Breast cryoablation for the treatment of fibroadenoma and breast cancer is safe and effective, and breast cryoablation performed as an outpatient procedure with local anesthesia alone is well tolerated by patients. Because use of this procedure is increasing, radiologists and proceduralists must understand the postcryoablation breast imaging algorithms, including the rationale for imaging, the appropriate timing for imaging, and appropriate imaging modalities. Radiologists must also be able to differentiate benign, expected posttreatment findings at the ablation zone from findings suggestive of residual, progressing, or recurrent malignancy on mammography, digital breast tomosynthesis, US, MRI, and contrast-enhanced mammography. Finally, radiologists must report postcryoablation breast imaging findings using appropriate descriptors and standardized reporting lexicon. Accurate and standardized reporting of postcryoablation breast imaging findings is important to guide clinical management, facilitate research on imaging findings' associated risk for malignancy, and permit comparison of radiologist performance and patient outcomes across facilities worldwide.

Fine-needle aspiration cytology (FNAC) is a key diagnostic method for salivary gland lesions. The Milan System for Reporting Salivary Gland Cytology (MSRSGC), a six-tiered classification system, standardises reporting and provides risk of malignancy (ROM) for each category. Although MSRSGC recommends ancillary tests such as immunocytochemistry (ICC), reports on their clinical application remain limited. This study aimed to investigate the utilisation rate of ancillary tests in MSRSGC classifications and assess their effectiveness, particularly with liquid-based cytology. Diagnostic records of salivary gland FNAC cases at Kurume University Hospital (January 2020 to December 2024) were reviewed, and those evaluated by MSRSGC were extracted. Utilisation rate of ancillary tests, FNAC sensitivity and specificity, and ROM were calculated in cases with histopathological follow-up. Among 321 salivary gland FNAC cases, 131 had histopathological follow-up. Ancillary tests were used in 22.1% of cases, most often in SUMP (IVB), Suspicious for Malignancy (V) and Malignant (VI). ICC yielded a definitive histological diagnosis in 37.9% and a suggestive diagnosis in 27.6%. ROM by MSRSGC category was: Non-Diagnostic (I) 0%; Non-Neoplastic (II) 12.5%; AUS (III) 35.7%; Benign Neoplasm (IVA) 0%; SUMP (IVB) 27.8%; Suspicious for Malignancy (V) 75.0%; and Malignant (VI) 100%. FNAC sensitivity and specificity were 97.3% and 98.2%, respectively. Ancillary testing, particularly ICC, enhances the reliability of MSRSGC and contributes to improved diagnostic accuracy.

Background: Thyroid nodules with cytological features of atypia of undetermined significance (AUS), particularly those with nuclear atypia, represent a diagnostic challenge due to their variable malignancy risk. The 2023 revision of the Bethesda System has refined AUS subcategories to improve malignancy risk stratification. The aim of this study was to evaluate the risk of malignancy in Bethesda Category III thyroid nodules with nuclear atypia by correlating cytological findings with post-thyroidectomy histopathological results. Material and Methods: This retrospective observational study included 156 patients who underwent thyroid fine-needle aspiration cytology between 2020 and 2024 and were diagnosed with AUS featuring nuclear atypia. All patients subsequently underwent thyroidectomy. Malignancy rates were determined based on final histopathological diagnoses. Statistical analysis was performed using SPSS version 29.0, applying Chi-square and Fisher’s exact tests, with a significance threshold set at p < 0.05. Results: The overall malignancy rate was 34.6%, increasing to 39.7% when NIFTP cases were included Fifty papillary carcinomas were identified, 28 of which were <1 cm. In 23 patients who received repeated AUS diagnoses, the malignancy rate reached 73.9% (p = 0.011). No statistically significant differences were found between benign and malignant groups in terms of age (p = 0.655), gender (p > 0.05), or lymphocytic thyroiditis (p = 0.3). The reported malignancy rates were exclusively to the cohort of Bethesda Category III nodules with nuclear atypia, which constituted the entire study population. Conclusion: Thyroid nodules classified as AUS with nuclear atypia are associated with a higher-than-expected risk of malignancy, especially in cases with repeated AUS diagnoses. These findings underscore the importance of subclassifying AUS cases to improve risk stratification and guide clinical decision-making.

To explore UK key-opinion leader perspectives on the future role of stem cell-derived islets (sc-islets) in islet transplantation for people with type 1 diabetes (T1D). Four UK-based key-opinion leaders evaluated current limitations of donor islet transplantation and reviewed emerging evidence, clinical pathways and logistical considerations for sc-islet transplantation, including alternative delivery sites and implications for kidney transplantation strategies. Conventional islet transplantation is constrained by donor scarcity, variable graft quality and lifelong immunosuppression, with associated risks of infection, malignancy and calcineurin inhibitor (CNI) nephrotoxicity. Stem cell-derived islets, generated from human embryonic and induced pluripotent stem cells, provide a scalable and standardised alternative. Early investigational products, including Zimislecel (VX-880), demonstrate potential for insulin independence and may offer an alternative to simultaneous pancreas-kidney (SPK) transplantation. Strategies to reduce or eliminate systemic immunosuppression particularly CNI immunosuppression through local immunomodulation, gene editing and encapsulation technologies may further broaden access. Ethics, infrastructural and economic considerations remain central to equitable implementation. Stem cell-derived islets may redefine islet transplantation for T1D by enabling more scalable, less invasive and sustainable therapeutic pathways while maintaining access to technological diabetes management options.

Animal cancer registries (ACRs) are vital tools in veterinary oncology, offering insights into tumor epidemiology and supporting comparative research. Despite cancer being a major cause of feline mortality, data on feline tumor epidemiology remain limited. This study aimed to investigate temporal trends in histologically diagnosed feline tumors and assess how breed, sex, neuter status, age, and geographic origin affect malignancy and tumor distribution. A modified Vet-ICD-O-canine-1 coding system was applied to 5,289 tumors from two pathology-based ACRs in central Italy (2008-2023). Data were analyzed for time trends by the Cochrane-Armitage test, and logistic regression was used to assess the impact of the variables on tumor behavior ("malignant" vs. "benign") and the development of major cancer types. Of all tumors, 4,264 (80.6%) were malignant. Fibrosarcomas (n = 926; 17.5%), adenocarcinomas (n = 814; 15.4%), squamous cell carcinomas (SCCs; n = 738; 14.0%), and lymphomas (n = 507; 9.6%) were the most common types of cancer. Malignancy risk increased by 8% per year of age (OR = 1.08; 95%CI 1.06-1.10). Females (OR = 1.39; 95%CI 1.19-1.62) and non-purebred cats (OR = 1.89; 95%CI 1.47-2.38) had higher odds of malignancy. Neutered status was associated with reduced adenocarcinoma risk (OR = 0.79; 95% CI 0.66-0.94). Temporal trends included rising SCCs (p = 0.001) and declining fibrosarcomas (p < 0.001). These findings support previous findings and identify previously unknown risk factors, underscoring the value of multicenter ACR-based surveillance.

The recombination activating gene 1 (RAG1) is essential for V(D)J recombination and lymphocyte development. While biallelic null RAG1 mutations cause severe combined immunodeficiency (SCID), hypomorphic variants have increasingly been associated with immune dysregulation and hematologic malignancies. This study aimed to present a pediatric case of Epstein-Barr virus (EBV)-negative Burkitt lymphoma carrying a novel homozygous RAG1 variant and to discuss its potential association with immune function and malignancy risk. A 9-year-old Turkish male from a consanguineous family was evaluated for hereditary cancer predisposition. Clinical, immunologic, and genetic assessments were performed, including whole-exome sequencing (WES), Sanger validation, and mRNA expression analysis. The patient presented with cervical lymphadenopathy and was diagnosed with EBV-negative Burkitt lymphoma; he had no recurrent infections, abnormal vaccine reactions, or SCID-related features. Immunologic testing, including lymphocyte subsets and immunoglobulin levels, was within normal limits. WES identified a homozygous RAG1 variant (NM_000448.2:c.460C>T; p.Leu154Phe), predicted to be deleterious and absent from population databases. Both the patient and his healthy dizygotic twin were homozygous, while parents were heterozygous carriers. RAG1 mRNA expression was reduced in heterozygotes but similar in homozygous and wild-type individuals; enzymatic activity was not assessed. The patient responded to chemotherapy and remains in remission under follow-up. In conclusion, this case expands the phenotypic spectrum of hypomorphic RAG1 variants to include EBV-negative Burkitt lymphoma without overt immunodeficiency, suggesting a possible link between partial RAG1 dysfunction and pediatric lymphoma susceptibility.

Studies have reported promising results regarding artificial intelligence (AI) as a tool for improved mammographic screening interpretive performance. We analyzed AI malignancy risk scores from two versions of the same commercial AI model. This retrospective cohort study used data from 117,709 screening examinations performed in BreastScreen Norway 2009-2018. The mammograms were processed by two versions of the commercially available AI model, Transpara (version 1.7 and 2.1). The distributions of exam-level risk scores (AI score 1-10) and risk categories were evaluated for both AI versions on all examinations, including 737 screen-detected and 200 interval cancers. Scores between 1-7 were categorized as low risk, 8-9 as intermediate risk, and 10 as high risk of malignancy. Area under the receiver operating curve was 0.908 (95% CI: 0.986-0.920) for version 1.7 and 0.928 (95% CI: 0.917-0.939) for 2.1 when screen-detected and interval cancers were considered as positive cases (p < 0.001). A total of 87.1% (642/737) and 93.5% (689/737) of the screen-detected cancers had an AI score of 10 with version 1.7 and 2.1, respectively. Among interval cancers, 45.0% (90/200) had AI score 10 with version 1.7 and 44.5% (89/200) had AI score 10 with version 2.1. A higher proportion of screen-detected breast cancers had the highest AI score of 10 with the newer version of the AI model compared to the older version. For interval cancers, there was no difference in the proportion of cases assigned to the highest score between the two versions. Question Studies have reported promising results regarding the use of AI in mammography screening, but comparisons of updated versus older versions are less studied. Findings In our study, 87.1% (642/737) of the screen-detected cancers were classified with a high malignancy risk score by the old version, while it was 93.5% (689/737) for the newer version. Clinical relevance Understanding how version updates of AI models might impact screening mammography performance will be important for future quality assurance and validation of AI models.

Primary pulmonary malignancies in single-ventricle patients are rare. Improved survival following surgical palliation has resulted in a growing Fontan population whose malignancy risk remains undefined. Standard oncologic approaches, especially for adenocarcinoma of the lung, need to be considered within the context of Fontan physiology. We present our management of primary lung adenocarcinoma in an adult with tricuspid atresia status postlateral tunnel Fontan palliation, highlighting considerations for this unique scenario.

Pulmonary nodules are mostly solitary focal opacities typically round or oval in shape, with a diameter of less than 3 cm. They are surrounded by aerated lung parenchyma or located subpleurally, and are not associated with abnormalities, such as lymphadenopathy or atelectasis. Pulmonary nodules are found in up to one-third of computed tomography scans taken in adults, whereas they are significantly less common in children. In adult patients, incidentally detected pulmonary nodules are more frequently associated with neoplastic processes, while they are primarily related to congenital disorders or inflammatory conditions in paediatric populations. The identification of single or multiple pulmonary nodules should always prompt an attempt to determine the likely aetiology. The so-called idiopathic nodules, for which no definitive cause can be established, are a particular subgroup. Although the majority of these lesions are benign in children, some may represent an early stage of malignancy. Due to the lack of standardised management guidelines for the paediatric population, clinical decisions regarding follow-up and further diagnostic workup are often challenging. This literature review outlines the potential causes of incidentally detected paediatric pulmonary nodules, from malignant tumours to other diseases that can present in this form, and discusses methods for assessing the malignant risk of pulmonary nodules in paediatric patients. Finally, a management strategy is proposed for asymptomatic pulmonary nodules detected on imaging, computed tomography in particular.

This nationwide cohort study compared long-term subsequent benign biliary events and biliary tract malignancy in patients with gallstone ileus treated with or without concomitant cholecystectomy. This retrospective cohort study used data from the Taiwan National Health Insurance Research Database. All patients diagnosed with gallstone ileus between 2000 and 2012 were included. Patients with a history of cholecystectomy, those of undetermined sex, and those aged < 18years were excluded. The patients were divided into two groups based on whether they underwent concomitant cholecystectomy at the index admission. Cholecystectomy was defined using ICD-9-OP codes. The primary endpoint was re-hospitalization with a diagnosis of biliary complications and malignancy of the biliary tree. All patients were followed up until the end of 2013 for biliary complications or death. We included 376 patients with a median follow-up of 34.23months (0.07-169.7months). There were no between-group differences in prior biliary events (p = 0.068) or in incident biliary events during follow-up (median time to event, 10.67months from index admission; p = 0.056). The NC group had a notably higher proportion of patients with histories of congestive heart failure, cerebrovascular disease, peptic ulcers, malignancy, hypertension, and hyperlipidemia. The NC group had similar 30-day mortality but a significantly shorter hospital stay and lower overall cost than the CC group, and a higher proportion but not statistically significant (p = 0.056) of overall biliary complications. A history of biliary complications was a risk factor for biliary complications. Concomitant cholecystectomy did not significantly prevent biliary complications, including benign biliary events or malignancy. Receiving concomitant cholecystectomy provided minimal benefit in reducing the long-term risk of biliary complications or malignancy. Therefore, the benefits of concomitant cholecystectomy during gallstone ileus treatment should be carefully evaluated.

Distinguishing high-risk intraductal papillary mucinous neoplasms (IPMNs) from low-risk lesions remains a clinical challenge, often resulting in unnecessary procedures due to limited specificity of current methods. While radiomics and deep learning (DL) have been explored for pancreatic cancer, cyst-level malignancy risk stratification of IPMNs remains untapped. Our multi-institutional assessed the feasibility of AI for predicting IPMN dysplasia grade using cyst-level image features using 359 T2-weighted (T2W) MRI images from seven centers. We developed and compared 2D and 3D radiomics-only, DL-only, and radiomics-DL fusion models using expert radiologist scoring as a baseline reference. Model performance was evaluated using held-out test data. The radiomics-DL fusion model showed the highest discriminatory ability on the test set AUC of 69.2%, outperforming the radiomics-only model, AUC of 66.5%. Expert accuracy varied widely from 37.4% to 66.7%, and the inter-rater agreement varied as well with weighted Cohen's kappa coefficients of 0.33-0.67. The fusion model, which combines DL with radiomics features from routine T2W MRI, shows promise for objective, cyst-level risk stratification of IPMNs in a multi-center cohort, outperforming radiomics-only models and nearly matching expert radiologists using only T2W and T1-weighted (T1W) sequences. While performance requires improvement for standalone clinical use, this approach offers a scalable, non-invasive method to potentially improve diagnostic accuracy and reduce unnecessary surgical interventions.

The risk and prognosis factors of second primary malignancies in hepatocellular carcinoma survivors.

Background/Objectives: Breast cancer is the most common malignancy among women, and early detection is critical for improving outcomes. The Breast Imaging Reporting and Data System (BI-RADS) standardizes reporting, but the BI-RADS 4 category presents a major challenge, with malignancy risk ranging from 2% to 95%. Consequently, most women in this category undergo biopsies that ultimately prove unnecessary. This study evaluated whether exhaled breath analysis could distinguish malignant from benign findings in BI-RADS 4 patients. Methods: Participants referred to the McGill University Health Centre Breast Center with BI-RADS 3–5 findings provided multiple breath specimens. Breathprints were captured using an electronic nose (eNose) powered breathalyzer, and diagnoses were confirmed by imaging and pathology. An autoencoder-based model fused the breath data with BI-RADS scores to predict malignancy. Model performance was assessed using repeated cross-validation with ensemble voting, prioritizing sensitivity to minimize false negatives. Results: The breath specimens of eighty-five participants, including sixty-eight patients with biopsy-confirmed benign lesions and seventeen patients with biopsy-confirmed breast cancer within the BI-RADS 4 cohort were analyzed. The model achieved a mean sensitivity of 88%, specificity of 75%, and a negative predictive value (NPV) of 97%. Results were consistent across BI-RADS 4 subcategories, with particularly strong sensitivity in higher-risk groups. Conclusions: This proof-of-concept study shows that exhaled breath analysis can reliably differentiate malignant from benign findings in BI-RADS 4 patients. With its high negative predictive value, this approach may serve as a non-invasive rule-out tool to reduce unnecessary biopsies, lessen patient burden, and improve diagnostic decision-making. Larger, multi-center studies are warranted.

In medical imaging, deep learning (DL) models often struggle to delineate ambiguous structures such as tumors or organ boundaries, leading to uncertainty in defining precise contours. This challenge is amplified by inter-rater variability, where experts may disagree on boundary delineations, resulting in inconsistent segmentation outcomes. Addressing these issues requires robust algorithms capable of quantifying uncertainty, standardizing annotation practices, and improving calibration to ensure reliable predictions, particularly in multi-class and multi-rater scenarios. When models are miscalibrated and overconfident, their outputs can mislead clinical decision-making, potentially influencing radiologists to over- or under-estimate malignancy risks. The CURVAS challenge (Calibration and Uncertainty for multiRater Volume Assessment in multiorgan Segmentation) was established to address these challenges by jointly assessing uncertainty, calibration, and segmentation quality, as well as promoting clinical relevance by evaluating organ volumes while accounting for annotation variability. To support this, a dataset of 90 contrast-enhanced CT scans from University Hospital Erlangen was curated, containing pancreas, liver, and kidney segmentations annotated by three experts. This resource provides a foundation for developing and benchmarking algorithms that balance segmentation accuracy, calibration, and reliability. A quantitative analysis of the annotations shows that kidney and liver segmentations exhibit strong consistency, whereas the pancreas remains challenging, emphasizing the need for refined labeling protocols and improved training strategies.

The objective of this systematic review was to identify the evidence of testicular cancer risk for people with intersex conditions. This assessment is hoped to help refine risk stratification tools for assessing gonadal malignancy risk and guide the development of more robust evidence-based management strategies. The literature was searched in Ovid MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health using a search string developed by a multidisciplinary team. The protocol was registered at Prospective Register of Systematic Reviews as CRD42021231313. A total of 3608 articles were found. After selection, 301 publications were included (1215 individuals). The results identified significant evidence that pre-pubertal gonadectomy may be linked to lower rates of malignant gonadal changes for patients with partial gonadal dysgenesis, Turner's syndrome with Y-chromosome material, complete androgen insensitivity, partial androgen insensitivity, and patients with ovotestis/es. The evidence was not significant for patients with complete gonadal dysgenesis, Klinefelter syndrome, nor WT1-related syndromes. Specific cancer outcomes were unable to be assessed due to small sample sizes and thus it is unknown if clinically significant cancer outcomes are meaningfully altered by pre-pubertal gonadectomy. Importantly, the quality of data on the topic of gonadal malignancy in intersex patients with testicular tissue was determined to be poor overall. The quality was relatively more robust regarding the conditions of Complete Androgen Insensitivity, Klinefelter syndrome, and patients with ovotestis/es. More high-quality research is needed to draw specific conclusions on the risks and benefits of performing pre-pubertal gonadectomy for intersex patients. When counseling these patients, clinicians should be transparent regarding the paucity of data supporting pre-pubertal gonadectomy.

This study aimed to analyze the natural history and radiological progression and malignancy of Bosniak IIF renal cysts based on the 2019 version of the classification. We conducted a single-center retrospective observational study, reviewing radiology reports from CT scans performed between March 2007 and December 2021. The final cohort included 85 patients with at least two imaging studies. Demographic, clinical, and radiological data, including cyst size, septal characteristics, and contrast-enhanced ultrasound (CEUS) findings, were analyzed. Kaplan-Meier survival analysis and Cox regression models were applied to identify potential predictors of cyst progression. During a median follow-up of 46months (IQR 30-71), 5 patients (6%) experienced cyst progression: 4 to Bosniak III and 1 to Bosniak IV with simultaneous detection of liver metastases. The median time to progression was 10.3months (IQR 9-24). Among the four surgically treated cases, histopathological analyses confirmed renal cell carcinoma in two, a multicystic nephroma in one, and a benign lesion in the remaining case. Contrast-enhanced ultrasound (CEUS) was performed in 45% of patients. On univariable analysis, larger cyst size (HR 1.02; 95% CI 1.01-1.04) and septal enhancement on CEUS (HR 12.4; 95% CI 1.28-120.7) were associated with progression. The risk of malignancy in Bosniak IIF cysts remains low, with a malignancy rate of 3.5%. Lesion size appears to be associated with progression, supporting its potential role in informing follow-up strategies. The first year of surveillance seems to be particularly critical, and an early reassessment at 6months may facilitate the identification of lesions at higher risk of progression.

IntroductionMyasthenia gravis (MG) is a rare, debilitating autoimmune disease associated with pathogenic immunoglobulin G autoantibodies directed against components of the neuromuscular junction. The autoimmune nature of the disease and long-term immunosuppressive treatment may increase susceptibility to infections and malignancies, but studies investigating the association between MG and infections or malignancies remain scarce.MethodsWe conducted a retrospective, observational study using Optum's deidentified Market Clarity Data (Market Clarity) to evaluate the incidence rate (IR) of infections and malignancies in US-based patients with MG in a real-world setting. Adults with ≥2 diagnosis claims of MG were identified over a 2-year period (2016-2019) and propensity score (PS) matched with controls from the general population without MG. Patients with malignancies in the 1-year look-back period were excluded.ResultsPatients with MG (N = 5002) were compared with the PS-matched general population (N = 20,008). The IR of serious infections (primary outcome) was higher in the MG cohort compared with the general population (52.81 vs 31.46 per 1000 person-years [PY], respectively). IRs of opportunistic infections (87.48 vs 57.01 per 1000 PY) and infection-related death (3.98 vs 1.94 per 1000 PY) were also higher in the MG cohort compared with the general population. The overall rate of malignancy was higher in the MG cohort compared with the general population (73.55 vs 50.01 per 1000 PY, respectively).ConclusionsIn this analysis, patients with MG were more susceptible to serious infections, infection-related death, and malignancies.

The dual risk profile of site-specific cancers in vitiligo: A systematic review and meta-analysis.

Background: Lung cancer screening using low-dose computed tomography (LDCT) demands not only early pulmonary nodule detection but also accurate estimation of malignancy risk. This remains challenging due to subtle nodule appearances, the large number of CT slices per scan, and variability in radiological interpretation. The objective of this study is to develop a unified computer-aided detection and diagnosis framework that improves both nodule localization and malignancy assessment while maintaining clinical reliability. Methods: We propose Seg-CADe-CADx, a dual-stage deep learning framework that integrates segmentation-guided detection and malignancy classification. In the first stage, a segmentation-guided detector with a lightweight 2.5D refinement head is employed to enhance nodule localization accuracy, particularly for small nodules with diameters of 6 mm or less. In the second stage, a hybrid 3D DenseNet–Swin Transformer classifier is used for malignancy prediction, incorporating probability calibration to improve the reliability of risk estimates. Results: The proposed framework was evaluated on established public benchmarks. On the LUNA16 dataset, the system achieved a competitive performance metric (CPM) of 0.944 for nodule detection. On the LIDC-IDRI dataset, the malignancy classification module achieved a ROC-AUC of 0.988, a PR-AUC of 0.947, and a specificity of 97.8% at 95% sensitivity. Calibration analysis further demonstrated strong agreement between predicted probabilities and true malignancy likelihoods, with an expected calibration error of 0.209 and a Brier score of 0.083. Conclusions: The results demonstrate that hybrid segmentation-guided CNN–Transformer architectures can effectively improve both diagnostic accuracy and clinical reliability in lung cancer screening. By combining precise nodule localization with calibrated malignancy risk estimation, the proposed framework offers a promising tool for supporting radiologists in LDCT-based lung cancer assessment.

Clonal haematopoiesis of indeterminate potential (CHIP) is an ageing-related condition associated with a substantial fraction of circulating leukocytes having descended from a single somatically mutated haematopoietic stem cell (HSC). CHIP increases the risk of haematological malignancies and several chronic diseases (for example, cardiovascular pathologies) and contributes to persistent, low-grade inflammation or inflammageing. Inflammageing, in turn, promotes functional impairment of normal HSCs, including reduced self-renewal potential. By contrast, CHIP-mutant HSCs not only are resistant to inflammageing-induced functional decline but also gain a selective expansion advantage in an inflammatory environment. A recent surge of discoveries has increased our understanding of the CHIP-inflammageing interplay, from a mechanistic and clinical perspective, highlighting its broader relevance to age-related diseases. In this Review, we discuss the molecular and cellular mechanisms that cause CHIP, its interplay with inflammageing, as well as the pathophysiological consequences and the translational implications for diseases that affect older individuals.