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1.
Thorac Cancer ; 15(4): 350-352, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38151843

ABSTRACT

Tracheal AERO stent collapse is a rare complication compared to bronchial AERO stent collapse due to differences in the nitinol framework thickness. A 58-year-old man with a bulky anaplastic thyroid carcinoma was referred to our hospital due to exacerbation of tracheal stenosis despite the administration of lenvatinib. His tracheal stenosis exhibited a severe extrinsic compression pattern with a length of 8 cm. Because tracheotomy was inappropriate, we placed an 18 × 80 mm AERO stent. Five months later, he was readmitted with severe dyspnea due to collapse of the distal portion of the stent caused by tumor growth. Because stent removal was difficult, we placed an additional AERO stent (18 × 60 mm) to cover the collapsed portion. The additional stent successfully expanded the collapse and improved his dyspnea. To our knowledge, this is the first case where a tracheal AERO stent collapse due to a poor prognosis tumor was treated with the stent-in-stent method.


Subject(s)
Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Tracheal Stenosis , Male , Humans , Middle Aged , Tracheal Stenosis/etiology , Tracheal Stenosis/surgery , Tracheal Stenosis/pathology , Thyroid Carcinoma, Anaplastic/complications , Stents/adverse effects , Thyroid Neoplasms/complications , Thyroid Neoplasms/surgery , Dyspnea
2.
J Transl Med ; 21(1): 780, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37924062

ABSTRACT

BACKGROUND: Follicular thyroid cancer (FTC) is a prevalent form of differentiated thyroid cancer, whereas anaplastic thyroid cancer (ATC) represents a rare, fast-growing, undifferentiated, and highly aggressive tumor, posing significant challenges for eradication. Ferroptosis, an iron-dependent cell death mechanism driven by the excessive production of reactive oxygen species and subsequent lipid peroxidation, emerges as a promising therapeutic strategy for cancer. It has been observed that many cancer cells exhibit sensitivity to ferroptosis, while some other histotypes appear to be resistant, by counteracting the metabolic changes and oxidative stress induced by iron overload. METHODS: Here we used human biopsies and in vitro approaches to analyse the effects of iron-dependent cell death. We assessed cell proliferation and viability through MTT turnover, clonogenic assays, and cytofluorimetric-assisted analysis. Lipid peroxidation assay and western blot were used to analyse molecular mechanisms underlying ferroptosis modulation. Two distinct thyroid cancer cell lines, FTC-133 (follicular) and 8505C (anaplastic), were utilized. These cell lines were exposed to ferroptosis inducers, Erastin and RSL3, while simulating an iron overload condition using ferric ammonium citrate. RESULTS: Our evidence suggests that FTC-133 cell line, exposed to iron overload, reduced their viability and showed increased ferroptosis. In contrast, the 8505C cell line seems to better tolerate ferroptosis, responding by modulating CD71, which is involved in iron internalization and seems to have a role in resistance to iron overload and consequently in maintaining cell viability. CONCLUSIONS: The differential tolerance to ferroptosis observed in our study may hold clinical implications, particularly in addressing the unmet therapeutic needs associated with ATC treatment, where resistance to ferroptosis appears more pronounced compared to FTC.


Subject(s)
Iron Overload , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Humans , Thyroid Carcinoma, Anaplastic/complications , Iron Overload/complications , Iron Overload/drug therapy , Iron Overload/metabolism , Cell Death , Iron/metabolism , Reactive Oxygen Species/metabolism
3.
Head Neck Pathol ; 16(2): 507-512, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34755265

ABSTRACT

The aim of this study is to present an elusive case of primary thyroid lymphoma (PTL), initially thought to be anaplastic thyroid carcinoma, then Rosai Dorfman disease, before the final diagnosis of PTL was made. An elderly female with hypothyroidism presented with compressive airway symptoms secondary to an enlarging neck mass. Imaging was suggestive of undifferentiated thyroid cancer. The initial biopsy was unexpectedly consistent with a lymphoproliferative disorder such as Rosai-Dorfman disease. A repeat biopsy with immunohistochemical analysis yielded a diagnosis of diffuse large B-cell lymphoma of germinal center subtype. The patient was spared thyroid surgery and started on appropriate chemotherapy. PTL is within the differential diagnosis that physicians must consider in a patient with a rapidly-enlarging neck mass. A clinical index of suspicion and early accurate diagnosis may spare the patient from unnecessary surgery that is required of most other non-hematopoeitic thyroid malignancies.


Subject(s)
Histiocytosis, Sinus , Lymphoma, Large B-Cell, Diffuse , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Aged , Female , Histiocytosis, Sinus/pathology , Humans , Lymphoma, Large B-Cell, Diffuse/diagnosis , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/diagnosis , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology
4.
BMC Endocr Disord ; 21(1): 213, 2021 Oct 24.
Article in English | MEDLINE | ID: mdl-34689780

ABSTRACT

BACKGROUND: Thyroid crisis is a life-threatening condition in thyrotoxic patients. Although differentiated thyroid cancer is one of the causes of hyperthyroidism, reports on thyroid crisis caused by thyroid cancer are quite limited. Here, we describe a case of thyroid crisis caused by metastatic thyroid cancer. CASE PRESENTATION: A 91-year-old woman was admitted to our hospital because of loss of appetite. Two years prior to this hospitalization, she presented with subclinical thyrotoxicosis and was diagnosed with histologically unidentified thyroid cancer with multiple metastases, and she refused aggressive medical interventions. On admission, she exhibited extreme thyrotoxicosis, and the presence of fever, severe tachycardia, impaired consciousness, and heart failure revealed the presence of thyroid crisis. All thyroid autoantibodies were negative. Multidisciplinary conservative treatment was initiated; however, she died on the fifth day after admission. Autopsy revealed the presence of primary anaplastic thyroid carcinoma and multiple metastatic foci arising from follicular thyroid carcinoma. Both primary and metastatic follicular thyroid carcinoma likely induced thyrotoxicosis, which could have been exacerbated by anaplastic thyroid carcinoma. CONCLUSIONS: Even though the trigger of thyroid crisis in this patient is not clear, the aggravated progression of her clinical course suggests that careful monitoring of thyroid hormones and appropriate intervention are essential for patients with thyroid cancer.


Subject(s)
Adenocarcinoma, Follicular/complications , Thyroid Carcinoma, Anaplastic/complications , Thyroid Crisis/etiology , Thyroid Gland/pathology , Thyroid Neoplasms/complications , Adenocarcinoma, Follicular/diagnostic imaging , Adenocarcinoma, Follicular/pathology , Adenocarcinoma, Follicular/secondary , Aged, 80 and over , Fatal Outcome , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Thyroid Carcinoma, Anaplastic/diagnostic imaging , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Crisis/diagnostic imaging , Thyroid Gland/diagnostic imaging , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/pathology , Tomography, X-Ray Computed , Ultrasonography
5.
Thyroid ; 30(11): 1676-1680, 2020 11.
Article in English | MEDLINE | ID: mdl-32633627

ABSTRACT

Concomitant thyroid cancer in patients with congenital thyroid dyshormonogenesis (TD) is extremely rare and few cases of differentiated thyroid cancer in patients with TD have been reported thus far. In this study, we describe anaplastic thyroid cancer in a 46-year-old woman with TD who had two germline thyroglobulin (TG) gene mutation, c.3790T>C (p, Cys1264Arg) in exon 17 and a novel c.7070T>C (p.Leu2357Pro) in exon 41 of the TG gene. Two affected younger sisters were also found to have the same TG mutation but not anaplastic thyroid cancer. Any thyroid nodular lesions that develop in patients with TD should be investigated carefully.


Subject(s)
Goiter/complications , Goiter/genetics , Mutation , Thyroglobulin/genetics , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Neoplasms/complications , Thyroid Neoplasms/genetics , Family Health , Female , Germ-Line Mutation , Heterozygote , Humans , Male , Middle Aged , Mutation, Missense , Pedigree
6.
Chirurgia (Bucur) ; 114(5): 659-663, 2019.
Article in English | MEDLINE | ID: mdl-31670642

ABSTRACT

Anaplastic thyroid carcinoma (ATC) is a rare but almost invariably lethal disease. In this manuscript, we present a case where the dominant manifestation of ATC beside the goitre was elevated CRP values and a persistent low-grade fever. The patient underwent surgical removal of the tumour, chemotherapy and radiotherapy treatment. She is still alive and healthy 11 months after the surgery. We aim to demonstrate that ATC can be present with no specific symptoms or findings and to raise awareness towards an earlier diagnosis.


Subject(s)
C-Reactive Protein/analysis , Fever/etiology , Thyroid Carcinoma, Anaplastic/diagnosis , Thyroid Neoplasms/diagnosis , Female , Humans , Thyroid Carcinoma, Anaplastic/blood , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/blood , Thyroid Neoplasms/complications , Thyroid Neoplasms/therapy , Treatment Outcome
9.
Endokrynol Pol ; 69(1): 28-31, 2018.
Article in English | MEDLINE | ID: mdl-29319130

ABSTRACT

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies and constitutes approximately 1.6-5% of the malignant neoplasms of the thyroid gland. ATC usually manifests itself with the local symptoms due to a rapidly enlarging thyroid mass, and as other thyroid cancers, has only seldom been reported to cause thyrotoxicosis. Up to now only 9 cases of ATC with concomitant thyrotoxicosis have been described. CASE REPORT: We report a rare case of a 66-year-old woman, who had had the preexisting large, euthyroid multinodular goiter for almost 50 years. She was consulted by a doctor because of a 4-week history of thyrotoxicosis, symptoms of the congestive heart failure and a rapid increase in the size of the goiter. Thyroid hormone levels were consistent with a hyperthyroid state. The fine-needle aspiration biopsy confirmed a diagnosis of the anaplastic thyroid carcinoma, the small cells variant. The 99m Tc-pertechnetate scintigraphy visualized non-homogenous tracer distribution with hot nodules. She was given a doxorubicin (20 mg/week) and required the continuous antithyroid treatment. The patient died a one year after the first symptoms of the disease occurred. DISCUSSION: The association between ATC and a thyrotoxic state is very rare. In most cases, thyrotoxicosis concomitant with ATC was thought to be a result of the destruction of the thyroid follicles by the rapid infiltration with malignant cells, resulting in the leakage of preformed hormones to the circulation. In that case the most probable cause of thyrotoxicosis was the multinodular goiter coexisting with ATC. A simultaneous onset of tumor growth, thyrotoxicosis and a relatively long survival time of our patient is worth to notice and discuss.


Subject(s)
Goiter, Nodular/complications , Thyroid Carcinoma, Anaplastic/complications , Thyroid Neoplasms/complications , Thyrotoxicosis/etiology , Aged , Antibiotics, Antineoplastic/therapeutic use , Biopsy, Fine-Needle , Doxorubicin/therapeutic use , Fatal Outcome , Female , Humans , Radionuclide Imaging , Sodium Pertechnetate Tc 99m , Thyroid Carcinoma, Anaplastic/diagnosis , Thyroid Carcinoma, Anaplastic/diagnostic imaging , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/drug therapy
10.
Intern Med ; 57(7): 1015-1019, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-29225265

ABSTRACT

Posterior reversible encephalopathy syndrome (PRES) is a rare reversible neurological syndrome that causes subcortical vasogenic brain edema and which is associated with the use of target-specific agents. Lenvatinib is a target-specific agent that was recently approved for inoperable thyroid cancer. We herein describe the case of a 66-year-old woman with anaplastic thyroid cancer (ATC) who was treated with lenvatinib and who subsequently developed PRES. The clinical and radiological findings improved after suspending therapy for 1 week, and there was no recurrence with intermittent lower-dose lenvatinib treatment. Lenvatinib may prolong survival in patients with ATC and can be administered intermittently, even after PRES onset.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Phenylurea Compounds/adverse effects , Phenylurea Compounds/therapeutic use , Posterior Leukoencephalopathy Syndrome/drug therapy , Posterior Leukoencephalopathy Syndrome/etiology , Quinolines/adverse effects , Quinolines/therapeutic use , Thyroid Carcinoma, Anaplastic/drug therapy , Aged , Fatal Outcome , Female , Humans , Neoplasm Recurrence, Local/complications , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Thyroid Carcinoma, Anaplastic/complications , Thyroid Neoplasms/complications , Thyroid Neoplasms/pathology
11.
Nat Rev Endocrinol ; 13(11): 644-660, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28707679

ABSTRACT

Anaplastic thyroid carcinoma (ATC) is a rare malignancy, accounting for 1-2% of all thyroid cancers. Although rare, ATC accounts for the majority of deaths from thyroid carcinoma. ATC often originates in a pre-existing thyroid cancer lesion, as suggested by the simultaneous presence of areas of differentiated or poorly differentiated thyroid carcinoma. ATC is characterized by the accumulation of several oncogenic alterations, and studies have shown that an increased number of oncogenic alterations equates to an increased level of dedifferentiation and aggressiveness. The clinical management of ATC requires a multidisciplinary approach; according to recent American Thyroid Association guidelines, surgery, radiotherapy and/or chemotherapy should be considered. In addition to conventional therapies, novel molecular targeted therapies are the most promising emerging treatment modalities. These drugs are often multiple receptor tyrosine kinase inhibitors, several of which have been tested in clinical trials with encouraging results so far. Accordingly, clinical trials are ongoing to evaluate the safety, efficacy and effectiveness of these new agents. This Review describes the updated clinical and pathological features of ATC and provides insight into the molecular biology of this disease. The most recent literature regarding conventional, newly available and future therapies for ATC is also discussed.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Radiotherapy , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/therapy , Thyroidectomy , Age Factors , Deglutition Disorders/etiology , Dyspnea/etiology , GTP Phosphohydrolases/genetics , Hoarseness/etiology , Humans , Membrane Proteins/genetics , Neck Pain/etiology , Neoplasm Staging , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Radiation Exposure/statistics & numerical data , Respiratory Sounds/etiology , Risk Factors , Stilbenes/therapeutic use , Telomerase/genetics , Thiazolidinediones/therapeutic use , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/complications , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology
12.
Clin. transl. oncol. (Print) ; 19(1): 12-20, ene. 2017. tab, graf
Article in English | IBECS | ID: ibc-159114

ABSTRACT

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumor and almost uniformly lethal in humans. The Boards of the Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the Grupo Español de Enfermedades Huérfanas e Infrecuentes of the Spanish Society of Oncology requested that an independent task force draft a more comprehensive consensus statement regarding ATC. All relevant literature was reviewed, including serial PubMed searches together with additional articles. This is the first, comprehensive Spanish consensus statement for ATC and includes the characteristics, diagnosis, initial evaluation, treatment goals, recommendations and modalities for locoregional and advanced disease, palliative care options, surveillance, and long-term monitoring. Newer systemic therapies are being investigated, but more effective combinations are needed to improve patient outcomes. Though more aggressive radiotherapy has reduced locoregional recurrences, median overall survival has not improved in more than 50 years (AU)


No disponible


Subject(s)
Humans , Male , Female , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/epidemiology , Thyroid Carcinoma, Anaplastic/genetics , Consensus , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/drug therapy , Thyroid Carcinoma, Anaplastic/radiotherapy , Adenocarcinoma, Papillary/complications , Adenocarcinoma, Papillary/drug therapy , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Quality of Life , Palliative Care
15.
Intern Med ; 55(12): 1637-9, 2016.
Article in English | MEDLINE | ID: mdl-27301519

ABSTRACT

Trousseau's syndrome is characterized by a cerebral or systemic thromboembolism caused by coagulation abnormalities in malignancy. We herein report a case of multiple ischemic strokes as the initial manifestation of anaplastic thyroid carcinoma (ATC). An 86-year-old man was admitted to our hospital due to a sudden-onset weakness of the left limbs. Brain magnetic resonance imaging revealed multiple ischemic lesions in the right middle cerebral artery territory and a mass in the left frontal lobe. Computed tomography revealed a thyroid mass and multiple lung tumors. A diagnosis of ATC was confirmed by a thyroid biopsy. Our case indicates that ATC should be considered as a cause of Trousseau's syndrome.


Subject(s)
Cerebral Infarction/etiology , Cerebral Infarction/therapy , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/pathology , Aged, 80 and over , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/pathology , Cerebral Infarction/diagnostic imaging , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Humans , Japan , Magnetic Resonance Imaging , Male , Syndrome , Thyroid Carcinoma, Anaplastic/diagnostic imaging , Tomography, X-Ray Computed
16.
Head Neck ; 38(1): 85-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25215461

ABSTRACT

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an uncommon thyroid malignancy with a poor prognosis. American Thyroid Association (ATA) guidelines acknowledge the complexity of airway management in these patients. We studied our local experience with the aim of providing guidance in airway management in ATC. METHODS: Patients with histologically confirmed ATC from January 2004 to December 2011 were identified from our institutional database. The data were retrospectively analyzed using hospital case notes. RESULTS: Twenty-six patients were identified with ATC, 25 of who died from the disease. Five of 26 patients (19%) had stridor at presentation. A further 6 of 26 patients (23%) developed stridor during or soon after radiotherapy. Nine patients (36%) died of airway obstruction. CONCLUSION: Tracheotomy can facilitate completion of palliative treatment in those patients with ATC and stridor. Given the short life expectancy of these patients, a balanced decision must be made regarding the role and timing of tracheotomy.


Subject(s)
Airway Obstruction/surgery , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/therapy , Tracheotomy , Aged , Aged, 80 and over , Airway Obstruction/etiology , Chemotherapy, Adjuvant/methods , Female , Humans , Male , Middle Aged , Palliative Care , Retrospective Studies , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/diagnosis , Thyroid Carcinoma, Anaplastic/mortality , Thyroid Neoplasms/complications , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/mortality , Tracheotomy/methods
17.
J Laryngol Otol ; 129(6): 568-71, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25990193

ABSTRACT

BACKGROUND: Anaplastic thyroid carcinoma is rare but carries a poor prognosis. Anaplastic thyroid carcinoma leads to tracheal compression, airway compromise and eventually death. Airway compromise, a particularly distressing symptom, can be palliated with tracheal stenting. METHOD: A retrospective case note analysis was conducted of patients diagnosed with anaplastic thyroid carcinoma between July 2003 and July 2013. RESULTS: Twelve patients with anaplastic thyroid carcinoma were identified. Four patients underwent palliative tracheal stenting. Three patients had no dyspnoea at the time of stenting. Two stented patients subsequently developed dyspnoea secondary to stent migration; this was managed successfully with stent exchange. The other stented patient remained asymptomatic with regards to dyspnoea. All non-stented patients died with or from airway compromise. CONCLUSION: Tracheal stenting is a relatively safe and effective method for palliation of distressing airway symptoms in patients with anaplastic thyroid carcinoma. Early prophylactic tracheal stenting in anaplastic thyroid carcinoma may be an effective option to prevent development of airway compromise as the disease progresses.


Subject(s)
Airway Obstruction/surgery , Palliative Care/methods , Stents , Thyroid Carcinoma, Anaplastic/surgery , Thyroid Neoplasms/surgery , Trachea/surgery , Aged , Aged, 80 and over , Airway Obstruction/diagnosis , Airway Obstruction/etiology , Female , Humans , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/diagnosis , Thyroid Neoplasms/complications , Thyroid Neoplasms/diagnosis , Tomography, X-Ray Computed
18.
Intern Med ; 54(6): 611-6, 2015.
Article in English | MEDLINE | ID: mdl-25786451

ABSTRACT

Anaplastic thyroid carcinoma is a rare disease, and cases associated with eosinophilia are even rarer. We herein report a case of anaplastic thyroid carcinoma accompanied by remarkable and uncontrollable eosinophilia. A 71-year-old man was diagnosed with end-stage anaplastic thyroid carcinoma. Throughout the aggressive clinical course of the cancer, eosinophilia dramatically progressed and became extremely refractory to steroid treatment. We measured the serum levels of hematopoietic cytokines potentially involved in eosinophilia, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5. Although the GM-CSF level was moderately elevated, both the IL-3 and IL-5 levels were within the normal ranges. In this case, the patient's eosinophilia may have been related to his severe dyspnea and was likely responsible for the allergic reaction to the anticancer drug. Therefore, it is essential to elucidate the etiology of eosinophilia in patients with thyroid cancer in order to improve the treatment for patients with anaplastic thyroid carcinoma.


Subject(s)
Dyspnea/etiology , Eosinophilia/complications , Granulocyte-Macrophage Colony-Stimulating Factor/blood , Thyroid Carcinoma, Anaplastic/complications , Thyroid Neoplasms/complications , Aged , Eosinophilia/blood , Fatal Outcome , Humans , Interleukin-3/blood , Interleukin-5/blood , Male , Thyroid Carcinoma, Anaplastic/blood , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/blood , Thyroid Neoplasms/pathology
19.
Am J Surg ; 209(6): 1013-9, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25242682

ABSTRACT

BACKGROUND: We investigated whether pre-existent goiter and well-differentiated thyroid cancer (WDTC) are associated with survival in anaplastic thyroid carcinoma (ATC). METHODS: We analyzed medical records from 94 ATC patients, drawn from the Netherlands Cancer Registry, diagnosed in 17 hospitals between 1989 and 2009. RESULTS: The 29 patients (31%) with pre-existent goiter, including 8 with WDTC, were younger than those without (median, 69 vs. 76 years; P = .02). One-year overall survival was 9% (95% confidence interval [CI], 3% to 14%) with no difference between pre-existent goiter or not (overall survival, 14%; 95% CI, 1% to 26% vs overall survival, 6%; 95% CI, 0% to 13%]). Higher age was associated with a worse survival (hazard rate, 1.03; 95% CI, 1.01 to 1.06]), whereas the hazard to die was lower after surgery and/or radiotherapy (hazard rate, .37; 95% CI, .21 to .67 and hazard rate, .22; 95% CI, .12 to .41, respectively). CONCLUSIONS: ATC patients with pre-existent goiter were younger, yet survival was not significantly different between those with or without pre-existent goiter or WDTC.


Subject(s)
Goiter/complications , Thyroid Carcinoma, Anaplastic/mortality , Thyroid Neoplasms/mortality , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Netherlands/epidemiology , Proportional Hazards Models , Registries , Survival Rate , Thyroid Carcinoma, Anaplastic/complications , Thyroid Carcinoma, Anaplastic/diagnosis , Thyroid Carcinoma, Anaplastic/therapy , Thyroid Neoplasms/complications , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/therapy
20.
J Clin Endocrinol Metab ; 100(2): 725-35, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25365311

ABSTRACT

CONTEXT: Anaplastic thyroid cancer (ATC) has no effective treatment, resulting in a high rate of mortality. We established cell lines from a primary ATC and its lymph node metastasis, and investigated the molecular factors and genomic changes associated with tumor growth. OBJECTIVE: The aim of the study was to understand the molecular and genomic changes of highly aggressive ATC and its clonal evolution to develop rational therapies. DESIGN: We established unique cell lines from primary (OGK-P) and metastatic (OGK-M) ATC specimen, as well as primagraft from the metastatic ATC, which was serially xeno-transplanted for more than 1 year in NOD scid gamma mice were established. These cell lines and primagraft were used as tools to examine gene expression, copy number changes, and somatic mutations using RNA array, SNP Chip, and whole exome sequencing. RESULTS: Mice carrying sc (OGK-P and OGK-M) tumors developed splenomegaly and neutrophilia with high expression of cytokines including CSF1, CSF2, CSF3, IL-1ß, and IL-6. Levels of HIF-1α and its targeted genes were also elevated in these tumors. The treatment of tumor carrying mice with Bevacizumab effectively decreased tumor growth, macrophage infiltration, and peripheral WBCs. SNP chip analysis showed homozygous deletion of exons 3-22 of the PARD3 gene in the cells. Forced expression of PARD3 decreased cell proliferation, motility, and invasiveness, restores cell-cell contacts and enhanced cell adhesion. Next generation exome sequencing identified the somatic changes present in the primary, metastatic, and primagraft tumors demonstrating evolution of the mutational signature over the year of passage in vivo. CONCLUSION: To our knowledge, we established the first paired human primary and metastatic ATC cell lines offering unique possibilities for comparative functional investigations in vitro and in vivo. Our exome sequencing also identified novel mutations, as well as clonal evolution in both the metastasis and primagraft.


Subject(s)
Cell Line, Tumor/pathology , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/pathology , Aged , Animals , Cell Proliferation , Humans , Male , Mice , Mice, Inbred NOD , Neoplasm Transplantation , Neutrophils/pathology , Splenomegaly/etiology , Splenomegaly/pathology , Thyroid Carcinoma, Anaplastic/complications , Thyroid Neoplasms/complications
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