CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.
- MeSH
- buněčné jádro patologie MeSH
- folikulární adenokarcinom * patologie epidemiologie diagnóza MeSH
- lékařská praxe - způsoby provádění statistika a číselné údaje MeSH
- lidé MeSH
- nádory štítné žlázy * epidemiologie patologie diagnóza MeSH
- papilární karcinom štítné žlázy epidemiologie patologie diagnóza MeSH
- papilární karcinom patologie epidemiologie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Asie MeSH
- Evropa MeSH
- Oceánie MeSH
- Severní Amerika MeSH
U nádorů gastrointestinálního traktu dnes vedle stanovení histologické diagnózy, grade a stage hraje zásadní roli rovněž tzv. prediktivní testování. To slouží zejména k identifikaci molekulárních cílů pro moderní onkologickou terapii. U karcinomů jícnu a žaludku je dnes standardem vyšetření exprese a amplifikace HER2, exprese proteinů mismatch repair (MMR) systému a vyšetření exprese PD-L1. U karcinomu žaludku se v blízké budoucnosti testování rozšíří o další markery, zejména exprese claudinu 18.2 či receptoru FGFR2a. U kolorektálního karcinomu je standardem prediktivního vyšetření stanovení mutací RAS (KRAS a NRAS), BRAF a dále zhodnocení mikrosatelitní instability, jen vzácně lze nalézt rovněž terapeuticky cílitelné genové fúze. U karcinomu pankreatu se lze setkat s případy deficience MMR, mutacemi BRCA1/2, zcela raritně lze identifikovat další cílitelné aberace. U nádorů žlučníku a žlučových cest hledáme zejména mutace IDH1 a IDH2, fúze a mutace genu FGFR2, amplifikace či mutace HER2, mutace BRAF či mutace BRCA1/2. Všechny výsledky by měly být projednány v rámci molekulárního tumor boardu.
In addition to the histological diagnosis, grade and stage, predictive testing plays a crucial role in gastrointestinal tumours today. This is mainly used to identify molecular targets for modern cancer therapy. In esophageal and gastric cancers, HER2 expression and amplification, mismatch repair (MMR) system protein deficiency and PD-L1 expression are tested routinely. In colorectal cancer, it is namely detection of RAS (KRAS and NRAS) and BRAF mutations, as well as the assessment of microsatellite instability; targetable gene fusions are found rarely only. In pancreatic cancer, cases of MMR deficiency, BRCA1/2 mutations and other targetable aberrations can be identified quite rarely. In gallbladder and biliary tract cancers, we are mainly looking for IDH1 and IDH2 mutations, FGFR2 gene fusions and mutations, HER2 amplifications or mutations, as well as mutations of BRAF or BRCA1/2. All results should be discussed within the molecular tumor board.
- MeSH
- diagnostické techniky molekulární MeSH
- gastrointestinální nádory * diagnóza genetika klasifikace MeSH
- genetické testování MeSH
- lidé MeSH
- mutace genetika MeSH
- nádorové biomarkery * genetika MeSH
- prediktivní hodnota testů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.
INTRODUCTION: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity. METHODS: Patients aged ≥ 18 years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8 Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis. RESULTS: Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0 months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression. CONCLUSION: SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought. TRIAL REGISTRATION: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.
- Publikační typ
- časopisecké články MeSH
- MeSH
- cytodiagnostika * metody MeSH
- kongresy jako téma MeSH
- lidé MeSH
- molekulární patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Východiska: Pankreatické cystické léze jsou poměrně častým nálezem a jejich počet neustále roste, což souvisí také s rozmachem zobrazovacích metod. Až 15 % karcinomů pankreatu vzniká z mucinózních cystických tumorů pankreatu, především z intraduktální papilární mucinózní neoplazie (IPMN). Jehlová konfokální laserová endomikroskopie (nCLE) představuje pokročilou diagnostickou metodu, která má potenciál zvýšit přesnost diagnostiky ložiskového postižení slinivky břišní. Cíl: Cílem práce je poskytnout recentní přehled postavení nCLE v diagnostice cystických lézí pankreatu a ně kte rých vlastních zkušeností. Metoda nCLE je založena na tzv. optické biopsii v reálném čase, což přináší lepší diagnostické výsledky ve srovnání s tradičními postupy, jako jsou CT, MR/MRCP a EUS, což potvrzují i vlastní data autorů. Přestože nCLE nabízí určité výhody, její širší využití v klinické praxi je omezováno vysokými náklady na vybavení, technickými obtížemi při vyšetření a nutností důkladného tréninku endoskopistů. Integrace všech diagnostických postupů (EUS, cytologie, nCLE a next-generation sekvenování) do algoritmů umělé inteligence by mohla minimalizovat nevýhody jednotlivých metod a zvýšit celkovou efektivitu diagnostiky cystických lézí pankreatu. Závěr: nCLE představuje inovativní metodu diagnostiky cystických lézí pankreatu, která v kombinaci s dalšími postupy (biopsie mikrokleštěmi, sekvenování nové generace, hodnocení nálezů nCLE a celkového rizika malignity pomocí umělé inteligence) může dále zvyšovat svou diagnostickou přesnost v této indikaci.
Background: Pancreatic cystic lesions are relatively common findings, and their prevalence continues to rise, which is also related to the expansion of imaging methods. Up to 15% of pancreatic cancers arise from mucinous cystic tumours of the pancreas, primarily from intraductal papillary mucinous neoplasia (IPMN). Needle-based confocal laser endomicroscopy (nCLE) represents an advanced diagnostic method with the potential to improve the accuracy of diagnosing focal pancreatic lesions. Aim: The aim of the work is to provide a recent overview of the position of nCLE in the diagnosis of pancreatic cystic lesions and some of our own experiences. The nCLE method is based on so-called real-time optical biopsy, which brings better diagnostic results compared to traditional methods such as CT, MRI/MRCP, and EUS, as confirmed by the authors‘ own data. Although nCLE offers certain advantages, its wider use in clinical practice is limited by the high costs of equipment, technical difficulties during examination, and the need for thorough training of endoscopists. The integration of all diagnostic procedures (EUS, cytology, nCLE, and next-generation sequencing) into artificial intelligence algorithms could minimize the disadvantages of individual methods and increase the overall efficiency of diagnosing pancreatic cystic lesions. Conclusion: nCLE represents an innovative method for diagnosing pancreatic cystic lesions, which, in combination with other procedures (microforceps biopsy, next-generation sequencing, assessment of nCLE findings, and overall malignancy risk using artificial intelligence), can further enhance its diagnostic accuracy in this context.
Chordoma is a rare malignant tumor with notochordal differentiation, usually affecting the axial skeleton of young patients. We report a case of a high-grade epithelioid tumor involving the synovium and soft tissues of the knee in a 74-year-old male patient. The preliminary biopsy was inconclusive, but a diagnosis of metastatic clear-cell carcinoma of unknown origin was suggested. However, imaging studies did not reveal any primary lesions. The resection specimen consisted of nests and sheets of oval to polygonal cells with discernible cell borders, clear or lightly amphophilic cytoplasm, and round to oval nuclei with occasional well-visible eosinophilic nucleoli. Rare atypical mitoses, necrotic areas, and bizarre nuclei were noted. The biopsy and resection specimens underwent a wide molecular genetic analysis which included methylation profiling. The DKFZ sarcoma classifier assigned the methylation class chordoma (dedifferentiated) with a calibrated score of 0.96, and additionally, a loss of SMARCB1 locus was noted in the copy number variation plot. To verify these findings, T-brachyury and SMARCB1 immunostaining was performed afterward, showing diffuse nuclear positivity and complete loss in the tumor cells, respectively. To assess the prevalence of T-brachyury immunopositivity among SWI/SNF-deficient tumors and to evaluate its specificity for poorly differentiated chordoma, we analyzed a series of 23 SMARCB1- or SMARCA4-deficient tumors, all of which were negative. After incorporating all the available data, including the absence of any morphological features of conventional chordoma, the case was diagnosed as poorly differentiated chordoma. As illustrated herein, the utilization of methylation profiling in the diagnostic process of some carefully selected unclassifiable soft tissue neoplasms may lead to an increased detection rate of such extremely rare soft tissue tumors and enable their better characterization.
- MeSH
- buněčná diferenciace MeSH
- chordom * patologie genetika diagnóza metabolismus MeSH
- fetální proteiny * genetika metabolismus MeSH
- gen SMARCB1 * genetika MeSH
- lidé MeSH
- metylace DNA * MeSH
- nádorové biomarkery * analýza genetika MeSH
- nádory měkkých tkání patologie diagnóza genetika metabolismus MeSH
- proteiny T-boxu * genetika metabolismus MeSH
- senioři MeSH
- transkripční faktory genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Correlative imaging of cutaneous tumors provides additional information to the standard histopathologic examination. However, the joint progress in the establishment of analytical techniques, such as Laser-Induced Breakdown Spectroscopy (LIBS) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in clinical practice is still limited. Their combination provides complementary information as it is also shown in our study in terms of major biotic (Ca, Mg, and P) and trace (Cu and Zn) elements. To elucidate changes in the elemental composition in tumors, we have compiled a set of malignant tumors (Squamous Cell Carcinoma, Basal Cell Carcinoma, Malignant Melanoma, and Epithelioid Angiosarcoma), one benign tumor (Pigmented Nevus) and one healthy-skin sample. The data processing was based on a methodological pipeline involving binary image registration and affine transformation. Thus, our paper brings a feasibility study of a practical methodological concept that enables us to compare LIBS and LA-ICP-MS results despite the mutual spatial distortion of original elemental images. Moreover, we also show that LIBS could be a sufficient pre-screening method even for a larger number of samples according to the speed and reproducibility of the analyses. Whereas LA-ICP-MS could serve as a ground truth and reference technique for preselected samples.
- MeSH
- bazocelulární karcinom diagnostické zobrazování MeSH
- hmotnostní spektrometrie metody MeSH
- laserová terapie MeSH
- lasery MeSH
- lidé MeSH
- melanom diagnostické zobrazování patologie MeSH
- nádory kůže * diagnostické zobrazování patologie MeSH
- pigmentový névus diagnostické zobrazování MeSH
- spektrální analýza metody MeSH
- spinocelulární karcinom diagnostické zobrazování patologie MeSH
- stopové prvky analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The diagnosis of malignant melanoma, often an inconspicuous but highly aggressive tumor, is most commonly done by histological examination, while additional diagnostic methods on the level of elements and molecules are constantly being developed. Several studies confirmed differences in the chemical composition of healthy and tumor tissue. Our study presents the potential of the LIBS (Laser-Induced-Breakdown Spectroscopy) technique as a diagnostic tool in malignant melanoma (MM) based on the quantitative changes in elemental composition in cancerous tissue. Our patient group included 17 samples of various types of malignant melanoma and one sample of healthy skin tissue as a control. To achieve a clear perception of results, we have selected two biogenic elements (calcium and magnesium), which showed a dissimilar distribution in cancerous tissue from its healthy surroundings. Moreover, we observed indications of different concentrations of these elements in different subtypes of malignant melanoma, a hypothesis that requires confirmation in a more extensive sample set. The information provided by the LIBS Imaging method could potentially be helpful not only in the diagnostics of tumor tissue but also be beneficial in broadening the knowledge about the tumor itself.
Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF) cells and TIM3+PD1+, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells. Conversely, CD8+ T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1+ PD1+ T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8+ T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that - at odds with NSCLC - HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1+PD1+ CD8+ T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.
- MeSH
- CD8-pozitivní T-lymfocyty MeSH
- ektopické lymfoidní struktury * MeSH
- fenotyp MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory plic * MeSH
- nádory vaječníků * patologie MeSH
- nemalobuněčný karcinom plic * MeSH
- tumor infiltrující lymfocyty MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
