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Thyroid
Diagnostic Accuracy of Preoperative Radiologic Findings in Papillary Thyroid Microcarcinoma: Discrepancies with the Postoperative Pathologic Diagnosis and Implications for Clinical Outcomes
Ying Li, Seul Ki Kwon, Hoonsung Choi, Yoo Hyung Kim, Sunyoung Kang, Kyeong Cheon Jung, Jae-Kyung Won, Do Joon Park, Young Joo Park, Sun Wook Cho
Endocrinol Metab. 2024;39(3):450-460.   Published online May 27, 2024
DOI: https://doi.org/10.3803/EnM.2023.1872
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups.
Methods
In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed.
Results
The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery.
Conclusion
Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.
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Thyroid
Clinicopathological Features and Molecular Signatures of Lateral Neck Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
Jinsun Lim, Han Sai Lee, Jin-Hyung Heo, Young Shin Song
Endocrinol Metab. 2024;39(2):324-333.   Published online April 4, 2024
DOI: https://doi.org/10.3803/EnM.2023.1885
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The predictive factors for lateral neck lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) remain undetermined. This study investigated the clinicopathological characteristics, transcriptomes, and tumor microenvironment in PTMC according to the LLNM status. We aimed to identify the biomarkers associated with LLNM development.
Methods
We retrospectively reviewed the medical records of patients with PTMC from two independent institutions between 2018 and 2022 (n=597 and n=467). We compared clinicopathological features between patients without lymph node metastasis (N0) and those with LLNM (N1b). Additionally, laser capture microdissection and RNA sequencing were performed on primary tumors from both groups, including metastatic lymph nodes from the N1b group (n=30; 20 primary tumors and 10 paired LLNMs). We corroborated the findings using RNA sequencing data from 16 BRAF-like PTMCs from The Cancer Genome Atlas. Transcriptomic analyses were validated by immunohistochemical staining.
Results
Clinicopathological characteristics, such as male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis showed associations with LLNM in PTMCs. Transcriptomic profiles between the N0 and N1b PTMC groups were similar. However, tumor microenvironment deconvolution from RNA sequencing and immunohistochemistry revealed an increased abundance of tumor-associated macrophages, particularly M2 macrophages, in the N1b group.
Conclusion
Patients with PTMC who have a male sex, multifocality, extrathyroidal extension, lymphatic invasion, and central node metastasis exhibited an elevated risk for LLNM. Furthermore, infiltration of M2 macrophages in the tumor microenvironment potentially supports tumor progression and LLNM in PTMCs.
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Thyroid
Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis
Mijin Kim, Chae Hwa Kwon, Min Hee Jang, Jeong Mi Kim, Eun Heui Kim, Yun Kyung Jeon, Sang Soo Kim, Kyung-Un Choi, In Joo Kim, Meeyoung Park, Bo Hyun Kim
Endocrinol Metab. 2021;36(5):1086-1094.   Published online October 28, 2021
DOI: https://doi.org/10.3803/EnM.2021.1132
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  • 5 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC.
Methods
Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues.
Results
The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher’s exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs.
Conclusion
This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.

Citations

Citations to this article as recorded by  
  • What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?
    Bobby White, Pawel Swietach
    Pflügers Archiv - European Journal of Physiology.2024; 476(4): 673.     CrossRef
  • Comprehensive Long-Read Sequencing Analysis Discloses the Transcriptome Features of Papillary Thyroid Microcarcinoma
    Yanqiang Wang, Binbin Zou, Yanyan Zhang, Jin Zhang, Shujing Li, Bo Yu, Zhekun An, Lei Li, Siqian Cui, Yutong Zhang, Jiali Yao, Xiuzhi Shi, Jing Liu
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(5): 1263.     CrossRef
  • Feasibility of whole‐exome sequencing in fine‐needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations
    Liyuan Ma, Luying Gao, Ya Hu, Xiaoyi Li, Chunhao Liu, Jiang Ji, Xinlong Shi, Aonan Pan, Yuang An, Nengwen Luo, Yu Xia, Yuxin Jiang
    Clinical Genetics.2024; 105(5): 567.     CrossRef
  • Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
    Dan-ni He, Na Wang, Xiao-Ling Wen, Xu-Hua Li, Yu Guo, Shu-heng Fu, Fei-fan Xiong, Zhe-yu Wu, Xu Zhu, Xiao-ling Gao, Zhen-zhen Wang, Hong-jiu Wang
    Frontiers in Genetics.2023;[Epub]     CrossRef
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Thyroid
Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway
Jun-Qing Jin, Jeong-Sun Han, Jeonghoon Ha, Han-Sang Baek, Dong-Jun Lim
Endocrinol Metab. 2021;36(5):1095-1110.   Published online October 14, 2021
DOI: https://doi.org/10.3803/EnM.2021.1155
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  • 11 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role in EMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells.
Methods
Half maximal inhibitory concentration (IC50) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression of PPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2 expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays.
Results
Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-β1)-induced EMT-associated processes such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasion in BCPAP and K1 cells. LGZ restored TGF-β1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore, LGZ and RGZ suppressed TGF-β1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Although there was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZ was hampered by GW9662, a PPAR-γ antagonist.
Conclusion
LGZ inhibits TGF-β1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.

Citations

Citations to this article as recorded by  
  • Associations between Diabetes Mellitus and Selected Cancers
    Monika Pliszka, Leszek Szablewski
    International Journal of Molecular Sciences.2024; 25(13): 7476.     CrossRef
  • Diabetes Mellitus and Thyroid Cancers: Risky Correlation, Underlying Mechanisms and Clinical Prevention
    Rongqian Wu, Junping Zhang, Guilin Zou, Shanshan Li, Jinying Wang, Xiaoxinlei Li, Jixiong Xu
    Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 809.     CrossRef
  • Clinicopathological Evaluation of Papillary Thyroid Microcarcinoma
    Ando Takahito, Kimihito Fujii, Hirona Banno, Masayuki Saito, Yukie Ito, Mirai Ido, Manami Goto, Yukako Mouri, Junko Kousaka, Tsuneo Imai, Shogo Nakano
    Cureus.2024;[Epub]     CrossRef
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    Guohao Huang, Mengfan Zhang, Manzhou Wang, Wenze Xu, Xuhua Duan, Xinwei Han, Jianzhuang Ren
    Oncology Letters.2024;[Epub]     CrossRef
  • The Activation of PPARγ by (2Z,4E,6E)-2-methoxyocta-2,4,6-trienoic Acid Counteracts the Epithelial–Mesenchymal Transition Process in Skin Carcinogenesis
    Enrica Flori, Sarah Mosca, Giorgia Cardinali, Stefania Briganti, Monica Ottaviani, Daniela Kovacs, Isabella Manni, Mauro Truglio, Arianna Mastrofrancesco, Marco Zaccarini, Carlo Cota, Giulia Piaggio, Mauro Picardo
    Cells.2023; 12(7): 1007.     CrossRef
  • Cumulative exposure to metabolic syndrome increases thyroid cancer risk in young adults: a population-based cohort study
    Jinyoung Kim, Kyungdo Han, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon
    The Korean Journal of Internal Medicine.2023; 38(4): 526.     CrossRef
  • Drug repositioning in thyroid cancer treatment: the intriguing case of anti-diabetic drugs
    Alessia Greco, Francesca Coperchini, Laura Croce, Flavia Magri, Marsida Teliti, Mario Rotondi
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids
    Salvatore Benvenga, Fausto Famà, Laura Giovanna Perdichizzi, Alessandro Antonelli, Gabriela Brenta, Francesco Vermiglio, Mariacarla Moleti
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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    Gabriella Guo Sciriha, Janet Sultana, Joseph Borg
    Expert Review of Clinical Pharmacology.2022; 15(12): 1423.     CrossRef
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Clinical Study
Clinical Outcomes of N1b Papillary Thyroid Cancer Patients Treated with Two Different Doses of Radioiodine Ablation Therapy
Meihua Jin, Jonghwa Ahn, Yu-Mi Lee, Tae-Yon Sung, Won Gu Kim, Tae Yong Kim, Jin-Sook Ryu, Won Bae Kim, Young Kee Shong, Min Ji Jeon
Endocrinol Metab. 2020;35(3):602-609.   Published online September 22, 2020
DOI: https://doi.org/10.3803/EnM.2020.741
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  • 2 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
The optimal dose of radioactive iodine (RAI) therapy for N1b papillary thyroid carcinoma (PTC) is controversial. We evaluated the clinical outcome of N1b PTC patients treated with either 100 or 150 mCi of RAI.
Methods
We retrospectively analyzed N1b PTC patients who underwent total thyroidectomy and postoperative RAI therapy at a tertiary referral center between 2012 and 2017. As the baseline characteristics differed between treatment groups, we performed exact matching for various pathological factors according to RAI dose. We evaluated the response to therapy and recurrence-free survival (RFS) in the matched patients. Structural recurrent/persistent disease was defined as new structural disease detected after initial therapy, which was confirmed by cytology or pathology.
Results
Of the total 436 patients, 37 (8.5%) received 100 mCi of RAI and 399 (91.5%) received 150 mCi of RAI. After an exact 1:3 matching, 34 patients in the 100 mCi group and 100 patients in the 150 mCi group remained. There was no significant difference in response to therapy between the groups in the matched population (P=0.63). An excellent response was achieved in 70.6% (n=24) of patients in the 100 mCi group and 76.0% (n=76) in the 150 mCi group. Two (5.9%) patients in the 100 mCi group and four (4.0%) in the 150 mCi group had recurrence and there was no significant difference in RFS between the groups in the matched population (P=0.351).
Conclusion
There were no differences in response to therapy and RFS in N1b PTC patients according to RAI dose.

Citations

Citations to this article as recorded by  
  • Controversies in the Management of Intermediate-Risk Differentiated Thyroid Cancer
    David Toro-Tobon, Juan P. Brito
    Endocrine Practice.2024; 30(9): 879.     CrossRef
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Clinical Study
Mechanisms of the Impact of Hashimoto Thyroiditis on Papillary Thyroid Carcinoma Progression: Relationship with the Tumor Immune Microenvironment
Oksana Sulaieva, Olena Chernenko, Oleksiy Selesnov, Oleksandr Nechay, Oleksandr Maievskyi, Tetyana Falalyeyeva, Nazarii Kobyliak, Olena Tsyryuk, Yurii Penchuk, Dmytro Shapochka
Endocrinol Metab. 2020;35(2):443-455.   Published online June 24, 2020
DOI: https://doi.org/10.3803/EnM.2020.35.2.443
  • 7,276 View
  • 175 Download
  • 13 Web of Science
  • 15 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The relationship between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains uncertain. We assessed the impact of HT on the tumor immune microenvironment (TIME) in PTC.
Methods
Thirty patients with PTC (group 1) and 30 patients with PTC and HT (group 2) were enrolled in this pilot study. The distribution and number of CD8+ lymphocytes, plasma cells (CD138+), regulatory T cells (forkhead box P3 [FOXP3+)], mast cell tryptase (MCT+), and M2 macrophages (CD163+) were evaluated. To test the hypothesis that HT impacts PTC development via signal transducer and activator of transcription 6 (STAT6) activation and M2 macrophage polarization, we investigated STAT6 expression in tumor and stromal cells. We also evaluated vascular endothelial growth factor (VEGF) expression by lymph node metastasis (LNM) status.
Results
TIME showed significant between-group differences. Group 1 patients demonstrated immune desert or immune-excluded immunophenotypes, while an inflamed phenotype with more CD8+ cells (P<0.001) predominated in group 2. Immune-excluded TIME was associated with the highest LNM rate. In PTC, LNM was associated with more numerous CD163+ cells. Moreover, LNM in group 1 was associated with increased numbers of mast cells peritumorally and FOXP3+ cells intratumorally and peritumorally. Group 2 demonstrated higher STAT6 but not higher VEGF expression in tumor cells. High VEGF expression was associated with LNM regardless of HT status.
Conclusion
Concomitant HT impacted PTC signaling via STAT6 and TIME by increasing the number of CD8+ cells. LNM is associated with increases in CD163+ cells and VEGF expression in PTC, whereas HT affected LNM through different mechanisms.

Citations

Citations to this article as recorded by  
  • The impact of Hashimoto’s thyroiditis on the clinical outcome of papillary thyroid cancer after radioactive iodine therapy: a propensity score matching study
    Jingjia Cao, Yaru Sun, Yang Liu, Yunfei Xu, Xiao Li, Wei Zhang, Ximing Wang
    Endocrine.2024;[Epub]     CrossRef
  • Clinical significance and diagnostic value of QPCT, SCEL and TNFRSF12A in papillary thyroid cancer
    Tairong Liang, Xiuqian Wu, Lan Wang, Zhengzhong Ni, Ying Fan, Peishan Wu, Hongzhi Wang, Yongdong Niu, Haihua Huang
    Pathology - Research and Practice.2023; 245: 154431.     CrossRef
  • Recommend with caution: A meta-analysis investigating papillary thyroid carcinoma tumor progression under active surveillance
    Peter P. Issa, Ruhul Munshi, Aaron L. Albuck, Mahmoud Omar, Ruba F. Abu Alhuda, Tyler Metz, Mohammad Hussein, Mohamed Shama, Grace S. Lee, Eman Toraih, Emad Kandil
    American Journal of Otolaryngology.2023; 44(6): 103994.     CrossRef
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    Hui Huang, Siyuan Xu, Song Ni, Wensheng Liu, Shaoyan Liu
    Journal of Cancer Research and Clinical Oncology.2023; 149(17): 15525.     CrossRef
  • A nomogram based on the risk factors of cervical lymph node metastasis in papillary thyroid carcinoma coexistent with Hashimoto’s thyroiditis
    Huanhuan Miao, Jingwen Zhong, Xuesha Xing, Jiawei Sun, Jiaqi Wu, Chengwei Wu, Yan Yuan, Xianli Zhou, Hongbo Wang
    Clinical Hemorheology and Microcirculation.2023; 85(3): 235.     CrossRef
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    Nese E. GULCELIK, Safak AKIN, Kadriye AYDIN, Cisel AYDIN MERICOZ, Yesim G. GULER TEZEL, Aydan USMAN
    Minerva Endocrinology.2023;[Epub]     CrossRef
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    Meiye Li, Jimei Zhang, Zongjing Zhang, Ying Qian, Wei Qu, Zhaoshun Jiang, Baochang Zhao
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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    Jin-Ming Yao, Jun-Yu Zhao, Fang-Fang Lv, Xue-Bo Yang, Huan-Jun Wang
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  • Hyperhomocysteinemia in the pathogenesis of cardiovascular and endocrine diseases: translational messages
    Rostyslav KAMINSKY, Andrii YANCHYSHYN, Natalia BELEMETS, Olena KURYK, Inga SAMBORSKA, Iryna DZEVULSKA, Rinaldo PELLICANO
    Minerva Biotechnology and Biomolecular Research.2022;[Epub]     CrossRef
  • Immune Microenvironment of Muscular-Invasive Urothelial Carcinoma: The Link to Tumor Immune Cycle and Prognosis
    Oleksandr Stakhovskyi, Nazarii Kobyliak, Oleg Voylenko, Eduard Stakhovskyi, Roman Ponomarchuk, Oksana Sulaieva
    Cells.2022; 11(11): 1802.     CrossRef
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    Yuepeng Zhang, Yueli Tian
    BMC Endocrine Disorders.2022;[Epub]     CrossRef
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    鑫 焦
    Advances in Clinical Medicine.2022; 12(12): 11503.     CrossRef
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    Georgia Karpathiou, Alexandra Papoudou-Bai, Elise Ferrand, Jean Marc Dumollard, Michel Peoc’h
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    Siyuan Xu, Hui Huang, Jiaxin Qian, Yang Liu, Ying Huang, Xiaolei Wang, Shaoyan Liu, Zhengang Xu, Jie Liu
    JAMA Network Open.2021; 4(7): e2118526.     CrossRef
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    D.I. Zabolotnyi, V.V. Kizim, D.D. Zabolotna, Y.V. Kizim, O.N. Sulaieva
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Thyroid
Clinical Outcomes of Differentiated Thyroid Cancer Patients with Local Recurrence or Distant Metastasis Detected in Old Age
Ji Min Han, Ji Cheol Bae, Hye In Kim, Sam Kwon, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2018;33(4):459-465.   Published online November 30, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.4.459
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  • 6 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background

Differentiated thyroid carcinoma (DTC) shows a very good prognosis, but older patients have a higher recurrence rate and those show poor prognosis than younger patients. The aim of this study was to determine the clinical outcomes of thyroid cancer patients who experienced recurrence in old age according to the treatment strategy used.

Methods

This retrospective observational cohort study was conducted at Asan Medical Center, Seoul, Korea. Among DTC patients with no evidence of disease after initial treatment, we enrolled 86 patients who experienced recurrence at an age >65 years from 1994 to 2012. Sixty-nine patients had local recurrence and 17 patients showed distant metastasis.

Results

The mean age of patients at recurrence was 72 years. Patients were followed up for a median of 4.1 years after recurrence. Sixty-three of the 69 patients with local recurrence received additional treatment, while the other six received conservative care. The cancer-specific mortality rate was 15.5% in the local recurrence group. Airway problems were the main cause of death in patients who did not receive further treatment for local recurrence. Among the 17 patients with distant metastasis, 10 underwent specific treatment for metastasis and seven received only supportive management. Seven of those 17 patients died, and the cancer-specific mortality rate was 35% in the distant metastasis group.

Conclusion

The overall cancer-specific mortality rate was 20% in DTC patients in whom recurrence was first detected at an age >65 years. Mortality due to uncontrolled local disease occurred frequently in patients who did not receive definitive management for recurrence.

Citations

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  • 125I seed implantation for lymph node metastasis from radioactive iodine-refractory differentiated thyroid carcinoma: a study on short-term efficacy and dosimetry
    Wenwen Zhang, Shanhu Hao, Zhiguo Wang, Tingting Ding, Guoxu Zhang
    Frontiers in Oncology.2024;[Epub]     CrossRef
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    Huiling Wang, Mian Lv, Yonghong Huang, Xiaoming Pan, Changyuan Wei
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  • Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up
    Zhong-Ling Qiu, Chen-Tian Shen, Zhen-Kui Sun, Hong-Jun Song, Chuang Xi, Guo-Qiang Zhang, Yang Wang, Quan-Yong Luo
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
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    Yangmeihui Song, Fang Liu, Weiwei Ruan, Fan Hu, Muhsin H. Younis, Zairong Gao, Jie Ming, Tao Huang, Weibo Cai, Xiaoli Lan
    Cancers.2021; 13(14): 3436.     CrossRef
  • Highly sensitive electrochemical immunosensor using a protein-polyvinylidene fluoride nanocomposite for human thyroglobulin
    Maria Oneide Silva de Moraes, João de Deus Pereira de Moraes Segundo, Marcos Marques da Silva Paula, Maria Goreti Ferreira Sales, Walter Ricardo Brito
    Bioelectrochemistry.2021; 142: 107888.     CrossRef
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Thyroid
Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea
Hosu Kim, Hye In Kim, Sun Wook Kim, Jaehoon Jung, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Hee Kyung Kim, Ho-Cheol Kang, Ji Min Han, Yoon Young Cho, Tae Hyuk Kim, Jae Hoon Chung
Endocrinol Metab. 2018;33(2):287-295.   Published online June 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.2.287
  • 6,202 View
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  • 32 Web of Science
  • 28 Crossref
AbstractAbstract PDFPubReader   ePub   
Background

Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea.

Methods

We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea.

Results

The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables.

Conclusion

The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

Citations

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  • Case report: A case of hyperthyroidism secondary to bone metastasis of differentiated thyroid cancer
    Tingyu Gu, Zhihong Zhao, Yuanyuan Shi, Zhenhua Sun, Yao Wang, Zhiyuan He, Kun Wang
    Frontiers in Oncology.2024;[Epub]     CrossRef
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    Luca Giovanella, Murat Tuncel, Atena Aghaee, Alfredo Campenni, Armando De Virgilio, Petra Petranović Ovčariček
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    Luca Giovanella, Maria Luisa Garo, Alfredo Campenní, Petra Petranović Ovčariček, Rainer Görges
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    Petra Petranović Ovčariček, Alfredo Campenni, Bart de Keizer, Desiree Deandreis, Michael C. Kreissl, Alexis Vrachimis, Murat Tuncel, Luca Giovanella
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Close layer
Review Articles
Bone Metabolism
Osteoblasts Are the Centerpiece of the Metastatic Bone Microenvironment
Hyo Min Jeong, Sun Wook Cho, Serk In Park
Endocrinol Metab. 2016;31(4):485-492.   Published online December 20, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.4.485
  • 4,442 View
  • 48 Download
  • 13 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   

The tumor microenvironment is comprised of diverse stromal cell populations in addition to tumor cells. Increasing evidence now clearly supports the role of microenvironment stromal cells in tumor progression and metastasis, yet the regulatory mechanisms and interactions among tumor and stromal cells remain to be elucidated. Bone metastasis is the major problem in many types of human malignancies including prostate, breast and lung cancers, and the biological basis of bone metastasis let alone curative approaches are largely undetermined. Among the many types of stromal cells in bone, osteoblasts are shown to be an important player. In this regard, osteoblasts are a key target cell type in the development of bone metastasis, but there are currently no drugs or therapeutic approaches are available that specifically target osteoblasts. This review paper summarizes the current knowledge on osteoblasts in the metastatic tumor microenvironment, aiming to provide clues and directions for future research endeavor.

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Close layer
Bone Metabolism
Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis
Yibin Kang
Endocrinol Metab. 2016;31(2):206-212.   Published online May 13, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.2.206
  • 5,584 View
  • 55 Download
  • 36 Web of Science
  • 35 Crossref
AbstractAbstract PDFPubReader   

Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

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Close layer
Original Article
Clinical Study
Radiographic Characteristics of Adrenal Masses in Oncologic Patients
Ji Hyun Lee, Eun Ky Kim, A Ram Hong, Eun Roh, Jae Hyun Bae, Jung Hee Kim, Chan Soo Shin, Seong Yeon Kim, Sang Wan Kim
Endocrinol Metab. 2016;31(1):147-152.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.147
  • 5,254 View
  • 44 Download
  • 9 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   
Background

We aimed to assess the usefulness of pre-contrast Hounsfield unit (HU) and mass size on computed tomography to differentiate adrenal mass found incidentally in oncologic patients.

Methods

From 2000 to 2012, 131 oncologic patients with adrenal incidentaloma were reviewed retrospectively. Receiver operating characteristic (ROC) curves were applied to determine the optimal cut-off value of the mean HU and size for detecting adrenal metastasis.

Results

The median age was 18 years, and 80 patients were male. The initial mass size was 18 mm, and 71 (54.2%) of these were on the left side. A bilateral adrenal mass was found in 11 patients (8.4%). Biochemically functional masses were observed in 9.2% of patients. Thirty-six out of 119 patients with nonfunctional masses underwent adrenalectomy, which revealed metastasis in 13. The primary cancers were lung cancer (n=4), renal cell carcinoma (n=2), lymphoma (n=2), hepatocellular carcinoma (n=2), breast cancer (n=1), and others (n=2). The area under the curve for the size and HU for clinically suspicious metastasis were 0.839 (95% confidence interval [CI], 0.761 to 0.900; P<0.001) and 0.959 (95% CI, 0.898 to 0.988; P<0.001), respectively. The cut-off value to distinguish between metastasis and benign masses were 22 mm for size and 20 for HU.

Conclusion

ROC curve results suggest that pre-contrast HU >20 can be used as a diagnostic reference to suggest metastasis in oncologic patients with adrenal masses.

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Close layer
Case Reports
Adrenal gland
Incidentally Detected Inoperable Malignant Pheochromocytoma with Hepatic Metastasis Treated by Transcatheter Arterial Chemoembolization
Joong Keun Kim, Bo Hyun Kim, Sung Min Baek, Dong Hun Shin, Won Jin Kim, Yun Kyoung Jeon, Sang Soo Kim, In Joo Kim
Endocrinol Metab. 2014;29(4):584-589.   Published online December 29, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.4.584
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AbstractAbstract PDFPubReader   

Malignant pheochromocytoma (PCC) is a rare condition. Although the liver is the second most frequent site of metastasis in malignant PCC, no definite treatments have been established. Herein, we report a case of liver metastasis of PCC that was successfully treated by transcatheter arterial chemoembolization (TACE). A 69-year-old man was admitted to the Department of Gastroenterology for evaluation of an incidental hepatic mass in August 2013. He had undergone right adrenalectomy in May 2005 and PCC had been confirmed on the basis of histopathological findings. Liver biopsy was performed, and metastatic PCC was diagnosed. The lesion appeared inoperable because of invasion of the portal vein and metastases in the lymph nodes along the hepatoduodenal ligament. Thus, TACE was performed instead. After TACE, symptoms including dizziness and cold sweating improved, and the patient's serum catecholamine levels decreased. On the basis of this case, we believe that TACE may be a useful treatment for liver metastasis in malignant PCC.

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    SHUJUN LU, YAJING ZHANG, WENLI YU
    Cellulose Chemistry and Technology.2023; 57(9-10): 1001.     CrossRef
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    Won-Young Lee
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    Yun Mi Choi, Tae‐Yon Sung, Won Gu Kim, Jong Jin Lee, Jin‐Sook Ryu, Tae Yong Kim, Won Bae Kim, Suck Joon Hong, Dong Eun Song, Young Kee Shong
    Journal of Surgical Oncology.2015; 112(8): 815.     CrossRef
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Thyroid
Solitary Skin Metastasis of Papillary Thyroid Carcinoma
Hyemi Kwon, Hyojung Kim, Sojung Park, Dong Eun Song, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinol Metab. 2014;29(4):579-583.   Published online December 29, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.4.579
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  • 7 Web of Science
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AbstractAbstract PDFPubReader   

A solitary skin metastasis is a rare manifestation of papillary thyroid carcinoma (PTC). A 55-year-old woman presented with a movable subcutaneous nodule in her anterior neck for several months. Three years ago, she underwent total thyroidectomy and remnant ablation for classical PTC (pT3N0M0) and was under thyroxine suppression therapy without any evidence of recurrent disease. The subcutaneous nodule was 0.4 cm in size, firm, and movable without any change in the overlying skin. Recurrent PTC was confirmed after excision biopsy. Eight months after, she got a new nodule along the previous excision site. After punch biopsy, metastatic PTC was confirmed in the deep dermis and was re-excised with a clear resection margin. This is the first report of a case of solitary skin metastasis of PTC in Korea. Although solitary skin metastasis of PTC is rare, it should be considered in patients with a skin nodule.

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  • Skin Metastasis Occurring 30 Years After Thyroidectomy for Papillary Thyroid Carcinoma
    Mohammed S Alwhaid, Olaa Mhish, Mutahir A Tunio, Salman AlMalki, Mushabbab Al Asiri, Khalid Al-Qahtani
    Cureus.2022;[Epub]     CrossRef
  • Solitary Nasopharyngeal Metastasis From Papillary Thyroid Carcinoma Shown on FDG PET/CT
    Anqi Xu, Xiao Jie, Yan Xiu, Hongcheng Shi
    Clinical Nuclear Medicine.2022; 47(5): e425.     CrossRef
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    Pooja Ramakant, Anand Mishra, Chanchal Rana, Kulranjan Singh
    Indian Journal of Endocrine Surgery and Research.2022; 17(1): 21.     CrossRef
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    Eleonora Farina, Fabio Monari, Giovanni Tallini, Andrea Repaci, Renzo Mazzarotto, Francesca Giunchi, Riccardo Panzacchi, Silvia Cammelli, Gilbert D. A. Padula, Francesco Deodato, Renato Pasquali, Stefano Fanti, Michelangelo Fiorentino, Alessio G. Morganti
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    Jonathan S. Leventhal, Irwin M. Braverman
    Seminars in Oncology.2016; 43(3): 335.     CrossRef
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    Lakshminarasimman Parasuraman, Shubhada V. Kane, Prathamesh S. Pai, Kintan Shanghvi
    Indian Journal of Surgical Oncology.2016; 7(1): 91.     CrossRef
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    Won Bae Kim
    Endocrinology and Metabolism.2015; 30(1): 1.     CrossRef
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    Won-Young Lee
    Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef
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Thyroid
Accelerated Disease Progression after Discontinuation of Sorafenib in a Patient with Metastatic Papillary Thyroid Cancer
Kyung-Jin Yun, Woohyeon Kim, Eun Hee Kim, Min-Hee Kim, Dong-Jun Lim, Moo-Il Kang, Bong-Yun Cha
Endocrinol Metab. 2014;29(3):388-393.   Published online September 25, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.3.388
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AbstractAbstract PDFPubReader   

Distant metastases from papillary thyroid carcinoma (PTC) are rare and are associated with a poor prognosis. Here, we describe a patient with metastatic PTC who was treated with a tyrosine kinase inhibitor (TKI, sorafenib) for several months that was acutely exacerbated by discontinuation. A 43-year-old male was diagnosed with PTC in February 2004 and underwent total thyroidectomy followed by two courses of high-dose radioactive iodine (RAI) therapy. Despite two additional courses of high-dose RAI therapy, lung and muscle metastases were developed. Treatment with sorafenib was begun in September 2010. After 11 months treatment of sorafenib, newly developed metastatic lesions were found in mediastinal lymph nodes, liver, and bones. Considered as treatment failure, the administration of sorafenib was discontinued. Two weeks after sorafenib treatment was stopped, the disease progressed abruptly and caused death of the patient by respiratory failure. In our patient, PTC progressed rapidly after the cessation of sorafenib treatment. Patients with several other types of cancer have also experienced such rapid disease progression, termed "flare-ups." Physicians should be aware that flare-ups may occur in advanced PTC patients following the cessation of TKI therapy.

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Solitary Pulmonary Metastasis of a Thyroid Papillary Microcarcinoma, Masquerading as Primary Lung Cancer.
Jong Hwan Lee, Se Jin Ahn, Hyung Jin Kim, Sang Eon Jang, Jae Soo Koh, Yun Yong Lee, Cheol Hyeon Kim, Jae Cheol Lee
Endocrinol Metab. 2011;26(1):78-83.   Published online March 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.1.78
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AbstractAbstract PDF
Although pulmonary metastasis of thyroid cancer is not uncommon, it mostly occurs as multiple discrete nodules on the lung parenchyma. Because thyroid cancer presenting with an isolated large lung mass is extremely rare and the diagnosis is frequently based on small pieces of tissue obtained by a fine needle, the wrong diagnosis such as lung cancer is prone to be made. A 60-year-old man was admitted for evaluation of a lung mass detected on chest radiography. Cytological examination of the bronchial washing specimens suggested adenocarcinoma. Surgery for early lung cancer was performed considering that no other abnormalities were found during the work-up that included 18-fludeoxyglucose positron emission tomography computer tomography (18FDG-PET/CT). Unexpectedly, the diagnosis of papillary thyroid cancer with lung metastasis was made, which prompted us to evaluate the thyroid gland and then remove the primary cancer by subsequent operation. Although it is uncommon, physician should be aware of this possibility, which could help to avoid the wrong diagnosis. Here we report on a typical case of solitary pulmonary metastasis of thyroid cancer and we summarize the previously reported cases with a review of the relevant literature.

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  • Lung nodule detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid cancer, negative 131I whole body scan, and undetectable serum-stimulated thyroglobulin levels: two case reports
    Chan-Hee Jung, Hyeon-Jeong Goong, Bo-Yeon Kim, Jung-Mi Park, Jeong-Ja Kwak, Chul-Hee Kim, Hyun-Sook Hong, Sung-Koo Kang, Ji-Oh Mok
    Journal of Medical Case Reports.2012;[Epub]     CrossRef
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