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
Renomedulární tumor z intersticiálních buněk je poměrně častý benigní renální nádor, který obvykle dosahuje malých rozměrů. Kazuistika popisuje náhodně zachycený renomedulární tumor velikosti 2,5 cm, na CT vyšetření vzhledu komplikované cysty. Kazuistika dále shrnuje charakteristické rysy a diferenciální diagnostiku renomedulárního tumoru na základních zobrazovacích vyšetřeních a při histologickém vyšetření.
Renomedullary interstitial cell tumor represents a relatively common benign renal tumor mostly with small size. This case report describes an incidental finding of renomedullary tumor of 2.5 cm with appearance of complicated cyst on CT examination. The article also summarises characteristic features and differential diagnostics of renomedullary tumor in common imaging methods and histopathological examination.
Fibroblast activation protein (FAP) is a membrane-bound protease that is upregulated in a wide range of tumours and viewed as a marker of tumour-promoting stroma. Previously, we demonstrated increased FAP expression in glioblastomas and described its localisation in cancer and stromal cells. In this study, we show that FAP+ stromal cells are mostly localised in the vicinity of activated CD105+ endothelial cells and their quantity positively correlates with glioblastoma vascularisation. FAP+ mesenchymal cells derived from human glioblastomas are non-tumorigenic and mostly lack the cytogenetic aberrations characteristic of glioblastomas. Conditioned media from these cells induce angiogenic sprouting and chemotaxis of endothelial cells and promote migration and growth of glioma cells. In a chorioallantoic membrane assay, co-application of FAP+ mesenchymal cells with glioma cells was associated with enhanced abnormal angiogenesis, as evidenced by an increased number of erythrocytes in vessel-like structures and higher occurrence of haemorrhages. FAP+ mesenchymal cells express proangiogenic factors, but in comparison to normal pericytes exhibit decreased levels of antiangiogenic molecules and an increased Angiopoietin 2/1 ratio. Our results show that FAP+ mesenchymal cells promote angiogenesis and glioma cell migration and growth by paracrine communication and in this manner, they may thus contribute to glioblastoma progression.
- 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
The proline-specific serine protease fibroblast activation protein (FAP) can participate in the progression of malignant tumors and represents a potential diagnostic and therapeutic target. Recently, we demonstrated an increased expression of FAP in glioblastomas, particularly those of the mesenchymal subtype. Factors controlling FAP expression in glioblastomas are unknown, but evidence suggests that transforming growth factor beta (TGFbeta) can trigger mesenchymal changes in these tumors. Here, we investigated whether TGFbeta promotes FAP expression in transformed and stromal cells constituting the glioblastoma microenvironment. We found that both FAP and TGFbeta-1 are upregulated in glioblastomas and display a significant positive correlation. We detected TGFbeta-1 immunopositivity broadly in glioblastoma tissues, including tumor parenchyma regions in the immediate vicinity of FAP-immunopositive perivascular stromal cells. Wedemonstrate for the first time that TGFbeta-1 induces expression of FAP in non-stem glioma cells, pericytes, and glioblastoma-derived endothelial and FAP+ mesenchymal cells, but not in glioma stem-like cells. In glioma cells, this effect is mediated by the TGFbeta type I receptor and canonical Smad signaling and involves activation of FAP gene transcription. We further present evidence of FAP regulation by TGFbeta-1 secreted by glioma cells. Our results provide insight into the previously unrecognized regulation of FAP expression by autocrine and paracrine TGFbeta-1 signaling in a broad spectrum of cell types present in the glioblastoma microenvironment.
- MeSH
- endopeptidasy genetika metabolismus MeSH
- fluorescenční protilátková technika MeSH
- fosforylace MeSH
- glioblastom etiologie metabolismus patologie MeSH
- imunohistochemie MeSH
- kultivované buňky MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí účinky léků genetika MeSH
- regulace genové exprese u nádorů * účinky léků MeSH
- transformující růstový faktor beta1 metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- biopsie MeSH
- diagnostické zobrazování MeSH
- histologické techniky MeSH
- kolorektální nádory * chirurgie patologie prevence a kontrola terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- počítačová rentgenová tomografie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Echinococcus multilocularis vyvolává agresivní formu hydatidózy, jejíž morfologický obraz není všeobecně znám. Prezentujeme kazuistiku 39leté ženy s neostře ohraničenými uzly v pravém laloku jater, které byla pro podezření na fokální nodulární hyperplazii (FNH) a hepatocelulární adenom provedena punkční biopsie. Histologický nález nekrotické fibrózní tkáně prostoupené úzkými pruhy epitelu a malých dutinek, které obsahovaly cytokeratin pozitivní materiál podporovaly diagnózu cholangiocelulárního karcinomu. Dodatečné vyšetření chirurgicky odstraněných nekrotických uzlů s vitální tkání na periferii odpovídalo reparativní fibróze s nápadnou duktulární proliferací. Serologické a genetické vyšetření prokázalo multilokulárního echinokoka. V našem sdělení chceme upozornit na neobvyklý histologický nález nekrotické fibrózní tkáně s duktulární reakcí v solidních ložiscích alveolární hydatidózy, který může v punkční biopsii připomínat regresivně změněný karcinom.
Echinococcus multilocularis causes an aggressive form of hydatidosis whose histomorphological picture is generally not well recognized. We report a case of 39-year-old women presenting with poorly circumscribed nodules in the right hepatic lobe. Owing to the clinical suspicion of focal nodular hyperplasia and hepatocellular adenoma, a core biopsy was performed. The histological findings of necrotic fibrous tissue infiltrated by narrow epithelial cords and small cysts containing cytokeratin positive material were in concordance with the diagnosis of cholangiocarcinoma. Subsequent examination of the surgically resected necrotic nodules with a vital tissue at the periphery corresponded to a reparative fibrosis accompanied by a striking ductular proliferation. Serological and mo-lecular genetic work-up led to the diagnosis of Echinococcus multilocularis. The aim of this report is to point out the unusual histological features of the solid foci of alveolar hydatidosis, which consisted of necrotic fibrous tissue with ductular reaction. Such findings in a core biopsy may simulate regressively altered carcinoma.
- MeSH
- albendazol terapeutické užití MeSH
- dospělí MeSH
- Echinococcus multilocularis MeSH
- echinokokóza jater * diagnóza patologie terapie MeSH
- imunohistochemie metody MeSH
- játra chirurgie diagnostické zobrazování patologie MeSH
- jehlová biopsie metody MeSH
- lidé MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Úvod: Multidisciplinární týmy (MDT) se staly standardní součástí péče o onkologické nemocné. V léčbě kolorektálního karcinomu (KRK) dle dostupných údajů vedou k signifikantnímu zlepšení přežívání. Mezi negativy se uvádějí možné prodloužení intervalu mezi stanovením diagnózy a zahájením adekvátní terapie a taktéž absence hodnocení kvality činnosti MDT. Cílem sdělení je zhodnotit přínos MDT na vlastní sestavě za rok 2017. Metody: V roce 2010 byl ustanoven v Ústřední vojenské nemocnici – Fakultní vojenské nemocnici v Praze MDT s povinnou referencí nemocných s KRK před zahájením terapie. Po standardizaci zápisu jsme v roce 2017 zavedli jednoduchý postup ke sledování kvality činnosti našeho MDT a přínosu pro pacienta: počet pacientů, počet referování s návrhem diagnosticko-terapeutického postupu, četnost a důvody změn původních plánů a četnost odchylky od závěrů MDT. Výsledky: V roce 2017 bylo v MDT referováno 405 pacientů s KRK, u kterých jsme zaznamenali 499 referencí. V souboru převažovali muži (61 %), věkový průměr byl 63 let (21–91), medián 64,5 roku. Nejčastěji navrhovaným postupem byla chirurgická léčba (59 %), dále systémová léčba, ev. radioterapie. Ve 24 % závěr neodpovídal původnímu navrhovanému postupu. Nejčastější změnou byl ústup od navrhované chirurgické léčby (66 %). Zaznamenali jsme rozdíl v kvalitě reference u nemocného, kterého referující osobně vyšetřil oproti pacientovi, u kterého byla pouze zaslána zdravotnická dokumentace. Terapeutickou odchylku v realizaci závěru MDT jsme nalezli u necelých 5 % pacientů. Závěr: Analýzou našich dat u nemocných s KRK referovaných MDT v roce 2017 jsme zjistili, že u 24 % nemocných vede MDT ke změně původního návrhu diagnosticko-terapeutického postupu. Shoda členů MDT na léčbě nemocného s KRK je zárukou optimálního postupu. Znalost konkrétního pacienta referujícím lékařem je zásadní. Soustavné sledování výstupů činnosti je podmínkou udržení kvality MDT a podkladem k hodnocení přínosu pro nemocné.
Introduction: Multidisciplinary teams (MDTs) have become a standard part of treating oncological patients. Based on the available data, they have lead to significantly higher survival rates in the treatment of colorectal cancer (CRC). Reported negatives include potentially longer times between diagnoses and the start of appropriate treatment, and the lack of quality controls over the MTDs‘ actions. This report aims to assess the benefits of MDTs using our own data set for 2017. Methods: Year 2010 saw the institution of an MDT at the Central Military University Hospital in Prague, with the obligation to refer CRC patients to the MDT before the start of treatment. Having standardized the registration, we have implemented a simple procedure to track the quality of our MDT’s involvement and its patient benefits: number of patients, number of referrals with proposed diagnostic and therapeutic procedure, frequency and reason of changes to original strategies, and the frequency of variations from the MDT’s conclusions. Results: 405 CRC patients were referred to the MDT in 2017; we have found 499 referrals in this group. The data set was formed predominantly by men (61%), with the mean age of 63 (21-91), and the median age of 64.5 years. Surgical treatment was the most commonly proposed procedure (59%), followed by systemic treatment or, as the case may be, radiotherapy. In 24% of the cases, the conclusion did not match the originally proposed procedure. The decision not to go through with the proposed surgical treatment was the most common change (66 %). We have found a difference in the quality of referral in patients examined specifically by the referring doctor, as opposed to patients whose medical records have just been sent in. We have found therapeutic variation in the MTD’s conclusions in less than 5% of patients. Conclusion: Having analyzed our data for CRC patients referred to the MDT in 2017, we have found out that in 24% of the patients, the MDT referral leads to a change in the originally proposed diagnostic and therapeutic procedure. Consensus among the MDT’s members on the CRC patient’s treatment guarantees an optimum procedure. What is fundamental is that the referring doctor knows the patient. Constant tracking of the MDT’s outputs forms a condition for sustaining the quality of its work and a base for assessing its benefits to the patients.
- MeSH
- dospělí MeSH
- kolorektální nádory * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- mladý dospělý MeSH
- nádory jater sekundární MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- týmová péče o pacienty * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- komentáře MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Eosinophilic angiocentric fibrosis (EAF) is a rare benign lesion of unknown aetiology, found predominantly in the upper respiratory tract. The fibrosis must be confirmed by considering other lesions in the differential diagnosis. The typical histological characteristics are the basis for establishing the diagnosis. We present a patient with long-term nasal obstruction caused by EAF. The patient had repeated resections of the lesion for its recurrences. As follows from the literature, radical resection is crucial for the treatment of EAF. This procedure may be difficult at times given the extent and localization of the disease.
