in Western Mexico.

Central nervous system tumors (CNSTs) represent a significant oncological challenge in pediatric populations, particularly in developing regions where access to diagnostic and therapeutic resources is limited. This research investigates the epidemiology, histological classifications, and survival outcomes of CNST in a cohort of pediatric patients aged 0 to 19years within a 25-year retrospective study at the Civil Hospital of Guadalajara, Mexico, from 1999 to 2024. Data was analyzed from 273 patients who met inclusion criteria, revealing a higher incidence in males (51.6%) with a mean age at diagnosis of 8.2years. Histological analysis revealed gliomas as the most common type (52.7%), followed by embryonal tumors (28.6%). High-grade tumors (WHO grade 4) comprised 49.8% of cases, demonstrating significantly poorer survival outcomes (median overall survival of 13.5months) compared to lower-grade tumors (up to 57months). The predominance of tumors in the supratentorial region and the notable differences in survival outcomes by tumor type underscore the varied impact of geographical and socioeconomic factors on pediatric oncology in Mexico. This study highlights the critical need for improved healthcare infrastructure and early diagnosis initiatives, as well as the importance of targeted research to address disparities in treatment and outcomes for pediatric CNST in this region.

Host tissue factors predict immune surveillance and therapeutic outcomes in gastric cancer.

The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma-an aggressive cancer often linked to chronic inflammation-remains poorly understood. We leveraged high-dimensional spectral cytometry to generate a comprehensive single-cell immune landscape of tumors, normal tissue, and lymph nodes from patients in the Western Hemisphere with gastric adenocarcinoma. The immune composition of gastric tumors could not be predicted by traditional metrics such as tumor histology, molecular classification, mutational burden, or PD-L1 expression via IHC. Instead, our findings revealed that innate immune surveillance within tumors could be anticipated by the immune profile of the normal gastric mucosa. Additionally, distinct T-cell states in the lymph nodes were linked to the accumulation of activated and memory-like CD8+ tumor-infiltrating lymphocytes (TILs). Unbiased re-classification of patients based on tumor-specific immune infiltrate generated four distinct subtypes with varying immune compositions. Tumors with a T-cell-dominant immune subtype, which spanned TCGA molecular subtypes, were exclusively associated with superior responses to immunotherapy. Parallel analysis of metastatic gastric cancer patients treated with immune checkpoint blockade showed that patients who responded to immunotherapy had a pre-treatment tumor composition that corresponded to a T-cell-dominant immune subtype from our analysis. Taken together, this work identifies key host-specific factors associated with intratumoral immune composition in gastric cancer and offers an immunological classification system that can effectively identify patients likely to benefit from immune-based therapies.

RNA analysis of patients with benign and malignant pulmonary nodules.

Pulmonary nodules are the main manifestations of early lung cancer. Non-small cell lung cancer is the most common histological type of lung cancer, and the main histological classification of non-small cell lung cancer is lung adenocarcinoma. The present study aimed to analyze the differentially expressed genes between patients with benign and malignant pulmonary nodules, and to identify potential therapeutic targets for lung adenocarcinoma. Sequencing data for benign and malignant pulmonary nodule samples and samples with no nodules were obtained from the National Center for Biotechnology Information Gene Expression Omnibus GSE135304 dataset. Differential gene analysis showed that S100 calcium binding protein P (S100P), ribonuclease A family member 2 (RNASE2), cytochrome c oxidase subunit 7C and mast cell expressed membrane protein 1 (C19orf59) were significantly upregulated among the blood samples collected from patients with malignant pulmonary nodules. Results from Kaplan-Meier plotter datasets showed that S100P, RNASE2 and C19orf59 were associated with the prognosis of lung cancer. RNASE2 expression was positively associated with nodule size and negatively associated with lung cancer prognosis. Moreover, RNASE2 was highly expressed in lung adenocarcinoma tissues compared with that in normal tissues. CCK-8 and Transwell assays indicated that overexpressed RNASE2 promoted the proliferation, migration and invasion of lung adenocarcinoma cells. In lung adenocarcinoma cells, RNASE2 was identified as a downstream target of microRNA (miR)-185-5p and was regulated by it. Inhibited cell proliferation, migration and invasion were observed following overexpression of miR-185-5p. Overexpression of RNASE2 reversed the inhibitory effect of miR-185-5p overexpression. In conclusion, in blood samples from patients with malignant pulmonary nodules and lung adenocarcinoma tissues, RNASE2 was found to be upregulated. High RNASE2 expression was associated with poor overall survival. miR-185-5p inhibited the proliferation, migration and invasion of lung adenocarcinoma cells by downregulating RNASE2 expression. These findings have implications for guiding therapeutic strategies.

Risk Factors for Symptoms in Patients With Heterotopic Gastric Mucosa in the Upper Esophagus.

Goal: This study is aimed at comparing the clinical characteristics and histological types of symptomatic and asymptomatic patients with heterotopic gastric mucosa in the upper esophagus (HGMUE) and exploring the factors influencing the occurrence and severity of laryngopharyngeal reflux (LPR) symptoms in these patients. Background: HGMUE is a potential cause of LPR symptoms. Study: This retrospective analysis evaluated 70 patients with HGMUE using a detailed questionnaire. Clinical, histological, high-resolution manometry, and 24-h pH impedance monitoring data were compared between symptomatic (n = 49) and asymptomatic (n = 21) patients. Results: The diameter of HGMUE was significantly larger in the symptomatic group (p < 0.05), and the incidence of LPR symptoms increased with larger diameter grades; male patients were more likely to have LPR symptoms. The incidence of LPR symptoms varied significantly across histological classifications, being highest in patients with the fundic type (χ 2 = 6.64, p < 0.05). Binary logistic regression analysis identified sex and histological type as risk factors for LPR symptoms, with odds ratios of 8.996 (95% confidence interval (CI): 1.350-59.962) and 8.493 (95% CI: 1.486-48.522), respectively. The mean nocturnal baseline impedance (MNBI) in the upper esophagus was significantly lower in the symptomatic group (1676.82 ± 739.09 Ω vs. 2441.01 ± 604.11 Ω; p < 0.05). Clinical and demographic characteristics did not significantly affect the severity of LPR symptoms. Conclusion: The diameter, histological type, and sex of patients are risk factors for the occurrence of LPR symptoms in patients with HGMUE. More attention should be paid to patients with these factors. The MNBI is an effective indicator of the symptoms and treatment.

Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS.

The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established. The objective of this analysis was to evaluate survival outcomes of patients with localized and metastatic aRMS and its association with fusion status and subtype (PAX3/7::FOXO1, FOXO1 break), and clinical prognostic factors. A total of 470 patients with aRMS ≤21 years of age enrolled in two CWS-trials and two registries was eligible for the analysis. The 5-year event-free survival (EFS) and overall survival (OS) rates for all patients with localized vs. metastatic tumors were: 56% and 65% vs. 18% and 22%, respectively. Of the 368 (78%) tumors tested, specific fusion was found in 330 (90%), considered "fusion positive" FP (PAX3::FOXO1 in 280, PAX7::FOXO1 in 49, FOXO1 break in 59 tumors). In patients with localized tumors, univariate analysis revealed that clinical group, tumor invasiveness (T1 vs.T2), regional lymph node involvement (N0 vs. N1) and FOXO1 fusion were significantly associated with EFS and OS, tumor size and PAX variant with OS only. In patients with metastatic aRMS, age, bone/marrow (B/BM) metastases, FOXO1 fusion and PAX variant were associated with EFS and OS, T status with OS only. Multivariate analysis identified PAX3::FOXO1 fusion as an independent adverse prognostic factor for EFS in patients with localized disease and for EFS and OS in patients with metastatic disease, B/BM metastases for EFS. PAX3::FOXO1 fusion should replace FOXO1 fusion as an adverse prognostic factor in risk stratification. The prognostic relevance of PAX7::FOXO1-positive and FOXO1 fusion negative aRMS, along with the clinical factors described in this report, allows further refinement of risk assessment of patients with localized and metastatic aRMS.

A Systematic Review of the Applications of Deep Learning for the Interpretation of Positron Emission Tomography Images of Patients with Lymphoma.

Background: Positron emission tomography (PET) is a valuable tool for the assessment of lymphoma, while artificial intelligence (AI) holds promise as a reliable resource for the analysis of medical images. In this context, we systematically reviewed the applications of deep learning (DL) for the interpretation of lymphoma PET images. Methods: We searched PubMed until 11 September 2024 for studies developing DL models for the evaluation of PET images of patients with lymphoma. The risk of bias and applicability concerns were assessed using the prediction model risk of bias assessment tool (PROBAST). The articles included were categorized and presented based on the task performed by the proposed models. Our study was registered with the international prospective register of systematic reviews, PROSPERO, as CRD42024600026. Results: From 71 papers initially retrieved, 21 studies with a total of 9402 participants were ultimately included in our review. The proposed models achieved a promising performance in diverse medical tasks, namely, the detection and histological classification of lesions, the differential diagnosis of lymphoma from other conditions, the quantification of metabolic tumor volume, and the prediction of treatment response and survival with areas under the curve, F1-scores, and R2 values of up to 0.963, 87.49%, and 0.94, respectively. Discussion: The primary limitations of several studies were the small number of participants and the absence of external validation. In conclusion, the interpretation of lymphoma PET images can reliably be aided by DL models, which are not designed to replace physicians but to assist them in managing large volumes of scans through rapid and accurate calculations, alleviate their workload, and provide them with decision support tools for precise care and improved outcomes.

A Comprehensive Literature Review of Histopathology of Hepatocelullar Carcinoma

Background: The literature surrounding hepatocellular carcinoma (HCC) reveals a complex interplay of histopathological features, molecular genetics, and clinical implications that shape the understanding and management of this prevalent malignancy. Literature Review: The molecular and genetic markers associated with HCC are explored by (El-Nakeep, 2022), who address the high mortality rates associated with HCC and the complex relationship between cirrhosis and HCC development. This discussion emphasizes the necessity for further investigation into the molecular pathways underlying HCC progression. The role of imaging in diagnosis and management is reinforced by (Chartampilas et al., 2022), highlighting the importance of dynamic imaging techniques in accurately staging HCC and assessing treatment responses. Moreover, localized studies, such as that by (Sweed et al., 2022), contribute to the understanding of HCC's heterogeneous nature, emphasizing morpho-molecular classifications that guide diagnosis and treatment. The immune landscape, as discussed by (Gryziak et al., 2022), introduces the implications of immune cell interactions within the tumor microenvironment, suggesting that immune profiles should be considered alongside histopathological features in tailoring treatment strategies. The mutational landscape of HCC and the potential for precision medicine are examined by (Gorji et al., 2023), advocating for personalized therapeutic strategies that account for the genetic diversity of HCC. Finally, (Hyuk Choi &amp; N. Thung, 2023) synthesize recent advancements in histological and molecular classification, emphasizing the importance of accurate pathological classification for effective management and prognostication. Conclusion: In conclusion, the literature collectively underscores the critical integration of histopathological analysis with molecular insights and clinical practices to enhance the understanding of HCC. This multifaceted approach is essential for improving diagnosis, treatment, and patient outcomes in the context of this complex malignancy.

A Comprehensive Literature Review of Histopathology of Renal Cell Carcinoma

Background: The histopathology of renal cell carcinoma (RCC) encompasses a diverse array of subtypes, each characterized by distinct morphological and genetic features that have significant implications for clinical outcomes and treatment strategies. The evolution of our understanding of RCC has been reflected in a series of pivotal studies over the years, which have contributed to the molecular and histological classification of this malignancy. Literature Review: The exploration of ancillary techniques by (Pradhan et al., 2009) further enriched the discourse on RCC by emphasizing the significance of integrating histomorphology with molecular and cytogenetic analyses. This multifaceted approach is vital for improving diagnostic accuracy and tailoring treatment plans to individual patient needs ((Pradhan et al., 2009)). The comprehensive molecular characterization conducted by The Cancer Genome Atlas ((J. Ricketts et al., 2018)) revealed distinct genetic drivers associated with various RCC subtypes, emphasizing the importance of understanding these alterations for developing effective treatment strategies ((J. Ricketts et al., 2018)). Recent advancements in digital pathology, as discussed by (Zhu et al., 2020) and (Abu Haeyeh et al., 2022), highlight the potential of deep learning techniques to enhance diagnostic accuracy and streamline the classification of RCC subtypes, thus improving clinical outcomes ((Zhu et al., 2020); (Abu Haeyeh et al., 2022)). Conclusion: The analysis of papillary renal cell carcinoma by (S. Chawla et al., 2023) underscores the unique biological characteristics of this subtype and the challenges in advancing therapeutic strategies compared to clear cell RCC ((S. Chawla et al., 2023)). The literature collectively illustrates the dynamic and evolving nature of RCC histopathology, emphasizing the need for ongoing research to refine classification systems and enhance understanding of tumor biology, ultimately aiming to improve patient outcomes.

Epidemiological analysis of adult-type diffuse lower-grade gliomas and incidence and prevalence estimates of diffuse IDH-mutant gliomas in France.

The recent advent of anti-IDH therapies and changes in the WHO classification of gliomas implies estimating the number of patients who could benefit (or not) from anti-IDH treatment. As published data on the current incidence of different subtypes of IDH-mutant gliomas (based on the latest histomolecular WHO classification) are lacking in many countries. The present analysis aims to review the main factors impacting the incidence of gliomas and lower-grade gliomas and to estimate the incidence and prevalence of IDH-mutant gliomas in France. Our analysis was based on data from the French Brain Tumor DataBase and literature. Case definition, recording methods, histological classifications, age, sex, ethnicity, ancestry, environment, genetics, etc., impact the incidence of gliomas overall and lower-grade gliomas. In France, for the year 2024, the incidence estimates of all gliomas and all adult-type diffuse IDH-mutant gliomas are 6.6/100,000 and 1/100,000 person-years, respectively. The incidence estimates of grades 2, 3, and 4 diffuse IDH-mutant gliomas are 0.5, 0.3, 0.2 per 100,000 person-years, respectively. Of note, the incidence estimate of grade 3 diffuse IDH-mutant glioma versus grade 2 or 4 is slightly more difficult to assess due to the possible variability in histological criteria to define tumor grade. The prevalence of diffuse IDH-mutant grade 2 glioma would be more than 6.57/100,000 persons. Our epidemiological analysis provides estimates of potential number of patients, but large prospective real-world studies are required to determine the positioning of anti-IDH treatments among all therapeutic strategies [surgery(ies), chemotherapy(ies), radiotherapy(ies), clinical/radiological follow-up, etc.].

Mitochondrial genome variability and metabolic alterations reveal new biomarkers of resistance in testicular germ cell tumors.

Aim: Mutations in the mitochondrial (mt) genome contribute to metabolic dysfunction and their accumulation relates to disease progression and resistance development in cancer cells. This study explores the mutational status of the mt genome of cisplatin-resistant vs. -sensitive testicular germ cell tumor (TGCT) cells and explores its association with their respiration parameters, expression of respiratory genes, and preferences for metabolic pathways to reveal new markers of therapy resistance in TGCTs. Methods: Using Illumina sequencing with Twist Enrichment Panel, the mutations of mt genomes of sensitive 2102EP, H12.1, NTERA-2, T-cam and resistant 2102EP Cis, H12.1 ODM, 1411HP, 1777NRpmet, NTERA-2 Cis and T-cam Cis cell lines were identified. The mt respiration of the cells was assessed using high-resolution respirometry method (O2k-respirometer Oroboros) and the differential expression profiles of mt respiratory genes were determined using RT-qPCR. Associated preferences for metabolic pathways were compared using Glycolysis/OXPHOS assay. Results: In resistant TGCT cells, new mutations in mt genes MT-ND1-6, MT-RNR, MT-CO1-3, MT-ATP6, and MT-CYB were recognized. The respiratory rates of the 1777NRpmet cell line were the highest, while those of the 1411HP line the lowest; rates of the control and all other TGCT cell lines fell between these two lines. The statistically significant differences in gene expression of the respiratory genes were recorded only in NTERA-2 Cis and T-cam Cis cell lines. Sensitive cell lines NTERA-2 and 2102EP preferred oxidative phosphorylation (OXPHOS), while glycolysis was typical for resistant NTERA-2 Cis, 2102EP Cis and 1411HP cell lines. Metastatic 1777NRpmet cells seem to utilize both. An isogenic pair of cell lines H12.1 and H12.1ODM showed the opposite dependence, sensitive H12.1 preferring glycolysis, while resistant H12.1ODM OXPHOS. Conclusion: In summary, our study identified new mutations in mt genes of resistant TGCT cell lines that are associated with different mt respiration parameters, gene expression patterns and preferences for metabolic pathways, providing potential novel molecular biomarkers that distinguish the resistant TGCT phenotype or specify its histological classification.

Prognostic impact of tumor‑associated stroma in triple-negative breast cancer.

To establish the histological categorization of tumor‑associated stroma (TAS) that reflects the biological behavior of triple-negative breast cancer (TNBC). One-hundred-and-twenty surgically resected cases of TNBC were examined. We histologically categorized the TAS in the invasive frontal region into two groups: mature stroma (MS) and immature stroma (IS). The designation of IS was applied for tumors in which the largest myxoid stroma filled a high-power magnification field. When there were no myxoid stroma that meet the criteria for IS, TAS was categorized as MS. The tumors with type MS were observed in 103 (85.8%) of patients, whereas 17 (14.2%) of patients had tumors with IS. In total, 72 out of 120 patients with TNBC exhibited high tumor-infiltrating lymphocytes (TILs) representing 60% of the cohort. The incidences of high TILs were 66% (68 out of 103) in the MS group but only 23.5% (4 of 17) in the IS group (p = 0.001). Progression-free survival (PFS) and overall survival (OS) curves were different between IS and MS groups (p < 0.001 each), and Cox multivariate regression analysis revealed that IS was an independent indicator for lower PFS and OS rates (p < 0.001; p = 0.008). Our findings suggest that TAS characteristics, particularly the distinction between IS and MS, play a significant role in the prognosis of TNBC. The presence of IS, associated with poor prognosis and low TILs, contrasts with the favorable outcomes observed in cases with MS. Understanding these TAS dynamics could aid in identifying patients with varying prognostic outcomes in TNBC, necessitating further research into the mechanisms behind these observations.

Anatomical and histological classification of the stellate ganglion: implications for clinical nerve blocks

PurposeThe stellate ganglion (SG), or cervicothoracic ganglion, is usually located anterior to the neck of the first rib. Various techniques, such as ultrasonographic imaging and fluoroscopic approaches, are used to assist in the anesthetic blockade of the SG. However, there are reported complications associated with SG block; some patients had medication-related or systemic side effects, and some had procedure-related or local side effects. So, understanding the anatomy of the SG is critical for diagnosis and treatment of nerve block accuracy and to avoid unnecessary nerve damage during surgical procedures. This study aimed to collect data for the gross shape of the SG and histologically investigate these different types.MethodsThe SG from 31 formalin-fixed adult cadavers (59 sides) were studied. The prevalence and shape of the SG were recorded and photographed. Next, the SG for each type was examined histologically.ResultsThe SG were classified into four types based on their shape: dumbbell, spindle, star, and inverted L shapes. The frequency of each type was as follows: spindle (47.46%), dumbbell (27.12%), star (23.73%), and L-inverted shapes (1.69%). Each type had a similar number of nerve cell bodies. Interestingly, the inverted-L shaped SG was histologically, discontinuous but grossly fused.ConclusionAn improved understanding of the SG’s macro and microanatomy can help better understand patient presentations and improve clinical and surgical results in procedures performed near this important neck structure.

FHL1 Inhibition by Mir-1301-3p Promotes Uterine Corpus Endometrial Carcinoma Cell Proliferation and Migration: A Prognostic Insight.

The impact of microRNA-1301-3p (miR-1301-3p) on various cancer subtypes is noteworthy. However, its specific role within the framework of uterine corpus endometrial carcinoma (UCEC) is yet to be clearly defined. The objective of this research was to investigate and clarify the function of miR-1301-3p in relation to UCEC. Sample data for our study were sourced from The Cancer Genome Atlas (TCGA). Using various statistical techniques, we assessed the potential of miR-1301-3p as a diagnostic and prognostic indicator, as well as its association with clinical characteristics. Additionally, we conducted an analysis of the genes targeted by miR-1301-3p. The expression levels of miR-1301-3p in uterine corpus endometrial carcinoma (UCEC) cell lines were determined by quantitative real-time PCR (qRT-PCR). Cellular viability and migratory capacity were measured using the CCK8 assay and Transwell migration assays, respectively. Moreover, the expression levels of genes and proteins targeted by miR-1301-3p were identified through dual-luciferase reporter gene assays and Western blot analysis. Expression patterns of miR-1301-3p varied across cancer subtypes, which were significantly linked to specific histological classifications, achieving statistical significance (p < 0.001). In UCEC, higher miR-1301-3p levels correlated with reduced overall survival (p = 0.012) and progression-free survival (p = 0.016), and it emerged as an independent prognostic marker for UCEC. A comparative analysis revealed significantly higher miR-1301-3p levels in UCEC cell lines compared to normal endometrial epithelial cells. Four and a half LIM domains 1 (FHL1) exhibited a negative correlation with miR-1301-3p levels within UCEC tissue samples. miR-1301-3p was shown to promote UCEC cell proliferation and migration through its binding to the 3'-untranslated region (UTR) of the FHL1 gene, thereby repressing FHL1 expression. Additionally, augmenting FHL1 levels was observed to counteract the enhancing impact of miR-1301-3p on UCEC cells. miR-1301-3p regulates the proliferation and migration of UCEC cells by interacting with the FHL1 gene. miR-1301-3p may serve as a promising prognostic biomarker in UCEC.

Prostaglandin pathways in equine myometrium regulations: endometrosis progression.

Prostaglandins (PG) are important regulators of the myometrial contractility in mammals. Endometrosis, a condition characterized by morphological changes in the equine endometrium, also affects endometrial secretory function. However, it remains unclear whether and how endometrosis affects myometrial function. This study investigated: (i) mRNA transcription of genes encoding specific enzymes responsible for PG synthesis, such as prostaglandin-endoperoxide synthase (PTGS2), PGE2 synthase (PTGES), PGF2α synthase (PTGFS) and PG receptors: PGE2 receptors (PTGER1- 4), and PGF2α receptor (PTGFS) in equine myometrium and, (ii) the effects of PGE2 and PGF2α on myometrial contractile activity, during endometrosis in mares. The myometria used in experiments 1 and 2 were collected from mares in the mid-luteal (n = 23) and follicular (n = 20) phases of the estrous cycle, according to the histological classification of the endometrium (Kenney and Doig categories I, IIA, IIB, and III). In experiment 1, changes in mRNA transcription of PG synthase or PG receptors in the myometrium during the course of endometrosis were determined using qPCR. During the mid-luteal phase, myometrial mRNA transcription of PTGES increased in mares with endometrial category IIB compared to category I. However, myometrial mRNA transcription of PTGER1 decreased during the progression of endometrosis compared to category I. During the follicular phase, mRNA transcription of PTGER1 and PTGER2 increased in mares with endometrial categories III or IIA, respectively. In addition, mRNA transcription of PTGFS increased in mares with endometrium category IIA compared to category I. In experiment 2, the force of myometrial contractions was measured using an isometric concentration transducer. In the follicular phase, PGE2 decreased the force of contractions in mares with endometrial categories IIA, IIB, and III compared to the respective control groups. Prostaglandin F2α increased the force of myometrial contractions in mares with category IIA endometrium, whereas it decreased in category IIB compared to the respective control groups. We concluded that in the progression of endometrosis there are changes in the myometrial transcription of mRNA encoding PG synthases and receptors, particularly PTGER1 and PTGER2. Mares with endometrosis had abnormal myometrial contractile responses to PG. These findings suggest that myometrial function may be compromised during the progression of endometrosis.

Classification of intrahepatic cholangiocarcinoma.

Cholangiocarcinoma is a heterogenous malignancy with various classifications based on location, morphological features, histological features, and actionable genetic mutations. Intrahepatic cholangiocarcinoma (ICC), which arises in and proximal to second order bile ducts, is the second most common primary liver malignancy after hepatocellular carcinoma. In this review, we will discuss ICC risk factors, precursor lesions, various growth, anatomic, morphologic, and histologic classifications, rare variants, and differential diagnoses.

Pre-Surgical Endoscopic Biopsies Are Representative of Esophageal and Esophago-Gastric Junction Adenocarcinoma Histologic Classes and Survival Risk.

Background and Objectives: The Esophageal Adenocarcinoma Study Group Europe (EACSGE) recently proposed a granular histologic classification of esophageal-esophago-gastric junctional adenocarcinomas (EA-EGJAs) based on the study of naïve surgically resected specimens that, when combined with the pTNM stage, is an efficient indicator of prognosis, molecular events, and response to treatment. In this study, we compared histologic classes of endoscopic biopsies taken before surgical resection with those of the surgical specimen, to evaluate the potential of the EACSGE classification at the initial diagnostic workup. Methods: A total of 106 EA-EGJA cases with available endoscopic biopsies and matched surgical resection specimens were retrieved from five Italian institutions. Histologic classification was performed on all specimens to identify well-differentiated glandular adenocarcinoma (WD-GAC), poorly differentiated glandular adenocarcinoma (PD-GAC), mucinous muconodular carcinoma (MMC), infiltrative mucinous carcinoma (IMC), diffuse desmoplastic carcinoma, diffuse anaplastic carcinoma (DAC), and mixed subtypes. Related risk subgroups (low-risk versus high-risk) were also assessed. The correlations of histologic classes and risk subgroups between diagnostic biopsies and surgical resection specimens were explored with Spearman's correlation test. Sensitivity, specificity, accuracy, positive predictive value, negative predictive value, true positives, true negatives, false positives, and false negatives were also calculated. Results: A strong positive correlation between biopsies and surgical specimens occurred for both histologic classes (coefficient: 0.75, p < 0.001) and risk subgroups (coefficient: 0.65, p < 0.001). The highest sensitivities and specificities were observed for MMC, IMC, and DAC (100% and 99% for all), followed by WD-GAC (sensitivity 91%, specificity 79%) and PD-GAC (sensitivity 722%, specificity 86%). The low-risk and high-risk groups presented a sensitivity and specificity of 89% and 76% (low-risk) and 76% and 89% (high-risk). Conclusions: The EACSGE histologic classification of EA-EGJAs and associated prognostic subgroups can be reliably assessed on pre-operative diagnostic biopsies. Further studies on larger and more representative cohorts of EA-EGJAs will allow us to validate our findings and confirm if the EA-EGJA biopsy histomorphology and clinical TNM staging will be as efficient as the surgical specimen histomorphology and pTNM in predicting patient prognoses and tailoring personalized therapeutic approaches.

Application value of contrast-enhanced ultrasound in the preoperative evaluation of renal cell carcinoma histological classification and RENAL score.

Renal cell carcinoma (RCC), the most common malignant renal tumor, is primarily treated by surgical resection, including radical nephrectomy (RN) and partial nephrectomy (PN). At present, the choice of surgery mainly depends on the comprehensive evaluation of patients' clinical data, including histological classification, such as clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC), and RENAL (radius, exophytic/endophytic, nearness, anterior/posterior, and location) score. Compared with biopsy and contrast-enhanced computed tomography (CECT), contrast-enhanced ultrasound (CEUS) is safer and less invasive. The purpose of this study was to assess the value of CEUS in the preoperative evaluation of histological classification and RENAL score of RCC. This retrospective study was conducted on a consecutive series of patients with renal tumors who underwent CEUS examination within 1 week prior to treatment at Lanzhou University Second Hospital between March 2021 and November 2023. The conventional ultrasound and CEUS features of RCCs were recorded and used to evaluate the RENAL score. Binary logistic regression was applied to analyze the independent risk factors of ccRCC. Diagnostic efficacy in evaluating ccRCC and nccRCC was compared between CEUS and CECT with the McNemar test. Among 246 patients, 248 RCCs were enrolled and were categorized into two groups: ccRCC (n=196) and nccRCC (n=52), with surgical pathology as the reference standard. The likelihood of hyperenhancement (P<0.001), heterogeneous enhancement (P<0.001), internal nonenhanced region ≤50% (P=0.001), and fast wash-in (P<0.001) in the ccRCC group was significantly higher than that in the nccRCC group, and these were independent risk factors of ccRCC. Moreover, the ccRCC group, as compared to the nccRCC, had a lower region of interest area of the largest range of tumor (Areamax) (P=0.045) and the difference between the local tumor and cortex in arrive time (∆ATtumor-cortex) (P=0.012) and shorter time to peak of the local tumor (TTPtumor) (P=0.022). The performance of CEUS in differentiating between ccRCC and nccRCC was comparable to that of CECT and showed high sensitivity (99.5%). Additionally, there was a significant difference in RENAL score based on the ultrasound features between the RN and PN group (P<0.001). The conventional ultrasound and CEUS features may help differentiate ccRCC from nccRCC and have significant potential in scoring the complexity prior to surgery, which could provide more precise and valuable information for diagnosis and treatment. CEUS has the capacity to optimize the treatment plan in a noninvasive manner and improve the prognosis of patients and should thus be further verified in multicenter, large-cohort, prospective research.

Image Quality Assessment and Reliability Analysis of Artificial Intelligence-Based Tumor Classification of Stimulated Raman Histology of Tumor Biobank Samples.

Stimulated Raman histology (SRH) is a label-free optical imaging method for rapid intraoperative analysis of fresh tissue samples. Analysis of SRH images using Convolutional Neural Networks (CNN) has shown promising results for predicting the main histopathological classes of neurooncological tumors. Due to the relatively low number of rare tumor representations in CNN training datasets, a valid prediction of rarer entities remains limited. To develop new reliable analysis tools, larger datasets and greater tumor variety are crucial. One way to accomplish this is through research biobanks storing frozen tumor tissue samples. However, there is currently no data available regarding the pertinency of previously frozen tissue samples for SRH analysis. The aim of this study was to assess image quality and perform a comparative reliability analysis of artificial intelligence-based tumor classification using SRH in fresh and frozen tissue samples. In a monocentric prospective study, tissue samples from 25 patients undergoing brain tumor resection were obtained. SRH was acquired in fresh and defrosted samples of the same specimen after varying storage durations at -80 °C. Image quality was rated by an experienced neuropathologist, and prediction of histopathological diagnosis was performed using two established CNNs. The image quality of SRH in fresh and defrosted tissue samples was high, with a mean image quality score of 1.96 (range 1-5) for both groups. CNN analysis showed high internal consistency for histo-(Cα 0.95) and molecular (Cα 0.83) pathological tumor classification. The results were confirmed using a dataset with samples from the local tumor biobank (Cα 0.91 and 0.53). Our results showed that SRH appears comparably reliable in fresh and frozen tissue samples, enabling the integration of tumor biobank specimens to potentially improve the diagnostic range and reliability of CNN prediction tools.