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JAMA Network Open Aug 2023To our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients...
IMPORTANCE
To our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident.
OBJECTIVE
To study the risk of second primary cancers in patients with PTC after the Chernobyl disaster.
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors.
MAIN OUTCOMES AND MEASURES
For analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios.
RESULTS
Of the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall.
CONCLUSIONS AND RELEVANCE
This cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.
Topics: Male; Humans; Female; Middle Aged; Neoplasms, Second Primary; Thyroid Cancer, Papillary; Chernobyl Nuclear Accident; Cohort Studies; Retrospective Studies; Thyroid Neoplasms; Disasters
PubMed: 37589974
DOI: 10.1001/jamanetworkopen.2023.29559 -
Frontiers in Endocrinology 2023The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However,...
BACKGROUND
The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated.
METHODS
DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching.
RESULTS
105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC.
CONCLUSION
RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Propensity Score; Retrospective Studies; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary
PubMed: 37664843
DOI: 10.3389/fendo.2023.1158581 -
Frontiers in Endocrinology 2023Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of...
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of follicular cell-derived TCs, and V600E, mutations, and gene fusions are well-established drivers. mutations were described in specific sets of TC patients but represent a rare event in adult TC patients.
METHODS
Here, we report the molecular characterization of 30 retrospective follicular cell-derived thyroid tumors, comprising PTCs (90%) and poorly differentiated TCs (10%), collected at our Institute. We performed DNA whole-exome sequencing using patient-matched control for somatic mutation calling, and targeted RNA-seq for gene fusion detection. Transcriptional profiles established in the same cohort by microarray were investigated using three signaling-related gene signatures derived from The Cancer Genome Atlas (TCGA).
RESULTS
The occurrence of V600E (44%), mutations (13%), and gene fusions (13%) was confirmed in our cohort. In addition, in two patients lacking known drivers, mutations of the gene (p.D1709N and p.D1810V) were identified. mutations occur in two adult patients with follicular-pattern lesions, and in one of them a second concurrent mutation (p.R459*) is also observed. Additional putative drivers include gene (p.P2130A mutation), identified in a patient with a rare solid-trabecular subtype of PTC. Transcriptomics indicates that tumors are RAS-like, whereas the -mutated tumor displays a borderline RAS-/BRAF-like subtype. We also provide an overview of and mutations in thyroid lesions by investigating the COSMIC database.
CONCLUSION
Even though small, our series recapitulates the genetic background of PTC. Furthermore, we identified mutations, one of which is previously unreported in thyroid lesions. For these less common alterations and for patients with unknown drivers, we provide signaling information applying TCGA-derived classification.
Topics: Humans; Adult; Transcriptome; Retrospective Studies; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Thyroid Neoplasms; Thyroid Cancer, Papillary; Mutation; Genomics; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 37867524
DOI: 10.3389/fendo.2023.1267499 -
Scientific Reports Aug 2023The most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). The BRAF gene encodes a protein-dependent kinase (PDK),... (Randomized Controlled Trial)
Randomized Controlled Trial
The most common BRAF mutation is thymine (T) to adenine (A) missense mutation in nucleotide 1796 (T1796A, V600E). The BRAF gene encodes a protein-dependent kinase (PDK), which is a key component of the mitogen-activated protein kinase pathway and essential for controlling cell proliferation, differentiation, and death. The BRAF mutation causes PDK to be activated improperly and continuously, resulting in abnormal proliferation and differentiation in PTC. Based on elastography ultrasound (US) radiomic features, this study seeks to create and validate six distinct machine learning algorithms to predict BRAF mutation in PTC patients prior to surgery. This study employed routine US strain elastography image data from 138 PTC patients. The patients were separated into two groups: those who did not have the BRAF mutation (n = 75) and those who did have the mutation (n = 63). The patients were randomly assigned to one of two data sets: training (70%), or validation (30%). From strain elastography US images, a total of 479 radiomic features were retrieved. Pearson's Correlation Coefficient (PCC) and Recursive Feature Elimination (RFE) with stratified tenfold cross-validation were used to decrease the features. Based on selected radiomic features, six machine learning algorithms including support vector machine with the linear kernel (SVM_L), support vector machine with radial basis function kernel (SVM_RBF), logistic regression (LR), Naïve Bayes (NB), K-nearest neighbors (KNN), and linear discriminant analysis (LDA) were compared to predict the possibility of BRAF. The accuracy (ACC), the area under the curve (AUC), sensitivity (SEN), specificity (SPEC), positive predictive value (PPV), negative predictive value (NPV), decision curve analysis (DCA), and calibration curves of the machine learning algorithms were used to evaluate their performance. ① The machine learning algorithms' diagnostic performance depended on 27 radiomic features. ② AUCs for NB, KNN, LDA, LR, SVM_L, and SVM_RBF were 0.80 (95% confidence interval [CI]: 0.65-0.91), 0.87 (95% CI 0.73-0.95), 0.91(95% CI 0.79-0.98), 0.92 (95% CI 0.80-0.98), 0.93 (95% CI 0.80-0.98), and 0.98 (95% CI 0.88-1.00), respectively. ③ There was a significant difference in echogenicity,vertical and horizontal diameter ratios, and elasticity between PTC patients with BRAF and PTC patients without BRAF. Machine learning algorithms based on US elastography radiomic features are capable of predicting the likelihood of BRAF in PTC patients, which can assist physicians in identifying the risk of BRAF in PTC patients. Among the six machine learning algorithms, the support vector machine with radial basis function (SVM_RBF) achieved the best ACC (0.93), AUC (0.98), SEN (0.95), SPEC (0.90), PPV (0.91), and NPV (0.95).
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Elasticity Imaging Techniques; Proto-Oncogene Proteins B-raf; Bayes Theorem; Carcinoma, Papillary; Mutation; Machine Learning
PubMed: 37537230
DOI: 10.1038/s41598-023-39747-6 -
Frontiers in Endocrinology 2023Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT.
METHODS
Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0.
RESULTS
In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients.
CONCLUSION
This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.
Topics: Humans; Thyroid Cancer, Papillary; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Thyroid Neoplasms; Lymphatic Metastasis; Prevalence; Carcinoma, Papillary; Mutation
PubMed: 38047109
DOI: 10.3389/fendo.2023.1273498 -
BMJ Case Reports Nov 2023Intestinal-type sinonasal adenocarcinoma is a rare epithelial malignancy primarily treated with surgery and chemoradiation. The combination of low-dose immunotherapy and...
Intestinal-type sinonasal adenocarcinoma is a rare epithelial malignancy primarily treated with surgery and chemoradiation. The combination of low-dose immunotherapy and a tyrosine kinase inhibitor in recurrent disease has not been previously studied.A man in his 20s with papillary adenocarcinoma of the sinonasal region, following surgical resection, was treated with six cycles of concurrent chemoradiotherapy, followed by four cycles of docetaxel, cisplatin and capecitabine. While on treatment, he was found to have extensive residual disease and he was started on low-dose nivolumab and cabozantinib. Repeat imaging after ten months of treatment revealed a significant reduction in lesions.Non-squamous head and neck cancers are often excluded from major trials, and the effect of immunotherapy in these histologies is poorly understood. The response seen with low-dose immunotherapy underscores the need for further research in this setting.
Topics: Humans; Male; Adenocarcinoma; Adenocarcinoma, Papillary; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Head and Neck Neoplasms; Nivolumab; Adult
PubMed: 37923331
DOI: 10.1136/bcr-2023-255021 -
Virchows Archiv : An International... Jan 2024Ceruminous glands are modified apocrine glands, situated in the external auditory canal (EAC) that, together with sebaceous glands, produce cerumen. The neoplastic...
Ceruminous glands are modified apocrine glands, situated in the external auditory canal (EAC) that, together with sebaceous glands, produce cerumen. The neoplastic transformation of these structures is exceedingly rare. We encounter two cases of EAC adenocarcinoma with ETV6::NTRK3 fusion. Despite this genetic overlap, the morphology and immunophenotype delineate its clear separation from secretory carcinoma. These cases demonstrate novel primary EAC adenocarcinoma with papillary morphology, which expands the ever-increasing list of ETV6::NTRK3-positive malignancies and which we would like to term ETV6::NTRK3-translocation associated papillary adenocarcinoma. We also advocate the use of molecular techniques in rare tumors of uncertain type or differentiation, to increase understanding and possibilities of reproducible classification of these rare neoplasms. Pathologists and oncologists should recognize this entity, which leads to a direct approach for detecting NTRK fusion for appropriate treatment.
PubMed: 38206384
DOI: 10.1007/s00428-024-03735-6 -
Human Pathology Feb 2024Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of...
BACKGROUND
Differentiated high-grade thyroid carcinomas (DHGTCs) are a new diagnostic entity most recently defined in the 2022 World Health Organization's (WHO) Classification of Endocrine and Neuroendocrine Tumors. This new entity has been minimally described in the literature, and additional cases classified as such are missing.
MATERIALS AND METHODS
Cases of DHGTCs diagnosed at our institution from 2012 to 2022 were identified, and the following were reviewed: cytologic and histologic diagnoses, ancillary testing, immunohistochemical staining, treatments, and patient outcomes. Immunohistochemical staining for Ki67 was performed on selected cases lacking this immunostain. A systematic literature review of the English literature on DHGTCs from 2013 to 2023 was performed using PubMed and Embase.
RESULTS
Case cohort included 32 cases of DHGTCs, with an average age of 52.6 years (range 17-84 years) and a male:female ratio of 1.3:1. All cases underwent fine needle aspiration (FNA) and were categorized by The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as follows: 14 cases as malignant (43.8 %), 10 as follicular neoplasm (31.3 %), 5 as atypia of undetermined significance (15.6 %), 2 as suspicious for malignancy (6.2 %), and 1 as non-diagnostic (3.1 %). The average tumor size was 5.15 cm, and most were papillary thyroid carcinoma (28, 87.5 %), with classic subtype being the most common. Twenty-one cases revealed tumor necrosis and the mitotic activity in lesions without necrosis averaged to 5.5 mitoses per 2 mm (range 0-7). The average Ki67 proliferative index was 5.6 %. Extrathyroidal extension was seen in 17, angioinvasion in 21, lymphatic invasion in 7, and perineural invasion in 1 case. Foci of solid or trabecular growth were identified in five cases. Lymph node metastases at the time of diagnosis were noted in 10 cases and 7 demonstrated distant metastases or locoregional recurrence. To date, 25 patients are alive, and one has died from disease.
CONCLUSIONS
Our institutional experience demonstrates that DHGTC is a rare, but aggressive thyroid tumor subtype that requires consideration in the setting of a well-differentiated thyroid neoplasm to appropriately assess for possible disease recurrence and determination of patient prognosis.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Ki-67 Antigen; Thyroid Neoplasms; Thyroid Cancer, Papillary; Necrosis; Adenocarcinoma, Follicular; Retrospective Studies
PubMed: 38244615
DOI: 10.1016/j.humpath.2024.01.002 -
Aging Feb 2024Senescence-induced therapy was previously considered as an effective treatment for tumors, and cellular senescence was initially regarded as an effective mechanism...
Senescence-induced therapy was previously considered as an effective treatment for tumors, and cellular senescence was initially regarded as an effective mechanism against cancer. However, whether cell senescence-related genes can be used to predict the prognosis of papillary thyroid carcinoma (PTC) and immunotherapy remains unclear. We developed and validated a cell senescence-related signature (CSRS) by analyzing the gene expression of 278 genes related to cellular senescence in 738 patients with PTC. Additionally, further analysis showed that CSRS was a reliable predictor of patient outcomes in combination with immune checkpoint expression and drug susceptibility, and patients with high risk scores may benefit from immunotherapy. The findings of this study demonstrate that CSRS serves as an immunotherapeutic response and prognosis biomarker affecting the tumor immune microenvironment of PTC.
Topics: Humans; Thyroid Cancer, Papillary; Cellular Senescence; Immunotherapy; Risk Factors; Tumor Microenvironment; Thyroid Neoplasms; Prognosis
PubMed: 38329430
DOI: 10.18632/aging.205520 -
The International Journal of Biological... Dec 2023Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in...
The clinical and pathological significance of increased expression of the cannabinoid receptors CB-1R and CB-2R in patients with papillary thyroid carcinomas compared to benign thyroid lesions.
INTRODUCTION
Papillary thyroid carcinoma is the most common malignancy of the endocrine system. Most papillary thyroid carcinoma patients enjoy excellent outcomes. However, in patients with biologically aggressive features, additional prognostic and predictive data may aid disease management. Dysregulation of the endocannabinoid system including the cannabinoid receptors 1 and 2 (CB-1R and CB-2R) during carcinogenesis has been extensively studied over the last few decades. The aim of this study was to evaluate immunohistochemically the expression levels of both receptors in patients with papillary thyroid carcinoma and benign diseases, and to compare these rates and the histopathologically and clinically prognostic features.
METHODS
The pathological materials and clinical data of 100 patients with papillary thyroid carcinoma and 40 with benign diseases were retrospectively re-evaluated. All tissues were immunohistochemically stained for CB-1R and CB-2R. The expression levels of CB-1R and CB-2R in papillary thyroid carcinomas, and benign lesions were recorded and compared with the pathological and clinical features.
RESULTS
The expression levels of both receptors were significantly higher in papillary thyroid carcinoma patients than in those with benign conditions (= 0.001). CB-1R expression correlated with both extrathyroidal extension (= 0.022) and capsular invasion (= 0.001). CB-2R expression was associated with the risk group of the American Thyroid Association stratification system (= 0.004).
CONCLUSION
Our study suggests that increased cannabinoid receptor expression contributes to thyroid carcinogenesis. The CB-2R expression level could provide additional information aiding risk management. Furthermore, the CB-1R and CB-2R antibodies might increase the accuracy of papillary thyroid carcinoma diagnosis when combined with the papillary thyroid carcinoma biomarkers assayed after fine-needle aspiration of neoplastic cells.
Topics: Humans; Carcinogenesis; Carcinoma, Papillary; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 37700679
DOI: 10.1177/03936155231200285