Five cases of patients with systemic connective tissue diseases (CTD) who developed connective tissue disease-associated interstitial lung disease (CTD-ILD) with progressive pulmonary fibrosis (PPF) are reported here. Unspecified ILD was diagnosed using high-resolution computed tomography (HRCT). Histologically, all cases were usual interstitial pneumonia (UIP) with findings of advanced (3/5) to diffuse (2/5) fibrosis, with a partially (4/5) to completely (1/5) formed image of a honeycomb lung. The fibrosis itself spread subpleurally and periseptally to more central parts (2/5) of the lung, around the alveolar ducts (2/5), or even without predisposition (1/5). Simultaneously, there was architectural reconstruction based on the mutual fusion of fibrosis without compression of the surrounding lung parenchyma (1/5), or with its compression (4/5). The whole process was accompanied by multifocal (1/5), dispersed (2/5), or organized inflammation in aggregates and lymphoid follicles (2/5). As a result of continuous fibroproduction and maturation of the connective tissue, the alveolar septa thickened, delimiting groups of alveoli that merged into air bullae. Few indistinctly visible (2/5), few clearly visible (1/5), multiple indistinctly visible (1/5), and multiple clearly visible (1/5) fibroblastic foci were present. Among the concomitant changes, areas of emphysema, bronchioloectasia, and bronchiectasis, as well as bronchial and vessel wall hypertrophy, and mucostasis in the alveoli and edema were observed. The differences in the histological appearance of usual interstitial pneumonia associated with systemic connective tissue diseases (CTD-UIP) versus the pattern associated with idiopathic pulmonary fibrosis (IPF-UIP) are discussed here. The main differences lie in spreading lung fibrosis, architectural lung remodeling, fibroblastic foci, and inflammatory infiltrates.

• MeSH
• dospělí MeSH
• idiopatická plicní fibróza patologie   komplikace   MeSH
• intersticiální plicní nemoci * patologie   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci pojiva * patologie   komplikace   MeSH
• plíce patologie   diagnostické zobrazování   MeSH
• počítačová rentgenová tomografie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

V našom článku, na podklade dvoch prípadov z praxe, popisujeme priebeh, diagnostiku a liečbu pľúcnej alveolárnej proteinózy (PAP). V prvom prípade ide o 52-ročnú ženu, v druhom o 34-ročného muža. Obaja pacienti boli vyšetrovaní spádovým pneumológom pre intersticiálne pľúcne ochorenie, v prvom prípade aj s prechodom do pľúcnej fibrózy. V rámci diferenciálnej diagnostiky boli hospitalizovaní v NÚTPCHaHCH vo Vyšných Hágoch. RTG hrudníka ukázalo nález difúznych obojstranných infiltrátov pľúc, ktoré u prvého pacienta vykazovali miestami splývavý charakter. CT hrudníka zobrazilo parenchýmové postihnutie pľúc s obojstrannými areálmi charakteru mliečneho skla („ground-glass opacity“/GGO) so zhrubnutými interlobulárnymi septami (crazy paving). U oboch pacientov bolo urobené bronchoskopické vyšetrenie s bronchoalveolárnou lavážou, ktorá mala charakteristický mliečne skalený vzhľad. Pacientom bola dodatočne indikovaná videotorakoskopická biopsia pľúc a histopatologicky potvrdená pľúcna alveolárna proteinóza. Terapeuticky pacienti podstúpili veľkoobjemovú laváž pľúc, po ktorej došlo k zlepšeniu ich klinického stavu a tiež zlepšeniu rádiologického nálezu. Poukazujeme na základné piliere diagnostiky pľúcnej alveolárnej proteinózy, ktorými sú vzor pľúcneho postihnutia v RTG a CT (resp. HRCT) obraze, charakteristický vzhľad bronchoalveolárnej lavážovej tekutiny a dodatočne dokumentujeme aj histopatologický obraz pľúcneho postihnutia pri tomto ochorení. Akcentujeme potrebu centralizácie manažmentu pacientov s pľúcnymi ochoreniami, ktorá je obzvlášť naliehavou v prípadoch raritných ochorení, kedy umožňuje rýchlu dostupnosť všetkých relevantných diagnostických a terapeutických možností, vrátane veľkoobjemovej laváže pľúc.

In this article, we describe the course and diagnosis of pulmonary alveolar proteinosis (PAP) based on two cases from our practice. The first case is a 52-yearold woman, the second a 34-year-old man. Both referred patients were examined by a pulmonologist for interstitial lung disease, in the first case also with transition to pulmonary fibrosis. As part of the differential diagnosis, these patients were hospitalized at the NÚTPCHaHCH in Vyšné Hágy. Chest X-ray showed diffuse bilateral lung infiltrates, in the first patient locally confluent. Chest CT showed parenchymal involvement of the lungs with bilateral ground-glass opacities with thickened interlobular septa (crazy paving). Bronchoscopic examination was performed in both patients with bronchoalveolar lavage, which had a characteristic milky-glazed appearance. Videothoracoscopic lung biopsy was additionally indicated and histopathologically there were pulmonary alveolar proteinosis confirmed. Therapeutically, the patients underwent large volume lung lavage, with clinical condition improvement, including radiological findings improvement. We point out the basic pillars of the diagnosis of pulmonary alveolar proteinosis, which are the pattern of pulmonary involvement in the radiographic and CT (or HRCT) images, the characteristic appearance of the bronchoalveolar lavage fluid, and additionally also the histopathologic pattern of pulmonary involvement in this disease. We emphasize the need for centralized management of patients with lung diseases, which is particularly urgent in cases of rare diseases, where it provides rapid availability of all relevant diagnostic and therapeutic options, including large-volume lung lavage.

• MeSH
• bronchoalveolární laváž metody   MeSH
• bronchoskopie metody   MeSH
• diagnostické zobrazování metody   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní alveolární proteinóza * diagnóza   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Rhabdomyosarcoma (RMS) of the urinary bladder in adults and elderly is an exceptionally rare neoplasm that displays poorly differentiated solid (alveolar-like) small cell pattern, frequently indistinguishable from small cell neuroendocrine carcinoma (SCNEC). However, the histogenesis of RMS and SCNEC and their inter-relationship have not been well studied and remained controversial. We herein analyzed 23 SCNEC and 3 small round cell RMS of the bladder for neuroendocrine (synaptophysin + chromogranin A) and myogenic (desmin + myogenin) marker expression and for TERT promoter mutations. In addition, the RMS cohort and one SCNEC that was revised to RMS were tested for gene fusions using targeted RNA sequencing (TruSight Illumina Panel which includes FOXO1 and most of RMS-related other genes). Overall, significant expression of myogenin and desmin was observed in one of 23 original SCNEC justifying a revised diagnosis to RMS. On the other hand, diffuse expression of synaptophysin was noted in 2 of the 4 RMS, but chromogranin A was not expressed in 3 RMS tested. TERT promoter mutations were detected in 15 of 22 (68%) SCNEC and in two of three (67%) assessable RMS cases, respectively. None of the four RMS cases had gene fusions. Our data highlights phenotypic and genetic overlap between SCNEC and RMS of the urinary bladder. High frequency of TERT promoter mutations in SCNEC is in line with their presumable urothelial origin. In addition, the presence of TERT promoter mutation in 2 of 3 RMS and lack of FOXO1 and other gene fusions in all 4 RMSs suggest a mucosal (urothelial) origin, probably representing extensive monomorphic rhabdomyoblastic transdifferentiation in SCNEC.

• MeSH
• buněčná diferenciace MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom * genetika   patologie   MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádory močového měchýře * patologie   genetika   MeSH
• neuroendokrinní karcinom * patologie   genetika   MeSH
• rhabdomyosarkom * genetika   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• telomerasa genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Východiska: Alveolárny sarkóm mäkkých tkanív (alveolar soft part sarcoma – ASPS) je veľmi zriedkavá mezenchýmová malignita nejasného pôvodu. Väčšinou postihuje mladých ľudí, pričom približne štvrtina prípadov sa diagnostikuje v detskom veku. Prípad: Jedenásťročné dievča pozorovalo nebolestivú podkožnú „hrčku“ v oblasti ľavého lakťa. Zobrazovacie vyšetrenia potvrdili solídnu mäkkotkanivovú intramuskulárnu rezistenciu suspektného vzhľadu. Vykonaná bola jej chirurgická excízia. Resekát pozostával z laločnatého nádoru rozmerov 35 × 20 × 12 mm. Histologicky bol tvorený organoidne rastúcou epiteloidnobunkovou populáciou s vyznačenou pseudoalveolárnou mikroarchitektonikou. Imunohistochemicky exprimoval TFE3 a geneticko-molekulová analýza preukázala fúziu génu ASPSCR1:: TFE3. Spektrum nálezov potvrdzovalo diagnózu ASPS. Následne bola vykonaná široká reexcízia jazvy bez mikroskopického dôkazu nádorových reziduí. Pacientka je v súčasnosti bez známok lokálnej recidívy či metastáz. Záver: ASPS sa považuje za agresívny a prognosticky nepriaznivý chemorezistentný nádor. U detí má lepšiu prognózu v porovnaní s dospelými. Z terapeutického hľadiska je kľúčové včasné rozpoznanie tumoru v lokalizovanom štádiu a jeho kompletné chirurgické odstránenie. Vzhľadom na tendenciu vzniku neskorých metastáz je nutný dlhodobý dôkladný follow-up pacienta.

Background: Alveolar soft part sarcoma (ASPS) is a very rare mesenchymal malignancy of uncertain origin. It mostly affects young people, with about a quarter of cases being diagnosed in children. Case: An 11-year-old girl had a painless subcutaneous “lump” in the left elbow area. Imaging exams revealed a solid soft-tissue intramuscular mass of suspicious appearance. A surgical excision of lesion was performed. The biopsy consisted of a lobular tumor measuring 35 × 20 × 12 mm. Histology revealed an epithelioid-cell population arranged in organoid pseudoalveolar pattern. It immunohistochemically expressed TFE3 and harbored the ASPSCR1:: TFE3 gene fusion. A diagnosis of ASPS was established. Subsequently, a wide re-excision of the scar was performed without microscopic residual tumor. The patient is currently without evidence of local recurrence or metastasis. Conclusion: ASPS is considered an aggressive and prognostically unfavorable chemoresistant neoplasm. Children have a better prognosis compared to adults. Early detection of tumor in a localized stage with complete surgical removal remains a mainstay therapeutic option. Due to its tendency to late metastases, a long-term thorough follow-up of the patient is necessary.

• MeSH
• alveolární sarkom měkkých tkání * chirurgie   diagnóza   MeSH
• diagnostické zobrazování metody   MeSH
• dítě MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Rhabdomyosarcomas (RMS) constitute a heterogeneous spectrum of tumors with respect to clinical behavior and tumor morphology. The paternal uniparental disomy (pUPD) of 11p15.5 is a molecular change described mainly in embryonal RMS. In addition to LOH, UPD, the MLPA technique (ME030kit) also determines copy number variants and methylation of H19 and KCNQ1OT1 genes, which have not been systematically investigated in RMS. All 127 RMS tumors were divided by histology and PAX status into four groups, pleomorphic histology (n = 2); alveolar RMS PAX fusion-positive (PAX+; n = 39); embryonal RMS (n = 70) and fusion-negative RMS with alveolar pattern (PAX-RMS-AP; n = 16). The following changes were detected; negative (n = 21), pUPD (n = 75), gain of paternal allele (n = 9), loss of maternal allele (n = 9), hypermethylation of H19 (n = 6), hypomethylation of KCNQ1OT1 (n = 6), and deletion of CDKN1C (n = 1). We have shown no difference in the frequency of pUPD 11p15.5 in all groups. Thus, we have proven that changes in the 11p15.5 are not only specific to the embryonal RMS (ERMS), but are often also present in alveolar RMS (ARMS). We have found changes that have not yet been described in RMS. We also demonstrated new potential diagnostic markers for ERMS (paternal duplication and UPD of whole chromosome 11) and for ARMS PAX+ (hypomethylation KCNQ1OT1).

• MeSH
• alveolární rhabdomyosarkom * genetika   MeSH
• chromozomy MeSH
• embryonální rhabdomyosarkom * genetika   patologie   MeSH
• lidé MeSH
• metylace DNA MeSH
• rhabdomyosarkom * genetika   MeSH
• uniparentální disomie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge of its expression patterns in soft tissue tumors is limited. PRAME immunohistochemistry (clone QR005) was assessed on whole tissue sections of 350 soft-tissue tumors and mimics (> 50 histotypes). PRAME immunoreactivity was evaluated as follows: 0 "negative" (0% positive cells); 1+ (1-25% positive cells); 2+ (26-50% positive cells); 3+ (51-75% positive cells), and 4+ "diffuse" (> 75% positive cells). PRAME was expressed in 111 lesions (0 benign, 6 intermediate malignancy, and 105 malignant), including fibrosarcomatous dermatofibrosarcoma protuberans (2/4, 0 diffuse), NTRK-rearranged spindle cell neoplasm (2/4, 0 diffuse), atypical fibroxanthoma (1/7, 0 diffuse), Kaposi sarcoma (1/5, 0 diffuse), myxoid liposarcoma (11/11, 9 diffuse), synovial sarcoma (11/11, 6 diffuse), intimal sarcoma (7/7, 5 diffuse), biphenotypic sinonasal sarcoma (3/3, 1 diffuse), angiosarcoma (10/15, 6 diffuse), malignant peripheral nerve sheath tumor (9/12, 4 diffuse), pleomorphic rhabdomyosarcoma (2/3, 2 diffuse), alveolar rhabdomyosarcoma (2/6, 0 diffuse), embryonal rhabdomyosarcoma (7/7, 4 diffuse), undifferentiated pleomorphic sarcoma (2/12, 1 diffuse), leiomyosarcoma (2/15, 1 diffuse), clear cell sarcoma of soft tissue (1/10, 0 diffuse), low-grade fibromyxoid sarcoma (1/5, 0 diffuse), Ewing sarcoma (2/10, 1 diffuse), CIC-rearranged sarcoma (8/8, 4 diffuse), BCOR-sarcoma (2/5, 1 diffuse), melanoma (20/20, 14 diffuse), and thoracic SMARCA4-deficient undifferentiated tumor (5/5, all diffuse). All tested cases of spindle cell lipoma, dedifferentiated/pleomorphic liposarcoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, inflammatory myofibroblastic tumor, myxoinflammatory fibroblastic sarcoma, nodular fasciitis, myxofibrosarcoma, epithelioid hemangioendothelioma, atypical vascular lesion, hemangioma, lymphangioma, vascular malformation, papillary endothelial hyperplasia, GIST, gastrointestinal clear-cell sarcoma, malignant melanotic nerve sheath tumor, neurofibroma, schwannoma, granular cell tumor, alveolar soft part sarcoma, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma, myoepithelioma, ossifying fibromyxoid tumor, angiomatoid fibrous histiocytoma, PEComa, dermatofibroma, pleomorphic dermal sarcoma, and chordoma were negative. PRAME shows imperfect specificity in soft-tissue pathology but may serve as a diagnostic adjunct in selected differential diagnoses that show contrasting expression patterns.

• MeSH
• antigeny nádorové MeSH
• diferenciální diagnóza MeSH
• DNA-helikasy MeSH
• dospělí MeSH
• Ewingův sarkom * diagnóza   MeSH
• fibrosarkom * diagnóza   MeSH
• imunohistochemie MeSH
• jaderné proteiny MeSH
• lidé MeSH
• melanom * patologie   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory kůže * patologie   MeSH
• nádory měkkých tkání * diagnóza   patologie   MeSH
• sarkom * diagnóza   patologie   MeSH
• transkripční faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Inhalation of nanomaterials may induce inflammation in the lung which if left unresolved can manifest in pulmonary fibrosis. In these processes, alveolar macrophages have an essential role and timely modulation of the macrophage phenotype is imperative in the onset and resolution of inflammatory responses. This study aimed to investigate, the immunomodulating properties of two industrially relevant high aspect ratio nanomaterials, namely nanocellulose and multiwalled carbon nanotubes (MWCNT), in an alveolar macrophage model. METHODS: MH-S alveolar macrophages were exposed at air-liquid interface to cellulose nanocrystals (CNC), cellulose nanofibers (CNF) and two MWCNT (NM-400 and NM-401). Following exposure, changes in macrophage polarization markers and secretion of inflammatory cytokines were analyzed. Furthermore, the potential contribution of epigenetic regulation in nanomaterial-induced macrophage polarization was investigated by assessing changes in epigenetic regulatory enzymes, miRNAs, and rRNA modifications. RESULTS: Our data illustrate that the investigated nanomaterials trigger phenotypic changes in alveolar macrophages, where CNF exposure leads to enhanced M1 phenotype and MWCNT promotes M2 phenotype. Furthermore, MWCNT exposure induced more prominent epigenetic regulatory events with changes in the expression of histone modification and DNA methylation enzymes as well as in miRNA transcript levels. MWCNT-enhanced changes in the macrophage phenotype were correlated with prominent downregulation of the histone methyltransferases Kmt2a and Smyd5 and histone deacetylases Hdac4, Hdac9 and Sirt1 indicating that both histone methylation and acetylation events may be critical in the Th2 responses to MWCNT. Furthermore, MWCNT as well as CNF exposure led to altered miRNA levels, where miR-155-5p, miR-16-1-3p, miR-25-3p, and miR-27a-5p were significantly regulated by both materials. PANTHER pathway analysis of the identified miRNA targets showed that both materials affected growth factor (PDGF, EGF and FGF), Ras/MAPKs, CCKR, GnRH-R, integrin, and endothelin signaling pathways. These pathways are important in inflammation or in the activation, polarization, migration, and regulation of phagocytic capacity of macrophages. In addition, pathways involved in interleukin, WNT and TGFB signaling were highly enriched following MWCNT exposure. CONCLUSION: Together, these data support the importance of macrophage phenotypic changes in the onset and resolution of inflammation and identify epigenetic patterns in macrophages which may be critical in nanomaterial-induced inflammation and fibrosis.

• MeSH
• celulosa metabolismus   MeSH
• epigeneze genetická MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nanotrubičky uhlíkové * toxicita   chemie   MeSH
• zánět metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.

• MeSH
• chemokin CXCL10 genetika   MeSH
• fibroblasty MeSH
• interleukin-8 * metabolismus   MeSH
• lidé MeSH
• lymfocyty MeSH
• stanovení celkové genové exprese * MeSH
• transkriptom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• náhlé příhody MeSH
• péče o pacienty v kritickém stavu MeSH
• rány a poranění MeSH
• terapie náhlých příhod MeSH
• Publikační typ
• atlasy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• urgentní lékařství
• NLK Publikační typ
• kolektivní monografie

In this study, an antimicrobial mumio-based hydrogel dressing was developed for wound healing application. The mechanism of gel formation was achieved via a double crosslink network formation between gelatin (GT) and polyvinyl alcohol (PVA) using polyethylene glycol diglycidyl ether (PEGDE) and borax as crosslinking agents. To enhance the mechanical integrity of the hydrogel matrix, bacterial cellulose (BC) was integrated into the GT-PVA hydrogel to produce a composite gel dressing. The obtained hydrogel was characterized by FTIR, SEM, TGA, and XRD. Gel fraction, in vitro swelling and degradation as well as compressive modulus properties of the gel dressing were investigated as a function of change in PVA and BC ratios. By increasing the ratios of PVA and BC, the composite dressing showed lower swelling but higher mechanical strength. Comparing to other formulations, the gel with 4 %w/v PVA and 1 %w/v BC demonstrated to be most suitable in terms of stability and mechanical properties. In vitro cell cytotoxicity by MTT assay on human alveolar basal epithelial (A549) cell lines validated the gels as non-toxic. In addition, the mumio-based gel was compared to other formulations containing different bioactive agents of beeswax and cinnamon oil, which were tested for microbial growth inhibition effects against different bacteria (S. aureus and K. pneumoniae) and fungi (C. albicans and A. niger) strains. Results suggested that the gel dressing containing combinations of mumio, beeswax and cinnamon oil possess promising future in the inhibition of microbial infection supporting its application as a suitable dressing for wound healing.

• MeSH
• antibakteriální látky farmakologie   MeSH
• antiinfekční látky * MeSH
• hojení ran MeSH
• hydrogely * MeSH
• lidé MeSH
• obvazy MeSH
• polyvinylalkohol MeSH
• Staphylococcus aureus MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH