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
- cribriform-morular thyroid carcinoma, familial adenomatous polyposis, thyroid gland,
- MeSH
- adenokarcinom * MeSH
- familiární adenomatózní polypóza * komplikace patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory štítné žlázy * diagnóza genetika MeSH
- tenkojehlová biopsie škodlivé účinky MeSH
- tyreoidektomie škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky 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.
- Klíčová slova
- FNAC, extent of surgery, fusion genes, molecular genetics, mutations, neck dissection, prognosis, surgical treatment, thyroid carcinoma,
- 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.
- Klíčová slova
- ACR-TIRADS, BRAF, FNAC, RAS, TERT, fusions, molecular testing, thyroid cancer, thyroid nodule,
- 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.
- Klíčová slova
- NTRK, clinicopathological feature, follow-up, fusion gene, outcome, papillary thyroid carcinoma, poorly differentiated thyroid carcinoma, prognosis,
- 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.
- Klíčová slova
- RNA targeted sequencing, fusion genes, papillary thyroid carcinoma, pediatric, rearrangements,
- 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
- Názvy látek
- BRAF protein, human MeSH Prohlížeč
- MET protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
- NTRK1 protein, human MeSH Prohlížeč
- NTRK3 protein, human MeSH Prohlížeč
- protoonkogenní proteiny B-Raf MeSH
- protoonkogenní proteiny c-met MeSH
- protoonkogenní proteiny c-ret MeSH
- receptor trkA MeSH
- receptor trkC MeSH
- RET protein, human MeSH Prohlížeč
There is a rise in the incidence of thyroid nodules in pediatric patients. Most of them are benign tissues, but part of them can cause papillary thyroid cancer (PTC). The aim of this study was to detect the mutations in commonly investigated genes as well as in novel PTC-causing genes in thyroid nodules and to correlate the found mutations with clinical and pathological data. The cohort of 113 pediatric samples consisted of 30 benign lesions and 83 PTCs. DNA from samples was used for next-generation sequencing to identify mutations in the following genes: HRAS, KRAS, NRAS, BRAF, IDH1, CHEK2, PPM1D, EIF1AX, EZH1 and for capillary sequencing in case of the TERT promoter. RNA was used for real-time PCR to detect RET/PTC1 and RET/PTC3 rearrangements. Total detection rate of mutations was 5/30 in benign tissues and 35/83 in PTCs. Mutations in RAS genes (HRAS G13R, KRAS G12D, KRAS Q61R, NRAS Q61R) were detected in benign lesions and HRAS Q61R and NRAS Q61K mutations in PTCs. The RET/PTC rearrangement was identified in 18/83 of PTCs and was significantly associated with higher frequency of local and distant metastases. The BRAF V600E mutation was identified in 15/83 of PTCs and significantly correlated with higher age of patients and classical variant of PTC. Germline variants in the genes IDH1, CHEK2 and PPM1D were found. In conclusion, RET/PTC rearrangements and BRAF mutations were associated with different clinical and histopathological features of pediatric PTC. RAS mutations were detected with high frequency in patients with benign nodules; thus, our results suggest that these patients should be followed up intensively.
- Klíčová slova
- benign, mutations, next-generation sequencing, papillary thyroid cancer, pediatric,
- Publikační typ
- časopisecké články MeSH
