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Cancer Imaging : the Official... Jun 2024The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model...
OBJECTIVE
The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice.
METHODS
Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics.
RESULTS
172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATM) was frequently accompanied by BRAF, TERT or gene fusions. ATM alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAF, KRAS or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%.
CONCLUSIONS
Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.
Topics: Humans; Lymphatic Metastasis; Thyroid Cancer, Papillary; Male; Female; Thyroid Neoplasms; Middle Aged; Mutation; Adult; Proto-Oncogene Proteins B-raf; Ataxia Telangiectasia Mutated Proteins; Nomograms; Biomarkers, Tumor; Telomerase; Radiomics
PubMed: 38886866
DOI: 10.1186/s40644-024-00719-2 -
BMC Gastroenterology Jun 2024Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in...
BACKGROUND
Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS.
METHODS
A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts.
RESULTS
Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3-11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19-18.84), and age (OR 1, 95% CI 1.01-1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57-83.33, OR 16.3, 95% CI 3.02-88.08).
CONCLUSION
MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Dilatation, Pathologic; Aged; Common Bile Duct; Pancreatic Intraductal Neoplasms; Endosonography; Pancreatic Cyst; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous
PubMed: 38886637
DOI: 10.1186/s12876-024-03291-y -
Journal of Thoracic Disease May 2024The preoperative differential diagnosis of nodular lung adenocarcinoma has long been a challenging issue for thoracic surgeons. This study aimed to explore differential...
BACKGROUND
The preoperative differential diagnosis of nodular lung adenocarcinoma has long been a challenging issue for thoracic surgeons. This study aimed to explore differential diagnosis of nodular lung adenocarcinoma by comprehensively analyzing its clinical, computed tomography (CT) imaging, and postoperative pathological and genetic features.
METHODS
The clinical, CT imaging, and postoperative pathological features of different classifications of nodular lung adenocarcinoma were retrospectively analyzed through univariate and multivariate statistical methods.
RESULTS
There were 132 patients with nodular lung adenocarcinoma enrolled. Firstly, compared with ground-glass nodular lung adenocarcinoma, solid nodular lung adenocarcinoma was more common in women [odds ratio (OR), 3.662; 95% confidence interval (CI): 1.066-12.577] and older adults (OR, 1.061; 95% CI: 1.007-1.119), and CT signs were mostly lobulation (OR, 4.957; 95% CI: 1.714-14.337) and spiculation (OR, 8.214; 95% CI: 2.740-24.621); the mean CT (CT) value of solid nodular lung adenocarcinoma was significantly higher than that of ground-glass nodular lung adenocarcinoma, and the optimal diagnostic threshold was -267.5 Hounsfield units (HU). Secondly, the maximum diameter of nodule size (NS) of invasive adenocarcinoma (IAC) was significantly greater than that of minimally IAC (MIA; OR, 6.306; 95% CI: 1.191-33.400) or atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS; OR, 189.539; 95% CI: 4.720-7,610.476), and the optimal diagnostic threshold between IAC and MIA was 1.35 cm; the CT value of IAC was significantly higher than that of MIA, and the optimal diagnostic threshold was -460.75 HU. Thirdly, lepidic-predominant adenocarcinoma (LPA) manifest more commonly as pure ground-glass nodule (pGGN; OR, 6.252; 95% CI: 1.429-27.358) or mixed ground-glass nodule (mGGN; OR, 4.224; 95% CI: 1.223-14.585). Moreover, the mutation rate of epidermal growth factor receptor () in IAC was 70.69% (41/58). The mutation rates of mGGNs (OR, 8.794; 95% CI: 1.489-51.933) and solid nodules (SNs; OR, 12.912; 95% CI: 1.597-104.383) were significantly higher than that of pGGNs. Furthermore, compared with those of micropapillary-predominant adenocarcinoma (MPA), solid-predominant adenocarcinoma (SPA), or invasive mucinous adenocarcinoma (IMA), there were significantly higher mutation rates in acinar-predominant adenocarcinoma/papillary-predominant adenocarcinoma (APA/PPA; OR, 55.925; 95% CI: 4.045-773.284) and LPA (OR, 38.265; 95% CI: 2.307-634.596).
CONCLUSIONS
Different classifications of nodular lung adenocarcinoma have their own clinicopathological and CT imaging features, and the latter is the main predictor.
PubMed: 38883620
DOI: 10.21037/jtd-24-510 -
Frontiers in Endocrinology 2024The mucosa-associated lymphoid tissue (MALT) lymphoma subtype, specifically extranodal marginal zone B-cell lymphoma, is a rare variant. Within this subtype, primary...
The mucosa-associated lymphoid tissue (MALT) lymphoma subtype, specifically extranodal marginal zone B-cell lymphoma, is a rare variant. Within this subtype, primary thyroid MALT lymphoma is an uncommon occurrence. The literature provides limited documentation on thyroid MALT lymphomas, as their prevalence is comparatively lower than in other organ sites. The coexistence of papillary thyroid carcinoma (PTC) and thyroid MALT lymphomas is exceedingly rare. It presents a rare case of primary thyroid MALT lymphoma accompanied by PTC, thyroid lymphoma not being considered before surgery. A 64-year-old female patient, who had been experiencing symptoms related to a substantial thyroid tumor for a duration of three years, she refused to do a needle biopsy before surgery and expressed a preference for surgical resection. Consequently, the patient underwent a total thyroidectomy along with lymphadenectomy of the central compartment. A histological examination subsequently confirmed the presence of papillary thyroid carcinoma (PTC) and mucosa-associated lymphoid tissue (MALT) lymphoma. Due to the favorable response of the MALT lymphoma to local treatment and the absence of metastasis in other organs, no further treatment was administered for the MALT lymphoma following the surgery. Currently, the patient exhibits no signs of tumor recurrence based on ultrasound and laboratory evaluations. We also provide an overview of the clinical findings on PTC and MALT lymphoma patients already reported and discuss the possible treatment strategy.
Topics: Humans; Lymphoma, B-Cell, Marginal Zone; Female; Middle Aged; Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroidectomy; Neoplasms, Multiple Primary
PubMed: 38883595
DOI: 10.3389/fendo.2024.1372661 -
Cancer Control : Journal of the Moffitt... 2024Cervical lymph node metastasis (CLNM) is considered a marker of papillar Fethicy thyroid cancer (PTC) progression and has a potential impact on the prognosis of PTC. The...
BACKGROUND AND OBJECTIVE
Cervical lymph node metastasis (CLNM) is considered a marker of papillar Fethicy thyroid cancer (PTC) progression and has a potential impact on the prognosis of PTC. The purpose of this study was to screen for predictors of CLNM in PTC and to construct a predictive model to guide the surgical approach in patients with PTC.
METHODS
This is a retrospective study. Preoperative dual-energy computed tomography images of 114 patients with pathologically confirmed PTC between July 2019 and April 2023 were retrospectively analyzed. The dual-energy computed tomography parameters [iodine concentration (IC), normalized iodine concentration (NIC), the slope of energy spectrum curve (λ)] of the venous stage cancer foci were measured and calculated. The independent influencing factors for predicting CLNM were determined by univariate and multivariate logistic regression analysis, and the prediction models were constructed. The clinical benefits of the model were evaluated using decision curves, calibration curves, and receiver operating characteristic curves.
RESULTS
The statistical results show that NIC, derived neutrophil-to-lymphocyte ratio (dNLR), prognostic nutritional index (PNI), gender, and tumor diameter were independent predictors of CLNM in PTC. The AUC of the nomogram was .898 (95% CI: .829-.966), and the calibration curve and decision curve showed that the prediction model had good predictive effect and clinical benefit, respectively.
CONCLUSION
The nomogram constructed based on dual-energy CT parameters and inflammatory prognostic indicators has high clinical value in predicting CLNM in PTC patients.
Topics: Humans; Male; Female; Lymphatic Metastasis; Thyroid Cancer, Papillary; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Adult; Thyroid Neoplasms; Nomograms; Neck; Lymph Nodes; Prognosis; Aged; Inflammation
PubMed: 38881040
DOI: 10.1177/10732748241262177 -
Zhonghua Zhong Liu Za Zhi [Chinese... Jun 2024To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft...
To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma. A retrospective analysis was performed on clinical and pathological data of 15 patients misdiagnosed as branchiogenic carcinoma at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2000 and December 2020. Among the 15 patients, 6 were nasopharyngeal squamous cell carcinoma, 4 tonsil squamous cell carcinoma, 2 tongue root squamous cell carcinoma, 2 hypopharyngeal squamous cell carcinoma and 1 thyroid papillary carcinoma. The median time from the diagnosis of branchial cleft carcinoma to the discovery of primary lesions was 3.58 months (0-76 months). The causes of misdiagnosis might be the lack of experience in the diagnosis and treatment of branchial cleft carcinoma, and not enough attention to comprehensive examination and close follow-up. Different from oropharyngeal cancer reported internationally, the proportion of misdiagnosed cases with nasopharyngeal carcinoma as the primary site in the current article is higher. As a country with a high incidence of nasopharyngeal carcinoma, the examination of nasopharynx should not be taken lightly. Most hidden cases can be found in the comprehensive examination in a short time, while a few cases need long-term follow-up. Finding the primary sites should not rely too much on imaging examination, and we cannot ignore the importance of clinical physical examination.
Topics: Humans; Lymphatic Metastasis; Retrospective Studies; Diagnostic Errors; Neoplasms, Unknown Primary; Branchioma; Nasopharyngeal Neoplasms; Female; Male; Middle Aged; Adult; Lymph Nodes; Neck; Thyroid Cancer, Papillary; Nasopharyngeal Carcinoma; Head and Neck Neoplasms; Tonsillar Neoplasms; Aged; Tongue Neoplasms; Hypopharyngeal Neoplasms
PubMed: 38880737
DOI: 10.3760/cma.j.cn112152-20231024-00248 -
Human Pathology Jun 2024Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have...
Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis.
Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.
PubMed: 38876201
DOI: 10.1016/j.humpath.2024.06.006 -
Thyroid : Official Journal of the... Jun 2024Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images...
Artificial intelligence (AI) is increasingly being applied in pathology and cytology, showing promising results. We collected a large dataset of whole slide images (WSIs) of thyroid fine-needle aspiration cytology (FNA), incorporating z-stacking, from institutions across the nation to develop an AI model. We conducted a multicenter retrospective diagnostic accuracy study using thyroid FNA dataset from the Open AI Dataset Project that consists of digitalized images samples collected from 3 university hospitals and 215 Korean institutions through extensive quality check during the case selection, scanning, labeling, and reviewing process. Multiple z-layer images were captured using three different scanners and image patches were extracted from WSIs and resized after focus fusion and color normalization. We pretested six AI models, determining Inception ResNet v2 as the best model using a subset of dataset, and subsequently tested the final model with total datasets. Additionally, we compared the performance of AI and cytopathologists using randomly selected 1031 image patches and reevaluated the cytopathologists' performance after reference to AI results. A total of 10,332 image patches from 306 thyroid FNAs, comprising 78 malignant (papillary thyroid carcinoma) and 228 benign from 86 institutions were used for the AI training. Inception ResNet v2 achieved highest accuracy of 99.7%, 97.7%, and 94.9% for training, validation, and test dataset, respectively (sensitivity 99.9%, 99.6%, and 100% and specificity 99.6%, 96.4%, and 90.4% for training, validation, and test dataset, respectively). In the comparison between AI and human, AI model showed higher accuracy and specificity than the average expert cytopathologists beyond the two-standard deviation (accuracy 99.71% [95% confidence interval (CI), 99.38-100.00%] vs. 88.91% [95% CI, 86.99-90.83%], sensitivity 99.81% [95% CI, 99.54-100.00%] vs. 87.26% [95% CI, 85.22-89.30%], and specificity 99.61% [95% CI, 99.23-99.99%] vs. 90.58% [95% CI, 88.80-92.36%]). Moreover, after referring to the AI results, the performance of all the experts (accuracy 96%, 95%, and 96%, respectively) and the diagnostic agreement (from 0.64 to 0.84) increased. These results suggest that the application of AI technology to thyroid FNA cytology may improve the diagnostic accuracy as well as intra- and inter-observer variability among pathologists. Further confirmatory research is needed.
Topics: Humans; Biopsy, Fine-Needle; Thyroid Neoplasms; Retrospective Studies; Artificial Intelligence; Thyroid Gland; Thyroid Cancer, Papillary; Reproducibility of Results; Sensitivity and Specificity; Thyroid Nodule; Cytology
PubMed: 38874262
DOI: 10.1089/thy.2023.0384 -
Nature Communications Jun 2024Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are...
Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.
Topics: Humans; Thyroid Cancer, Papillary; Chernobyl Nuclear Accident; Lymphatic Metastasis; Male; Adult; Female; Thyroid Neoplasms; Mutation; Iodine Radioisotopes; Adolescent; Proto-Oncogene Proteins B-raf; Young Adult; Lymph Nodes; Proto-Oncogene Proteins c-ret; Child; Genomics; Middle Aged; Homeodomain Proteins; Gene Expression Profiling; MicroRNAs; Neoplasms, Radiation-Induced; Neck; Gene Expression Regulation, Neoplastic
PubMed: 38871684
DOI: 10.1038/s41467-024-49292-z -
International Journal of Gynecological... Jul 2024Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of...
Ovarian mesonephric-like adenocarcinoma (MLA) is a rare tumor with potential origins in endometriosis and Müllerian-type epithelial tumors. The morphologic patterns of MLA overlap with those of endometrioid ovarian carcinoma (EnOC). We speculated that a subset of MLAs would be classified as EnOCs. In this study, we attempted to identify MLAs from malignant endometrioid tumors. Given that the study patients with MLAs had both endometrioid-like and mesonephric-like morphologies, we defined mesonephric-like differentiation (MLD) as an endometrioid tumor with focal or diffuse MLA morphology and immunophenotype. Twelve patients exhibited mesonephric-like morphologic patterns. Immunohistochemistry analysis for CD10, TTF-1, estrogen receptor (ER), GATA3, calretinin, and PAX8 expression was done using whole-section slides. Two patients without the MLA immunophenotype were excluded. Ten patients with EnOCs with MLD (8.3%) were identified from a cohort of 121 patients with malignant endometrioid tumors. All 10 patients were positive for TTF-1 and/or GATA3. Most patients were ER-negative. Morphologically, MLD was associated with papillary thyroid carcinoma-like nuclei, flattened cells, tubular, nested, reticular, or glomeruloid architecture, and infiltrative growth. All 10 patients had pre-existing endometriosis and/or adenofibromas. Among the EnOCs with MLD, 5 had coexisting components such as EnOC grade 1 [(G1), cases 4, 7, and 9], mucinous borderline tumor (case 1), and dedifferentiated carcinoma (case 10), with distinct borders between EnOC with MLD and the other components. Nine of the 10 MLA patients (90%) harbored KRAS hotspot mutations. In addition, 4 patients harboring other components shared common KRAS hotspot mutations. No significant prognostic differences were observed between patients with and without MLD. Based on our findings, we suggest that EnOC with MLD, especially in the early stages and without high-grade components, should be considered a subtype of EnOC. Overtreatment should be avoided in such patients, particularly in the early stages. In this study, as the characteristics between EnOC with MLD and MLA were not distinguishable, we considered both conditions to be on the same spectrum. EnOCs with MLD exhibit the MLA phenotype during disease progression and are prematurely classified as MLA. Nevertheless, more patients with EnOC who have MLD/MLA are required for a more robust comparison between conventional EnOC according to staging and grading.
Topics: Humans; Female; Ovarian Neoplasms; Carcinoma, Endometrioid; Middle Aged; Adult; Aged; Immunohistochemistry; Biomarkers, Tumor; Adenocarcinoma; GATA3 Transcription Factor; PAX8 Transcription Factor; Cell Differentiation; Endometriosis
PubMed: 38870078
DOI: 10.1097/PGP.0000000000001002