CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.
- MeSH
- buněčné jádro patologie MeSH
- folikulární adenokarcinom * patologie epidemiologie diagnóza MeSH
- lékařská praxe - způsoby provádění statistika a číselné údaje MeSH
- lidé MeSH
- nádory štítné žlázy * epidemiologie patologie diagnóza MeSH
- papilární karcinom štítné žlázy epidemiologie patologie diagnóza MeSH
- papilární karcinom patologie epidemiologie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Asie MeSH
- Evropa MeSH
- Oceánie MeSH
- Severní Amerika MeSH
Background: Recent studies have suggested that pathogenic variants of the DICER1 gene could be a driver of alterations in some pediatric thyroid nodules, but data are still limited. The aim of this study was to detect variants in the DICER1 gene in a large cohort of pediatric thyroid nodules and then correlate them with clinicopathological data, with a focus on the disease prognosis in patients with thyroid carcinoma. Methods: This retrospective cohort study consisted of 350 pediatric and young adult patients (aged 2-21 years) with thyroid nodules, from whom 275 fresh-frozen thyroid nodule samples and 92 fine-needle aspiration biopsy (FNAB) samples were collected. After an analysis of variants in major genetic alterations of thyroid tumors, variants in the DICER1 gene were identified using next-generation sequencing and multiplex ligation-dependent probe amplification methods. Peripheral blood was analyzed from patients with DICER1-positive tumors. The results of genetic analysis were then correlated with clinicopathological data. Results: Variants in the DICER1 gene were detected in a total of 24/350 (6.9%; 95%CI [4.4;10.0]) pediatric and young adult patients, respectively, in 10/119 (8.4%; [4.1;14.9]) patients with benign fresh-frozen tissue, in 8/141 (5.7%; [1.9;9.5]) with papillary thyroid carcinoma (PTC) and in 6/86 (7.0%; [4.1;14.6]) patients with FNAB. No other gene alteration was found in DICER1-positive samples. Germline DICER1 variants were identified in 11/24 (45.8%; [25.6;67.2]) patients. Two somatic (biallelic) variants in the DICER1 gene were found in 9/24 (37.5%; [18.8;59.4]) thyroid nodules. Somatic deletions of at least 3 Mbp long were revealed in 2/24 (8.3%; [1.0;27.0]) cases. DICER1-positive PTCs were significantly associated with the follicular subtype of PTC (p = 0.001), encapsulation (p = 0.006) and were larger in size (p = 0.035), but with no extrathyroidal extension (p = 0.039), and less frequent lymph node metastases (p = 0.003) compared with DICER1-negative PTCs. Patients with DICER1-positive PTC had an excellent response to treatment in 75% of cases. Conclusions: Variants of the DICER1 gene are frequently found in the thyroid nodules of pediatric and young adult patients. In our patients, DICER1-positive PTCs showed low invasiveness. Our findings support considering more conservative management for DICER1-positive low-risk PTCs.
- MeSH
- DEAD-box RNA-helikasy * genetika MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory štítné žlázy * genetika patologie MeSH
- papilární karcinom štítné žlázy genetika patologie MeSH
- předškolní dítě MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- ribonukleasa III * genetika MeSH
- tenkojehlová biopsie MeSH
- uzle štítné žlázy * genetika patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy * genetika patologie MeSH
- mikro RNA * genetika MeSH
- mutace * MeSH
- nádorové biomarkery genetika MeSH
- nádory štítné žlázy * genetika patologie MeSH
- papilární karcinom štítné žlázy * genetika patologie MeSH
- protoonkogenní proteiny B-Raf * genetika MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Thyroid cancer is associated with a broad range of different mutations, including RET (rearranged during transfection) fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients. Samples were analyzed for known driver mutations occurring in thyroid cancer. Negative samples were subjected to extensive RET fusion gene analyses using next-generation sequencing and real-time PCR. RET fusion genes were not detected in any low-risk neoplasm or benign thyroid tissue and were detected only in papillary thyroid carcinomas (PTCs), in 113/993 (11.4%) patients, three times more frequently in pediatric and adolescent patients (29.8%) than in adult patients (8.7%). A total of 20 types of RET fusions were identified. RET fusion-positive carcinomas were associated with aggressive tumor behavior, including high rates of lymph node (75.2%) and distant metastases (18.6%), significantly higher than in NTRK fusion, BRAF V600E and RAS-positive carcinomas. Local and distant metastases were also frequently found in patients with microcarcinomas positive for the RET fusions. 'True recurrences' occurred rarely (2.4%) and only in adult patients. The 2-, 5-, 10-year disease-specific survival rates were 99%, 96%, and 95%, respectively. RET fusion-positive carcinomas were associated with high invasiveness and metastatic activity, but probably due to intensive treatment with low patient mortality.
- MeSH
- dítě MeSH
- dospělí MeSH
- karcinom * MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- nádory štítné žlázy * genetika patologie MeSH
- papilární karcinom štítné žlázy MeSH
- prognóza MeSH
- protoonkogenní proteiny B-raf genetika MeSH
- protoonkogenní proteiny c-ret genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- autoimunitní tyreoiditida diagnóza farmakoterapie MeSH
- diagnostické zobrazování MeSH
- jehlová biopsie metody MeSH
- lidé MeSH
- lymfatické metastázy terapie MeSH
- mladiství MeSH
- papilární karcinom štítné žlázy * chirurgie diagnóza terapie MeSH
- radioizotopy jodu terapeutické užití MeSH
- struma etiologie MeSH
- těhotenství MeSH
- thyroxin aplikace a dávkování terapeutické užití MeSH
- tyreoidektomie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: A low-risk thyroid tumour, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced in 2016. NIFTP criteria require a thorough histological examination to rule out capsular and lymphovascular invasion, which denies the possibility of preoperative cytological diagnosis. Nevertheless, since the adoption of the new entity, the cytology of NIFTP has been a subject of interest. OBJECTIVES: The present systematic review and meta-analysis investigate the cytological diagnosis of NIFTP. METHOD: An online PubMed literature search was conducted between March 1, 2020, and June 30, 2020, for all original articles considering the cytology of histologically proven NIFTP. The studies including data on fine needle aspiration specimens classified by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) categories, risk of malignancy (ROMs) in the TBSRTC categories, and cytomorphological features of NIFTP were included in the meta-analysis. Non-English studies and case reports were excluded. The data were tabulated and statistical analysis was performed with Open Meta-Analyst program. RESULTS: Fifty-eight studies with a total of 2,553 NIFTP cases were included in the study. The pooled prevalence of NIFTP cases was calculated among 25,892 surgically resected cases from 20 studies and the results show that NIFTP consisted 4.4% (95% confidence interval [CI]: 3.5-5.4%) of all cases. Most of the NIFTP cases (79.0%) belonged to the intermediate categories of TBSRTC. The pooled distribution of NIFTP cases in each TBSRTC category was 1.3% (95% CI: 0.8-1.7%) in non-diagnostic (ND), 8.9% (95% CI: 6.9-10.8%) in benign, 29.2% (95% CI: 25.0-33.4%) in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 24.2% (95% CI: 19.6-28.9%) in follicular neoplasm (FN), 19.5% (95% CI: 16.1-22.9%) in suspicious for malignancy (SM), and 6.9% (95% CI: 5.2-8.7%) in malignant. Compared to pre-NIFTP era, the pooled risk differences of ROM were reduced by 2.4% in ND, 2.7% in benign, 8.2% in AUS/FLUS, 8.2% in FN, 7.3% in SM, and 1.1% in the malignant category. The cytomorphological features of NIFTP were similar to follicular variant of papillary thyroid carcinoma (FVPTC) but lesser to papillary thyroid carcinoma (PTC). CONCLUSIONS: Based on our results, NIFTP remains a histological diagnosis. Although cytomorphological features cannot be used in differentiating NIFTP from FVPTC, they may guide in separating NIFTP from PTC. Features such as papillae, microfollicles, giant cells, psammoma bodies, and the amount of papillary-like nuclear features should be taken into account when suspicious of NIFTP. NIFTP should not have papillae or psammoma bodies, and giant cells were rarely observed.
- Klíčová slova
- lenvatinib,
- MeSH
- antitumorózní látky aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- chinoliny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- doba přežití bez progrese choroby MeSH
- fenylmočovinové sloučeniny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- gastrointestinální nemoci MeSH
- hmotnostní úbytek MeSH
- lidé MeSH
- nenasazení léčby MeSH
- nežádoucí účinky léčiv MeSH
- papilární karcinom štítné žlázy * farmakoterapie komplikace patologie MeSH
- trombocytopenie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Cancer cells hijack developmental growth mechanisms but whether tissue morphogenesis and architecture modify tumorigenesis is unknown. Here, we characterized a new mouse model of sporadic thyroid carcinogenesis based on inducible expression of BRAF carrying a Val600 Glu (V600E) point mutation (BRAFV600E) from the thyroglobulin promoter (TgCreERT2). Spontaneous activation of this Braf-mutant allele due to leaky activity of the Cre recombinase revealed that intrinsic properties of thyroid follicles determined BRAF-mutant cell fate. Papillary thyroid carcinomas developed multicentrically within a normal microenvironment. Each tumor originated from a single follicle that provided a confined space for growth of a distinct tumor phenotype. Lineage tracing revealed oligoclonal tumor development in infancy and early selection of BRAFV600E kinase inhibitor-resistant clones. Somatic mutations were few, non-recurrent and limited to advanced tumors. Female mice developed larger tumors than males, reproducing the gender difference of human thyroid cancer. These data indicate that BRAFV600E-induced tumorigenesis is spatiotemporally regulated depending on the maturity and heterogeneity of follicles. Moreover, thyroid tissue organization seems to determine whether a BRAF-mutant lineage becomes a cancerized lineage. The TgCreERT2;BrafCA/+ sporadic thyroid cancer mouse model provides a new tool to evaluate drug therapy at different stages of tumor evolution.
- MeSH
- antitumorózní látky * MeSH
- bodová mutace MeSH
- inhibitory proteinkinas farmakologie MeSH
- mutace genetika MeSH
- myši MeSH
- nádorové mikroprostředí MeSH
- nádory štítné žlázy * genetika metabolismus patologie MeSH
- papilární karcinom štítné žlázy genetika patologie MeSH
- protoonkogenní proteiny B-raf genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
V kazuistice popisujeme případ 51-leté pacientky, která podstoupila totalizaci thyreoidektomie – resekci pravého laloku štítné žlázy pro růstovou progresi největšího uzlu. Z dominantního uzlu byla provedena aspirační biopsie tenkou jehlou (FNAB), která byla suspektní z malignity. V resekátu popsaný uzel odpovídal solidní, šedobělavé afekci, mikroskopicky s neobvyklou morfologií a imunoprofilem. Nález svědčil pro vzácný podtyp karcinomu štítné žlázy, tzv. kribriformně – morulární tyreoidální karcinom (CMTC). Nádor se většinou chová indolentně, je asociován s dobrou prognózou. Může se vyskytovat familiárně i sporadicky, převážně jako solitární léze, nebo multifokálně, často ve spojitosti s autozomálně dominantním syndromem familiární adenomatózní polypózy (FAP), proto je nutno při této diagnóze na něj cíleně poukázat. U pacientky byl vyloučen syndrom familiární polypózy, mutace genu APC byla somatická.
We present a case report of a 51-year-old patient who underwent totalization of thyroidectomy – resection of the right thyroid lobe for growth progression of the largest nodule from which a fine needle aspiration biopsy (FNAB) was performed and was cytologically suspected of malignancy. Nodule was a graywhite colored tumor with a solid structure, histologically with an unusual morphology and immunoprofile, called cribriform morular thyroid carcinoma (CMTC). Usually, the tumor behaves indolently with a good prognosis. CMTC can be familial or sporadic, predominantly as a solitary or a multifocal lesion, often associated with autosomal dominant adenomatous polyposis syndrome (FAP), so it is necessary to point this out in the report. The syndrome of familial adenomatous polyposis was ruled out, the APC gene mutation was somatic.
- Klíčová slova
- kribriformně-morulární tyreoidální karcinom,
- MeSH
- diferenciální diagnóza MeSH
- familiární adenomatózní polypóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- papilární karcinom štítné žlázy * chirurgie diagnóza genetika MeSH
- štítná žláza anatomie a histologie chirurgie patologie MeSH
- tyreoidektomie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Paraneoplastické projevy u dobře diferencovaných karcinomů štítné žlázy nejsou časté, ale mohou být prvním signálem nádorového onemocnění. Prezentujeme případ muže s mikropapilárním karcinomem štítné žlázy, u něhož byl zjištěn Raynaudův fenomén v oblasti prstů dolních končetin. Klinické příznaky Raynaudova jevu s ulcerací a gangrénou prstů obou dolních končetin se objevily v době náhle zjištěné hypotyreózy a několik měsíců před stanovením diagnózy papilárního mikrokarcinomu štítné žlázy. Byly zvýšeny sérové protilátky proti peroxidáze i protilátky proti tyreoglobulinu. Základní revmatologický screening byl negativní. Předoperační ultrazvuk štítné žlázy zobrazil atrofickou tkáň s nodulární strukturou. Vazospastické komplikace se nezlepšily navzdory hormonální substituční terapii, ale vymizely po léčbě, která zahrnovala totální tyreoidektomii a aplikaci radioaktivního jódu 131I. Pro tuto zjevnou souvislost Raynaudova fenoménu s karcinomem štítné žlázy, byl označen jako paraneoplastický. Podezření, že se jedná o paraneoplastický syndrom, lze vyslovit na základě určitých anamnestických a klinických rysů, ale definitivní diagnózu lze stanovit až po rozpoznání nádoru. Mezi nejdůležitější známky paraneoplazie patří pozdní manifestace příznaků po 50. roce s akutním začátkem, rychlou progresí a atypickým vývojem.
Paraneoplastic manifestations of well-differentiated thyroid carcinoma are not common but they can be the first cancer sign. We present a case of a man with Raynaud's phenomenon in the area of the lower limb fingers. Clinical signs of Raynaud's phenomenon with ulceration and gangrene of fingers of both lower limbs appeared at the time of suddenly discovered hypothyreosis and several months before the diagnosis of papillary thyroid microcarcinoma. Both serum thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. The primary rheumatologic screening was negative. Preoperative ultrasound showed a nodular structure in the atrophic thyroid gland. Vasospastic complications did not improve despite hormone replacement therapy, but they disappeared after treatment which included total thyroidectomy and application of radioactive iodine 131I. Raynaud's phenomenon was marked as paraneoplastic for obvious connection with thyroid carcinoma. Suspicion of the paraneoplastic syn- drome can be pronounced based on certain anamnestic and clinical features. However, a definitive diagnosis can be determined after recognition of a tumor. A late manifestation of symptoms after the 50th year of life with acute onset, rapid progression and atypical development belongs to the most significant traces of paraneoplasia.
- MeSH
- biopsie MeSH
- hypotyreóza farmakoterapie MeSH
- klinické laboratorní techniky metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- papilární karcinom štítné žlázy chirurgie komplikace radioterapie MeSH
- Raynaudova nemoc * etiologie farmakoterapie MeSH
- tyreoidektomie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
