Search Results (326)

Background/Objectives: Accurate diagnosis of thyroid cancer is critical but challenging due to overlapping ultrasound (US) features of benign and malignant nodules. This study aimed to evaluate the diagnostic performance of non-invasive and minimally invasive US techniques, including B-mode US, shear wave elastography (SWE), color Doppler, superb microvascular imaging (SMI), and TI-RADS, in patients with suspected thyroid lesions and to assess their reliability and cost effectiveness compared with fine needle aspiration (FNA) biopsy. Methods: A prospective, single-center study (October 2023–February 2025) enrolled 300 patients with suspected thyroid cancer at a Spanish tertiary hospital. Of these, 296 patients with confirmed diagnoses underwent B-mode US, SWE, Doppler, SMI, and TI-RADS scoring, followed by US-guided FNA and Bethesda System cytopathology. Lasso-penalized logistic regression and a bootstrap analysis (1000 replicates) were used to develop diagnostic models. A utility function was used to balance diagnostic reliability and cost. Results: Thyroid cancer was diagnosed in 25 patients (8.3%). Elastography combined with SMI achieved the highest diagnostic performance (Youden index: 0.69; NPV: 97.4%; PPV: 69.1%), outperforming Doppler-only models. Intranodular vascularization was a significant risk factor, while peripheral vascularization was protective. The utility function showed that, when prioritizing cost, elastography plus SMI was cost effective (α < 0.716) compared with FNA. Conclusions: Elastography plus SMI offers a reliable, cost-effective diagnostic rule for thyroid cancer. The utility function aids clinicians in balancing reliability and cost. SMI and generalizability need to be validated in higher prevalence settings. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Background/Objectives: Thyroid nodules are commonly found through sensitive imaging methods like ultrasonography. While most nodules are benign and asymptomatic, certain characteristics may indicate malignancy, prompting fine needle aspiration biopsy. Factors like age and gender affect cancer risk, complicating ultrasound-based risk systems. We aimed to determine whether the cytological malignancy rate of thyroid nodules could be adjusted for several clinical parameters. Methods: Data from patients aged 18 and above with thyroid nodules assessed via fine needle aspiration (FNA) were retrospectively reviewed. Malignancy classification was based on cytopathology and histopathology results. The study examined how various clinical parameters, adjusted for the ACR TI-RADS category, affected thyroid nodule malignancy rates, including age, sex, Body Mass Index (BMI), nodule size, presence of autoimmunity, and thyroxine therapy. Additionally, we analyzed the performance of ACR TI-RADS in predicting malignant cytology across different age subgroups of thyroid nodules. Results: The study included 1128 thyroid nodules from 1001 adult patients, with a median age of 48 years and predominantly female (76.68%). Malignancy rates varied across ACR TI-RADS categories, with higher rates associated with larger nodules and younger age groups. Age emerged as a significant predictor of malignancy, with a consistent decrease in the odds ratio for malignant cytology with advancing age across all ACR TI-RADS categories, indicating its potential utility in risk assessment alongside nodule size and sex. Conclusions: Raising the size threshold for recommending FNA of TR3-3 nodules and incorporating patients’ age and gender into the evaluation process could enhance the system’s accuracy in assessing thyroid nodules and guiding clinical management decisions. Full article

Background: Atypical carcinoid of the thymus is an exceptionally rare neuroendocrine tumor originating from neuroendocrine cells within the thymus. These tumors often present with no symptoms or with nonspecific clinical signs, making early diagnosis particularly challenging. Despite their rarity, atypical carcinoids are clinically significant due to their aggressive nature and relatively poor prognosis. Early detection and appropriate management are therefore crucial to improving patient outcomes. Results: In this report, we present the case of a 64-year-old patient in whom an atypical carcinoid of the thymus was incidentally discovered following a thoracic computed tomography scan performed for unrelated reasons. Imaging revealed a suspicious anterior mediastinal mass, which was subsequently surgically resected. Histopathological examination, supported by immunohistochemical analysis, confirmed the diagnosis of an atypical carcinoid of the thymus. The tumor demonstrated coexpression of epithelial and neuroendocrine markers, consistent with this rare entity. Conclusions: This case adds to the limited body of literature on atypical carcinoid of the thymus and highlights the importance of considering this diagnosis when evaluating anterior mediastinal masses. It also underscores the value of thorough radiological and pathological assessment in identifying early-stage disease, which may significantly influence prognosis and therapeutic strategies. Full article

Acyl-CoA dehydrogenase 9 deficiency is considered as a rare neuromuscular syndrome with an autosomal recessive transmission. The ACAD9 protein presents two essential functions, i.e., the limiting step enzyme of the fatty acid β-oxidation pathway and one of the complex’s compounds involved in the respiratory chain complex I assembly. Thus, loss-of-function mutations are known to convey mitochondrial cytopathologies. A patient with a mild and late-onset phenotype, suffering from exercise intolerance and hypertrophic cardiomyopathy, was diagnosed as a compound heterozygote of the ACAD9 gene. The first c.1240C> T p.Arg414Cys variant has been previously reported and is known to be responsible for ACAD9 deficiency. However, the second c.1636G> A p.Val546Met variant has never been described. The goal was to investigate the eventual pathogenicity of this new genetic variant. For this purpose, molecular cloning was generated to express the ACAD9 gene with the V546M variant in a cell line (ACAD9mut) and compared to cells expressing the wild-type ACAD9. Then, the mitochondrial respiration, ATP production, the mitochondrial network, and the oxidative phosphorylation’s composition were investigated to reveal the effects of the V546M variant. While avoiding to affect the amount of the respiratory chain’s complexes, the new ACAD9 variant was entirely responsible for reducing over 50% of the mitochondrial complex I activity. Full article

Objectives: Oncocyte-rich indeterminate thyroid nodules (O-ITNs) present diagnostic and management challenges due to overlapping features between benign and malignant lesions and differing cytological classifications. This study aimed primarily to assess the ultrasound (US) characteristics and US-based risk of O-ITNs using the American College of Radiology Thyroid Imaging Reporting And Data Systems (ACR TI-RADS). A secondary objective was to compare the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) cytological systems regarding classification and clinical management implications for O-ITNs. Methods: A retrospective study was conducted on 177 ITNs (TIR3A and TIR3B) evaluated between June 2023 and December 2024 at CTO-Alesini, Rome (Italy). Nodules were assessed with US, cytology, and histology. Oncocyte predominance was defined as >70% oncocytes on fine-needle aspiration (FNA). US features were analyzed according to ACR TI-RADS. Nodules were reclassified by BSRTC, and potential differences in clinical case management (CCM) were analyzed. Results: O-ITNs comprised 47.5% of the sample. Compared to non-O-ITNs, O-ITNs were larger and more frequently showed low-risk US features, including a higher prevalence of ACR TI-RADS 3 nodules. However, no progressive increase in the risk of malignancy (ROM) was observed across ACR TI-RADS classes within O-ITNs. Histological malignancy was identified in 47.1% of O-ITNs, a lower proportion compared to non-O-ITNs, though the difference was not statistically significant. Classification discordance with potential management impact was lower in O-ITNs (20.2%) than in non-O-ITNs (38.7%). Conclusions: O-ITNs typically exhibit benign-appearing US features and lower classification discordance between BSRTC and ICCRTC, yet US risk stratification fails to differentiate malignancy risk within O-ITNs. A tailored approach integrating cytology and cautious US interpretation is essential for optimal O-ITN management. Full article

Background: The integration of artificial intelligence (AI) into cervical cancer diagnostics has shown promising advancements in recent years. AI technologies, particularly in the analysis of cytological images, offer potential improvements in diagnostic accuracy and screening efficiency. However, challenges regarding model generalizability, explainability, and operational integration into clinical workflows persist, impeding widespread adoption. Aim: This narrative review aims to critically evaluate the current state of AI in cervical cancer diagnostic cytology, identifying trends, key developments, and areas requiring further research. It also explores the potential for AI to improve diagnostic processes, alongside examining international guidelines and consensus on its adoption. Methods: A narrative review was conducted through a comprehensive search of PubMed and Scopus databases. Thirty studies published between 2020 and 2025 were selected based on their relevance. Results: The literature review reveals a growing interest in the application of AI for cervical cancer diagnostics, particularly in the automated interpretation. However, large-scale clinical adoption remains limited. Most studies are experimental or application-based in controlled settings. Consensus efforts and specific recommendations for this domain are still limited and not specific. Key barriers include limited model generalizability, lack of explainability, challenges in integration into clinical workflows, and regulatory and infrastructural constraints. Conclusions: A sustainable and meaningful integration of AI in cervical cancer diagnostics requires a unified framework that addresses both technical challenges and operational needs, supported by context-specific strategies and broader consensus-building efforts. Full article

The need to improve medical diagnosis is of utmost importance in medical research, consisting of the optimization of accurate classification models able to assist clinical decisions. To minimize the errors that can be caused by using a single classifier, the voting ensemble technique can be used, combining the classification results of different classifiers to improve the final classification performance. This paper aims to compare the existing voting ensemble techniques with a new game-theory-derived approach based on Shapley values. We extended this method, originally developed for binary tasks, to the multi-class setting in order to capture complementary information provided by different classifiers. In heterogeneous clinical scenarios such as thyroid nodule diagnosis, where distinct models may be better suited to identify specific subtypes (e.g., benign, malignant, or inflammatory lesions), ensemble strategies capable of leveraging these strengths are particularly valuable. The motivating application focuses on the classification of thyroid cancer nodules whose cytopathological clinical diagnosis is typically characterized by a high number of false positive cases that may result in unnecessary thyroidectomy. We apply and compare the performance of seven individual classifiers, along with four ensemble voting techniques (including Shapley values), in a real-world study focused on classifying thyroid cancer nodules using proteomic features obtained through mass spectrometry. Our results indicate a slight improvement in the classification accuracy for ensemble systems compared to the performance of single classifiers. Although the Shapley value-based voting method remains comparable to the other voting methods, we envision this new ensemble approach could be effective in improving the performance of single classifiers in further applications, especially when complementary algorithms are considered in the ensemble. The application of these techniques can lead to the development of new tools to assist clinicians in diagnosing thyroid cancer using proteomic features derived from mass spectrometry. Full article

Mitotic figures in tumor tissues are an important criterion for diagnosing malignant lesions, and physicians often search for the presence of mitosis in whole slide imaging (WSI). However, prolonged visual inspection by doctors may increase the likelihood of human error. With the advancement of deep learning, AI-based automatic cytopathological diagnosis has been increasingly applied in clinical settings. Nevertheless, existing diagnostic models often suffer from high computational costs and suboptimal detection accuracy. More importantly, when assessing cellular abnormalities, doctors frequently compare target cells with their surrounding cells—an aspect that current models fail to capture due to their lack of intercellular information modeling, leading to the loss of critical medical insights. To address these limitations, we conducted an in-depth analysis of existing models and propose an Inter–Intra Hypergraph Neural Network (II-HGNN). Our model introduces a block-based feature extraction mechanism to efficiently capture deep representations. Additionally, we leverage hypergraph convolutional networks to process both intracellular and intercellular information, leading to more precise diagnostic outcomes. We evaluate our model on publicly available datasets under varying imaging conditions, and experimental results demonstrate that our approach consistently outperforms baseline models in terms of accuracy. Full article

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) and inflammation status are emerging prognostic markers in various cancers, but their significance in high-grade serous ovarian carcinoma (HGSC) remains unclear. Our objective was to evaluate different TIL subtypes and inflammation status in relation to progression-free survival (PFS) in primary HGSC. Methods: CD3⁺/CD4⁺/CD8⁺/PD-1+ stromal TILs (sTILs) and intraepithelial TILs (iTILs) were evaluated by manual assessment and digital image analysis (DIA), following TIL Working Group recommendations. Inflammation status was evaluated through the following scores: systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), CA125, and lactate dehydrogenase (LDH). Results: CD8⁺ TILs were the most prevalent subtype in both iTILs and sTILs. However, sTILs were significantly more abundant than iTILs (p < 0.001) among all subsets, except for PD-1+ cells. DIA results of TIL assessments were in agreement with manual assessments. High stromal CD3⁺ and CD8⁺ TILs, PIV, CA125, and LDH, were associated with improved PFS. Potential independent prognostic factors for PFS in manual assessment were PIV (HR = 0.32, CI 95% = 0.12–0.82) and CD8⁺ sTILs (HR = 0.30, CI 95% = 0.12–0.79), whereas in DIA assessment they were CD3⁺ sTILs (HR = 0.31, CI 95% = 0.15–0.67), PIV (HR = 0.35, 95% CI 0.13–0.96), and residual disease (HR = 0.21 95% CI 0.08–0.53). Conclusions: CD3⁺/CD8⁺ sTILs and PIV are promising prognostic indicators in HGSC; however, further research is needed to confirm their clinical utility. Full article

Malignant Triton Tumors (MTTs) are rare, high-grade malignant peripheral nerve sheath tumors (MPNSTs) frequently associated with Type 1 Neurofibromatosis (NF1). NF1, an autosomal dominant disorder, predisposes approximately 10% of affected individuals to developing MPNSTs, with 50% of these tumors occurring in NF1 patients, while others arise sporadically or in association with radiation exposure. MTTs predominantly affect anatomical regions rich in large nerves, such as the limbs, spinal root, and cranial nerves. Mediastinal presentations are exceedingly rare, posing significant diagnostic and therapeutic challenges. Current treatment strategies include surgical resection, chemotherapy, radiotherapy, and lung-sparing procedures for metastatic disease. Molecular studies of MPNSTs have revealed that NF1 mutations lead to dysregulation of the RAS signalling pathway, while epigenetic alterations (e.g., SUZ12/EED mutations) further contribute to tumor progression. Dysregulated phylogenetically conserved pathways, including Wnt/beta-catenin and non-canonical SHH signalling, play a role in sarcoma progression and Schwann cell transformation. Recent advances in miRNA research highlight their involvement in tumor invasion and progression, with dysregulated miRNA expression and chromatin remodeling contributing to the pathogenesis of these neoplasms. However, the distinct molecular profiles for MTTs remain incompletely understood. Further investigation of the genetic and epigenetic landscape is essential for improving our understanding and identifying potential therapies. Herein, we present a single-center retrospective case series of three patients with an intrathoracic triton tumor treated at our University Hospital between 2000 and 2024, serving as a starting point for future insights into MPNST pathobiology. Full article

Objective: Early diagnosis and treatment of metastatic pericardial disease are crucial to prevent the life-threatening complication of cardiac tamponade. Thin Layer Cytology (TLC), a widely adopted technique in cytology, has gained significant acceptance for most specimens. Our study aimed to assess the utility of TLC in diagnosing metastatic neoplasms and their origins in pericardial effusions, as well as monitoring response to chemotherapy. Methods: We examined 184 pericardial fluids collected by pericardiocentesis and processed using the ThinPrep liquid-based technique. Various immunocytochemical markers were used to determine the site of metastatic neoplasms. We also evaluated the response to therapy in 53 patients with lung and breast cancer. Results: Out of 184 specimens, 113 pericardial fluids were diagnosed as positive for malignancy, while 71 were negative. Twenty-three cases of unknown primary site were included in the total positive cases. Ninety cases positive for malignancy had a known primary site of origin, including 31 lung carcinomas, 22 breast carcinomas, 10 ovarian carcinomas, 6 T-cell lymphomas, 3 urinary bladder carcinomas, 4 renal carcinomas, 5 adenocarcinomas of the colon, 5 prostate carcinomas, 2 parotid adenocarcinomas, and 2 melanomas. Regarding the 53 cases with chemotherapy treatment, the cytologic examination of pericardial fluid showed a remarkable reduction in neoplastic burden after the third dose of cisplatin or thiotepa instilled into the pericardial cavity. ThinPrep provided excellent preservation of cytomorphological features, high cellularity per slide, and a clear background. This comprehensive analysis provides crucial information about the types and distribution of cancerous cells present in the samples. Conclusions: Thin Layer Cytology (TLC) is a valuable diagnostic tool for detecting metastatic pericardial malignancy. It allows the examination of exfoliated cells from the pericardial fluid, providing crucial information for diagnosis, management, and monitoring the acute responsiveness to intrapericardial chemotherapy. Immunocytochemistry (IHC) can identify specific markers for various types of cancer, enabling a more accurate diagnosis and guiding further treatment decisions. Full article

Background/Objectives: This study aims to evaluate whether fine-needle aspiration biopsy (FNAB) of melanocytic uveal tumors (MUTs) using 27-gauge (27G) needles yields aspirates like those obtained using 25-gauge (25G) needles for cytology. Methods: A retrospective review was conducted on 32 primary uveal melanomas (PUMs). Tumors were sampled at three adjacent sites, first using a 27G needle for gene expression profile (GEP) testing, second and third with 27G and 25G needles for cytology. The endpoints evaluated were the sufficiency of aspirates for cytopathology and GEP. Results: Among the 32 patients, 17 tumors were choroidal, 6 ciliochoroidal, 7 iridociliochoroidal, and 2 exclusively iridic. Tumor diameter ranged from 3.3 mm to 23 mm (mean 13.2 mm), and thickness ranged from 0.5 mm to 12 mm (mean 6.4 mm). Aspirates from both needle sizes were sufficient for cytopathological diagnosis and GEP in 31 of 32 cases (96.9%). The single insufficient aspirate was insufficient with both the 27G and 25G needles. The cytopathology was identical in all other cases. The tumors were Class 1 in 22 cases (71.0%) and Class 2 in 9 cases (29.0%). Conclusions: FNAB aspirates of MUTs using 27G needles appear sufficient for cytology and GEP in most cases, showing a similar diagnostic yield compared to 25G needles. Full article

Background: Although complete excision of suspicious melanocytic lesions is mandatory, it carries the risk of unnecessary scarring on one hand and inadequate treatment of misdiagnosed lesions on the other. Objectives: We evaluated the sensitivity, specificity, and predictive value of reflectance confocal microscopy (RCM) in diagnosing pigmented lesions with clinically ambiguous features―the so-called “gray zone” ―and compared its performance with the more established technique of epiluminescence microscopy (ELM). Results: Between 2019 and 2020, a total of 2282 melanocytic lesions were assessed using both ELM and RCM. Histopathological diagnosis aligned with the ELM risk classification in 91.6% of melanocytic lesions, specifically in 92.0% of very-high-risk lesions, 88.5% of high-risk lesions, 66.3% of medium-risk lesions, 96.3% of low-risk lesions, and 98.0% of very low-risk lesions. Similarly, histopathological diagnosis of these lesions corresponded with the RCM risk assessment in 91.2% of cases, including 90.9% of very-high-risk lesions, 84.4% of high-risk lesions, 93.1% of medium-risk lesions, 90.5% of low-risk lesions, and 96.2% of very low-risk lesions. Conclusions: Although ELM is a valuable tool for increasing the efficacy of clinical diagnosis, its reliability decreases for a group of lesions that appear suspicious during clinical skin examination. RCM, as a newer technique, appears to improve malignancy detection in suspicious melanocytic lesions without requiring excision; its sensitivity and specificity remain high even in lesions classified by ELM as posing a medium risk of malignancy. Full article

Breast cancer (BC) is globally becoming a great challenge, being both the most diagnosed cancer and the leading cause of death in women. In addition to cancer cells, many bacteria co-inhabit BC, which differ in type and number from the resident microbiota found in healthy breast tissue. While many reports have demonstrated the ability of different bacteria to dysregulate BC’s metabolites, the reciprocal effect of these metabolites on the bacterial microbiota has not yet been investigated. Herein, we assess the effect of conditioned media (CM) from a triple-negative BC cell line (MDA-MB-231) on the metabolic profile of Pseudomonas aeruginosa (P. aeruginosa), an important breast resident Gram-negative bacteria that influence oncogenesis. Optical density and scanning electron microscopes were used to assess the impact of MDA-MB-231-CM (BC-CM) on P. aeruginosa growth and morphological changes, respectively. In addition, liquid chromatography–high-resolution mass spectrometry was used to identify metabolic changes in P. aeruginosa and their secretomes in response to the BC-CM. The BC-CM significantly suppressed the growth of P. aeruginosa in the log phase and induced concentration-dependent cytopathological changes in their cell walls. The metabolites of P. aeruginosa were dysregulated considerably depending on the time of exposure to the BC-CM. When treated with the BC-CM, P. aeruginosa induced the purine alkaloid spliceostatin (FR901464), a prominent antitumor metabolite. The BC-CM also promoted other P. aeruginosa metabolites such as amino acids, phosphoribosyl-AMP, 2-aminoacetophenone, pyochelin I, guanosine monophosphate, riboflavin, and terpenoids, which are capable of interfering with oncogenesis. Nine of the significantly identified metabolites from the 0–3 h comparison and four of those identified from the 0–6 h comparison have potential roles in influencing cancer cell behavior. Our findings demonstrate the ability of triple-negative BC-CM not only to alter the growth and morphology of P. aeruginosa but also to modulate their metabolic profile. A better understanding of the influence of BC on certain resident breast microbiomes, such as P. aeruginosa, may open a new therapeutic intervention opportunity for the treatment of cancer. Full article