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
Carcinomas of the thyroid gland are some of the most common malignancies of the endocrine system. The causes of tumor transformation are genetic changes in genes encoding cell signaling pathways that lead to an imbalance between cell proliferation and apoptosis. Some mutations have been associated with increased tumor aggressiveness, metastatic lymph node spread, tendency to dedifferentiate, and/or reduced efficiency of radioiodine therapy. The main known genetic causes of thyroid cancer include point mutations in the BRAF, RAS, TERT, RET, and TP53 genes and the fusion genes RET/PTC, PAX8/PPAR-γ, and NTRK. Molecular genetic testing of the fine needle aspiration cytology of the thyroid tissue in the preoperative period or of the removed thyroid tissue in the postoperative period is becoming more and more common in selected institutions. Positive detection of genetic changes, thus, becomes a diagnostic and prognostic factor and a factor that determines the extent of the surgical and nonsurgical treatment. The findings of genetic research on thyroid cancer are now beginning to be applied to clinical practice. In preoperative molecular diagnostics, the aggressiveness of cancers with the most frequently occurring mutations is correlated with the extent of the planned surgical treatment (radicality of surgery, neck dissection, etc.). However, clear algorithms are not established for the majority of genetic alterations. This review aims to provide a basic overview of the findings of the most commonly occurring gene mutations in thyroid cancer and to discuss the current recommendations on the extent of surgical and biological treatment concerning preoperatively detected genetic changes.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The aim of our study was to address the potential for improvements in thyroid cancer detection in routine clinical settings using a clinical examination, the American College of Radiology Thyroid Imaging Reporting and Database System (ACR TI-RADS), and fine-needle aspiration cytology (FNAC) concurrently with molecular diagnostics. A prospective cohort study was performed on 178 patients. DNA from FNA samples was used for next-generation sequencing to identify mutations in the genes BRAF, HRAS, KRAS, NRAS, and TERT. RNA was used for real-time PCR to detect fusion genes. The strongest relevant positive predictors for malignancy were the presence of genetic mutations (p < 0.01), followed by FNAC (p < 0.01) and ACR TI-RADS (p < 0.01). Overall, FNAC, ACR TI-RADS, and genetic testing reached a sensitivity of up to 96.1% and a specificity of 88.3%, with a diagnostic odds ratio (DOR) of 183.6. Sensitivity, specificity, and DOR decreased to 75.0%, 88.9%, and 24.0, respectively, for indeterminate (Bethesda III, IV) FNAC results. FNA molecular testing has substantial potential for thyroid malignancy detection and could lead to improvements in our approaches to patients. However, clinical examination, ACR TI-RADS, and FNAC remained relevant factors.
- Publikační typ
- časopisecké články MeSH
Chromosomal rearrangements of NTRK genes are oncogenic driver mutations in thyroid cancer (TC). This study aimed to identify NTRK fusion-positive thyroid tumors and to correlate them with clinical and pathological data and determine their prognostic significance. The cohort consisted of 989 different TC samples. Based on the detected mutation, samples were triaged, and those that were positive for a BRAF, HRAS, KRAS, NRAS, RET, RET/PTC or PAX8/PPARγ mutation were excluded from further analyses. NTRK fusion gene testing was performed in 259 cases, including 126 cases using next-generation sequencing. NTRK fusion genes were detected in 57 of 846 (6.7%) papillary thyroid carcinomas and in 2 of 10 (20.0%) poorly differentiated thyroid carcinomas. A total of eight types of NTRK fusions were found, including ETV6/NTRK3, EML4/NTRK3, RBPMS/NTRK3, SQSTM1/NTRK3, TPM3/NTRK1, IRF2BP2/NTRK1, SQSTM1/NTRK1 and TPR/NTRK1.NTRK fusion-positive carcinomas were associated with the follicular growth pattern, chronic lymphocytic thyroiditis and lymph node metastases. NTRK1-rearranged carcinomas showed a higher frequency of multifocality and aggressivity than NTRK3-rearranged carcinomas. Tumor size, presence of metastases, positivity for the NTRK3 or NTRK1 fusion gene and a late mutation event (TERT or TP53 mutation) were determined as factors affecting patient prognosis. NTRK fusion genes are valuable diagnostic and prognostic markers.
- Publikační typ
- časopisecké články MeSH
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
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
Zhoubné nádory štítné žlázy jsou nejčastějšími endokrinními malignitami, jejich léčba je multidisciplinární a multimodální. Nádory štítné žlázy jsou heterogenní původem vzniku, morfologií, biologickým chováním a možnostmi terapeutického řešení. Zásadní pokrok v diagnostických metodách karcinomu štítné žlázy vede k záchytu časnějších stadií onemocnění s možností cíleného terapeutického ovlivnění a zlepšení prognózy pacienta. Vedle chirurgické léčby, hormonální suprese a léčby radiojódem se v posledních dekádách dostává do popředí zájem o cílenou molekulární léčbu, jejímž předpokladem je genetické vyšetření. Ve sdělení uvádíme přehled dosažených znalostí genetického podkladu jednotlivých typů karcinomů štítné žlázy s možností terapeutického řešení .
Thyroid cancer is the most common endocrine malignancy, the treatment is multidisciplinary and multimodal. Thyroid tumors are heterogeneous in origin, morphology, biological behavior and therapeutic options. Substantial advances in diagnostic methods for thyroid cancer have led to detection of earlier stages of the disease that have the possibility of targeted therapeutic treatment and improved patient prognosis. In addition to surgical treatment, hormonal suppression and radioiodine therapy, targeted molecular therapy, which requires genetic testing, has come to the fore in recent decades. In the summary, we present an overview of current knowledge on the genetic background of individual types of thyroid carcinomas and the possibilities of therapeuticintervention.
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH