Histologic Follow-up Research Articles

Utility of The Paris System (TPS) for upper urinary tract cytopathology: correlation with histology follow-up and UroVysion fluorescence in situ hybridization (FISH) analysis

The Paris System (TPS) provides a uniform reporting system of urine cytology based on well-defined cytologic criteria. Due to their rarity, there are limited data on the utility of TPS in upper urinary tract (UUT) lesions and follow-up histology of cases with abnormal cytology. We aimed to evaluate the utility of TPS for UUT lesions by correlating the cytologic diagnoses using TPS criteria with subsequent histology. Additionally, the diagnostic utility of UroVysion (Abbott) fluorescence in situ hybridization (FISH) was assessed. A total of 148 UUT cytology specimens were retrospectively identified (2018-2022). Cytologic interpretation was performed using TPS, and then correlated with the findings of concurrent or subsequent histologic specimens. The performance of UroVysion FISH was analyzed. Sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting high-grade urothelial carcinoma (HGUC) were determined. Among 83 patients who had concurrent or subsequent histologic specimens, cyto-histologic discrepancy was seen in 7 cases (8.4%). The sensitivity, specificity, PPV, and NPV using TPS criteria for detecting HGUC were 87%, and 92%, 96.4%, and 73%, respectively. UroVysion FISH was performed in 21 patients with atypical cytologic findings. The sensitivity and specificity of UroVysion for detecting HGUC was 75% and 86%, respectively, while PPV and NPV were 86% and 75%, respectively. In our experience, the application of TPS criteria for reporting upper urinary cytology was reliable at detecting UUT lesions, especially HGUC. UroVysion FISH was a valuable ancillary test for detecting HGUC of UUT.

Diagnostic Role of The Bethesda System of Reporting Thyroid Cytopathology and Immunohistochemistry as an Adjunct to Fine Needle Aspiration Cytology in Differentiating Benign and Malignant Thyroid Lesions: A Cross-sectional Study

Introduction: Fine Needle Aspiration Cytology (FNAC) plays a crucial role in the preoperative assessment of thyroid nodules. The Bethesda System of Reporting Thyroid Cytopathology (TBSRTC; 2023) is a standardised system for reporting thyroid FNAC. However, diagnostic challenges can occur in each category of TBSRTC. Aim: To categorise thyroid FNAC according to TBSRTC and revisit the challenges of cytological diagnosis in each category. Materials and Methods: A cross-sectional, observational study was conducted from November 2018 to April 2020 (18 months) in the Department of Pathology at ABVIMS and Dr. RML Hospital in New Delhi, India. The study included all 470 thyroid FNA cases received in the department from patients presenting with palpable thyroid nodules or ultrasonographically detected solid thyroid lesions, regardless of their age or sex. The cases were classified according to TBSRTC. Diagnostic tests were used to calculate sensitivity, specificity, Negative Predictive Value (NPV), Positive Predictive Value (PPV), and diagnostic accuracy of TBSRTC. Immunoexpression for Human Bone Marrow Endothelium marker-1 (HBME-1) and p63 was studied in Bethesda III to VI category cases, i.e., atypia of undetermined significance (AUS), Suspicious for Malignancy (SFM) and malignant cases only, and not in categories I and II. Results: The study included 470 thyroid FNA cases with a mean age of 39.72 years. Cytohistological follow-up was available for 50 cases, of which six cases were discordant and the remaining 44 cases were concordant. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of TBSRTC were calculated as 50%, 97.06%, 32%, 80.49%, and 82%, respectively. Three cases with diagnostic challenges were revisited and discussed. Immunohistochemistry was performed on a total of 33 FNAC cases. However, histological follow-up was available for only 18 cases, of which seven cases were diagnosed as Papillary Thyroid Carcinoma (PTC) on histological follow-up. HBME-1 and p63 were positive in 57.14% and 42.86% of these cases, respectively. Conclusion: The TBSRTC, 2023, is an excellent reporting system for thyroid FNA and serves as an initial investigative tool for thyroid lesions. Present study findings reveal that it has high specificity and diagnostic accuracy. The Risk of Malignancy (ROM) was comparable to other studies, except for the Bethesda II category. Immunoexpression of HBME-1 and p63 was useful in isolated cases; however, it is not sufficient for cytological diagnosis.

Role of fine-needle aspiration cytology in the evaluation of salivary gland lesion with utilization of Milan system for reporting

Background: Fine-needle aspiration cytology (FNAC) plays a role in the pre-operative diagnosis of salivary gland mass lesion. Salivary gland neoplasm accounts for 6% of all head and neck tumors. It is widely used safe and relatively non-traumatic procedure that can quickly provide important information. “The Milan system for reporting salivary gland cytopathology” (MSRSGC) was introduced, providing a guide for diagnosis and management according to the risk of malignancy (ROM) in different categories. Aims and Objectives: The objectives of the study are as follows: (1) To evaluate different types of salivary gland lesion in tertiary care center. (2) To see application of Milan system in the present scenario. Materials and Methods: A hospital-based and prospective study was conducted between March 2021 and September 2022 on all cases of salivary gland lesions who were referred for FNAC to the Department of Pathology at Netaji Subhash Chandra Bose Medical College Hospital in Jabalpur, Madhya Pradesh. In the present study, we categorize salivary gland cytopathology result as per Milan system (MSRSGC) and calculated diagnostic accuracy and ROM in each category of Milan system (MSRSGC). Results: Seventy seven cases distributed according to Milan category as follows: Non-diagnostic (ND) (2.59), non-neoplastic (NN) (29.33%), atypia of undetermined significance (AUS) (1.29%), 4a. Benign (29.87%), 4b. Salivary gland neoplasm of uncertain malignant potential (SUMP) (1.29%), suspicious of malignancy (SOM) (1.29%), and malignancy (10.38%). Out of 77 cases, histological follow-up was available in 27 cases and the ROM was calculated. The ROM for each category of the Milan system is as follows: ND (0%), NN (6.66%), AUS (100%), 4a. Benign (9.09%), 4b. SUMP (0%), SOM (100%), and Malignancy (100%). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 77.7%, 100%, 100%, 92.59%, and 94.11%. Conclusion: FNAC of the salivary gland lesions is a safe, minimum invasive, and reliable diagnostic procedure. The Milan system of reporting is a risk stratification system which can improve the overall effectiveness of reporting.

Whole-body MRI with diffusion-weighted imaging as an adjunct to18 F-fluorodeoxyglucose positron emission tomography and CT in patients with suspected recurrent colorectal cancer.

The aim was to explore how findings of whole-body MRI including diffusion-weighted imaging (DW-MRI) compared to the routine diagnostic workup with CT and/or 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with suspected recurrent colorectal cancer (CRC). This was an exploratory retrospective analysis of 55 patients with a clinical suspicion of recurrent CRC who underwent DW-MRI following CT and/or FDG-PET/CT. Two readers in consensus interpreted all clinical imaging reports and converted each described lesion into a confidence score (1 = definitely benign to 5 = definitely malignant). DW-MRI findings were compared to the most recent previous CT or PET/CT. Any discrepant or additional DW-MRI findings were documented and compared with histology and/or clinical follow-up (if available). Whole-body MRI including diffusion-weighted imaging (DW-MRI) resulted in discrepant/additional findings in 26/55 (47%) cases; 23/37 (62%) compared to previous CT and 3/18 (17%) compared to previous PET/CT. These included 10 cases where DW-MRI converted previously inconclusive CT (n = 8) or PET/CT (n = 2) findings into a conclusive diagnosis, one where it contradicted a previous CT diagnosis of recurrence, five where DW-MRI diagnosed recurrent disease not previously reported on CT and 10 cases where DW-MRI detected additional lesions compared to CT (n = 9) or PET/CT (n = 1). Eighty-eight per cent of cases with discrepant/additional findings concerned patients with recurrent/metachronous peritoneal metastases. In total, DW-MRI resulted in 42 discrepant/additional lesions; the DW-MRI diagnosis was correct in 76% of these lesions and incorrect (false positive) in 7%. In the remaining 17%, no standard of reference was available. This explorative study suggests that DW-MRI may be of added value to patients with a clinical suspicion for recurrent CRC, in particular to identify patients with peritoneal metastases. DW-MRI mainly has potential as a 'problem-solver' in patients with inconclusive or negative findings on previous imaging (in particular CT) and to detect additional disease sites in patients already diagnosed with recurrent disease.

Diagnostic Value of Concurrent Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Fine-Needle Core Biopsy in Cytology Categories of Pancreatic Solid Lesions: An Institutional Experience

Abstract Introduction/Objective Endoscopic ultrasound is the current standard of care in the evaluation of pancreatic solid lesions. Two methods have been employed in obtaining EUS-guided pancreatic specimens; fine needle aspiration (EUS-FNA) and fine needle core biopsy (EUS-FNB). EUS-FNA may have certain limitations, including the inability to assess the histological architecture and a limited sample size for immunohistochemical staining on cell blocks. EUS- FNB, which employs a larger needle for core biopsy, was developed to address these limitations. However, it is still uncertain which method is better suited for specific lesions. In this study, we evaluated the diagnostic efficacy of concurrent EUS-FNA and EUS-FNB from pancreatic solid lesions. Methods/Case Report We reviewed our institutional database for cases that had EUS-FNA from pancreatic solid lesions with a subsequent definitive diagnosis on histology. Similarly, the concurrent EUS-FNB findings were recorded. The cases were categorized based on the World Health Organization pancreaticobiliary cytology reporting system. Furthermore, the absolute risk of malignancy (ARM) of each diagnostic category (defined as the presence of high-grade dysplasia or worse on the histologic follow-up) was calculated. Results (if a Case Study enter NA) A total of 108 cases were reviewed for the study from 1/1/2019 to 6/1/2022. The patients were 47% male and 53% female with an average age of 68. No case was categorized as non-diagnostic or neoplastic high-grade. There were 20 benign, 7 atypical, 3 neoplastic low-grade, 6 suspicious for malignancy, and 72 malignant cases, and the associated ARM related to each category was 40%, 86%, 33%, 33%, and 96% respectively. Concurrent EUS-FNB was performed in 23 cases in total (12 in malignant and 11 in other categories). EUS-FNB exhibited 95% positive and 100% negative predictive values (PPV and NPV) in all categories combined and 89% PPV and 100% NPV in non-malignant and indeterminate categories (categories II, III, IV, VI) for correlating to the histologic follow-up. Conclusion Cases diagnosed in all categories except the malignant category demonstrated ARM rates higher than expected. When approaching a solid pancreatic lesion, EUS-FNB may increase the diagnostic value, especially in cases of non-malignant and indeterminate categories. Moreover, categorizing the cases in the benign category may require additional supporting data, and placing them in the nondiagnostic category may be more appropriate warranting re-sampling if there is a clinical vs pathologic discrepancy.

To Help the Practitioner: Imaging of Ovarian Masses According to the O-RADS MRI Ovarian Malignancy Categorical Risk Scale

Objective: to study the informativity of the Ovarian-Adnexal Imaging-Reporting-Data System Magnetic Resonance Imaging (O-RADS MRI) in detection of ovarian cancer in the practice of a radiologist.Material and methods. The study included 271 women who underwent pelvic magnetic resonance imaging (MRI) in the period from August to November, 2021. Two radiologists with 6-year (Researcher 1) and 2-year (Researcher 2) experience retrospectively analyzed MR images, in which all ovarian masses were evaluated according to O-RADS MRI categorical risk scale from 0 to 5. The analysis of true positive, true negative, false positive and false negative rates according to MRI data compared to the reference data (histology or 1-year follow-up) was performed.Results. O-RADS MRI categorial risk scale had high diagnostic performance for the characterization of adnexal lesions (sensitivity 87.5% and 87.5%, specificity 97.84% and 96.75%, area under curve (AUC) 0.991 and 0.986 for Researchers 1 and 2, respectively), as well as good interreader agreement (Cohen’s kappa coefficient 0,83). Researchers’ mistakes were analyzed, as well as controversial issues of categorial affiliation of ovarian masses that caused false positive and false negative results. Visual aids for ovarian MRI in accordance with O-RADS MRI classification were made for quick orientation in the system to simplify creating the radiology report.Conclusion. O-RADS MRI categorial risk scale proved to be a reliable working tool for the communication between radiologist and gynecologist-oncologist. However, the question of categorial affiliation of a number of nosological names that are not reflected in O-RADS MRI and require further study continues to be debated.

Binary subclassification scheme (AUS-Nuclear versus AUS-Other) adequately risk-stratifies thyroid fine needle aspiration specimens classified as Atypia of Undetermined Significance

The Bethesda System for Reporting Thyroid Cytopathology previously described 4subclassesof atypia within the Atypia of Undetermined Significance (AUS) category: nuclear (AUS-Nuc), architectural (AUS-A), oncocytic (AUS-Onc), and atypia not otherwise specified (AUS-NOS). Accumulating evidence supports a binary AUS subclassification scheme based primarily on the presence of nuclear atypia only. The purpose of this study is to compare the risk stratification of binary versus 4-tier AUS subclassification systems among AUS nodules with molecular and/or histologic follow-up. Thyroid aspirates classified as AUS and tested using Afirma (Veracyte, Inc.) between 6/2013 and 7/2021 were included. For resected nodules, histological classification was considered as the final outcome. For unresected nodules, benign Afirma results were considered low-risk outcomes, similar to histologically benign nodules. Suspicious or nondiagnostic Afirma results were considered indeterminate outcomes. The prevalence of outcomes warranting surgery (noninvasive follicular thyroid neoplasm with papillary-like nuclear features [NIFTP] or cancer) was calculated for each AUS subclass. A total of 559 AUS nodules with Afirma testing were identified. Excluding nodules with indeterminate molecular outcomes, NIFTP/cancer prevalence for AUS-Nuc was 21% (57/266), which was higher than that for AUS-A (6%, 11/188), AUS-Onc (8%, 4/53), and AUS-NOS (0%, 0/9). A binary AUS subclassification scheme based on nuclear atypia showed a significant difference in NIFTP/cancer prevalence (21% versus 6%, P < 0.0001). Binary reporting of AUS subclasses based on nuclear atypia distinguishes cases with a higher risk of NIFTP/cancer. There is a low but non-negligible prevalence of NIFTP/cancer in cases without nuclear atypia.

Colloid and pigmented histiocytes in lymph node aspirates as a clue to metastasis in patients with a history of papillary thyroid carcinoma.

Cystic changes, calcification, colloid material, and multinucleated giant cells are frequently associated with primary and metastatic papillary thyroid carcinoma (PTC). These features are sometimes present in negative lymph node fine-needle aspiration cytology (FNAC). This study aims to review nodal aspirates of PTC to elucidate the significance of these cytological features in aspirates without tumor cells. FNAC specimens from patients with PTC confirmed on thyroidectomy were reviewed for cystic changes, tumor-associated features, and lymphoid components. Histologic follow-up of the lymph nodes were retrieved for correlation. A total of 113 aspirates were retrieved, of which 79 showed tumor cells on the FNAC specimen, and 95 were matched to a positive lymph node histology. At univariable analysis, calcification (n = 18/113, p = .044), colloid material (n = 40/113, p = .001), multinucleated giant cells (n = 29/113, p = .028), tumor cells (n = 79/133, p < .001), foamy histiocytes (n = 36/113, p = .002) and pigmented histiocytes (n = 62/113, p < .001) were associated with a positive histology. Presence of lymphoid fragments (n = 11/113, p < .001) and abundant background lymphocytes correlated with a negative histologic follow-up (n = 45/113, p = .005). In aspirates without tumor cells, multivariable analysis demonstrated colloid material (p < .001) and pigmented histiocytes (p = .003) to be independently predictive of metastatic PTC, whereas lymphoid fragments (p < .001) were independently associated with a negative histologic follow up. Colloid material and pigmented histiocytes, and to lesser degree calcification and multinucleated giant cells, when seen in an aspirate without tumor cells, raises suspicion metastatic disease. On the contrary, the lymphoid fragments can be regarded as supportive evidence of adequate sampling and a true negative result.

Course of sarcoidosis in patients treated with systemic corticosteroids

The treatment of sarcoidosis remains uncertain despite 70 years of studies. The conventional approach is to initiate corticosteroids in individuals who require treatment. However, to date, there are no strict dosing regimens for systemic corticosteroids (SСS), and patients who were treated with SСS develop relapses more frequently than those who have not received these drugs. The aim of this work was to evaluate the course and outcomes of pulmonary sarcoidosis in patients who were prescribed systemic corticosteroids. Methods. The study was retrospective and noninterventional. 493 (32.5%) of 1,518 patients with sarcoidosis were prescribed corticosteroids during follow-up. Only 333 cases were selected because they had histologic confirmation and follow-up of 1 year or more. The data at the time of diagnosis and at the time of analysis were compared (patients remained under the supervision of the same physicians thereafter). Results. After at least one year of follow-up, the positive effect of SCS (resolution or stabilization of the process) was achieved only in half of the cases, while the rest of the patients required more courses of SCS or the use of alternative drugs. Worsening was more common when multiple organs were involved, when SCS were administered immediately after diagnosis without a follow-up period, and when the duration of the first course of hormone therapy was less than 7 months. 33.6% of patients treated with SCS had clinically significant adverse events (AEs), and 13.2% had to discontinue or replace one hormonal drug with another. Older age and repeated courses of SCS were associated with the development of fibrosis, whereas transition to second-line drugs was not. Conclusion. SCS remain the first-line drugs in the treatment of sarcoidosis. The analysis performed allows us to recommend them after an observation period (if the patient’s condition allows it) and for at least 6 months. In case of exacerbation or recurrence of sarcoidosis after treatment with SCS, subsequent therapy with second-line drugs is more effective that a repeated course of SCS.

Eosinophilic Ulcer of the Tongue in Smokeless Tobacco "Shamma User”: Case Series Report

Oral eosinophilic ulcers (OEU) are rare, benign, reactive, and often self-limiting lesions. As the lesion is self-limiting, it develops rapidly,usually disappearing after several weeks. Although the exact pathogenetic mechanisms are unknown, the possibility that trauma may play a rolehas been postulated. The lesion frequently misleads to the suspicion of squamous cell carcinoma because of its prolonged duration. Despite traumabeing suggested as the main culprit of oral eosinophil ulcers, the exact pathogenesis mechanism of this disease remains controversial. However, itmay misdiagnose as malignancy, particularly in smokeless tobacco "Shamma users." The study emphasizes the clinical and histopathological aspectsof diagnosing and treating this pathology. The study aims to demonstrate the importance of knowledge and its course. The novelty of our studycan be described in terms of thorough early clinical diagnosis with confirmatory histopathological findings that can aid towards perfect diagnosis,as part of treatment - removal of etiological factors (trauma) saw the Oral eosinophilic ulcers (OEU) completely healed, which was earlier can bemisdiagnosed as malignancy based on the use of Shamma smokeless tobacco by patients for a longer period. We present the two male cases ofSaudi residents with a long history of painful ulcers on the lateral borders of the tongue. Both had a long history of being "Shamma users" ofsmokeless tobacco. The ulcers were ulceration with indurated and elevated borders and no evidence of regional lymph node involvement.Histopathologically, the lesion showed an infiltrate with several eosinophils, was ulcerated, and no cellular atypia was observed. After the treatment,the ulcer rapidly healed with an incisional biopsy and the cause removal. A definite diagnosis was achieved by combining histologic findings andclinical follow-up. A biopsy is not only the best approach for a proper diagnosis but also for its therapeutic management. Understanding thisdisease is necessary since its lesion can mimic an oral squamous cell carcinoma occurring as an indurated ulceration coupled with its frequentoccurrence on the tongue.

Application of The Paris System in neobladder washing cytology: Comparison between the original diagnosis and correlation with histopathology.

In urinary diversion after radical cystectomy, the incidence of recurrent urothelial carcinoma (UC) in upper urinary tract or urethra are reported in 2%-17% of the patients. Urine cytology plays a pivotal role in detecting the recurrence of UC. However, cytologic diagnosis in urinary diversion including neobladder is often challenging due to significant degenerative changes and necro-inflammatory background. Since the proposal of The Paris System (TPS) for reporting cytology, the utility of TPS in urinary diversion specimen has not been studied yet. The objective of this study is to evaluate the diagnostic usefulness of TPS compared with the original diagnosis and correlate with the matched histopathological results. Urinary diversion cytology specimens with concurrent or subsequent biopsy or resection at EUMC in recent 16 years (from January 2002 to December 2018) are retrospectively reviewed and reclassified according to TPS criteria. The TPS categories and the original diagnoses were compared and correlated with follow-up histology. Concurrent or subsequent biopsy or resection within a 6-month period was available in 45 cases from 28 patients. When applying TPS, the rate of atypical and suspicious categories decreased by 13.4% and 11.1%. Using TPS increased the value of sensitivity, NPV, and accuracy to 93.75%, 93.75%, and 90.91%, respectively. Application of TPS reduced the rate of indeterminate diagnoses and moreover, improved the sensitivity and accuracy of urinary diversion cytology. Therefore, we believe that diversion urine cytology diagnosis according to TPS is useful to screen patients for detection of recurrence in routine clinical practice.

False-Positive Atypical Endocervical Cells in Conventional Pap Smears: Cyto-Histological Correlation and Analysis

Introduction: Endocervical glandular atypia is relatively rarely diagnosed by Pap smears. A significant proportion of follow-up histological samples show no premalignant or malignant lesions. The observed cytomorphological findings in premalignant glandular lesions overlap with histologically proven reactive lesions. Methods: A total of 45 conventional Pap smears diagnosed as atypical endocervical cells, not otherwise specified (AEC, NOS) with human papillomavirus (HPV) status available were blindly evaluated in a search for 38 cytomorphological features representing background, architectural, cellular, and nuclear features. Of the cases, 30 represented histologically proven benign changes, and 15 represented histologically proven adenocarcinoma in situ (AIS) or endocervical adenocarcinoma (EAC) cases. The benign biopsies were re-evaluated, and the associations of the cytomorphological features or combinations of them with specific histological features and entities were statistically examined. Results: The most frequent histological findings in the benign group were squamous metaplasia, inflammation, tubal metaplasia, and microglandular hyperplasia. The statistical analysis revealed cytological features associated with squamous metaplastic changes, inflammation, and microglandular hyperplasia. Unfortunately, no cytomorphological feature was sufficiently specific to confidently leave the lesion without follow-up and histological correlation. Degeneration and nuclear crowding were the most salient features that distinguished the instances of glandular atypia with benign follow-up histology from those with histologically proven AIS or EAC (26.7 vs. 60.0%, p = 0.030, and 50.0 vs. 86.7%, p = 0.017). Conclusion: Additional methods besides cytomorphology are required to reliably distinguish smears with AEC, NOS harbouring only benign histological changes from those exhibiting endocervical glandular malignancy.

Evidence for Alloimmune Sinusoidal Injury in De Novo Nodular Regenerative Hyperplasia After Liver Transplantation.

Posttransplant nodular regenerative hyperplasia (NRH) mostly remains unexplained. Microvascular injury due to antibody-mediated rejection (AMR) is suspected, but lack of donor specific antibody (DSA) testing makes it difficult to prove. Centered around a 1-year period of routine DSA testing, concomitant protocol, and indicated posttransplant liver biopsies (LB), recipients with NRH (n = 18) were compared with a matched control group (n = 36). All index, previous, and subsequent LB were reviewed. Both groups were similar in terms of demographics, timing of index LB, and DSA. In the index LB, the NRH group had higher sinusoidal C4d positivity (p = 0.029) and perisinusoidal fibrosis (p = 0.034), both independently associated with NRH (p = 0.038 and 0.050, respectively). Features of "possible" chronic AMR were detected in 28.5% of the NRH group without a known cause and 0% of the control group (p = 0.009). The NRH group had more preceding indicated LB with increased incidence of rejection and biliary obstruction pattern. In the follow-up histology, overall, sinusoidal and portal C4d positivity, sinusoidal microvasculitis, and perisinusoidal fibrosis were also higher (all p < 0.050). In conclusion, we provide evidence towards the hypothesis that some cases of posttransplant NRH are related to preceding active and persistent AMR. Large multicenter studies with protocol DSA testing are required to confirm.

Contrast-enhanced ultrasound-guided biopsy of suspicious breast lesions on contrast-enhanced mammography and contrast-enhanced MRI: a case series.

To assess the effectiveness of contrast-enhanced ultrasound (CEUS) in guiding biopsies of breast lesions that were detected on contrast-enhanced mammography (CEM) or contrast-enhanced breast MRI (CE-MRI) but were not clearly visible on B-mode ultrasound (B-US). In this study, 23 lesions in 16 patients were selected for CEUS-guided biopsy due to poor visualization on B-US despite being detected on CEM (n = 20) or CE-MRI (n = 3). B-US, color Doppler ultrasound (CDUS), and CEUS were used to visualize the suspicious lesions, followed by a CEUS-guided core needle biopsy using Sonazoid as the contrast agent. The accuracy of the biopsy was assessed based on pathology-radiology concordance and 12-month imaging follow-up. The conspicuity scores for lesion visualization were evaluated using a 5-point conspicuity scale agreed upon by two breast radiologists. The enhancing lesions detected on CEM/CE-MRI had an average size of 1.6 ± 1.3cm and appeared as mass-enhancing (61%) or non-mass-enhancing (39%). The lesions had mean conspicuity scores of 2.30 on B-US, 2.78 on CDUS, and 4.61 on CEUS, with 96% of the lesions showing contrast enhancement on CEUS. CEUS-guided biopsy showed increased visibility in 96% and 91% of the lesions compared to B-US and CDUS, respectively. The overall accuracy of CEUS-guided biopsy was 100% based on concordance with histology and 12-month follow-up. CEUS enhances the visibility of suspicious CEM/CE-MRI lesions that are poorly visible on B-US during biopsy procedures.

Impact of apolipoprotein A1 on tumor immune microenvironment, clinical prognosis and genomic landscape in hepatocellular carcinoma.

Current knowledge on apolipoprotein A1 (APOA1) in hepatocellular carcinoma (HCC) is fragmented and even contradictory. Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism. We collected 49 RNA-seq datasets, 40 cell line types data and 70 scRNA pan-cancer datasets public available, including 17 HCC datasets (1754 tumor samples), and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics. APOA1 impacting on the HCC tumor microenvironment (TME) was analyzed using intensive data mining. Methylation sequencing, flow cytometry, quantitative PCR, western blot, immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation. The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC, primarily involved in cholesterol efflux. Consistent findings at histology, serology, and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCC. Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC. The cell cycle, DNA replication, mismatch repair pathways, and tumor cell proliferation were less observed in the HCC APOA1high subgroup. The favorable immunoregulatory abilities of APOA1 showed interesting findings: a positive correlation between APOA1 and anti-tumor immune cells (NK, CD8+T cells) and a negative association with immune cells exerting immunosuppressive effects, including M2 macrophages. This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments. Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinical target for HCC assessment and intervention in the future.

The effect of different doses of nonylphenol on the blood-testicular barrier integrity, hormone level, and DNA damage in the testes of rats.

Determining the molecular characteristics of the damage caused by NP exposure in the testis is very important for understanding the source of the damage and developing treatment methods accordingly. Therefore, in this study, it is aimed to evaluate the toxic effects that different doses of NP may cause in the testis, including blood-testicular barrier integrity and sperm DNA damage. For this purpose, 50 adult male Wistar albino rats were used in the study. Low, medium, and high-dose NP groups and the corn oil group were formed. After NP administration at determined doses for 15 days, the testis tissue taken under anesthesia was fixed in formaldehyde. Paraffin blocks were embedded using the routine histological tissue follow-up method. Histopathological and immunohistochemical analyses were performed by taking 5μm thick sections from paraffin blocks. The other testicular tissue was taken for the Western blot, Elisa, and comet methods, and the findings of sperm DNA analysis and the blood-testicular barrier were examined. NP caused the seminiferous epithelium to be disorganized and have significantly fewer cells in the testes of rats in different dose NP-induced groups. Compared with the control group, mTOR, Cx43, SCF, and HSP70 protein levels were decreased, while the expression of MMP-9 levels was increased in the different NP dose groups. Furthermore, tissue testosterone and inhibin B levels and SF-1 immunoreactivity intensity gradually decreased depending on the dose increase of NP. DNA damage of testicular tissues were increased in NP groups depending on NP dose. These results suggest that it is evident that NP, a commonly used industrial chemical, is an endocrine disrupting chemical (EDC) with estrogenic activity exerting adverse effects on health and that urgent measures are needed regarding the use.

Probability of malignancy and molecular alterations as determined by ThyroSeq v3 genomic classifier in Bethesda Category IV.

ThyroSeq molecular testing assesses the probability of malignancy (POM) in thyroid fine-needle aspiration cytology (FNAC) with indeterminate cytology. The aim was to investigatewhether Bethesda category IV (BIV) subcategories are associated with specific molecular alterations, molecular-derived risk of malignancy (MDROM), and risk of malignancy (ROM). FNAC slides, associated ThyroSeq, version 3, Genomic Classifier results, and surgical follow-up were retrieved for BIV nodules. Nodules were subcategorized as follicular neoplasm (FN) with or without cytologic atypia or oncocytic follicular neoplasm (OFN). The MDROM, ROM, and frequency of molecular alterations in FN and OFN were analyzed. p < .05 was considered significant. A total of 92 FNAC were identified and subcategorized into 46 FN (15 with and 31 without cytologic atypia) and 46 OFN. The benign call rate and the positive call rate were 49% and 51%, respectively. The MDROM in BIV was 34.3%, trending lower in OFN than in FN. RAS mutations were significantly more frequent in FN when compared to OFN (p = .02). Chromosomal copy number alterationswere more often present in OFN than in FN (p < .01). On histologic follow-up, ROM in OFN was trending lower than in FN (p = .1). The most common diagnosis in OFN was oncocytic adenoma, whereas follicular variant papillary thyroid carcinoma was most common in FN. The MDROM and ROM were trending lower in OFN compared with FN, and the molecular alterations differed between OFN and FN subcategories.

Value of TI-RADS and elastography strain ratio in predicting malignant thyroid nodules: experience from a single center in Egypt

IntroductionThyroid nodules are highly prevalent in the general population; therefore, it is crucial to discriminate benign from malignant nodules. A practical thyroid imaging reporting and data system (TI-RADS) for thyroid nodules and ultrasound elastography are valuable tools not only for characterization of nodules but also for the selection of tumors for fine-needle aspiration cytology (FNAC).ObjectiveThis study aimed to evaluate the diagnostic accuracy of US evaluation in the prediction of malignant thyroid nodules and evaluate the role of the elastography score, strain ratio (SR), and the TI-RADS scoring system as non-invasive tools in differentiation between malignant and benign thyroid nodules.Material and methodsA total of 1269 patients were evaluated between February 2017 and April 2020 by a single expert thyroid ultrasound operator. The final diagnosis was achieved from cytological and/or histological evaluation and follow-up for at least 1 year.ResultsThere were 1088 females and 181 males with a mean age of 44 ± 10 SD. The final diagnosis was 1197 benign nodules and 72 malignant nodules. Most malignant nodules were scored elastography score 4 (83.3%) and TI-RADS category 5 (86.11%). We found that nodules with antero-posterior to transverse (A-P/T) diameter > 1, have 21 times more risk to be malignant than those with A-P/T diameter < 1, patients with solitary thyroid nodules have 4.5 times to develop malignancy compared to those with multinodular goiter (MNG), nodules with absent halo have 4 times more risk of malignancy. Furthermore, microcalcifications in thyroid nodules increase the risk of malignancy 9 times compared to those without calcifications. SR was found to be an excellent discriminator to differentiate between benign and malignant nodules with P < 0.001. Also, we found that for every unit increase in SR, the risk of malignancy increased by 20%. We reported that the accuracy of ultrasonography in the detection of malignant thyroid nodules had a sensitivity of 89%, specificity of 98%, 70% PPV, and 99.3% NPV, with an overall accuracy of 97.2%.ConclusionThe application of ultrasonographic non-invasive criteria for thyroid nodules in clinical practice might significantly reduce the number of unnecessary FNAC. Elastography, SR, and TI-RADS classification could be good predictors for malignant thyroid nodules.

Characterization and Short-Term Outcome of Potential Celiac Disease in Children.

Background and Objectives: Potential Celiac Disease (PCD) is defined by positive celiac serology without villous atrophy. We aimed to describe the short-term outcome of pediatric PCD while consuming a gluten-containing diet (GCD). Materials and Methods: Retrospective analysis of pediatric PCD patients continuing GCD, between December 2018-January 2022. Baseline demographics, celiac serology and duodenal biopsy results were reviewed. Follow-up data included repeated serology and biopsy results when performed. Minimum follow-up was 12 months unless celiac disease (CeD) was diagnosed earlier. Results: PCD was diagnosed in 90 children (71% females) with a mean age of 7.2 (range 1.8-16.5) years. Baseline anti-tissue transglutaminase (TTG) levels were above 10 times the upper limit of normal (ULN) in 17/90 (18.9%), 3-10 × ULN in 56/90 (62.2%) and 1-3 × ULN in 17/90 (18.9%). During follow-up, the mean time was 17.6 (range 5-35) months, TTG normalized in 34/90 (37.8%), was stable in 48/90 (53.3%), and increased or remained >10 × ULN in 8/90 (8.9%). In 20/90 (22.2%) patients, a repeat endoscopy was performed, leading to CeD diagnosis in 12/20 (60%). Thus, at the end of follow-up, CeD was diagnosed in 12/90 (13.3%). In patients with TTG >10 × ULN at diagnosis, TTG normalized in 5/17, decreased to 3-10 × ULN in 8/17, and remained above 10 × ULN in 4/17. Conclusions: During the short-term follow-up of pediatric PCD patients, less than 15% progressed to CeD. A third had normalized TTG levels, including children with TTG >10 × ULN, indicating the need for periodic serological and histological follow-up among PCD patients.

Atypical urothelial cells classified according to the Paris System for Reporting Urinary Cytology: A 2-year experience with histological correlation from a Finnish tertiary care center-low rate and high risk of malignancy.

The Paris System for Reporting Urinary Cytology (TPS) was issued to shift the focus of urine cytology to high-grade lesions to increase the diagnostic accuracy of urine cytology. The aim of this study was to evaluate the power of TPS in the atypical urothelial cells (AUC) category with histological correlation and follow-up. The data cohort consisted of 3741 voided urine samples collected during a 2-year period between January 2017 and December 2018. All samples were prospectively classified using TPS. This study focuses on the subset of 205 samples (5.5%) classified as AUC. All cytological and histological follow-up data were analyzed until 2019, and the time between each sampling was documented. Of the 205 AUC cases, cytohistological correlation was possible in 97 (47.3%) cases. Of these, 36 (12.7%) were benign in histology, 27 (13.2%) were low-grade urothelial carcinomas, and 34 (16.6%) were high-grade urothelial carcinomas. Overall, the risk of malignancy was 29.8% for all cases in the AUC category, and 62.9% in the histologically confirmed cases. The risk of high-grade malignancy was 16.6% in all the AUC category samples and 35.1% in the histological follow-up group. The performance of 5.5% AUC cases is considered good and within the limits proposed by TPS. TPS is widely accepted by cytotechnologists, cytopathologists, and clinicians; it improves communication and patient management.