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
Autori prezentujú kazuistiku 38-ročnej pacientky, ktorá prichádza na kliniku otorinolaryngológie a chirurgie hlavy a krku v Ružomberku pre 18 mesiacov trvajúce vertigo, pravostranný tinitus, percepčnú poruchu sluchu a parézu tvárového nervu. Bol diagnostikovaný tumor spánkovej kosti o veľkosti 8 mm lokalizovaný v oblasti laterálneho, zadného polkruhovitého kanálika a vestibula, ktorý bol peroperačne identifikovaný ako extrémne vzácny low-grade agresívny adenokarcinóm saccus endolymphaticus. V kazuistike autori rozoberajú anatómiu, diagnostiku, CT a MR snímky, zvolený operačný postup, následnú dispenzarizáciu pacientky a prehľad príslušnej literatúry.
The authors present a case report of a 38-year-old female patient admitted at the Department of Otorhinolaryngology and Head and Neck Surgery in Ružomberok with an 18-month history of vertigo, right-sided tinnitus, sensorineural hearing loss and facial nerve paresis. The patient was diagnosed with an 8 mm temporal bone tumor, located in the area of the lateral posterior semicircular canal and vestibule, which was intraoperatively identified as an extremely rare aggressive low-grade adenocarcinoma of the endolymphatic sac. In the case report, the authors discuss the anatomy, diagnosis, CT and MRI images, the chosen surgical procedure and the subsequent dispensarization of the patient as well as an overview of the relevant literature.
- MeSH
- dospělí MeSH
- lidé MeSH
- papilární adenokarcinom * chirurgie diagnóza MeSH
- saccus endolymphaticus chirurgie patologie MeSH
- spánková kost chirurgie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské 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
Previous studies suggest that there may be an association between cancer and autoimmune diseases. We describe the case of a 59-year-old patient who did not have any significant diseases in the last year. She had new onset of fever of unknown aetiology, headache, fatigue and night sweats. We used laboratory methods to rule out infectious diseases. Significant laboratory findings reported increased signs of inflammation and anti-nuclear antibody (ANA) positivity. Positron emission tomography/computed tomography (PET/CT) imaging showed the origin of the patient's difficulties, arteritis, with increased metabolic activity in the aortic wall and other arteries. Doppler ultrasonography of the arteries did not show pathology in the temporal arteries but found accelerated blood flow in the superior mesenteric artery (AMS). Another finding from PET/CT was a tumour in the thyroid gland, later verified histologically as papillary thyroid carcinoma (PTC). We investigated the link between rheumatological disease and papillary carcinoma, applying similar therapy, corticosteroids and immunosuppressants.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory štítné žlázy * komplikace patologie MeSH
- obrovskobuněčná arteritida * komplikace diagnóza MeSH
- papilární karcinom štítné žlázy MeSH
- PET/CT MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky 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.
