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Curtis D. Klaassen - One of the best experts on this subject based on the ideXlab platform.
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Thyroid Cancer in Humans
2016Co-Authors: Curtis D. Klaassen, M. HoodAbstract:The effects of microsomal enzyme inducers on thyroid hormone homeostasis and the thyroid gland are of concern. We have investigated the effects of microsomal enzyme inducers on thyroid Follicular Cell proliferation and thyroid hormone metabolism in rats. We have shown that small increases in serum TSH can result in large increases in thyroid Follicular Cell proliferation. Furthermore, only those microsomal enzyme inducers that increase serum TSH—that is, phenobarbi tal (PB) and pregnenolone-16-carbonitrile (PCN)—increase thyroid Follicular Cell proliferation, whereas those microsomal enzyme inducers that do not increase serum TSH— that is, 3-methylcholanthrene (3MC) and Aroclor 1254 (PCB)—do not increase thyroid Follicular Cell proliferation. Deiodination does not appear to be the reason why serum T3 concentrations are maintained in microsomal enzyme inducer–treated rats. We have also shown that those microsomal enzyme inducers that increase serum TSH increase T3 UDP-glucuronosyltransferase (UGT) activity, whereas those microsomal enzyme inducers that do not increase serum TSH do not increase T3 UGT activity. This nding suggests that induction of T3 glucuronidation, rather than T4 glucuronidation, mediates increases in serum TSH of microsomal enzyme inducer treated rats
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inhibition of gap junctional interCellular communication in thyroid Follicular Cells by propylthiouracil and low iodine diet
Toxicology, 2000Co-Authors: Kyle L. Kolaja, Jay S. Petrick, Curtis D. KlaassenAbstract:Propylthiouracil (PTU) or low-iodine diet (LID) treatment increases thyroid-Follicular-Cell proliferation, possibly by disrupting the movement of small molecules (<1.2 kD) through membrane channels called gap junctions. Numerous tumor promoters and proliferative disease states exhibit inhibited gap-junctional-interCellular communication (GJIC) prior to the induction of Cell proliferation, yet the association between GJIC and apoptosis is unclear. In the present study, we used an ex vivo method to examine whether GJIC is inhibited in the thyroid of PTU- or LID-treated rats. In addition, the effect of these models of hypothyroidism on thyroid-Follicular-Cell proliferation and apoptosis was examined to determine the association between GJIC and Cell homeostasis. After 14 days of treatment of either PTU or LID (plus 1% KClO4 in the drinking water), serum tri-iodothyronine (T3) and thyroxine, (T4) was decreased to nearly undetectable levels and serum TSH was increased in PTU- and LID-treated rats. At the same time point, GJIC was decreased 30–35% in PTU- and LID-treated rats while thyroid-Follicular-Cell proliferation increased nearly threefold in both treatment groups. Interestingly, apoptosis increased twofold in both hypothyroid treatment groups. These data suggest that PTU or LID treatment inhibit thyroid GJIC during a state of increased thyroid-Follicular-Cell proliferation and apoptosis. While the increase in proliferation was anticipated, the paradoxical increase in apoptosis during decreased GJIC in thyroid-Follicular Cells warrants further examination.
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effects of microsomal enzyme inducers on thyroid Follicular Cell proliferation hyperplasia and hypertrophy
Toxicology and Applied Pharmacology, 1999Co-Authors: Alan Hood, Raj Hashmi, Curtis D. KlaassenAbstract:Abstract The microsomal enzyme inducer (MEI), phenobarbital (PB), has been proposed to promote thyroid tumors by increasing the biotransformation and elimination of T 4 , resulting in an increase in serum thyroid-stimulating hormone (TSH). In turn, TSH stimulates thyroid gland function, growth, and ultimately neoplasia. The dose-dependent effects of MEI on thyroid-Follicular Cell proliferation, a measure of thyroid gland growth, has not been reported. In the present study, it was hypothesized that MEIs that increase TSH would stimulate thyroid-Follicular Cell proliferation and the total number of thyroid-Follicular Cells. Male Sprague–Dawley rats were fed either a basal diet or a diet containing PB (at 300, 600, 1200, or 2400 ppm), pregnenolone-16α-carbonitrile (PCN) (at 200, 400, 800, or 1600 ppm), 3-methylcholanthrene (3MC) (at 50, 100, 200, or 400 ppm), or Aroclor 1254 (PCB) (at 25, 50, 100, or 200 ppm) for 7 days. PB and PCN increased TSH 65% and 95%, respectively, whereas 3MC and PCB did not appreciably affect TSH. PB and PCN increased thyroid-Follicular Cell proliferation 625% and 1200%, respectively, whereas 3MC and PCB did not have a consistent or appreciable effect. The total number of thyroid-Follicular Cells was not significantly increased by MEI treatment. In conclusion, small increases in TSH by PB and PCN produced large increases in thyroid-Follicular Cell proliferation, which did not result in a comparable increase in the total number of thyroid-Follicular Cells. Furthermore, MEI that did not increase TSH did not consistently or appreciably increase thyroid-Follicular Cell proliferation or Cell number.
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sensitivity of thyroid gland growth to thyroid stimulating hormone tsh in rats treated with antithyroid drugs
Toxicological Sciences, 1999Co-Authors: Alan M Hood, Ya Ping Liu, Vincent H Gattone, Curtis D. KlaassenAbstract:Antithyroid drugs and phenobarbital (PB) have been shown to promote thyroid tumors in rats. It has been proposed that increased thyroid-stimulating hormone (TSH) mediates the thyroid tumor-promoting effect of antithyroid drugs and PB, and is increased because of decreased thyroxine (T4) concentration. However, PB is much less effective than antithyroid drugs at increasing TSH. It has been proposed that small increases in serum TSH produced by PB treatment is sufficient to promote thyroid tumors. However, the level to which TSH must be increased to stimulate the thyroid gland has not been reported. Therefore, we have examined the effect of increasing serum TSH concentration on thyroid growth by measuring thyroid gland weight and thyroid Follicular Cell proliferation. Serum TSH concentrations were increased by feeding rats various concentrations of propylthiouracil (PTU) or methimazole (MMI) for 21 days. Serum total T4, free T4, total T3 (triiodothyronine), free T3, and TSH concentrations were measured by radioimmunoassay. Thyroid Follicular Cell proliferation was measured by autoradiography and expressed as a labeling index (LI). PTU and MMI treatments reduced total and free T4 more than 95% by day 21, whereas total and free T3 were reduced 60%. TSH, thyroid Follicular Cell proliferation and thyroid weight were increased 560%, 1400%, and 200%, respectively, by day 21. TSH was significantly correlated with thyroid weight and LI. Moderate increases in serum TSH of between 10 and 20 ng/ml increased the number of proliferating thyroid Follicular Cells, but had no effect on thyroid weight. These results support that small increases in serum TSH can be sufficient to stimulate thyroid Follicular Cell proliferation. Furthermore, thyroid Follicular Cell proliferation may be more useful than thyroid weight alone for assessing alterations in thyroid growth in rats treated with chemicals that produce only small to moderate increases in serum TSH.
Ronald Ghossein - One of the best experts on this subject based on the ideXlab platform.
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poorly differentiated carcinoma of the thyroid gland current status and future prospects
Thyroid, 2019Co-Authors: Tihana Ibrahimpasic, Ronald Ghossein, Jatin P Shah, Ian GanlyAbstract:Background: Poorly differentiated thyroid cancer (PDTC) is a rare but clinically highly significant entity because it accounts for most fatalities from non-anaplastic Follicular Cell–derived thyroi...
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time course and predictors of structural disease progression in pulmonary metastases arising from Follicular Cell derived thyroid cancer
Thyroid, 2016Co-Authors: Mona M Sabra, Ronald Ghossein, Michael R TuttleAbstract:Background: With the advent of molecular targeted therapy for the management of radioactive iodine (RAI) refractory, progressive metastatic thyroid cancer, it becomes important to define the time course and risk factors for structural disease progression in Follicular Cell–derived thyroid cancer (FCDTC) patients. This will help in defining the optimal time to start these therapies and better define their impact on structural disease progression. Objectives: This retrospective review of 199 consecutive patients with FCDTC presenting with lung metastasis examined the progression-free survival (PFS) in thyroid cancer patients with lung metastasis treated with surgery and RAI, and who had not received molecular targeted therapy or chemotherapy. Results: The median overall survival (OS) was 10.45 years, while the median PFS was 3.65 years. A strong correlation was found between OS and PFS. PFS is shorter in patients with RAI refractory disease, poorly differentiated/Hurthle Cell histologies, male sex, fluorode...
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pediatric differentiated thyroid carcinoma of Follicular Cell origin prognostic significance of histologic subtypes
Thyroid, 2016Co-Authors: Sadana Balachandar, Ronald Ghossein, Michael R Tuttle, Michael P La Quaglia, Glenn Heller, Charles A SklarAbstract:Background: Thyroid cancers are rare in the pediatric age group, and unlike in adults, few data are available regarding the clinical implication of histologic subtypes in the pediatric population. The purpose of the current study was to determine the prognostic significance of histologic subtypes of differentiated thyroid cancer (DTC) in a large series of children and adolescents followed at a single institution. Methods: A retrospective review was conducted of all pediatric DTC patients who were treated and followed between 1988 and 2012. Sixty-two patients (median age at diagnosis 13.8 years, median age at follow-up 18 years, 77% female) were assessed. The most common subtypes included classic papillary thyroid carcinoma (PTC; 48%), diffuse sclerosing PTC (16%), and Follicular variant PTC (15%); 37% were considered “high-risk” histologies based on adult criteria. Results: In a multivariate model, only extensive extrathyroidal extension (ETE), defined as the presence of two or more microscopic foci of tu...
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prognostic impact of extent of vascular invasion in low grade encapsulated Follicular Cell derived thyroid carcinomas a clinicopathologic study of 276 cases
Human Pathology, 2015Co-Authors: Laura Y Wang, Michael R Tuttle, Ian Ganly, Ronald GhosseinAbstract:Continuous controversy surrounds the predictive value of the degree of vascular invasion (VI) in low-grade encapsulated Follicular Cell-derived thyroid carcinomas (LGEFCs). Some guidelines advocate conservative therapy in LGEFCs with focal VI. There is therefore a need to assess the survival rates of LGEFC patients with various degrees of VI to better stratify patients for subsequent therapy. Furthermore, the prognostic effect of VI within the different histotypes of LGEFCs is not well known. A total of 276 patients with LGEFCs were subjected to a meticulous histopathologic analysis. They were classified as encapsulated papillary thyroid carcinoma, encapsulated Follicular carcinoma (EFC), and encapsulated Hurthle Cell carcinoma (EHCC). Of the 276 patients, 24 had extensive VI (EVI) (≥4 foci) and 28 displayed focal (<4 foci) VI. EHCC and EFC showed a much higher rate of EVI than encapsulated papillary thyroid carcinoma. Median follow-up was 6 years. All 14 tumors with adverse behavior harbored distant metastases (DMs), of which 9 had DMs at presentation. All 3 patients without EVI who had aggressive carcinomas harbored DMs at presentation. EVI was an independent predictor of poor recurrence-free survival. Excluding cases with DMs at presentation, only patients with EVI had recurrence, and all relapsed cases were EHCC. EVI is an independent predictor of recurrence-free survival in LGEFCs. EHCC with EVI has a particularly high risk of recurrence. When DMs are not found at presentation, patients with focal VI are at a very low risk of recurrence even if not treated with radioactive iodine.
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Encapsulated Thyroid Carcinoma of Follicular Cell Origin
Endocrine Pathology, 2015Co-Authors: Ronald GhosseinAbstract:Encapsulated carcinomas of Follicular Cell origin are subject to considerable controversies. This group includes an encapsulated/well-circumscribed (E/WC) Follicular variant of papillary carcinoma (FVPTC) and encapsulated Follicular and Hurthle Cell carcinoma (EFC, EHC respectively). FVPTC usually presents as an E/WC tumor and less commonly as an infiltrative neoplasm. E/WC FVPTC rarely metastasizes to lymph nodes, whereas infiltrative tumors often present with cervical nodal metastases. Many studies revealed FVPTC in general to be genetically close to the Follicular adenomas (FA)/EFC group of tumors. This is particularly true for the E/WC FVPTC which has a high rate of RAS and lack BRAF V600E mutations. Infiltrative FVPTC has an opposite molecular profile closer to classical papillary carcinoma than to FA/EFC ( BRAFV600E > RAS mutations). Noninvasive E/WC FVPTCs are extremely indolent even if treated with lobectomy alone. While EFC and EHC with capsular invasion only have an exCellent outcome, those with extensive (≥4 foci) lymphovascular invasion (LVI) have a significant rate of distant recurrence. The prognosis of those with focal LVI seems good, but more studies are needed to confirm their behavior. In EHC, those with extensive/significant LVI have a different RNA expression profile than those with less LVI. EHC appear to recur earlier, are less RAI avid, and have a different mutation profile than EFC. Noninvasive E/WC FVPTC should be treated conservatively. There is therefore a need to reclassify the E/WC FVPTC in order to prevent overtreatment. In view of their molecular and behavioral differences, EHC should not be considered a subset of EFC.
Edna Teruko Kimura - One of the best experts on this subject based on the ideXlab platform.
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Image_1_The Highly Expressed FAM83F Protein in Papillary Thyroid Cancer Exerts a Pro-Oncogenic Role in Thyroid Follicular Cells.TIF
2019Co-Authors: Cesar Seigi Fuziwara, Suzana Garcia Leoni, Kelly Cristina Saito, Ângela Flávia Logullo Waitzberg, Edna Teruko KimuraAbstract:Thyroid cancer is the most common endocrine cancer with predominant prevalence of papillary thyroid cancer (PTC) histotype. MAPK signaling genetic alterations are frequent in PTC, affecting more than 80% of cases. These alterations constitutively activate MAPK signaling cross-regulating different pro-oncogenic pathways. However, additional molecular alterations associated with thyroid cancer are not completely understood. In this extent, the new family of proteins named FAM83 (FAMily with sequence similarity 83) was recently identified as mediator of oncogenic signaling in different types of cancer. Here we report FAM83F as a novel highly expressed protein in PTC. We evaluated FAM83F levels in 106 PTC specimens, 34 goiter, and 41 adjacent non-tumoral human thyroid, and observed FAM83F cytoplasmic overexpression in 71% of PTC (76 of 106) while goiter tissues showed nuclear positivity and normal thyroid showed no staining by immunohistochemistry. Moreover, TSH-induced goiter and BRAFT1799A-induced PTC animal models also showed FAM83F activation. In vitro, we generated a stable thyroid Cell line PCCL3 with FAM83F overexpression and observed that FAM83F deregulates thyroid Follicular Cell biology leading to loss of thyroid differentiation genes such as Sodium-Iodide Symporter (NIS), reactivation of stem Cell markers such as LIN28B and SOX2, induction of Cell migration and resistance to doxorubicin-induced apoptosis. Moreover, FAM83F activates MAPK signaling through interaction with BRAF and RAF while impairs TGFβ antiproliferative signaling transduction. In this study, we showed FAM83F as a new pro-oncogenic protein overexpressed in thyroid cancer that modulates thyroid Follicular Cell biology and differentiation through cross-regulation of MAPK and TGFβ signaling.
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Table_1_The Highly Expressed FAM83F Protein in Papillary Thyroid Cancer Exerts a Pro-Oncogenic Role in Thyroid Follicular Cells.DOC
2019Co-Authors: Cesar Seigi Fuziwara, Suzana Garcia Leoni, Kelly Cristina Saito, Ângela Flávia Logullo Waitzberg, Edna Teruko KimuraAbstract:Thyroid cancer is the most common endocrine cancer with predominant prevalence of papillary thyroid cancer (PTC) histotype. MAPK signaling genetic alterations are frequent in PTC, affecting more than 80% of cases. These alterations constitutively activate MAPK signaling cross-regulating different pro-oncogenic pathways. However, additional molecular alterations associated with thyroid cancer are not completely understood. In this extent, the new family of proteins named FAM83 (FAMily with sequence similarity 83) was recently identified as mediator of oncogenic signaling in different types of cancer. Here we report FAM83F as a novel highly expressed protein in PTC. We evaluated FAM83F levels in 106 PTC specimens, 34 goiter, and 41 adjacent non-tumoral human thyroid, and observed FAM83F cytoplasmic overexpression in 71% of PTC (76 of 106) while goiter tissues showed nuclear positivity and normal thyroid showed no staining by immunohistochemistry. Moreover, TSH-induced goiter and BRAFT1799A-induced PTC animal models also showed FAM83F activation. In vitro, we generated a stable thyroid Cell line PCCL3 with FAM83F overexpression and observed that FAM83F deregulates thyroid Follicular Cell biology leading to loss of thyroid differentiation genes such as Sodium-Iodide Symporter (NIS), reactivation of stem Cell markers such as LIN28B and SOX2, induction of Cell migration and resistance to doxorubicin-induced apoptosis. Moreover, FAM83F activates MAPK signaling through interaction with BRAF and RAF while impairs TGFβ antiproliferative signaling transduction. In this study, we showed FAM83F as a new pro-oncogenic protein overexpressed in thyroid cancer that modulates thyroid Follicular Cell biology and differentiation through cross-regulation of MAPK and TGFβ signaling.
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The Highly Expressed FAM83F Protein in Papillary Thyroid Cancer Exerts a Pro-Oncogenic Role in Thyroid Follicular Cells
Frontiers Media S.A., 2019Co-Authors: Cesar Seigi Fuziwara, Suzana Garcia Leoni, Kelly Cristina Saito, Ângela Flávia Logullo Waitzberg, Edna Teruko KimuraAbstract:Thyroid cancer is the most common endocrine cancer with predominant prevalence of papillary thyroid cancer (PTC) histotype. MAPK signaling genetic alterations are frequent in PTC, affecting more than 80% of cases. These alterations constitutively activate MAPK signaling cross-regulating different pro-oncogenic pathways. However, additional molecular alterations associated with thyroid cancer are not completely understood. In this extent, the new family of proteins named FAM83 (FAMily with sequence similarity 83) was recently identified as mediator of oncogenic signaling in different types of cancer. Here we report FAM83F as a novel highly expressed protein in PTC. We evaluated FAM83F levels in 106 PTC specimens, 34 goiter, and 41 adjacent non-tumoral human thyroid, and observed FAM83F cytoplasmic overexpression in 71% of PTC (76 of 106) while goiter tissues showed nuclear positivity and normal thyroid showed no staining by immunohistochemistry. Moreover, TSH-induced goiter and BRAFT1799A-induced PTC animal models also showed FAM83F activation. In vitro, we generated a stable thyroid Cell line PCCL3 with FAM83F overexpression and observed that FAM83F deregulates thyroid Follicular Cell biology leading to loss of thyroid differentiation genes such as Sodium-Iodide Symporter (NIS), reactivation of stem Cell markers such as LIN28B and SOX2, induction of Cell migration and resistance to doxorubicin-induced apoptosis. Moreover, FAM83F activates MAPK signaling through interaction with BRAF and RAF while impairs TGFβ antiproliferative signaling transduction. In this study, we showed FAM83F as a new pro-oncogenic protein overexpressed in thyroid cancer that modulates thyroid Follicular Cell biology and differentiation through cross-regulation of MAPK and TGFβ signaling
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Differential gene expression analysis of iodide-treated rat thyroid Follicular Cell line PCCl3.
Genomics, 2008Co-Authors: Suzana Garcia Leoni, Julio C. Ricarte-filho, Pedro A F Galante, Edna Teruko KimuraAbstract:Abstract The inhibitory effect of supraphysiological iodide concentrations on thyroid hormone synthesis (Wolff–Chaikoff effect) and on thyrocyte proliferation is largely known as iodine autoregulation. However, the molecular mechanisms by which iodide modulates thyroid function remain unclear. In this paper, we analyze the transcriptome profile of the rat Follicular Cell lineage PCCl3 under untreated and treated conditions with 10 − 3 M sodium iodide (NaI). Serial analysis of gene expression (SAGE) revealed 84 transcripts differentially expressed in response to iodide ( p ≤ 0.001). We also showed that iodide excess inhibits the expression of essential genes for thyroid differentiation: Tshr , Nis , Tg , and Tpo. Relative expression of 14 of 20 transcripts selected by SAGE was confirmed by real-time PCR. Considering the key role of iodide organification in thyroid physiology, we also observed that both the oxidized form of iodide and iodide per se are responsible for gene expression modulation in response to iodide excess.
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Differential gene expression analysis of iodide-treated rat thyroid Follicular Cell line PCCl3.
Genomics, 2008Co-Authors: Suzana Garcia Leoni, Julio C. Ricarte-filho, Pedro A F Galante, Edna Teruko KimuraAbstract:The inhibitory effect of supraphysiological iodide concentrations on thyroid hormone synthesis (Wolff-Chaikoff effect) and on thyrocyte proliferation is largely known as iodine autoregulation. However, the molecular mechanisms by which iodide modulates thyroid function remain unclear. In this paper, we analyze the transcriptome profile of the rat Follicular Cell lineage PCCl3 under untreated and treated conditions with 10(-3) M sodium iodide (NaI). Serial analysis of gene expression (SAGE) revealed 84 transcripts differentially expressed in response to iodide (p
Giuditta Perozzi - One of the best experts on this subject based on the ideXlab platform.
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proteomic analysis of zn depletion repletion in the hormone secreting thyroid Follicular Cell line frtl 5
Nutrients, 2018Co-Authors: Barbara Guantario, Angela Capolupo, Maria Chiara Monti, Guido Leoni, Giulia Ranaldi, Alessandra Tosco, Liberato Marzullo, Chiara Murgia, Giuditta PerozziAbstract:Zinc deficiency predisposes to a wide spectrum of chronic diseases. The human Zn proteome was predicted to represent about 10% of the total human proteome, reflecting the broad array of metabolic functions in which this micronutrient is known to participate. In the thyroid, Zn was reported to regulate Cellular homeostasis, with a yet elusive mechanism. The Fischer Rat Thyroid Cell Line FRTL-5 Cell model, derived from a Fischer rat thyroid and displaying a Follicular Cell phenotype, was used to investigate a possible causal relationship between intraCellular Zn levels and thyroid function. A proteomic approach was applied to compare proteins expressed in Zn deficiency, obtained by treating Cells with the Zn-specific chelator N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylene-diamine (TPEN), with Zn repleted Cells. Quantitative proteomic analysis of whole Cell protein extracts was performed using stable isotope dimethyl labelling coupled to nano-ultra performance liquid chromatography-mass spectrometry (UPLC-MS). TPEN treatment led to almost undetectable intraCellular Zn, while decreasing thyroglobulin secretion. Subsequent addition of ZnSO4 fully reversed these phenotypes. Comparative proteomic analysis of Zn depleted/repleted Cells identified 108 proteins modulated by either treatment. Biological process enrichment analysis identified functions involved in calcium release and the regulation of translation as the most strongly regulated processes in Zn depleted Cells.
Michael R Tuttle - One of the best experts on this subject based on the ideXlab platform.
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time course and predictors of structural disease progression in pulmonary metastases arising from Follicular Cell derived thyroid cancer
Thyroid, 2016Co-Authors: Mona M Sabra, Ronald Ghossein, Michael R TuttleAbstract:Background: With the advent of molecular targeted therapy for the management of radioactive iodine (RAI) refractory, progressive metastatic thyroid cancer, it becomes important to define the time course and risk factors for structural disease progression in Follicular Cell–derived thyroid cancer (FCDTC) patients. This will help in defining the optimal time to start these therapies and better define their impact on structural disease progression. Objectives: This retrospective review of 199 consecutive patients with FCDTC presenting with lung metastasis examined the progression-free survival (PFS) in thyroid cancer patients with lung metastasis treated with surgery and RAI, and who had not received molecular targeted therapy or chemotherapy. Results: The median overall survival (OS) was 10.45 years, while the median PFS was 3.65 years. A strong correlation was found between OS and PFS. PFS is shorter in patients with RAI refractory disease, poorly differentiated/Hurthle Cell histologies, male sex, fluorode...
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pediatric differentiated thyroid carcinoma of Follicular Cell origin prognostic significance of histologic subtypes
Thyroid, 2016Co-Authors: Sadana Balachandar, Ronald Ghossein, Michael R Tuttle, Michael P La Quaglia, Glenn Heller, Charles A SklarAbstract:Background: Thyroid cancers are rare in the pediatric age group, and unlike in adults, few data are available regarding the clinical implication of histologic subtypes in the pediatric population. The purpose of the current study was to determine the prognostic significance of histologic subtypes of differentiated thyroid cancer (DTC) in a large series of children and adolescents followed at a single institution. Methods: A retrospective review was conducted of all pediatric DTC patients who were treated and followed between 1988 and 2012. Sixty-two patients (median age at diagnosis 13.8 years, median age at follow-up 18 years, 77% female) were assessed. The most common subtypes included classic papillary thyroid carcinoma (PTC; 48%), diffuse sclerosing PTC (16%), and Follicular variant PTC (15%); 37% were considered “high-risk” histologies based on adult criteria. Results: In a multivariate model, only extensive extrathyroidal extension (ETE), defined as the presence of two or more microscopic foci of tu...
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prognostic impact of extent of vascular invasion in low grade encapsulated Follicular Cell derived thyroid carcinomas a clinicopathologic study of 276 cases
Human Pathology, 2015Co-Authors: Laura Y Wang, Michael R Tuttle, Ian Ganly, Ronald GhosseinAbstract:Continuous controversy surrounds the predictive value of the degree of vascular invasion (VI) in low-grade encapsulated Follicular Cell-derived thyroid carcinomas (LGEFCs). Some guidelines advocate conservative therapy in LGEFCs with focal VI. There is therefore a need to assess the survival rates of LGEFC patients with various degrees of VI to better stratify patients for subsequent therapy. Furthermore, the prognostic effect of VI within the different histotypes of LGEFCs is not well known. A total of 276 patients with LGEFCs were subjected to a meticulous histopathologic analysis. They were classified as encapsulated papillary thyroid carcinoma, encapsulated Follicular carcinoma (EFC), and encapsulated Hurthle Cell carcinoma (EHCC). Of the 276 patients, 24 had extensive VI (EVI) (≥4 foci) and 28 displayed focal (<4 foci) VI. EHCC and EFC showed a much higher rate of EVI than encapsulated papillary thyroid carcinoma. Median follow-up was 6 years. All 14 tumors with adverse behavior harbored distant metastases (DMs), of which 9 had DMs at presentation. All 3 patients without EVI who had aggressive carcinomas harbored DMs at presentation. EVI was an independent predictor of poor recurrence-free survival. Excluding cases with DMs at presentation, only patients with EVI had recurrence, and all relapsed cases were EHCC. EVI is an independent predictor of recurrence-free survival in LGEFCs. EHCC with EVI has a particularly high risk of recurrence. When DMs are not found at presentation, patients with focal VI are at a very low risk of recurrence even if not treated with radioactive iodine.
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clinical outcomes following empiric radioiodine therapy in patients with structurally identifiable metastatic Follicular Cell derived thyroid carcinoma with negative diagnostic but positive post therapy 131i whole body scans
Thyroid, 2012Co-Authors: Mona M Sabra, Ravinder K Grewal, Hernan Tala, S Larson, Michael R TuttleAbstract:Background: While radioiodine (RAI) therapy remains the most effective treatment modality for RAI-avid distant metastatic Follicular Cell–derived thyroid cancer, the therapeutic utility of empiric RAI therapy in patients with structurally identifiable distant metastases that demonstrate RAI avidity only on the post-therapy scan (negative diagnostic whole-body scan [DxWBS]) remains uncertain. Methods: We report a retrospective assessment of the structural response to RAI therapy in 27 patients (median age 54 years, 59% male) with metastatic thyroid cancer (45% classical papillary thyroid cancer, 21% poorly differentiated, 15% tall-Cell variant, 15% Follicular variant, and 4% Hurthle Cell carcinoma) with structurally identifiable distant metastases (86% pulmonary metastases) in whom a properly conducted DxWBS was negative, and the post-therapy scan showed RAI-avid metastatic lesions at the time of RAI remnant ablation. Results: In response to the initial RAI ablation, none of the selected patients demonstra...