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
Programmed cell death ligand (PD-L1)/PD-1 expression has been studied in a variety of cancers and blockage of PD-L1/PD-1 pathway is a cornerstone of immunotherapy. We studied PD-L1/PD-1 immunohistochemical expression in 47 thyroid gland specimens in groups of (1) Hashimoto thyroiditis (HT) only; (2) HT and follicular epithelial dysplasia (FED); and (3) HT, FED, and papillary thyroid carcinoma (PTC). PD-1 positivity was found in immune cells, namely in lymphocytes, macrophages, and plasma cells with mean values for lymphocytes and macrophages 9% in HT group, 4% in FED group, and 4% in PTC group. PD-L1 positivity was identified in both immune cells and in the normal epithelial cells. In the HT group, mean PD-L1 staining on immune cells was 6%, in FED group 5%, and in PTC group 7%. The mean PD-L1 staining on the epithelial cells in the inflammatory parenchyma was 11.7% in HT, 13.4% in FED, and 8.3% in PTC group. The mean PD-L1 staining of FED foci was 47.2% in FED group and 33.6% in PTC group. The mean tumor proportion score (TPS) was 10.4%, and the mean combined positive score (CPS) was 15.5. At the moment, PTC is not a target of immunotherapy. However, understanding the complex issue of concurrent inflammation and autoimmunity can importantly influence the cancer treatment in future.
Background: Pediatric papillary thyroid carcinoma (PTC) is a rare malignancy, but with increasing incidence. Pediatric PTCs have distinct clinical and pathological features and even the molecular profile differs from adult PTCs. Somatic point mutations in pediatric PTCs have been previously described and studied, but complex information about fusion genes is lacking. The aim of this study was to identify different fusion genes in a large cohort of pediatric PTCs and to correlate them with clinical and pathological data of patients. Methods: The cohort consisted of 93 pediatric PTC patients (6-20 years old). DNA and RNA were extracted from fresh frozen tissue samples, followed by DNA and RNA-targeted next-generation sequencing analyses. Fusion gene-positive samples were verified by real-time polymerase chain reaction. Results: A genetic alteration was found in 72/93 (77.4%) pediatric PTC cases. In 52/93 (55.9%) pediatric PTC patients, a fusion gene was detected. Twenty different types of RET, NTRK3, ALK, NTRK1, BRAF, and MET fusions were found, of which five novel, TPR/RET, IKBKG/RET, BBIP1/RET, OPTN/BRAF, and EML4/MET, rearrangements were identified and a CUL1/BRAF rearrangement that has not been previously described in thyroid cancer. Fusion gene-positive PTCs were significantly associated with the mixture of classical and follicular variants of PTC, extrathyroidal extension, higher T classification, lymph node and distant metastases, chronic lymphocytic thyroiditis, and frequent occurrence of psammoma bodies compared with fusion gene-negative PTCs. Fusion-positive patients also received more doses of radioiodine therapy. The most common fusion genes were the RET fusions, followed by NTRK3 fusions. RET fusions were associated with more frequent lymph node and distant metastases and psammoma bodies, and NTRK3 fusions were associated with the follicular variant of PTC. Conclusions: Fusion genes were the most common genetic alterations in pediatric PTCs. Fusion gene-positive PTCs were associated with more aggressive disease than fusion gene-negative PTCs.
- MeSH
- bodová mutace MeSH
- dítě MeSH
- fenotyp MeSH
- fúze genů * MeSH
- genetická predispozice k nemoci MeSH
- genová přestavba MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádorové biomarkery genetika MeSH
- nádory štítné žlázy genetika patologie terapie MeSH
- papilární karcinom štítné žlázy genetika patologie terapie MeSH
- prognóza MeSH
- protoonkogenní proteiny B-raf genetika MeSH
- protoonkogenní proteiny c-met genetika MeSH
- protoonkogenní proteiny c-ret genetika MeSH
- receptor trkA genetika MeSH
- receptor trkC genetika MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The rising incidence of thyroid cancer observed in the last few decades requires an improvement in diagnostic tools and management techniques for patients with thyroid nodules. AIMS: The aim of this study was to assess serum concentrations of IGF-1 and IGF-1R in patients diagnosed with thyroid cancers. METHODS: 36 patients diagnosed with papillary thyroid cancer (PTC), 11 subjects with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and 19 subjects with multinodular nontoxic goiter (MNG) were enrolled to the study. The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum IGF-1 and IGF-1R concentrations were measured using specific ELISA methods. RESULTS: Significantly higher concentrations of IGF-1 were found in patients with PTC as compared with controls but not that obtained from subjects diagnosed with MNG. The concentration of IGF-1R was significantly elevated in subjects with PTC and ATC as compared with healthy volunteers. Similarly, patients diagnosed with PTC or ATC presented significantly higher serum concentration of IGF-1R in comparison to the MNG group. CONCLUSIONS: Our results show that the IGF-1 - IGF-1R axis plays a significant role in the development of PTC and ATC and imply that serum concentrations of both cytokines may be considered as additional markers for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors. These results indicate that IGF-1R serum concentrations allow us to differentiate between MNG and PTC or ATC. Moreover IGF-1R serum values appear to be better predictor of PTC and ATC than IGF-1 concentrations.
- MeSH
- dospělí MeSH
- folikulární adenokarcinom krev patologie MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádory štítné žlázy krev patologie MeSH
- papilární karcinom štítné žlázy krev patologie MeSH
- receptor IGF typ 1 krev MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- uzlová struma krev patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Papillary thyroid carcinoma with desmoid-type fibromatosis or nodular fasciitis-like stroma is an extremely unusual and poorly understood subtype of papillary thyroid cancer. Although prior studies have demonstrated alterations in the Wnt/β-catenin signaling pathway in some of these tumors, controversy still exists regarding the nature of the stromal spindle component. We have studied seven cases of papillary thyroid carcinoma with prominent myofibroblastic stroma, including six men and one woman aged 20-65 years (mean age = 44). All cases displayed areas consistent with conventional papillary thyroid carcinoma embedded in abundant myofibroblastic-like stroma. The myofibroblastic stroma in six cases resembled desmoid-type fibromatosis and in one case it more closely resembled nodular fasciitis. By immunohistochemical staining, the stromal spindle component showed positivity for SMA and low MIB1 proliferation index in all cases, and there was at least patchy strong nuclear positivity for beta-catenin in six/seven cases. Stains for cytokeratin AE1/AE3 and PAX8 were positive in the epithelial elements but negative in the stromal component. Next-generation sequencing was performed on six of seven cases. CTNNB1 gene mutations were identified in six/seven cases. The epithelial component showed BRAF mutations in two cases and an NRAS mutation in one case. The case with fasciitis-like stroma was negative for beta-catenin by sequencing and immunostaining as well as negative for USP6 gene rearrangement. Our findings indicate that papillary thyroid carcinoma with prominent myofibroblastic stroma may represent more than one category of lesions.
- MeSH
- beta-katenin genetika metabolismus MeSH
- buňky stromatu metabolismus patologie MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutace MeSH
- myofibroblasty metabolismus patologie MeSH
- nádorové biomarkery metabolismus MeSH
- nádory štítné žlázy genetika metabolismus patologie MeSH
- papilární karcinom štítné žlázy genetika metabolismus patologie MeSH
- protoonkogenní proteiny B-raf genetika metabolismus MeSH
- senioři MeSH
- štítná žláza metabolismus patologie MeSH
- transkripční faktor PAX8 genetika metabolismus MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Předložená kazuistika se zaměřuje na problematiku diagnostiky a léčby uzlových změn ve štítné žláze. Cílem sdělení je zdůraznit význam molekulárně-genetického vyšetření punktátu ze sonograficky suspektního uzlu štítné žlázy.
The presented case report focuses on the issue of diagnosis and treatment of nodular changes in the thyroid gland. The aim of the article is to emphasize the importance of molecular-genetic examination of a puncture sample from a sonographically suspicious thyroidnode.
- MeSH
- diagnostické techniky molekulární metody MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory štítné žlázy diagnostické zobrazování patologie MeSH
- papilární karcinom štítné žlázy * genetika patologie MeSH
- radioizotopy jodu terapeutické užití MeSH
- tenkojehlová biopsie MeSH
- tyreoidektomie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Aberantní laterární tkáň štítné žlázy se může vyskytovat prakticky kdekoliv v oblastiod kořene jazyka po mediastinum. V práci prezentujeme případ mladého muže s kla-sickou, a tedy maligní formou.
Aberrant lateral thyroid tissue may occur practically anywhere from base of the tongueto the mediastinum. We present a case of a young male with a classic and thereforemalignant form.
- MeSH
- dysgeneze štítné žlázy diagnostické zobrazování patologie MeSH
- lidé MeSH
- metastázy nádorů diagnostické zobrazování patologie MeSH
- mladý dospělý MeSH
- nádory štítné žlázy * MeSH
- papilární karcinom štítné žlázy chirurgie diagnostické zobrazování patologie radioterapie MeSH
- radioizotopy jodu terapeutické užití MeSH
- tyreoidektomie MeSH
- ultrasonografie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
