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EBioMedicine Nov 2023Although per- and polyfluoroalkyl substances (PFAS) exposure is a potential contributor to the increasing thyroid cancer trend, limited studies have investigated the...
BACKGROUND
Although per- and polyfluoroalkyl substances (PFAS) exposure is a potential contributor to the increasing thyroid cancer trend, limited studies have investigated the association between PFAS exposure and thyroid cancer in human populations. We therefore investigated associations between plasma PFAS levels and thyroid cancer diagnosis using a nested case-control study of patients with thyroid cancer with plasma samples collected at/before cancer diagnosis.
METHODS
88 patients with thyroid cancer using diagnosis codes and 88 healthy (non-cancer) controls pair-matched on sex, age (±5 years), race/ethnicity, body mass index, smoking status, and year of sample collection were identified in the BioMe population (a medical record-linked biobank at the Icahn School of Medicine at Mount Sinai in New York); 74 patients had papillary thyroid cancer. Eight plasma PFAS were measured using untargeted analysis with liquid chromatography-high resolution mass spectrometry and suspect screening. Associations between individual PFAS levels and thyroid cancer were evaluated using unconditional logistic regression models to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).
FINDINGS
There was a 56% increased rate of thyroid cancer diagnosis per doubling of linear perfluorooctanesulfonic acid (n-PFOS) intensity (OR, 1.56, 95% CI: 1.17-2.15, P = 0.004); results were similar when including patients with papillary thyroid cancer only (OR, 1.56, 95% CI: 1.13-2.21, P = 0.009). This positive association remained in subset analysis investigating exposure timing including 31 thyroid cancer cases diagnosed ≥1 year after plasma sample collection (OR, 2.67, 95% CI: 1.59-4.88, P < 0.001).
INTERPRETATION
This study reports associations between exposure to PFAS and increased rate of (papillary) thyroid cancer. Thyroid cancer risk from PFAS exposure is a global concern given the prevalence of PFAS exposure. Individual PFAS studied here are a small proportion of the total number of PFAS supporting additional large-scale prospective studies investigating thyroid cancer risk associated with exposure to PFAS chemicals.
FUNDING
National Institutes of Health grants and The Andrea and Charles Bronfman Philanthropies.
Topics: Humans; Prospective Studies; Environmental Pollutants; Thyroid Cancer, Papillary; Case-Control Studies; Fluorocarbons; Thyroid Neoplasms
PubMed: 37884429
DOI: 10.1016/j.ebiom.2023.104831 -
Clinical Journal of Gastroenterology Oct 2023Triple gallbladder represents a rare congenital anatomical abnormality that can be a diagnostic challenge in reason to its rarity and consequential difficulties with... (Review)
Review
Triple gallbladder represents a rare congenital anatomical abnormality that can be a diagnostic challenge in reason to its rarity and consequential difficulties with diagnosis and identification. A systematic review of all published literature between 1958 and 2022 was performed. We identified 20 previous studies that provided 20 cases of triple gallbladder; our case was also included in the analysis, making a total of 21 patients. All patients underwent on diagnostic imaging examinations. After 1985, 9 patients underwent US examination which allowed prompt recognition of triple gallbladder in 2 patients only. CT was performed in 3 patients and allowed the correct diagnosis in a case. In 4 patients, was performed MRCP which allowed the correct diagnosis of triple gallbladder in all patients. Preoperative imaging allows the recognition of triple gallbladder in 9 of 21 patients (43%); in 12 patients (57%) the diagnosis was intraoperative. On patients considered, 16/21 underwent cholecystectomy. In 15 cases, the excised gallbladders were submitted for histopathological characterization with detection of metaplasia of the mucosa in 3 patients, while papillary adenocarcinoma was found in one. Imaging plays a key role in the identification of the anatomical variants of gallbladder, especially triple gallbladder, as modern imaging techniques allow a detailed assessment of the course of the biliary tract for a correct preoperative diagnosis. It is also crucial to be aware of the association between this condition and the metaplasia phenomena with the development of adenocarcinoma, as this may influence the patient's course of treatment.
PubMed: 37563490
DOI: 10.1007/s12328-023-01829-3 -
Pathology International Aug 2023Papillary adenocarcinoma is defined as carcinoma with a well-defined papillary or villous structure. Despite sharing clinicopathological and morphological features with...
Papillary adenocarcinoma is defined as carcinoma with a well-defined papillary or villous structure. Despite sharing clinicopathological and morphological features with tubular adenocarcinomas, papillary adenocarcinomas frequently show microsatellite instability. The present study aimed to clarify the clinicopathological features, molecular classification, and programmed death-ligand 1 (PD-L1) expression characteristics of papillary adenocarcinoma, especially tumors with microsatellite instability. We examined the microsatellite status and expression of mucin core proteins and PD-L1 as well as the clinicopathological features in 40 gastric papillary adenocarcinomas. Surrogate immunohistochemical analysis of p53 and mismatch repair proteins along with Epstein-Barr virus-encoded RNA in situ hybridization were performed for molecular classification. Female predominance and frequent microsatellite instability were observed in papillary adenocarcinoma in comparison with tubular adenocarcinoma. The presence of microsatellite instability in papillary adenocarcinoma was significantly correlated with older age, tumor-infiltrating lymphocytes, and Crohn's-like lymphoid reactions. Surrogate examination demonstrated that the genomically stable type (17 cases, 42.5%) was the most common, followed by the microsatellite-unstable type (14 cases, 35%). Among the seven cases showing PD-L1-positive expression in tumor cells, four involved carcinomas with microsatellite instability. These results reveal the clinicopathological and molecular characteristics of gastric papillary adenocarcinoma.
Topics: Humans; Female; Male; Microsatellite Instability; B7-H1 Antigen; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Stomach Neoplasms; Biomarkers, Tumor
PubMed: 37341602
DOI: 10.1111/pin.13345 -
The American Journal of Surgical... Oct 2023Digital papillary adenocarcinoma (DPA) is a rare sweat gland neoplasm that has exceptionally been reported outside acral locations. Recently, human papillomavirus 42 was...
Digital papillary adenocarcinoma (DPA) is a rare sweat gland neoplasm that has exceptionally been reported outside acral locations. Recently, human papillomavirus 42 was identified as the main oncogenic driver of DPA. Herein, we report 5 tumors arising in extra-acral locations predominantly in the female anogenital skin. Four patients were female and 1 patient was male. The mean age at the diagnosis time was 65 years (range: 55 to 82 y). Tumors were located on the vulva (n=3), perianal area (n=1), and forearm (n=1). Histologically, all tumors were lobular and mainly solid and composed of sheets of cells with rare focal papillae and frequent glandular structures in a "back-to-back" pattern and lined by atypical basophilic cells. Immunohistochemistry showed diffuse positivity for SOX10. Epithelial membrane antigen and carcinoembryonic antigen highlighted the luminal cells and staining for p63 and p40 revealed a consistent and continuous myoepithelial component around glandular structures. Follow-up was available in 3 cases (mean duration: 12 mo [range: 8 to 16 mo]). One patient developed local recurrence and 1 experienced regional lymph node metastases. HPV Capture Next-generation sequencing revealed the presence of the HPV42 genome in all samples. Viral reads distributions were compatible in the 5 cases with an episomal nature of the viral genome, with a recurrent deletion in the E1 and/or E2 open reading frames. In conclusion, this study demonstrates that digital DPA may rarely present in nonacral locations mainly in the female anogenital area, usually with a more solid pattern as compared with those cases presenting on the digits and it is also associated with HPV42.
Topics: Humans; Male; Female; Middle Aged; Aged; Aged, 80 and over; Sweat Gland Neoplasms; Bone Neoplasms; Breast Neoplasms; Neoplasms, Connective Tissue; Biomarkers, Tumor; Adenocarcinoma, Papillary
PubMed: 37505796
DOI: 10.1097/PAS.0000000000002096 -
JCI Insight Mar 2024Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis...
Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.
Topics: Tumor Microenvironment; Humans; Thyroid Carcinoma, Anaplastic; Animals; Mice; Thyroid Cancer, Papillary; Thyroid Neoplasms; Immunotherapy; Chemokine CXCL13; Tertiary Lymphoid Structures; Single-Cell Analysis; Prognosis; T-Lymphocytes; Female; Immune Checkpoint Inhibitors; Male
PubMed: 38478516
DOI: 10.1172/jci.insight.173712 -
Annales de Pathologie Mar 2024
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 38341313
DOI: 10.1016/j.annpat.2023.12.006 -
Biomedicine & Pharmacotherapy =... Apr 2024Oxidative stress (OS) is recognized as a contributing factor in the development and progression of thyroid cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) is... (Review)
Review
Oxidative stress (OS) is recognized as a contributing factor in the development and progression of thyroid cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor involved in against OS generated by excessive reactive oxygen species (ROS). It governs the expression of a wide array of genes implicated in detoxification and antioxidant pathways. However, studies have demonstrated that the sustained activation of Nrf2 can contribute to tumor progression and drug resistance in cancers. The expression of Nrf2 was notably elevated in papillary thyroid cancer tissues compared to normal tissues, indicating that Nrf2 may play an oncogenic role in the development of papillary thyroid cancer. Nrf2 and its downstream targets are involved in the progression of thyroid cancer by impacting the prognosis and ferroptosis. Furthermore, the inhibition of Nrf2 can increase the sensitivity of target therapy in thyroid cancer. Therefore, Nrf2 appears to be a potential therapeutic target for the treatment of thyroid cancer. This review summarized current data on Nrf2 expression in thyroid cancer, discussed the function of Nrf2 in thyroid cancer, and analyzed various strategies to inhibit Nrf2.
Topics: Humans; Thyroid Cancer, Papillary; NF-E2-Related Factor 2; Thyroid Neoplasms; Oxidative Stress; Antioxidants; Reactive Oxygen Species
PubMed: 38422655
DOI: 10.1016/j.biopha.2024.116324 -
Journal of Cancer Research and... 2023Solitary thyroid nodule should raise a suspicion of malignancy, which is very common in middle-aged females. Papillary carcinoma thyroid is the most common thyroid...
Solitary thyroid nodule should raise a suspicion of malignancy, which is very common in middle-aged females. Papillary carcinoma thyroid is the most common thyroid malignancy. Warthin-like papillary carcinoma is one of its rare variants. It has a frequent association with Hashimoto's thyroiditis. Here, we report a case of 43-year-old female who presented with swelling in the anterior aspect of neck for 1 month. Fine-needle aspiration cytology features were suggestive of papillary carcinoma thyroid and biopsy confirmed the diagnosis of Warthin-like papillary carcinoma thyroid. This variant is of great clinical and prognostic significance as it carries an excellent prognosis.
Topics: Middle Aged; Female; Humans; Adult; Carcinoma, Papillary; Thyroid Cancer, Papillary; Thyroid Neoplasms; Biopsy, Fine-Needle
PubMed: 37787334
DOI: 10.4103/jcrt.jcrt_1028_21 -
Scientific Reports Oct 2023Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy with a rapidly increasing incidence. The pathogenesis of PTC is unclear, but metabolic and...
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy with a rapidly increasing incidence. The pathogenesis of PTC is unclear, but metabolic and lipidomic reprogramming may play a role in tumor growth. We applied ultra-performance liquid chromatography-tandem mass spectrometry to perform widely targeted metabolomics and lipidomics on plasma samples from 94 patients with PTC and 100 healthy controls. We identified 113 differential metabolites and 236 differential lipids, mainly involved in branched-chain amino acid metabolism, glutamate and glutamine metabolism, tricarboxylic acid cycle, and lipid metabolism. We also screened three potential metabolite biomarkers: sebacic acid, L-glutamine, and indole-3-carboxaldehyde. These biomarkers showed excellent diagnostic performance for PTC in both discovery and validation cohorts, with areas under the receiver operating characteristic curves of 0.994 and 0.925, respectively. Our findings reveal distinct metabolic and lipidomic features of PTC and provide novel targets for diagnosis and treatment.
Topics: Humans; Thyroid Cancer, Papillary; Lipidomics; Thyroid Neoplasms; Carcinoma, Papillary; Metabolomics; Metabolome; Biomarkers; Biomarkers, Tumor
PubMed: 37848492
DOI: 10.1038/s41598-023-41176-4