The diagnosis of myoid gonadal stromal tumor (MSGT) can represent a difficult challenge, both for the extreme rarity of this neoplasm and for the clinical-radiological characteristics similar to ...other neoplasms of the testicle. The case management we present suggests how a complete differential diagnosis can be obtained by integrating ultrasonographic and pathological data.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pleomorphic rhabdomyosarcoma (PRMS) is a rare but highly aggressive soft tissue tumor, accounting for 3% of soft tissue sarcomas. PRMS is the most frequent subtype of RMS in adulthood and it is ...mainly located in the large muscles of the extremities, particularly the lower limbs and the trunk, more rarely in other locations especially in the bladder. At our knowledge, only six cases of adult pleomorphic rhabdomyosarcoma of the bladder have been reported in the literature.
In this study, we report a case of PRMS of bladder with a very poor prognosis. In fact, the patient died a month after surgery. The tumor was characterized by poorly differentiated, medium-sized sometimes rhabdoid cells, mixed with large-sized and pleomorphic elements with evident anisonucleosis, and with large areas of necrosis. We used an extensive immunohistochemical panel to exclude other tumors much more frequently reported at this site. The positivity for myogenic markers such as actin, desmin, myogenin and MyoD1 allowed the correct diagnosis. Furthermore, since preliminary studies highlighted a series of specific molecular alterations in PMRS cell lines, we analyzed a panel of specific mutations and gene rearrangements by RT-PCR and FISH methods.
We showed a copy gains of CCND1 and MALT genes in our samples, suggesting an accurate molecular characterization of PRMS to establish a better management of patients and new therapeutic opportunities.
Narrow Band Imaging is a noninvasive optical diagnostic tool. It allows the visualization of sub-mucosal vasculature; four patterns of shapes of submucosal capillaries can be recognized, increasingly ...associated with neoplastic transformation. With such characteristics, it has showed high effectiveness for detection of Oral Squamous Cell Carcinoma. Still, scientific literature highlights several bias/confounding factors, such as Oral Lichen Planus. We performed a retrospective observational study on patients routinely examined with Narrow Band Imaging, investigating for bias, confounding factors and conditions that may limit its applicability.
Age, sex, smoking, use of dentures, history of head & neck radiotherapy, history of Oral Squamous Cell Carcinoma, site of the lesion and thickness of the epithelium of origin were statistically evaluated as possible bias/confounding factors. Pearson's Chi-squared test, multivariate logistic regression, Positive Predictive Value, Negative Predictive Value, Sensitivity, Specificity, Positive Likelihood Ratio, Negative Likelihood Ratio and accuracy were calculated, normalizing the cohort with/without patients affected by Oral Lichen Planus, to acknowledge its role as bias/confounding factor.
Five hundred fifty-six inspections were performed on 106 oral cavity lesions from 98 patients. Age, sex, smoking, use of dentures and anamnesis of Oral Squamous Cell Carcinoma were not found to influence Narrow Band Imaging. History of head & neck radiotherapy was not assessed due to insufficient sample. Epithelium thickness does not seem to interfere with feasibility. Presence of Oral Lichen Planus patients in the cohort led to false positives but not to false negatives. Among capillary patterns, number IV was the most significantly associated to Oral Squamous Cell Carcinoma (p < 0.001), not impaired by the presence of Oral Lichen Planus patients in the cohort (accuracy: 94.3, 95% confidence interval: 88.1-97.9%; odds ratio: 261.7, 95% confidence interval: 37.7-1815.5).
Narrow Band Imaging showed high reliability in detection of Oral Squamous Cell Carcinoma in a cohort of patients with oral cavity lesions not normalized for bias/confounding factors. Still, Oral Lichen Planus may lead to false positives. Narrow Band Imaging could help in the follow-up of patients with multiple lesions through detection of capillary pattern IV, which seems to be the most significantly associated to neoplastic epithelium.
Abstract Background Cytotoxin-associated gene-A (CagA) antigen is expressed by some virulent strains of Helicobacter pylori ( H. pylori ). The role of CagA antigen in coronary instability is unknown. ...We performed a clinico-pathological study and a meta-analysis in the attempt to shed new light on this complex issue. Methods In the clinico-pathological study, 38 patients with unstable angina (UA), 25 patients with stable angina (SA), 21 patients with normal coronary arteries (NCA) and 50 age and sex matched healthy volunteers were enrolled. Serology for CagA was assessed in all patients. Specimens of atherosclerotic plaques were obtained from all patients by directional coronary atherectomy, and prepared for immunohistochemistry using anti-CagA monoclonal antibodies. The meta-analysis includes 9 studies assessing the association between seropositivity to CagA strains and acute coronary events. Results The titre of anti-CagA antibodies was significantly higher in patients with unstable angina (161 ± 90 RU/ml) compared to those with stable angina (83 ± 59 RU/ml p < 0.02), NCA (47.3 ± 29 RU/ml p < 0.01) and healthy controls (73 ± 69 p < 0.02). Anti-CagA antibodies recognized antigens localized inside coronary atherosclerotic plaques in all specimens from both stable and unstable patients. In the meta-analysis, seropositivity to CagA was significantly associated with the occurrence of acute coronary events with an odds ratio (OR) of 1.34 (95% CI, 1.15–1.58, p = 0.0003). Conclusions Taken together these findings suggest that in a subset of patients with unstable angina, an intense immune response against CagA-positive H. pylori strains might be critical to precipitate coronary instability mediated by antigen mimicry between CagA antigen and a protein contained in coronary atherosclerotic plaques.
Penile cancer (PC) is an extremely rare malignancy, and the patients at advanced stages have currently limited treatment options with disappointing results. Immune checkpoint inhibitors ...anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are currently changing the treatment of several tumors. Furthermore, the microsatellite instability (MSI) and the deficient mismatch repair system (dMMR) proteins represent predictive biomarkers for response to immune checkpoint therapy. Until present, few data have been reported related to PD-L1 expression and MSI in PC. The main aim of our study was the evaluation of PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) in immune cells and the analysis of dMMR/MSI status in a large series of PCs.
A series of 72 PC, including 65 usual squamous cell carcinoma (USCC), 1 verrucous, 4 basaloid, 1 warty, and 1 mixed (warty-basaloid), was collected. Immunohistochemistry (IHC) was performed to assess PD-L1 expression using two different anti-PD-L1 antibodies (clone SP263 and SP142 Ventana) and MMR proteins expression using anti-MLH1, anti-PMS2, anti-MSH2, and anti-MSH6 antibodies. PCR analysis was performed for the detection of MSI status.
Of the 72 PC cases analyzed by IHC, 45 (62.5%) cases were TC positive and 57 (79%) cases were combined positive score (CPS) using PDL1 SP263. In our cohort, TILs were present in 62 out of 72 cases (86.1%), 47 (75.8%) out of 62 cases showed positivity to PDL1 clone SP142. In our series, 59 cases (82%) had pMMR, 12 cases (16.7%) had lo-paMMR, and only 1 case (1.3%) had MMR. PCR results showed that only one case lo-paMMR was MSI-H, and the case dMMR by IHC not confirmed MSI status.
Our findings showed that PD-L1 expression and MSI status represent frequent biological events in this tumor suggesting a rationale for a new frontier in the treatment of patients with PC based on the immune checkpoint inhibitors.
Identification of Protein Disulfide Isomerase as a Cardiomyocyte Survival Factor in Ischemic Cardiomyopathy Anna Severino, Mara Campioni, Stefania Straino, Fadi N. Salloum, Nina Schmidt, Ulrike ...Herbrand, Stilla Frede, Gabriele Toietta, Giuliana Di Rocco, Rossana Bussani, Furio Silvestri, Maddalena Piro, Giovanna Liuzzo, Luigi M. Biasucci, Pasquale Mellone, Florinda Feroce, Maurizio Capogrossi, Feliciano Baldi, Joachim Fandrey, Michael Ehrmann, Filippo Crea, Antonio Abbate, Alfonso Baldi The Protein Disulfide Isomerase (PDI) gene is up-regulated in the viable peri-infarct myocardium of human hearts within the first days after infarction. This up-regulation is inversely correlated with cardiomyocyte apoptosis and with signs of remodeling. An in vitro model of cardiac hypoxia-ischemia confirms the up-regulation of PDI after hypoxic stress and its anti-apoptotic effects. These actions of PDI are mediated by cooperation with endoplasmic reticulum oxidoreductin 1 and by its modulation of the activity of zinc-superoxide dismutase. Finally, adenovirus-mediated PDI over-expression to the heart in a mouse model of myocardial infarction reduces cardiomyocyte apoptosis and prevents cardiac remodeling.
Noncoding RNAs (ncRNAs) identify a large family of RNAs that do not encode proteins and represent an important group of tumor biomarkers, directly involved in the process of tumor pathogenesis and ...progression. Many of them have also been identified in biological fluids of patients with cancer, especially blood, suggesting their role as an emerging class of circulating biomarkers. Many ncRNAs, both miRNAs and lncRNAs, are deregulated in sarcoma tissues, with the most consistent data in osteosarcomas. In patients with osteosarcoma, the role of ncRNAs as circulating biomarkers is taking enormous value, above all for their ability to vary expression levels during disease progression and in response to therapy. In this mini‐review, we summarize the main studies supporting the role of circulating ncRNAs in monitoring disease status in patients with osteosarcoma.
In this mini‐review, we summarize the main studies supporting the role of circulating noncoding RNAs in monitoring disease status in patients with osteosarcoma.
•Hierarchical Cell-to-Tissue (HACT) representation: A novel multi-level hierarchical entity-graph representation of a histology image to model the hierarchical composition of the tissue by encoding ...comprehensible histological entities (cells and tissue-regions) as well as the intra- and inter-entity level interactions.•HACT-Net: A hierarchical graph neural network to operate on the hierarchical entity-graph representation to map the tissue structure to tissue functionality.•BReAst Carcinoma Subtyping (BRACS) dataset: Introduce (BRACS) dataset, a large cohort of Haematoxylin & Eosin-stained breast tumor regions-of-interest.•Domain expert comparison: Benchmarking of the proposed methodology with three expert pathologists on the BRACS test set.•Quantitative evaluation: Experimentations on BRACS dataset and public BACH dataset to demonstrate the efficacy of the proposed methodology in breast cancer subtyping compared to state-of-the-art computer-aided diagnostic approaches.•Qualitative evaluation: Demonstration of salient regions in the histopathology image during the inference with HACT-Net.
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Cancer diagnosis, prognosis, and therapy response predictions from tissue specimens highly depend on the phenotype and topological distribution of constituting histological entities. Thus, adequate tissue representations for encoding histological entities is imperative for computer aided cancer patient care. To this end, several approaches have leveraged cell-graphs, capturing the cell-microenvironment, to depict the tissue. These allow for utilizing graph theory and machine learning to map the tissue representation to tissue functionality, and quantify their relationship. Though cellular information is crucial, it is incomplete alone to comprehensively characterize complex tissue structure. We herein treat the tissue as a hierarchical composition of multiple types of histological entities from fine to coarse level, capturing multivariate tissue information at multiple levels. We propose a novel multi-level hierarchical entity-graph representation of tissue specimens to model the hierarchical compositions that encode histological entities as well as their intra- and inter-entity level interactions. Subsequently, a hierarchical graph neural network is proposed to operate on the hierarchical entity-graph and map the tissue structure to tissue functionality. Specifically, for input histology images, we utilize well-defined cells and tissue regions to build HierArchical Cell-to-Tissue (HACT) graph representations, and devise HACT-Net, a message passing graph neural network, to classify the HACT representations. As part of this work, we introduce the BReAst Carcinoma Subtyping (BRACS) dataset, a large cohort of Haematoxylin & Eosin stained breast tumor regions-of-interest, to evaluate and benchmark our proposed methodology against pathologists and state-of-the-art computer-aided diagnostic approaches. Through comparative assessment and ablation studies, our proposed method is demonstrated to yield superior classification results compared to alternative methods as well as individual pathologists. The code, data, and models can be accessed at https://github.com/histocartography/hact-net.
Electrochemotherapy (ECT) is a novel anticancer therapy that is currently being evaluated in human and pet cancer patients. ECT associates the administration of an anti-tumor agent to the delivery of ...trains of appropriate waveforms. The increased uptake of chemotherapy leads to apoptotic death of the neoplasm thus resulting in prolonged local control and extended survival. In this paper we describe the histological features of a broad array of spontaneous tumors of companion animals receiving pulse-mediated chemotherapy. Multivariate statistical analysis of the percentage of necrosis and apoptosis in the tumors before and after ECT treatment, shows that only a high percentage of necrosis and apoptosis after the ECT treatment were significantly correlated with longer survivals of the patients (p < 0.0001 and p = 0.004, respectively). Further studies on this topic are warranted in companion animals with spontaneous tumors to identify new molecular targets for electrochemotherapy and to the develop new therapeutical protocols to be translated to humans.
During the last 20 years, an increasing incidence of basal cell carcinoma (BCC) has been demonstrated by several studies.
A ten-year retrospective analysis on 7,266 cases of primary BCC of the ...Department of Dermatology and Plastic Surgery of the
University of Rome âLa Sapienzaâ and the Department of Dermatology of the University of Naples âFederico IIâ is reported.
Among a population aged over 35 years, BCC cases increased from 618 in 1994 up to 749 cases in 2003, while among the younger
population (<35 years), BCC cases increased from 30 in 1994 to 47 cases in 2003. Anatomic site distribution of BCC among people
aged <35 years was: head and neck=51.54%, trunk=41.40%, limbs=5.91%, others=1.12%. On histological examination aggressive-growth
BBC was recorded in 48 out of 355 cases (13.52%) among people aged <35 years and in 841 out of 6,755 cases (12.45%) among
patients >35 years. In conclusion, an increasing incidence of basal cell carcinoma among young people over the past 20 years
was reported. No significant difference in tumour aggressiveness between the young and the elderly patients was observed.
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