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Journal of Endocrinological... Jun 2024Papillary thyroid carcinoma (PTC) is characterized by lymph-node metastasis (LNM), which affects recurrence and prognosis. This study analyzed PTC LNM by single-cell RNA...
PURPOSE
Papillary thyroid carcinoma (PTC) is characterized by lymph-node metastasis (LNM), which affects recurrence and prognosis. This study analyzed PTC LNM by single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing (RNA-seq) to find diagnostic markers and therapeutic targets.
METHODS
ScRNA-seq data were clustered and malignant cells were identified. Differentially expressed genes (DEGs) were identified in malignant cells of scRNA-seq and bulk RNA-seq, respectively. PTC LNM diagnostic model was constructed based on intersecting DEGs using glmnet package. Next, PTC samples from 66 patients were used to validate the two most significant genes in the diagnostic model, S100A2 and type 2 deiodinase (DIO2) by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC). Further, the inhibitory effect of DIO2 on PTC cells was verified by cell biology behavior, western blot, cell cycle analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay, and xenograft tumors.
RESULTS
Heterogeneity of PTC LNM was demonstrated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. A total of 19 differential genes were used to construct the diagnostic model. S100A2 and DIO2 differ significantly at the RNA (p < 0.01) and protein level in LNM patient tissues (p < 0.001). And differed in PTC tissues with different pathologic typing (p < 0.001). Further, EdU (p < 0.001) and cell biology behavior revealed that PTC cells overexpressed DIO2 had reduced proliferative capacity. Cell cycle proteins were reduced and cells are more likely to be stuck in G2/M phase (p < 0.001).
CONCLUSIONS
This study explored the heterogeneity of PTC LNM using scRNA-seq. By combining with bulk RNA-seq data, diagnostic markers were explored and the model was established. Clinical diagnostic efficacy of S100A2 and DIO2 was validated and the treatment potential of DIO2 was discovered.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Biomarkers, Tumor; Lymphatic Metastasis; Single-Cell Analysis; Animals; Mice; Sequence Analysis, RNA; Female; Male; S100 Proteins; Prognosis; Gene Expression Regulation, Neoplastic; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Cell Proliferation; Middle Aged; Gene Expression Profiling; Chemotactic Factors
PubMed: 38146045
DOI: 10.1007/s40618-023-02262-6 -
Pediatric Radiology Jun 2024Identifying the associations between BRAF mutation, the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) and clinicopathological...
Associations of BRAF mutation with the American College of Radiology Thyroid Imaging Reporting and Data System and clinicopathological characteristics in pediatric patients with papillary thyroid carcinoma.
BACKGROUND
Identifying the associations between BRAF mutation, the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) and clinicopathological characteristics could assist in making appropriate treatment strategies for pediatric patients with papillary thyroid carcinoma.
OBJECTIVE
To retrospectively assess the associations between BRAF mutation, TI-RADS, and clinicopathological characteristics in pediatric patients with papillary thyroid carcinoma.
MATERIALS AND METHODS
Between May 2013 and May 2023, pediatric patients with papillary thyroid carcinoma who underwent thyroidectomy were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to determine the associations between BRAF mutation, TI-RADS, and clinicopathological characteristics. The diagnostic performance of TI-RADS to predict BRAF mutation was assessed.
RESULTS
The BRAF mutation was found in 59.1% (39/66) of pediatric patients with papillary thyroid carcinoma. Multivariate analyses showed that hypoechoic/very hypoechoic [odds ratio (OR) = 8.48; 95% confidence interval (CI) = 1.48-48.74); P-value = 0.02] and punctate echogenic foci (OR = 24.3; 95% CI = 3.80-155.84; P-value = 0.001) were independent factors associated with BRAF mutation. In addition, BRAF mutation was significantly associated with TI-RADS 5 (OR = 12.61; 95% CI = 1.28-124.49; P-value = 0.03). There were no associations between BRAF mutation and nodule size, composition, shape, margin, cervical lymph node metastasis, or Hashimoto's thyroiditis (P-value > 0.05). Combined with hypoechoic/very hypoechoic and punctate echogenic foci, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.7%, 85.2%, 89.7%, 85.2%, and 87.9%, respectively.
CONCLUSIONS
Hypoechoic/very hypoechoic, punctate echogenic foci, and TI-RADS 5 are independently associated with BRAF mutation in pediatric patients with papillary thyroid carcinoma.
Topics: Humans; Male; Female; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Child; Thyroid Neoplasms; Retrospective Studies; Mutation; Adolescent; United States; Radiology Information Systems; Thyroidectomy; Child, Preschool
PubMed: 38771344
DOI: 10.1007/s00247-024-05943-3 -
American Journal of Otolaryngology 2023Papillary thyroid carcinoma (PTC) is an indolent disease with favorable outcomes. The non-surgical treatment approach known as active surveillance (AS) has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Papillary thyroid carcinoma (PTC) is an indolent disease with favorable outcomes. The non-surgical treatment approach known as active surveillance (AS) has been introduced as an alternative treatment instead of the traditional thyroidectomy. However, 10-15 % of PTC tend to progress. We sought to determine factors predicting the progression of PTC under AS.
METHODS
A systematic search was performed in January 2022 using PubMed, Embase, Google Scholar, Web of Science, and ScienceDirect. PRISMA guidelines were used by multiple reviewers to extract study characteristics (author name, publication date, journal name, country, institution, and study design), as well as main outcomes and measures. A combination of utilization of thyroid replacement therapy, baseline tumor size and volume, follow-up tumor size and volume, and the presence of lymph node metastasis and its distribution, as well as surveillance duration, were the main measures of this study.
RESULTS
Nine studies with 4166 patients were included, of which 354 showed tumor progression during AS (15 %; 95%CI = 7 % - 23 %). The average follow-up period was 41.58 months. The mean tumor maximum diameter was 8.54 mm (95%CI = 7.04-10.03). Tumor progression was most commonly secondary to an increase in volume by ≥50 % (75 %; 95%CI = 68 % - 80 %), then increase in diameter by ≥3 mm (41 %; 95%CI = 13 % - 76 %), and finally the development of lymph node metastasis (13 %; 95%CI = 9 % - 19 %). Approximately only 2 % of all patients thus developed new lymph node metastasis. Patient age, sex, and tumor size were not associated with higher risks of tumor progression. 12 % of AS patients eventually underwent surgery, though only 40 % (95%CI = 27 % - 53 %) of these patients displayed tumor progression.
CONCLUSIONS
Our meta-analysis determined a tumor progression rate of 15 % in patients who underwent AS management, 13 % of which (2 % of all patients) developed lymph node metastasis. We found no protective or risk factors for tumor progression, and that almost half of all patients who underwent delayed surgery did so for reasons other than tumor progression. While not biopsying small (<1 cm) or very low suspicious nodules is already recommended, AS may be an appropriate treatment option in patients appropriately counseled, considering the low risk of advanced tumor progression but also the considerable patient population who fail to adhere to treatment. Alternatively, in aim of preventing overtreatment in patients who would rather take proactive measures against their low-risk carcinoma, minimally-invasive ablation techniques may be an attractive option.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Lymphatic Metastasis; Watchful Waiting; Carcinoma, Papillary; Thyroidectomy; Risk Factors; Retrospective Studies
PubMed: 37607459
DOI: 10.1016/j.amjoto.2023.103994 -
The Malaysian Journal of Pathology Aug 2023Thyroid carcinoma is uncommon. Papillary thyroid carcinoma (PTC) represents the majority of differentiated thyroid carcinoma and is a recognised complication of prior...
Thyroid carcinoma is uncommon. Papillary thyroid carcinoma (PTC) represents the majority of differentiated thyroid carcinoma and is a recognised complication of prior exposure to ionizing radiation. Even more uncommon is the synchronous occurrence of PTC with Hodgkin lymphoma (HL) as multiple primary malignancies. We report a 33-year-old mother of three who developed asymptomatic thyroid nodule for four years, and neck swelling for the recent ten months. She denied constitutional symptoms or B symptoms, and thyroid profiles were normal. Initially, metastatic thyroid cancer was suspected based on ultrasound scan findings of enlarged left thyroid gland and enlarged supraclavicular lymph nodes (LN). However, fine needle aspiration examinations of the thyroid nodule were inconclusive, and the supraclavicular LN was suspicious of HL. Computerised tomography scan detected a large mass at the thyroid glands and lymphadenopathies in the mediastinal, hilar, subcarinal and axilla with dimensions up to 6 cm. Left hemi-thyroidectomy with left supraclavicular LN biopsy revealed PTC in the left thyroid lobe measuring 38 x 25 x 18 mm, and the left supraclavicular LN was not definitive of HL. Completion thyroidectomy on the right side, bilateral central neck dissection and excision biopsy of the right supraclavicular LN revealed the presence of HL in the right supraclavicular LN, and both HL and metastatic PTC in right central LN. After multidisciplinary discussions, the patient received chemotherapy at four weeks postoperatively and achieved complete remission. This report highlights the importance of patient-centered approach and multidisciplinary consensus within lack of established guidelines, given rarity of the case.
Topics: Female; Humans; Adult; Thyroid Cancer, Papillary; Hodgkin Disease; Thyroid Nodule; Thyroid Neoplasms; Biopsy, Fine-Needle
PubMed: 37658537
DOI: No ID Found -
Diagnostic Pathology Aug 2023Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid...
BACKGROUND
Cancer progression can be promoted by chronic inflammation. Local immune response may be associated with favourable or unfavourable prognosis of Papillary Thyroid Carcinoma (PTC). Regulatory T (Treg) cells and T helper 17 (Th17) cells exert opposing function and their balance may have a vital role in promotion of tumor growth. Treg cells in tumor microenvironment (TME) may promote tumor progression and reduced survival of patients. Whereas, Th17 cells can promote or inhibit tumor progression depending on phenotypic characteristics of tumor. In this study, we aimed to analyse the kind of immune response developed and its prognostic impact in future therapeutics.
METHODS
Cytometric Bead Array (CBA) analysis of pro and anti-inflammatory cytokines (IFN-gamma, IL-2, IL-6, IL-17 A, TNF-alpha and IL-4, IL-10) was done in 15 PTC irrespective of Lymphocytic Thyroiditis (LT) and 16 Hashimoto's Thyroiditis (HT) cases. Immunohistochemical expression of FoxP3 and IL-17 A was studied in 27 cases of PTC with LT. Whereas, quantitative gene expression of both was analysed in 10 cases.
RESULTS
All the pro-inflammatory cytokines showed mild elevation in PTC with LT. On IHC, IL-17 A expression was observed in 74% PTC with LT. Whereas, FoxP3 was present in only 40% cases. Also, IL-17 A expression was significantly associated with age group (> 45 years), tumor size ≤ 1 cm and disease progression.
CONCLUSIONS
Increased expression of cytokines suggested correlation between inflammatory factors and progression of thyroid tumors. Along with this, the balance between IL-17 A and FoxP3 may play an important role in PTC development, prognosis and future management.
Topics: Humans; Middle Aged; Carcinoma, Papillary; Cytokines; Disease Progression; Forkhead Transcription Factors; Hashimoto Disease; Interleukin-17; Thyroid Cancer, Papillary; Thyroid Neoplasms; Tumor Microenvironment
PubMed: 37563607
DOI: 10.1186/s13000-023-01362-4 -
Radiology Apr 2024
Topics: Humans; Thyroid Cancer, Papillary; Overtreatment; Thyroid Neoplasms
PubMed: 38563672
DOI: 10.1148/radiol.240207 -
Current Opinion in Otolaryngology &... Apr 2024The aim of this study was to provide a timely and relevant review of the latest findings and explore appropriate management of aggressive variants of papillary thyroid... (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to provide a timely and relevant review of the latest findings and explore appropriate management of aggressive variants of papillary thyroid cancer (AVPTC).
RECENT FINDINGS
In general, AVPTCs tend to exhibit more invasive characteristics, a lack of responsiveness to radioiodine, increased occurrences of regional spreading, distant metastases and higher mortality rates. Meanwhile, each variant showcases unique clinical and molecular profiles.
SUMMARY
Given the elevated risk of recurrence postsurgery, a more aggressive strategy may be necessary when suspected preoperatively, particularly for those presenting with invasive features. Decision on the extent of surgical treatment and adjuvant therapy is individualized and made by experienced clinicians and multidisciplinary teams based on the clinical presentation, presence of aggressive features and molecular profile. Future studies on development of personalized medicine and molecular target therapy may offer tailored treatment options.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Prognosis; Carcinoma, Papillary; Iodine Radioisotopes
PubMed: 38116795
DOI: 10.1097/MOO.0000000000000952 -
Annals of Surgical Oncology Aug 2023The clinical behaviour and oncologic outcome of diffuse sclerosing papillary thyroid carcinoma (DS-PTC) is poorly understood. The objectives of this study were to...
Diffuse Sclerosing Papillary Thyroid Carcinoma: Clinicopathological Characteristics and Prognostic Implications Compared with Classic and Tall Cell Papillary Thyroid Cancer.
BACKGROUND
The clinical behaviour and oncologic outcome of diffuse sclerosing papillary thyroid carcinoma (DS-PTC) is poorly understood. The objectives of this study were to compare the clinicopathological characteristics and oncological outcomes of DS-PTC to classic PTC (cPTC) and tall cell PTC (TC-PTC).
METHODS
After institutional review board approval, 86 DS-PTC, 2,080 cPTC, and 701 TC-PTC patients treated at MSKCC between 1986 and 2021 were identified. Clinicopathological characteristics were compared by using chi-square test. Kaplan-Meier and log rank were used to compare recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). DS-PTC patients were propensity matched to cPTC and TC-PTC patients for further comparison.
RESULTS
DS-PTC patients were younger with more advanced disease than cPTC and TC-PTC (p < 0.05). Lymphovascular invasion (LVI), extranodal extension, and positive margins were more common in DS-PTC (p < 0.02). Propensity matching confirmed more aggressive histopathological features in DS-PTC. The median number of metastatic lymph nodes was significantly greater and DS-PTC metastases were RAI avid. DS-PTC 5-year RFS was 50.4% compared with 92.4% in cPTC and 88.4% in TC-PTC (p < 0.001). Multivariate analysis confirmed DS-PTC as an independent prognostic factor of recurrence. Ten-year DSS for DS-PTC was 100% compared with 97.1% in cPTC and 91.1% in TC-PTC. Differentiated high-grade, thyroid carcinoma DS had more advanced T-stage and worse 5-year RFS than DS-PTC.
CONCLUSIONS
DS-PTC presents with more advanced clinicopathological features than cPTC and TC-PTC. Large-volume nodal metastases and LVI are characteristic features. Almost half of patients develop recurrence despite aggressive initial management. Despite this, with successful salvage surgery DSS is excellent.
Topics: Humans; Thyroid Cancer, Papillary; Prognosis; Carcinoma, Papillary; Neoplasm Recurrence, Local; Thyroid Neoplasms; Retrospective Studies
PubMed: 37154968
DOI: 10.1245/s10434-023-13589-y -
Frontiers in Endocrinology 2023The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of...
CONTEXT
The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). and promoter mutations have been shown to correlate with the histopathological features and outcome of DTC. Our objectives were to study the correlation of these molecular markers with these clinicopathological-staging systems.
PATIENTS AND METHODS
We studied 296 unselected patients, 214 females and 82 males with a median age of 36 years (IQR 23.3-49.0). and promoter mutations were tested by PCR-based Sanger sequencing. Data were extracted from medical records and analysed using Chi-Square and Fisher Exact tests and Kaplan Meier analysis.
RESULTS
Of 296 patients tested, 137 (46.3%) had -positive tumors and 72 (24.3%) were positive for promoter mutations. The mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of persistent disease (PD) ( 0.12). Unlike , promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.006) and in TNM stages III and IV than lower stages (0.0001). promoter mutations also predicted the outcome, being present in 37.2% of patients with PD compared to only 15.4% in those without evidence of disease (0.0001). The same pattern was also seen when and promoter mutations were combined.
CONCLUSION
promoter mutations alone or in combination with mutation, but not mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems.
Topics: Male; Female; Humans; Young Adult; Adult; Middle Aged; Neoplasm Staging; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Carcinoma, Papillary; Promoter Regions, Genetic; Telomerase; Thyroid Neoplasms; Adenocarcinoma; Mutation
PubMed: 37859987
DOI: 10.3389/fendo.2023.1270796 -
Neuroradiology Feb 2024To comprehensively summarize the clinical data and CT/MRI characteristics of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA).
PURPOSE
To comprehensively summarize the clinical data and CT/MRI characteristics of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA).
METHODS
Twenty-seven lesions from 25 study articles identified through a systematic review and three lesions from our institution associated with TL-LGNPPA were evaluated.
RESULTS
The mean age of the patients at diagnosis was 35.7 years, and the male-to-female ratio was nearly half. The chief complaint was nasal obstruction, followed by epistaxis. All patients underwent excision. None of the patients had neck nodes or distant metastases. All patients survived with no locoregional/distant recurrence during 3-93 months of follow-up. All lesions were located at the posterior edge of the nasal septum, attached to the nasopharyngeal parietal wall, and showed no laterality. The mean lesion diameter was 1.7 cm. The margins of lesions were well-defined and lobulated, followed by well-defined smooth margins. None of lesions were associated with parapharyngeal space or skull base destruction. All lesions were iso- and low-density on non-contrast CT. Adjacent skull base sclerosis was detected in 63.6% of lesions. High signal intensity on T2-weighted imaging and mostly iso-signal intensity on T1-weighted imaging compared to muscle tissue. Most lesions were heterogeneous and exhibited moderate contrast enhancement. Relatively large lesions (≥1.4 cm) tended to be more lobulated than smooth margins compared to relatively small lesions (<1.4 cm) (p = 0.016).
CONCLUSION
We summarized the clinical and radiological features of TL-LGNPPA to facilitate accurate diagnosis and appropriate management.
Topics: Adult; Female; Humans; Male; Adenocarcinoma, Papillary; Magnetic Resonance Imaging; Thyroid Gland
PubMed: 38103083
DOI: 10.1007/s00234-023-03254-2