BACKGROUND: Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model. METHODS: We evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions. RESULTS: hree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant. CONCLUSIONS: These findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.

• MeSH
• dospělí MeSH
• hyperplazie MeSH
• karotická tělíska * patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mladý dospělý MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nádory hlavy a krku * genetika   patologie   diagnostické zobrazování   MeSH
• paragangliom * genetika   diagnostické zobrazování   patologie   MeSH
• počítačová rentgenová tomografie MeSH
• pozitronová emisní tomografie MeSH
• transkripční faktory bHLH * genetika   analýza   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Endometrial biopsies are important in the diagnostic workup of women who present with abnormal uterine bleeding or hereditary risk of endometrial cancer. In general, approximately 10% of all endometrial biopsies demonstrate endometrial (pre)malignancy that requires specific treatment. As the diagnostic evaluation of mostly benign cases results in a substantial workload for pathologists, artificial intelligence (AI)-assisted preselection of biopsies could optimize the workflow. This study aimed to assess the feasibility of AI-assisted diagnosis for endometrial biopsies (endometrial Pipelle biopsy computer-aided diagnosis), trained on daily-practice whole-slide images instead of highly selected images. Endometrial biopsies were classified into 6 clinically relevant categories defined as follows: nonrepresentative, normal, nonneoplastic, hyperplasia without atypia, hyperplasia with atypia, and malignant. The agreement among 15 pathologists, within these classifications, was evaluated in 91 endometrial biopsies. Next, an algorithm (trained on a total of 2819 endometrial biopsies) rated the same 91 cases, and we compared its performance using the pathologist's classification as the reference standard. The interrater reliability among pathologists was moderate with a mean Cohen's kappa of 0.51, whereas for a binary classification into benign vs (pre)malignant, the agreement was substantial with a mean Cohen's kappa of 0.66. The AI algorithm performed slightly worse for the 6 categories with a moderate Cohen's kappa of 0.43 but was comparable for the binary classification with a substantial Cohen's kappa of 0.65. AI-assisted diagnosis of endometrial biopsies was demonstrated to be feasible in discriminating between benign and (pre)malignant endometrial tissues, even when trained on unselected cases. Endometrial premalignancies remain challenging for both pathologists and AI algorithms. Future steps to improve reliability of the diagnosis are needed to achieve a more refined AI-assisted diagnostic solution for endometrial biopsies that covers both premalignant and malignant diagnoses.

• MeSH
• biopsie MeSH
• hyperplazie MeSH
• lidé MeSH
• počítače * MeSH
• reprodukovatelnost výsledků MeSH
• studie proveditelnosti MeSH
• umělá inteligence * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation. Concomitantly, regeneration disrupted PF network maturation, resulting in permanent PF hyperplasia and impaired ventricular conduction. Proliferation assays, genetic impairment of PF recruitment, lineage tracing and clonal analysis revealed that PF network hyperplasia results from excessive recruitment of PFs due to increased trabecular fate plasticity. These data indicate that PF network hyperplasia is a consequence of trabeculae participation in myocardial regeneration.

• MeSH
• buněčný rodokmen MeSH
• hyperplazie patologie   MeSH
• kardiomyocyty patologie   fyziologie   MeSH
• myši transgenní MeSH
• myši MeSH
• novorozená zvířata * MeSH
• proliferace buněk MeSH
• Purkyňova vlákna * patofyziologie   fyziologie   patologie   MeSH
• regenerace * fyziologie   MeSH
• srdeční komory * patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Pachydermodaktylie (PDD) je vzácná benigní dermatóza charakterizovaná asymptomatickým progredujícím zbytněním periartikulární měkké tkáně, především laterálních částí proximálních interfalangeálních (PIP) kloubů. Nejčastěji bývají symetricky postiženy II.–IV. prst, postižení I. a V. prstu je vzácné. Periartikulární tkáň prstů nohou není zasažena nikdy. Postihuje především mladé muže, nejčastěji adolescenty, s poměrem zastoupení muži : ženy 3,9 : 1. Zduření PIP kloubů se vyvíjí asymptomaticky po několik let s následnou stabilizací stavu. Správná diagnóza PDD předchází zbytečnému vyšetřování pacienta a nevhodně zvolené, často imunosupresivní léčbě. Autoři uvádějí případ 21letého muže s 6 let trvajícím, neprogredujícím postižením, jeho diferenciální diagnózu a přehled současné literatury.

Pachydermodactyly (PDD) is a rare, benign dermatosis characterized by asymptomatic, progressive swelling of the periarticular soft tissue mainly of the lateral parts of the second through fourth PIP joints. The thumb is usually spared. The periarticular tissue of the toes is never affected. It mainly affects young men, most often adolescents, with a male : female ratio of 3.9 : 1. Swelling of the PIP joints develops asymptomatically for several years with subsequent stabilization of the condition. Correct diagnosis of PDD prevents unnecessary examination of the patient and inappropriately chosen often immunosuppressive treatment. The authors present the case of a 21year-old man with non-progressive infliction lasting 6 years, its differential diagnosis and a review of the current literature.

• Klíčová slova
• pachydermodaktylie,
• MeSH
• dermatózy ruky * diagnóza   etiologie   klasifikace   patologie   MeSH
• diferenciální diagnóza MeSH
• histologické techniky MeSH
• hyperplazie diagnóza   etiologie   klasifikace   patologie   MeSH
• kloub prstu ruky * patologie   MeSH
• kůže patologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

AIMS: To investigate DNA methylation of specific gene promoters in endometrial hyperplasia compared to normal endometrial tissue. MATERIALS AND METHODS: To search for epigenetic events, methylation-specific multiplex ligation-dependent probe amplification was employed to compare the methylation status of 64 tissue samples with atypical endometrial hyperplasia, 60 tissue samples with endometrial hyperplasia without atypia, and 40 control tissue samples with normal endometrium. RESULTS: Differences in DNA methylation among the groups were found in PTEN, CDH13, and MSH6 promoters (PTEN: atypical hyperplasia 32%, benign hyperplasia 6.8%, normal endometrium 10%; P=0.004; CDH13: atypical hyperplasia, 50%; benign hyperplasia, 43%; normal endometrium 8.1%; P=0.003; MSH6 atypical hyperplasia 84%, benign hyperplasia, 62%; normal endometrium, 52%; P=0.008.) Higher rates of CDH13 promoter methylation were identified in the groups with both forms of endometrial hyperplasia when compared to the control group (atypical hyperplasia, P=0.003, benign hyperplasia, P=0.0002). A higher rate of DNA methylation of the PTEN and MSH6 promoters was observed in samples with atypical endometrial hyperplasia than in samples with benign endometrial hyperplasia (PTEN: P=0.02; MSH6: P=0.01) and samples with normal endometrial tissue (PTEN, P=0.04; MSH6, P=0.006). CONCLUSION: DNA methylation of CDH13, PTEN, and MSH6 appear to be involved in the development of endometrial hyperplasia.

• MeSH
• DNA vazebné proteiny genetika   MeSH
• hyperplazie endometria * genetika   patologie   MeSH
• hyperplazie genetika   MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• nádory endometria * genetika   patologie   MeSH
• tumor supresorové geny MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The dysplasia grading of Barrett's esophagus (BE), based on the histomorphological assessment of formalin-fixed, paraffin-embedded (FFPE) tissue, suffers from high interobserver variability leading to an unsatisfactory prediction of cancer risk. Thus, pre-analytic preservation of biological molecules, which could improve risk prediction in BE enabling molecular and genetic analysis, is needed. We aimed to evaluate such a molecular pre-analytic fixation tool, PAXgene-fixed paraffin-embedded (PFPE) biopsies, and their suitability for histomorphological BE diagnostics in comparison to FFPE. In a ring trial, 9 GI pathologists evaluated 116 digital BE slides of non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and esophageal adenocarcinomas (EAC) using virtual microscopy. Overall quality, cytological and histomorphological parameters, dysplasia criteria, and diagnosis were analyzed. PFPE showed better preservation of nuclear details as chromatin and nucleoli, whereas overall quality and histomorphologic parameters as visibility of basal lamina, goblet cells, and presence of artifacts were scored as equal to FFPE. The interobserver reproducibility with regard to the diagnosis was best for NDBE and EAC (κF = 0.72-0.75) and poor for LGD and HGD (κF = 0.13-0.3) in both. In conclusion, our data suggest that PFPE allows equally confident histomorphological diagnosis of BE and EAC, introducing a novel tool for molecular analysis and parallel histomorphological evaluation.

• MeSH
• adenokarcinom * diagnóza   genetika   patologie   MeSH
• Barrettův syndrom * diagnóza   patologie   MeSH
• fixace tkání MeSH
• hyperplazie MeSH
• lidé MeSH
• nádory jícnu * diagnóza   patologie   MeSH
• prekancerózy * patologie   MeSH
• progrese nemoci MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH

Pancreatic polypeptide cell hyperplasia (PPY-H) is a multiplication of the neuroendocrine cells producing pancreatic polypeptide (PPY). The development and role of PPY-H and its corresponding clinical and imaging findings still need to be fully elucidated. We present 12 cases of PPY-H accompanying pancreatic neuroendocrine neoplasias (NEN). PPY-H was analyzed with the help of immunohistochemistry and confocal microscopy; preoperative clinical data and imaging studies were evaluated retrospectively. We observed PPY-H emerging from pancreatic ducts, and in some cases, we observed simultaneous NKX6.1 positivity in ducts and PPY-H. Additional clinical-pathological correlations suggests that gastrointestinal symptoms (e.g., epigastric pain and cholestasis) could be more related to PPY-H than to NEN hormonal production. In particular cases, SSTR2 expression was strong in PPY-H and correlated with distinguishable accumulation of activity next to NEN on 99 mTc EDDA/Hynic-TOC SPECT/CT. In another case, 18F-FDG-PET/CT showed increased metabolic activity in the area of PPY-H surrounding NEN. Our data suggest that PPY-H originates in the lining of pancreatic ducts. Confirmation of SSTR2 in PPY-H, using immunohistochemistry, suggests the utility of 99 mTc EDDA/Hynic-TOC or 68Ga-DOTA radiotracers in clinical diagnostics; however, studies with larger cohort are needed.

• MeSH
• EDTA analogy a deriváty   MeSH
• hyperplazie MeSH
• lidé MeSH
• nádory slinivky břišní * patologie   MeSH
• neuroendokrinní nádory * patologie   MeSH
• nukleární lékařství * MeSH
• organotechneciové sloučeniny MeSH
• pankreatický polypeptid MeSH
• PET/CT MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Bronchial asthma is a heterogeneous respiratory condition characterized by chronic airway inflammation, airway hyperresponsiveness and airway structural changes (known as remodeling). The clinical symptoms can be evoked by (non)specific triggers, and their intensity varies over time. In the past, treatment was mainly focusing on symptoms' alleviation; in contrast modern treatment strategies target the underlying inflammation, even during asymptomatic periods. Components of airway remodeling include epithelial cell shedding and dysfunction, goblet cell hyperplasia, subepithelial matrix protein deposition, fibrosis, neoangiogenesis, airway smooth muscle cell hypertrophy and hyperplasia. Among the other important, and frequently forgotten aspects of airway remodeling, also loss of epithelial barrier integrity, immune defects in anti-infectious defence and mucociliary clearance (MCC) dysfunction should be pointed out. Mucociliary clearance represents one of the most important defence airway mechanisms. Several studies in asthmatics demonstrated various dysfunctions in MCC - e.g., ciliated cells displaying intracellular disorientation, abnormal cilia and cytoplasmic blebs. Moreover, excessive mucus production and persistent cough are one of the well-recognized features of severe asthma and are also associated with defects in MCC. Damaged airway epithelium and impaired function of the ciliary cells leads to MCC dysfunction resulting in higher susceptibility to infection and inflammation. Therefore, new strategies aimed on restoring the remodeling changes and MCC dysfunction could present a new therapeutic approach for the management of asthma and other chronic respiratory diseases.

• MeSH
• bronchiální astma * farmakoterapie   MeSH
• hyperplazie MeSH
• lidé MeSH
• mukociliární clearance fyziologie   MeSH
• remodelace dýchacích cest * MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Condylar hyperplasia is one of the causes of facial asymmetry and malocclusion, characterized by enlargement of the lower jaw due to excessive condyle growth activity. The aim of this study was to use micro-computed tomography (micro-CT) to evaluate the bone architecture of the condylar head and determine whether there are differences between patients with various forms of unilateral condylar hyperplasia (UCH): hemimandibular hyperplasia, elongation, and mixed form. The cohort consisted of 28 patients with a mean age of 21.9 years. All patients underwent surgical treatment (condylar shaving) for active pathological growth activity. The portion of the condylar head removed was imaged by micro-CT and subsequently evaluated. Micro-CT imaging and semiquantitative and quantitative evaluation of the bone structure (percentage bone volume, surface density, trabecular thickness, trabecular separation, degree of anisotropy, and porosity of the subchondral bone) did not reveal significant differences between the individual types of condylar hyperplasia (P > 0.05). There were no significant differences in bone structure between the anterior and posterior portions of the condylar head. No statistically significant differences between individual groups of UCH were found in the micro-CT evaluation of the condylar head bone architecture.

• MeSH
• asymetrie obličeje * diagnostické zobrazování   chirurgie   etiologie   MeSH
• dospělí MeSH
• hyperplazie diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• mandibula patologie   MeSH
• mladý dospělý MeSH
• processus condylaris mandibulae * diagnostické zobrazování   chirurgie   patologie   MeSH
• rentgenová mikrotomografie škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

• MeSH
• dospělí MeSH
• hyperplazie MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk * genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory ledvin * genetika   patologie   MeSH
• nekróza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sukcinátdehydrogenasa genetika   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
• časopisecké články MeSH