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V Lazar

Publications and source records attributed to V Lazar.

At least 19 recordsLinked to original sources

Analysis of interleukin-18, interleukin-1 converting enzyme (ICE) and interleukin-18-related cytokines in Crohn's disease lesions.

A local increase of interleukin-18 (IL-18) expression has been recently demonstrated in Crohn's disease (CD), suggesting a role for mature IL-18 (cleaved by ICE protease) in the induction of proinflammatory cytokines and Th1 polarization observed in CD lesions. The aim of this study was to investigate IL-18 modulation and its potential immune consequences in CD lesions. We showed increased IL-18 production in chronic CD lesions and identified epithelial cells and macrophages as IL-18-producing cells. A twofold increase in ICE alpha, beta, and/or gamma mRNA that encodes for the complete mature peptide was required for ICE activity, and a marked increase in IL-18R-positive immune cells was observed in chronic lesions compared to uninvolved areas or normal control samples. Chronic lesions also displayed intense transcription of IL-18-induced cytokines, IFN-gamma, IL-1beta, TNF-alpha, and IL-8. By contrast, when neither IL-18 nor ICE mRNAs were enhanced (early asymptomatic CD lesions), IL-18-induced cytokines were not up-regulated. These results are in accordance with a putative role of mature IL-18 in the pathogenesis of CD.

Base Sequence↗

Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome.

The thrombocytopenia and absent radii (TAR) syndrome is a rare disease associating bilateral radial agenesis and congenital thrombocytopenia. Here, we investigated in vitro megakaryocyte (MK) differentiation and expression of c-mpl in 6 patients. Using blood or marrow CD34(+) cells, the colony-forming unit (CFU)-MK number was markedly reduced. CD34(+) cells were also cultured in liquid medium in the presence of a combination of 3 cytokines (stem cell factor, interleukin-3, and interleukin-6) or megakaryocyte growth and development factor (PEG-rHuMGDF) with or without SCF. In the presence of PEG-rHuMGDF, the majority of mature megakaryocytes (CD41 high, CD42 high) underwent apoptosis. This phenomenon was also observed in cultures stimulated by three cytokines. However, this last combination of cytokines allowed a more complete terminal MK differentiation. Surprisingly, a homogeneous population of CD34(-)CD41(+)CD42(-) cells accumulated during the cultures. This population was unable to differentiate along the myeloid pathways. This result suggests that a fraction of MK cells is unable to differentiate in the TAR syndrome. We subsequently investigated whether this could be related to an abnormality in c-mpl. No mutation or rearrangement in the c-mpl gene was found by Southern blots or by sequencing of the c-mpl coding region and its promoter in any of the patients. Using Western blot analysis, a decreased level of Mpl was found in patient platelets. A decreased level of c-mpl messenger RNA in TAR platelets was also detected with a lower c-mpl-P to c-mpl-K ratio in comparison to adult platelets. Altogether, these results demonstrate that the thrombocytopenia of the TAR syndrome is associated with a dysmegakaryocytopoiesis characterized by cells blocked at an early stage of differentiation. (Blood. 2000;95:1633-1641)

Adolescent↗

Diabetic state induces lipid loading and altered expression and secretion of lipoprotein lipase in human monocyte-derived macrophages.

Non-insulin-dependent diabetes mellitus (NIDDM) is frequently associated with macroangiopathies and coronary heart diseases. Lipoprotein lipase (LPL), an enzyme known to undergo significant functional alterations in diabetic state, is also a potential atherogenic protein. Since, to the best of our knowledge, there are no data concerning LPL secreted by macrophages of NIDDM patients we conducted a study to assess the expression and activity of LPL secreted by monocyte-derived macrophages from NIDDM patients with cardiovascular complications versus cardiovascular patients without diabetes (controls). Isolated cells from NIDDM patients, after 7 days in culture in the presence of 20% autologous serum, readily exhibit a foam cell phenotype, in contrast to the cells from controls. Macrophages were mainly loaded with triglycerides, whose cellular amount was well correlated to triglyceridemia of NIDDM subjects. Concomitantly, macrophages from NIDDM patients displayed a approximately six-fold decrease of mRNA expression and a approximately two-fold reduction of the activity of secreted LPL, as compared to control cells. These data suggest that in complicated diabetic state, macrophage loading leading to foam cell formation is accelerated, at least in part, due to a diminished expression and activity of LPL. These observations add and extend the data that may explain the occurrence of accelerated atherogenesis and of the atherosclerotic complications associated with diabetes.

Adult↗

Expression of Na+/I- symporter and Pendred syndrome genes in trophoblast cells.

Placental iodide transport is critical for the fetal thyroid function, but the molecular mechanisms of this transport are not understood. The expression of two recently identified iodide transporters, namely the sodium/iodide symporter (NIS) and pendrin, the product of the gene responsible for the Pendred syndrome (PDS), was studied using real-time kinetic quantitative PCR and immunohistochemistry 1) in placental tissues collected at different gestational ages and 2) in primary cultures of villous cytotrophoblast cells (VCT) that differentiate and fuse over 2-3 days in vitro to form villous syncytiotrophoblast (VSCT) cells. Both NIS and PDS genes are expressed in placenta, albeit at low levels compared with those in thyroid tissue. NIS gene expression in placental samples from first trimester and term pregnancies was similar. In contrast, the expression of PDS gene was higher in term than in first trimester pregnancy samples. In vitro, NIS gene was expressed at a high level in VCT obtained from first trimester pregnancy, and its expression decreased by 3- to 4-fold during the differentiation of VCT in VSCT. Expression of NIS was lower (up to 30-fold) in VCT obtained in placental samples from third trimester than from first trimester pregnancy. In contrast, the expression of PDS gene was low in VCT and increased by 5- to 10-fold during VSCT formation; this was observed in cells isolated from placental samples of both first trimester and term pregnancies. Immunohistochemical analysis showed that NIS protein was present on the entire membrane of VCT, whereas pendrin was mainly located at the brush border membrane of VSCT, facing the mother. In conclusion, 1) NIS and PDS genes are differently expressed in the placenta during gestation; and 2) whereas pendrin is expressed at the brush border membrane of syncytiotrophoblast cells, NIS protein is mainly located in the cytotrophoblast layer.

Carrier Proteins↗

Expression of pendrin and the Pendred syndrome (PDS) gene in human thyroid tissues.

The gene recently cloned that is responsible for the Pendred syndrome (PDS), an autosomal recessive disease characterized by goiter and congenital sensorineural deafness, is mainly expressed in the thyroid gland. Its product, designated pendrin, was shown to transport chloride and iodide. To investigate whether the PDS gene is altered during thyroid tumorigenesis, PDS gene expression and pendrin expression were studied using real-time kinetic quantitative PCR and antipeptide antibodies, respectively, in normal, benign, and malignant human thyroid tissues. The results were then compared to those observed for sodium/iodide symporter (NIS) expression. In normal tissue, pendrin is localized at the apical pole of thyrocytes, and this in contrast to the basolateral location of NIS. Immunostaining for pendrin was heterogeneous both inside and among follicles. In hyperfunctioning adenomas, the PDS messenger ribonucleic acid level was in the normal range, although immunohistochemical analysis showed strong staining in the majority of follicular cells. In hypofunctioning adenomas, mean PDS gene expression was similar to that detected in normal thyroid tissues, but pendrin immunostaining was highly variable. In thyroid carcinomas, PDS gene expression was dramatically decreased, and pendrin immunostaining was low and was positive only in rare tumor cells. This expression profile was similar to that observed for the NIS gene and its protein product. In conclusion, our study demonstrates that pendrin is located at the apical membrane of thyrocytes and that PDS gene expression is decreased in thyroid carcinomas.

Adenoma↗

Trends in untreated caries in primary teeth of children 2 to 10 years old.

BACKGROUND: This article is the second in a series of three that focus on recent changes in the caries status of children and adolescents in the United States. METHODS: This study is based on analyses of data regarding untreated carious primary teeth among children 2 to 10 years of age from the first and third National Health and Nutrition Examination Surveys, or NHANES I and NHANES III. The NHANES is conducted periodically by the National Center for Health Statistics of the Centers for Disease Control and Prevention. RESULTS: Overall, the number of carious primary teeth among children 2 to 10 years old decreased from 1.42 as measured in NHANES I to 0.63 as measured in NHANES III. The number of carious primary teeth in children 2 to 10 years old also decreased across four demographic variables: age, sex, race and poverty level. CONCLUSIONS: The number of untreated carious primary teeth among children has declined. Since the 1970s, the absolute difference in untreated caries between disadvantaged children in the United States and the rest of the U.S. child population has narrowed, although not to the same extent as in permanent teeth. PRACTICE IMPLICATIONS: On average, children of preschool and elementary-school age have less untreated caries than in the past. More often, dentists do not need to treat on a first visit. This provides more opportunity to introduce these children to preventive dentistry at an early age.

Age Distribution↗

Trends in total caries experience: permanent and primary teeth.

BACKGROUND: This article is the last in a series of three that focuses on recent changes in the caries status of children aged 18 years or younger in the United States. METHODS: This study is based on analyses of data regarding total carious (treated and untreated) permanent and primary teeth among children 6 to 18 years old and children 2 to 10 years old from the first and third National Health and Nutrition Examination Surveys, or NHANES I and NHANES III. The NHANES is periodically conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. RESULTS: The cumulative number of carious permanent teeth, both treated and untreated, among 6- to 18-year-olds decreased 57.2 percent, from 4.44, as measured in NHANES I, to 1.90, as measured in NHANES III. The cumulative number of carious primary teeth, both treated and untreated, among 2- to 10-year-olds decreased 39.7 percent, from 2.29, as measured in NHANES I, to 1.38, as measured in NHANES III. CONCLUSIONS: Since the 1970s, the cumulative number of carious permanent and primary teeth, both treated and untreated, has declined substantially among children in the United States. PRACTICE IMPLICATIONS: Effective prevention has reduced caries in children. As a result, dental practice will be more focused on maintaining intact dentitions than on repairing teeth damaged by disease.

Adolescent↗

Thromboxane synthase has the same pattern of expression as platelet specific glycoproteins during human megakaryocyte differentiation.

Regulation of the platelet formation process is poorly understood. It has been shown that p45NF-E2 deficient mice have a profound defect in platelet formation and recently the first platelet/megakaryocytic gene regulated by NF-E2, thromboxane synthase (TXS), has been identified. In this study, we investigated TXS expression as a model of a gene regulated by NF-E2 during MK differentiation. Megakaryocytic cells derived from blood CD34+ cells were purified according to their stage of maturation on the basis of expression of CD34, CD41a and CD42a, permitting to define different stages in MK differentiation. By means of real-time quantitative RT-PCR, we could determine that the level of TXS increased during differentiation in parallel with the expression of c-mpl and GPIIb (CD41). However, amounts of TXS transcripts increased about 1.6-fold more than that of GPIIb or c-mpl transcripts during maturation. Expression of TXS and MK specific proteins such as CD41a, CD42a and vWF was also correlated in maturing MKs. In addition, staining by anti-TXS antibody of proplatelet bearing MKs was not increased in comparison to that observed in mature MK, suggesting that TXS is not upregulated during platelet formation. In addition, we investigated whether TXS and cyclooxygenase could be involved in platelet formation by adding aspirin into the cultures. No significant decrease of platelet production was observed. In conclusion, this study shows that TXS is coordinately expressed with the other platelet proteins during MK differentiation but is not directly involved in platelet formation.

Antigens, CD34↗

A single human myosin light chain kinase gene (MLCK; MYLK).

The myosin light chain kinase (MLCK) gene, a muscle member of the immunoglobulin gene superfamily, yields both smooth muscle and nonmuscle cell isoforms. Both isoforms are known to regulate contractile activity via calcium/calmodulin-dependent myosin light chain phosphorylation. We previously cloned from a human endothelial cell (EC) cDNA library a high-molecular-weight nonmuscle MLCK isoform (EC MLCK (MLCK 1) with an open reading frame that encodes a protein of 1914 amino acids. We now describe four novel nonmuscle MLCK isoforms (MLCK 2, 3a, 3b, and 4) that are the alternatively spliced variants of an mRNA precursor that is transcribed from a single human MLCK gene. The primary structure of the cDNA encoding the nonmuscle MLCK isoform 2 is identical to the previously published human nonmuscle MLCK (MLCK 1) (J. G. N. Garcia et al., 1997, Am. J. Respir. Cell Mol. Biol. 16, 489-494) except for a deletion of nucleotides 1428-1634 (D2). The full nucleotide sequence of MLCK isoforms 3a and 3b and partial sequence for MLCK isoform 4 revealed identity to MLCK 1 except for deletions at nucleotides 5081-5233 (MLCK 3a, D3), double deletions of nucleotides 1428-1634 and 5081-5233 (MLCK 3b), and nucleotide deletions 4534-4737 (MLCK 4, D4). Northern blot analysis demonstrated the extended expression pattern of the nonmuscle MLCK isoform(s) in both human adult and human fetal tissues. RT-PCR using primer pairs that were designed to detect specifically nonmuscle MLCK isoforms 2, 3, and 4 deletions (D2, D3, and D4) confirmed expression in both human adult and human fetal tissues (lung, liver, brain, and kidney) and in human endothelial cells (umbilical vein and dermal). Furthermore, relative quantitative expression studies demonstrated that the nonmuscle MLCK isoform 2 is the dominant splice variant expressed in human tissues and cells. Further analysis of the human MLCK gene revealed that the MLCK 2 isoform represents the deletion of an independent exon flanked by 5' and 3' neighboring introns of 0.6 and 7.0 kb, respectively. Together these studies demonstrate for the first time that the human MLCK gene yields multiple nonmuscle MLCK isoforms by alternative splicing of its transcribed mRNA precursor with differential distribution of these isoforms in various human tissues and cells.

Amino Acid Sequence↗

Screening for multiple endocrine neoplasia type 1 and hormonal production in apparently sporadic neuroendocrine tumors.

Screening was performed in 130 consecutive patients with apparently sporadic neuroendocrine tumors (NET) to assess the prevalence of multiple endocrine neoplasia type 1 (MEN1) and hormonal production. Screening for MEN1 included measurement of serum calcium and PTH [PTH-(1-84)], gastrin, PRL, and insulin-like growth factor type I (IGF-I) levels. MEN1 genetic testing was performed in patients with two components of the MEN1 syndrome. Screening for hormonal production included measurement of serum neuron-specific enolase (NSE), calcitonin (CT), glycoprotein alpha-subunit (GP alpha), hCG beta-subunit (free hCG beta), and somatostatin levels. Twenty-four-hour urinary free cortisol (UFC) and 5-hydroxyindolacetic acid (5-HIAA) determinations were also performed. Four patients had hyperparathyroidism, none of whom had pituitary or familial disease. Hyperprolactinemia was compatible with a pituitary disease in one patient. No acromegalic feature or any increase in IGF-I was found. Hypergastrinemia, compatible with an associated pancreatic NET, was found in one patient. Genetic screening of the MEN1 gene was performed in five of the six patients with two components of the MEN1 syndrome. A nonsense mutation (Arg108stop) was identified in the tumor of one patient. Elevated NSE, 5-HIAA, CT, GP alpha, free hCG beta, SMS, and nonsuppressible UFC were found in 47%, 46%, 14%, 19%, 12%, 3%, and 6% of NET patients, respectively. Production of CT, GP alpha, and free hCG beta was highly related to the primary site: all but two of these secretions originated in foregut NET. 5-HIAA secretion was found in 27% of foregut-derived and 85% of midgut-derived NET. In conclusion, MEN1 is a rare event in patients presenting with apparently sporadic NET. It occurred mainly in foregut NET and should be screened for by serum calcium and PTH-(1-84) measurements. Routine hormonal measurements should depend on the primary site. NSE, 5-HIAA, CT, and alphaGP should be routinely measured in foregut-derived NET; only serum NSE and 5-HIAA measurements are recommended in midgut-derived NET.

Adult↗

Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes.

The expression of 4 thyroid tissue-specific genes [Na+/I- symporter (NIS), thyroid peroxidase (TPO), thyroglobulin (Tg), TSH receptor (TSH-R)] as well as of the glucose transporter type 1 (Glut1) gene was analyzed in 90 human thyroid tissues Messenger ribonucleic acids were extracted from 43 thyroid carcinomas (38 papillary and 5 follicular), 24 cold adenomas, 5 Graves' thyroid tissues, 8 toxic adenomas, and 5 hyperplastic thyroid tissues; 5 normal thyroid tissues were used as reference. A kinetic quantitative PCR method, based on the fluorescent TaqMan methodology and real-time measurement of fluorescence, was used. NIS expression was decreased in 40 of 43 thyroid carcinomas (10- to 1200-fold) and in 20 of 24 cold adenomas (2- to 700-fold); it was increased in toxic adenomas and Graves' thyroid tissues (up to 140-fold). TPO expression was decreased in thyroid carcinomas, but was normal in cold adenomas; it was increased in toxic adenomas and Graves' thyroid tissues Tg expression was decreased in thyroid carcinomas, but was normal in the other tissues. TSH-R expression was normal in most tissues studied and was decreased in only some thyroid carcinomas. In thyroid cancer tissues, a positive relationship was found between the individual levels of expression of NIS, TPO, Tg and TSH-R. No relationship was found with the age of the patient. Higher tumor stages (stages >I vs stage I) were associated with lower expression of NIS (P = 0.03) and TPO (P < 0.01). Expression of the Glut1 gene was increased in 1 of 24 adenomas and in 8 of 43 thyroid carcinomas. In 6 thyroid carcinoma patients, 131I uptake was studied in vivo; NIS expression was low in all samples; 3 patients with normal Glut-1 gene expression had 131I uptake in metastases, whereas the other 3 patients with increased Glut-1 gene expression had no detectable 131I uptake. In conclusion, this study shows 1) a reduced expression of NIS gene in most hypofunctioning benign and malignant thyroid tumors; 2) a differential regulation of the expression of thyroid-specific genes; 3) an increased expression of Glut-1 gene in some malignant tumors that may suggest a role for glucose derivative tracers to detect in vivo thyroid cancer metastases by positron emission tomography scanning.

Adenocarcinoma, Follicular↗

Trends in untreated caries in permanent teeth of children 6 to 18 years old.

BACKGROUND: This article is the first in a series of three that focus on recent changes in the caries status of children and adolescents in the United States. METHODS: This study is based on analyses of data regarding untreated carious permanent teeth among children 6 to 18 years of age from the first and third National Health and Nutrition Examination Surveys, or NHANES I and NHANES III. The NHANES is periodically conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. RESULTS: Overall, the number of carious permanent teeth among children 6 to 18 years old decreased from 1.43, as measured in NHANES I, to 0.33, as measured in NHANES III. The number of carious permanent teeth in children 6 to 18 years old also decreased across four demographic variables: age, sex, race and poverty level. CONCLUSIONS: The number of untreated carious permanent teeth among children has declined dramatically. Since the 1970s, the absolute difference in untreated caries between disadvantaged children and the rest of the child population has narrowed substantially. PRACTICE IMPLICATIONS: The reduction in untreated caries, the major oral disease among children, has been dramatic in all subgroups of children. This may reinforce the already apparent shift from restorative to preventive dental services.

Adolescent↗

Trends in the dental health work force.

BACKGROUND AND OVERVIEW: Using data from various American Dental Association projects (Distribution of Dentists Survey, the Survey of Dental Practice, the Dental Workforce Model, and the Survey of Predoctoral Dental Educational Institutions), the authors analyzed trends and projections for the dental work force. The article presents work-force projections overall and by sex, when available, through the first 20 years of the 21st century. The number of women practicing dentistry has been increasing rapidly, while the increase in the number of male dentists has been more modest. In the future, the number of female dentists is projected to increase while the number of male dentists is projected to decrease. CONCLUSIONS: Estimates based on the ADA census data place the overall growth in the number of active private practitioners at 19.1 percent between 1982 and 1997. This growth signifies a substantial expansion of capacity to produce dental services in the United States. Growth will be slower in the future. PRACTICE IMPLICATIONS: Changes in the dental work-force capacity and demographic distributions merit careful monitoring and analysis, because they no doubt will determine the dental profession's future ability to deliver needed dental services and influence practitioners level of busyness.

Age Distribution↗

Trend analysis of dental practice rent and mortgage expenses: 1989-1995.

BACKGROUND: The authors analyzed trends for rent and mortgage, as reported by independent active private practitioners, for the period of 1989-1995. Rent and mortgage were analyzed overall and by different characteristics. METHODS: In the ADA's annual "Survey of Dental Practice," dentists reported gross billings and net incomes, as well as itemized practice expenses. The authors tabulated survey responses over time to develop trends and compare rent and mortgage expenses for each year. If trends over time were not exhibited, the authors combined multiple years of data to develop more reliable statistics. RESULTS: Approximately three-fourths of independent active private practitioners reported rent but no mortgage expenses. The percentages of practitioners who reported rent or mortgage was stable over time. The percentage reporting rent only as an expense increased with the number of dentists in the practice, the age of the reporting dentist and the number of office locations. In contrast, the opposite was true for dentists reporting mortgage only as an expense. CONCLUSIONS: The authors found that office rental is more common than is office ownership and that mortgages as a percentage of gross billings and in dollar amounts were similar to rents. They also found that because the cost of office space as a percentage of gross billings decreased as the number of dentists in the practice increased, limited economies of scale may be present in the cost of dental office space. PRACTICE IMPLICATIONS: There is not a large financial advantage to ownership, so renting is likely to remain an important way to acquire office space. As only limited economies of scale exist in office space expenses, many group practices may choose to rent office space.

Capital Expenditures↗

Dental care utilization: how saturated is the patient market?

BACKGROUND: Dental care utilization is the percentage of the population who access dental services over a specified period. In this article, the authors report on the results of several dental care utilization studies. METHODS: To date, dental utilization data have been gathered by large national studies via telephone interviews, face-to-face interviews or written surveys. In this article, the authors report on and compare dental care utilization rates provided by the Centers for Disease Control and Prevention, the National Center for Health Statistics, the Agency for Health Care Policy and Research and the American Dental Association. RESULTS: As captured by the various studies, the percentage of people who indicated they visited a dentist within the past year increased gradually between 1983 and 1997. The authors found that dental care utilization rates are higher among women than they are among men, and they decrease with age and increase with income and educational level. CONCLUSIONS: Although the available data vary, they suggest that more Americans are visiting a dentist. The demand for dental care is increasing overall, as well as across educational, racial and economic lines. PRACTICE IMPLICATIONS: If, as recent studies suggest, approximately 75 percent of the population visits a dentist annually, there is only modest room for further expansion of dental care utilization. However, if dental care utilization rates are substantially lower as reported in older studies, then there is a greater potential for increased dental care utilization.

Adult↗

Retirement savings of dentists in private practice.

BACKGROUND: Retirement planning is an issue that concerns all working people. In this article, the authors present their analysis of the results of a 1995 American Dental Association survey that asked dentists questions about their plans to finance their retirement. METHODS: The ADA's Survey Center conducts a periodic "Survey of Current Issues in Dentistry," which gauges dentists' opinions about a variety of topics of interest to dentistry. The authors analyzed the results of the 1995 survey in which retirement savings was one of the topics. RESULTS: The majority of responding owner/dentists whose primary occupation was private practice (40.7 percent) indicated that they were relying only "a little" on the sales of their practices to finance their retirements. Overall, dentists whose primary occupation was private practice reported saving an average of 10.5 percent of their income specifically for retirement. The average total amount of money dentists invested in various retirement plans increased with age and was highest for the 55 to 59 and the 60 to 64 years of age cohorts. The only exception was the 401(k) plan, in which the peak occurred in the 65 years of age and older cohort. CONCLUSIONS: Fifteen years ago most dentists retired between the ages of 60 and 69 years. Recent trends show that dentists are retiring at younger ages. This means that while in practice, dentists must save enough to support themselves for 20 or more years of retirement. PRACTICE IMPLICATIONS: The transition from private practice to retirement can be difficult. Therefore, planning for the future is important. Dentists can benefit from making appropriate decisions based on age, investment goals, risk tolerance, monetary constraints and time until retirement.

Adult↗

Gastroenteropancreatic neuroendocrine tumor metastases to the thyroid gland: differential diagnosis with medullary thyroid carcinoma.

Neuroendocrine tumors (NET) of the thyroid gland are rare. Apart from medullary thyroid carcinoma (MTC), metastases of gastroenteropancreatic (GEP) NET may also occur. Features of six patients (five men, one female: age range, 39-67 years) with thyroid metastases from a GEP-NET are described. Thyroid metastases were bilateral in all patients and were associated with enlarged neck lymph nodes in five. In four cases, the thyroid tumor was either the first sign of the disease (n = 2) or was an isolated site of recurrence (n = 2). The tumors were well (n = 3) or poorly differentiated (n = 3). Five tumors for which the primary site could be determined corresponded to foregut-derived tumors (3 lungs, 1 thymus and 1 pancreatic NET). One tumor demonstrated calcitonin (CT) production as shown by immunohistochemistry and elevated plasma CT levels. However, the disease history and the clinical features strongly favored a metastasizing GEP-NET. No tumoral RET proto-oncogene mutation was found in this patient. The differential diagnosis between metastatic GEP-NET and MTC is crucial because prognosis, work-up, and treatment differ greatly.

Adult↗