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Trichophyton verrucosum is a pathogen causing superficial mycoses in cattle worldwide and is one of the few zoophilic dermatophytes. Farmers and veterinarians are at a higher risk for infection owing to frequent direct animal contact. An increase in cases among humans has been observed in the past few years. We report a rare case of T verrucosum of the forearm in a 51-year-old cattle farmer, who after initial treatment with antibiotics and surgery, and in whom diagnosis was delayed, was finally successfully treated with terbinafine and itraconazole.
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Arthrodermataceae , Tinha , Animais , Bovinos , Fazendeiros , Antebraço , Humanos , Tinha/diagnóstico , Tinha/tratamento farmacológico , Tinha/veterinária , TrichophytonRESUMO
AIMS: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS AND RESULTS: This article reports the autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. CONCLUSIONS: This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.
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COVID-19/patologia , Capilares/patologia , Doenças Vasculares/patologia , Doenças Vasculares/virologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Capilares/virologia , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
AIMS: Immune checkpoint inhibitors have become a successful treatment in metastatic melanoma. The high response rates in a subset of patients suggest that a sensitive companion diagnostic test is required. The predictive value of programmed death ligand 1 (PD-L1) staining in melanoma has been questioned due to inconsistent correlation with clinical outcome. Whether this is due to predictive irrelevance of PD-L1 expression or inaccurate assessment techniques remains unclear. The aim of this study was to develop a standardised digital protocol for the assessment of PD-L1 staining in melanoma and to compare the output data and reproducibility to conventional assessment by expert pathologists. METHODS AND RESULTS: In two cohorts with a total of 69 cutaneous melanomas, a highly significant correlation was found between pathologist-based consensus reading and automated PD-L1 analysis (r = 0.97, P < 0.0001). Digital scoring captured the full diagnostic spectrum of PD-L1 expression at single cell resolution. An average of 150 472 melanoma cells (median 38 668 cells; range = 733-1 078 965) were scored per lesion. Machine learning was used to control for heterogeneity introduced by PD-L1-positive inflammatory cells in the tumour microenvironment. The PD-L1 image analysis protocol showed excellent reproducibility (r = 1.0, P < 0.0001) when carried out on independent workstations and reduced variability in PD-L1 scoring of human observers. When melanomas were grouped by PD-L1 expression status, we found a clear correlation of PD-L1 positivity with CD8-positive T cell infiltration, but not with tumour stage, metastasis or driver mutation status. CONCLUSION: Digital evaluation of PD-L1 reduces scoring variability and may facilitate patient stratification in clinical practice.
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Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/análise , Interpretação de Imagem Assistida por Computador/métodos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
BACKGROUND: No evidence is available on how to treat intraoperatively detected band-shaped strangulation marks of the bowel wall originating from an adhesive band or hernia ring. The authors prefer to resect these hazardous strangulation marks to avoid secondary small bowel perforation. This retrospective study investigated the prevalence of intraoperatively unrecognized ulceration and transmural necrosis at the site of the strangulation marks. METHODS: From July 2003 to July 2011, a total of 31 of 461 patients with acute bowel obstruction underwent small bowel resection due to strangulation marks, exclusively. Seven patients had two strangulation marks, resulting in 38 strangulation marks to be analyzed. RESULTS: From 38 examined strangulation marks, 14 (36.8 %) exhibited deep ulceration or transmural necrosis. Four (10.5 %) necrotic lesions had already been recognized intraoperatively, while 7 (18.4 %) unsuspicious strangulation marks showed deep ulceration and 3 (7.9 %) showed transmural necrosis exclusively at final histopathologic examination. The number of strangulation marks that needed to be resected for prevention of one missed deep ulceration and/or transmural necrosis of the small bowel was 3.4. The presence of deep ulceration or transmural necrosis is associated with an obvious decrease in bowel diameter caudad to the strangulation mark. No anastomotic leak occurred. CONCLUSION: The severity of small bowel damage at the site of band-shaped strangulation marks may be underestimated by surgeons. The present series showed favorable results with a resection-per-principle policy for these strangulation marks. If an obvious decrease of bowel diameter aborally to the strangulation mark is present, resection or seromuscular invagination of the later is particularly recommended.
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Obstrução Intestinal/patologia , Obstrução Intestinal/cirurgia , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Estudos Retrospectivos , Adulto JovemRESUMO
Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods: The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12-18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results: As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion: SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.
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BACKGROUND: Studies of Merkel cell polyomavirus (MCPyV) in nonmelanoma skin cancers (NMSC) other than Merkel cell carcinoma (MCC) produced controversial results. Therefore, we studied the prevalence of MCPyV in basal cell carcinoma (BCC) and in squamous cell carcinoma (SCC). METHODS: Tissue specimens were analyzed for the presence of MCPyV DNA by conventional polymerase chain reaction (PCR). Expression of MCPyV large T protein was determined by immunohistochemistry. RESULTS: MCPyV DNA was frequently detected in skin cancers by PCR, in 36 of 88 BCCs, in 21 of 75 SCCs and in 10 of 47 normal skin samples. In BCC, a significant difference in the detection rate compared to normal skin was observed. In contrast, weak reactivity for MCPyV large T antigen was detected only sporadically in immunosuppressed patients (2 of 88 BCCs, 1 of 75 SCCs). Mutations of the large T antigen of MCPyV were more frequently observed in MCC than in BCC/SCC. CONCLUSIONS: Our results suggest that the frequent detection of the MCPyV genome in NMSC by PCR reflects ubiquitous spread of the virus. However, the low immunohistochemical detection rate of MCPyV and the lack of MCC-specific MCPyV mutations argue against an essential role of MCPyV in the development of skin cancers other than MCC.
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Antígenos Virais de Tumores , Carcinoma Basocelular , Carcinoma de Células Escamosas , Regulação Neoplásica da Expressão Gênica , Regulação Viral da Expressão Gênica , Poliomavírus das Células de Merkel/metabolismo , Neoplasias Cutâneas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais de Tumores/biossíntese , Antígenos Virais de Tumores/genética , Antígenos Virais de Tumores/imunologia , Carcinoma Basocelular/genética , Carcinoma Basocelular/imunologia , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma Basocelular/virologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Regulação Viral da Expressão Gênica/genética , Regulação Viral da Expressão Gênica/imunologia , Genoma Viral/genética , Genoma Viral/imunologia , Humanos , Masculino , Poliomavírus das Células de Merkel/genética , Poliomavírus das Células de Merkel/imunologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologiaRESUMO
Identification of bacterial pathogens in formalin fixed, paraffin embedded (FFPE) tissue samples is limited to targeted and resource-intensive methods such as sequential PCR analyses. To enable unbiased screening for pathogens in FFPE tissue samples, we established a whole genome sequencing (WGS) method that combines shotgun sequencing and metagenomics for taxonomic identification of bacterial pathogens after subtraction of human genomic reads. To validate the assay, we analyzed more than 100 samples of known composition as well as FFPE lung autopsy tissues with and without histological signs of infections. Metagenomics analysis confirmed the pathogenic species that were previously identified by species-specific PCR in 62% of samples, showing that metagenomics is less sensitive than species-specific PCR. On the other hand, metagenomics analysis identified pathogens in samples, which had been tested negative for multiple common microorganisms and showed histological signs of infection. This highlights the ability of this assay to screen for unknown pathogens and detect multi-microbial infections which is not possible by histomorphology and species-specific PCR alone.
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Bactérias , Metagenômica , Bactérias/genética , Formaldeído , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Metagenômica/métodos , Inclusão em Parafina , Sequenciamento Completo do GenomaRESUMO
Coronavirus disease 2019 (COVID-19) mortality can be estimated based on reliable mortality data. Variable testing procedures and heterogeneous disease course suggest that a substantial number of COVID-19 deaths is undetected. To address this question, we screened an unselected autopsy cohort for the presence of SARS-CoV-2 and a panel of common respiratory pathogens. Lung tissues from 62 consecutive autopsies, conducted during the first and second COVID-19 pandemic waves in Switzerland, were analyzed for bacterial, viral and fungal respiratory pathogens including SARS-CoV-2. SARS-CoV-2 was detected in 28 lungs of 62 deceased patients (45%), although only 18 patients (29%) were reported to have COVID-19 at the time of death. In 23 patients (37% of all), the clinical cause of death and/or autopsy findings together with the presence of SARS-CoV-2 suggested death due to COVID-19. Our autopsy results reveal a 16% higher SARS-CoV-2 infection rate and an 8% higher SARS-CoV-2 related mortality rate than reported by clinicians before death. The majority of SARS-CoV-2 infected patients (75%) did not suffer from respiratory co-infections, as long as they were treated with antibiotics. In the lungs of 5 patients (8% of all), SARS-CoV-2 was found, yet without typical clinical and/or autopsy findings. Our findings suggest that underreporting of COVID-19 contributes substantially to excess mortality. The small percentage of co-infections in SARS-CoV-2 positive patients who died with typical COVID-19 symptoms strongly suggests that the majority of SARS-CoV-2 infected patients died from and not with the virus.
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OBJECTIVE: Very recently it has been shown that hyperbilirubinemia is a specific predictor of perforation in acute appendicitis. We compared the diagnostic importance of bilirubin, C-reactive protein (CRP), leukocyte count and age as markers of perforation in acute appendicitis. MATERIAL AND METHODS: A two-center retrospective cohort study was completed. Patients with acute appendicitis (n = 725) were divided into two groups, group A with perforation (n = 155) and group B without (n = 570). RESULTS: In group A an elevated CRP (> 5 mg/l) was measured in 98% of cases versus 72.5% in group B. Hyperbilirubinemia (> 20 micromol/l) was measured in 38% of cases in group A versus 22.3% in group B. Leukocytosis (> 10 x 10(9)/l) was measured in 85% of cases in group A versus 79.3% in group B. Analysis of qualitative and quantitative data showed every marker to be significantly correlated with perforation except elevated white cell blood count. However CRP showed the strongest correlation. The logistic regression model showed CRP to be by far the most significant marker of perforation. CONCLUSIONS: Our results confirm hyperbilirubinemia to be a statistically significant marker of perforation in acute appendicitis. However, CRP is superior to bilirubin for anticipation of perforation in acute appendicitis.
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Apendicite/sangue , Apendicite/diagnóstico , Bilirrubina/sangue , Proteína C-Reativa/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Estudos de Coortes , Feminino , Humanos , Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Coronavirus Disease 19 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has grown to a worldwide pandemic with substantial mortality. Immune mediated damage has been proposed as a pathogenic factor, but immune responses in lungs of COVID-19 patients remain poorly characterized. Here we show transcriptomic, histologic and cellular profiles of post mortem COVID-19 (n = 34 tissues from 16 patients) and normal lung tissues (n = 9 tissues from 6 patients). Two distinct immunopathological reaction patterns of lethal COVID-19 are identified. One pattern shows high local expression of interferon stimulated genes (ISGhigh) and cytokines, high viral loads and limited pulmonary damage, the other pattern shows severely damaged lungs, low ISGs (ISGlow), low viral loads and abundant infiltrating activated CD8+ T cells and macrophages. ISGhigh patients die significantly earlier after hospitalization than ISGlow patients. Our study may point to distinct stages of progression of COVID-19 lung disease and highlights the need for peripheral blood biomarkers that inform about patient lung status and guide treatment.
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Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Linfócitos T CD8-Positivos/imunologia , COVID-19 , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Interferons/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , SARS-CoV-2 , Carga ViralRESUMO
Cell cycle and apoptosis regulatory proteins are markers of tumor progression in colorectal cancer. In a series of 1,274 mismatch repair-proficient colorectal cancers, immunohistochemical analysis of p21, p27, p53, and bcl-2 expression was performed using the tissue microarray technique. In univariate analysis, p21 expression was associated with tumor location and pN0; p27 expression with tumor location, lower tumor grade, early pT, and pN; p53 expression with tumor location; and bcl-2 with early pT and pN. Expression of p27 identified subgroups with worse prognosis in pT3 N0 and pT3 N+ patients. None of the 4 tumor markers were independent prognostic indicators of survival. The multimarker phenotypes p21/p27/p53 and p21/p27/bcl-2 were associated with survival. In mismatch repair-proficient colorectal cancer, p27 expression is associated with a better prognosis, and pT, pN, and vascular invasion are independent prognostic factors. In addition, multimarker phenotypes are useful to identify colorectal cancer subgroups with different prognoses.
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Proteínas Reguladoras de Apoptose/análise , Proteínas de Ciclo Celular/análise , Neoplasias Colorretais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Prognóstico , Antígeno Nuclear de Célula em Proliferação/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas p21(ras)/análise , Análise de Sobrevida , Proteína Supressora de Tumor p53/análiseRESUMO
Urinary cytology is limited by high interobserver variability in the evaluation of cells with little atypia. We set up an online quiz on urinary cytology and tested the performance of 246 international participants. The quiz consisted of still images of 42 urinary specimens with equivocal morphologic features and 10 control cases with an unequivocal cytologic diagnosis. The nature of the cells on the 292 quiz images had been verified by multitarget fluorescence in situ hybridization in addition to the information obtained by cystoscopy, clinical follow up, and/or histologic examination. The original quiz cases and the percentage of answers given by the participants can be viewed at: http://kathrin.unibas.ch/urinzyto/. High-grade cancers were diagnosed correctly in 76.0% and low-grade cancers in only 33.9%. Remarkably, 54.5% of all participants misclassified decoy cells as malignant. This study shows that large-scale international online quizzes may be used to find educational deficits in cytopathology.
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Classificação/métodos , Citodiagnóstico , Telepatologia , Urinálise , Urina/citologia , Doenças Urológicas/diagnóstico , Competência Clínica , Erros de Diagnóstico , Educação Médica Continuada , Avaliação Educacional , Escolaridade , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Doenças Urológicas/urinaRESUMO
To explore molecular mechanisms of prostate cancer progression, we applied tissue microarrays (TMAs) to analyze expression of candidate gene targets discovered by cDNA microarray analysis of the CWR22 xenograft model system. A TMA with 544 clinical specimens from different stages of disease progression was probed by mRNA in situ hybridization and protein immunohistochemistry. There was an excellent correlation (r = 0.96; n = 16) between the expression levels of the genes in the xenografts by cDNA microarray and mRNA in situ hybridization on a TMA. One of the most highly overexpressed genes in hormone-refractory CWR22R xenografts was the S100P gene. This gene, coding for a calcium signaling molecule implicated in the loss of senescence, was also significantly associated with progression in clinical tumors by TMA analysis (P < 0.001), suggesting dysregulation of this pathway in hormone-refractory and metastatic prostate cancers. Conversely, two genes that were down-regulated during tumor progression in the CWR22 model system were validated in vivo: crystallin mu (CRYM) and a LIM-domain protein LMO4 both showed significantly lower mRNA levels in hormone-refractory tumors as compared with primary tumors (P < 0.001). These results illustrate a strategy for rapid clinical validation at the mRNA and protein level of gene targets found to be differentially expressed in cDNA microarray experiments of model systems of cancer.
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Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Próstata/genética , Animais , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Camundongos , Transplante de Neoplasias , RNA Mensageiro/análise , Transplante Heterólogo , Células Tumorais Cultivadas , Cristalinas muRESUMO
Purpose. Liver cirrhosis associated with high perioperative morbidity/mortality. This retrospective study determines whether liver cirrhosis represents a risk factor for anastomotic leakage after colonic anastomosis or not. Methods. Based on a prospective database with all consecutive colorectal resections performed at the authors' institution from 07/2002 to 07/2012 (n = 2104) all colonic and rectal anastomoses were identified (n = 1875). A temporary loop ileostomy was constructed in 257 cases (13.7%) either due to Mannheimer Peritonitis-Index > 29 or rectal anastomosis below 6 cm from the anal verge. More than one-third of the patients (n = 691) had postoperative contrast enema, either at the occasion of another study or prior to closure of ileostomy. The presence of liver cirrhosis and the development of anastomotic leakage were assessed by chart review. Results. The overall anastomotic leakage rate was 2.7% (50/1875). In patients with cirrhosis/severe fibrosis, the anastomotic leakage rate was 12.5% (3/24), while it was only 2.5% (47/1851) in those without (p = 0.024). The difference remained statistically significant after correction for confounding factors by multivariate analysis. Conclusion. Patients with liver cirrhosis/severe fibrosis have an increased risk of leakage after colonic anastomosis.
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BACKGROUND: Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have been recently approved for treatment of patients with metastatic melanoma and non-small cell lung cancer (NSCLC). Despite important clinical benefits, these therapies are associated with a diverse spectrum of immune-related adverse events (irAEs) that are typically transient, but occasionally severe or even fatal. CASE PRESENTATION: This autopsy case illustrates that clinically overt irAEs may represent only a fraction of the total spectrum of immune-related organ pathology in patients treated with immune checkpoint inhibitors. We report a comprehensive analysis of systemic irAE pathology based on the autopsy of a 35-year-old female patient with metastatic melanoma treated first with ipilimumab and then nivolumab. The clinical course was characterized by a mixed tumor response with regression of skin and lung metastases and fatal progression of metastatic disease in the small bowel, peritoneum and brain. During therapy with ipilimumab, radiographic features of immune-related pneumonitis were noted. The autopsy examination established a sarcoid-like granulomatous reaction of the lung, pulmonary fibrosis and diffuse alveolar damage. Importantly, a clinically unapparent but histologically striking systemic inflammation involving the heart, central nervous system, liver and bone marrow was identified. Severe immune-related end-organ damage due to lymphocytic myocarditis was found. CONCLUSIONS: Autopsy studies are an important measure of quality control and may identify clinically unapparent irAEs in patients treated with immunotherapy. Pathologists and clinicians need to be aware of the broad spectrum of irAEs for timely management of treatment-related morbidity.
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B cells often infiltrate the microenvironment of human tumors. B cells can both positively and negatively regulate antitumor immune responses. In several human cancers, higher numbers of CD20(+) TAB are associated with a favorable prognosis, whereas in human primary melanomas, this association is contentious. In this study, we determined the association of TAB numbers in cutaneous primary melanoma tissue samples and patients' overall survival. The CD20 immunohistochemistry on archival nonmetastasized and metastasized cutaneous primary melanoma tissues from 2 independent patient cohorts was performed. One cohort was used in class comparison for metastasis, the most important prognostic factor for overall survival, and the other cohort for a subsequent survival analysis. Survival association was further validated with RNA data from a third independent cohort. Whole tissue sections were read automatically via quantitative digital imaging and analysis. Survival data were analyzed by Cox proportional hazard modeling. We discovered that cutaneous primary melanomas without metastasis contain significantly more TAB than primary melanomas that had metastasized. At time of first diagnosis, a higher number of TAB is associated with a significantly better overall survival in patients with cutaneous primary melanomas of >1 mm Breslow depth. Also, higher CD20/CD19 tumor mRNA levels are correlated with a significantly better overall survival. Thus, our data support TAB numbers as a prognostic biomarker in cutaneous primary melanoma patients with a tumor of >1 mm Breslow depth. For a survey in larger studies, whole tissue section analysis seems to be key to accurate assessment of TAB numbers.
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Linfócitos B/imunologia , Linfócitos do Interstício Tumoral/imunologia , Melanoma/imunologia , Neoplasias Cutâneas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD19/análise , Antígenos CD19/genética , Antígenos CD20/análise , Antígenos CD20/genética , Áustria , Linfócitos B/patologia , Biomarcadores Tumorais/análise , Bases de Dados Genéticas , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/patologia , Masculino , Melanoma/genética , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Suíça , Fatores de Tempo , Microambiente TumoralRESUMO
BACKGROUND: Dermatologic toxicity is an important adverse effect of immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) or PD ligand 1 (PD-L1). Skin toxicity most commonly includes a maculopapular erythematous rash and pruritus. Rarely life threatening complications such as Steven's Johnson syndrome or toxic epidermal necrolysis may occur. CASE PRESENTATION: Here we report the uncommon event of a drug-induced transient acantholytic dermatosis (Grover's disease) in a 73-year-old Caucasian male treated with ipilimumab for metastatic melanoma. Five weeks after initiation of therapy, the patient developed a widespread polymorphic papulovesicular dermatosis on the trunk and proximal extremities with intense pruritus. Skin biopsy showed acantholytic dyskeratosis with interface dermatitis consistent with a Grover's-like drug eruption. CONCLUSIONS: These findings should raise awareness for uncommon immune-related dermatological toxicities of immunomodulatory antibodies targeting the CTLA-4 signaling axis. We recommend biopsies of unexpected skin lesions to rapidly identify dermatological adverse events of immune checkpoint inhibitors.
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AIMS: Pulmonary bone marrow embolism (BME) and pulmonary bone fragment embolism (BFE) are two types of non-thrombotic pulmonary embolism (NTPE). While BME can be found consistently in autopsies, BFE is a rarely observed event. Both these conditions have bone lesions as source of embolism and are not considered to be causative for death. METHODS: A retrospective autopsy study was performed and lung whole tissue slides were reviewed for the presence of pulmonary embolism. Clinicopathological data were screened for osseous lesions considered as risk factors for BME and BFE. RESULTS: We reviewed 985 consecutive, unselected autopsies and identified 29 cases of BME (2.9%) and 5 cases of BFE (0.5%). Both conditions were mutually exclusive. While BME showed a significant association with costal fractures, BFE was significantly associated with osteomyelitis and previously performed femur nailing. There were between 1 and 346 bone emboli in BFE with a density ranging from 0.74 to 30.5 emboli/cm(2) with mean embolic diameter of 45.8±37.6 µm. In two patients, BFE contributed significantly to fatal outcome. CONCLUSIONS: BME was associated with costal fractures, while BFE was associated with orthopaedic procedures and osteomyelitis. BFE can result in patient death. Both conditions appeared exclusively, indicating that although they originate from osseous lesions their underlying pathogenesis may likely be different.
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Embolia Pulmonar/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Medula Óssea/patologia , Feminino , Fraturas Ósseas/patologia , Humanos , Incidência , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , Suíça/epidemiologiaRESUMO
We report a case of a 63 year old woman with progressive small red spots that can not be diminished with pressure. They appeared on the feet first and spread out to the legs, trunk and arms. This was accompanied with non-bloody diarrhoea and the laboratory diagnostics showed minor impairment of the kidney. The biopsy of the skin showed deposits of immunoglobulin A and C3 complement in the stratum papillare of the small vessels and a necrosis of the wall, which made the diagnosis of the Schönlein-Henoch purpura clear. It was accompanied by a systemic participation of the gastrointestinal tract. The quick reversible renal insufficiency was rather interpreted as a prerenal cause, than as an origin of the Schönlein-Henoch purpura. We further discussed the diagnostic methods, the aetiology and the possible therapy options.
Assuntos
Diarreia/etiologia , Dermatoses do Pé/etiologia , Vasculite por IgA/diagnóstico , Púrpura/etiologia , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Vasculite por IgA/patologia , Imunoglobulina A/análise , Microscopia de Fluorescência , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Pele/patologiaRESUMO
OBJECTIVE: The epidemiology and the aetiology of inflammatory diseases of the vermiform appendix remain poorly understood. The prevalence of appendiceal diverticulosis and diverticulitis in patients undergoing appendectomy for suspected acute appendicitis was investigated. METHODS: A retrospective study was completed on patients who underwent appendectomy for suspected acute appendicitis. Pathology reports of all patients were screened for diverticula of the vermiform appendix. Patients with either diverticulitis of the vermiform appendix or normal appendicitis were compared. RESULTS: Out of two sets of consecutive patients (n = 1073), nine (0.8%) were identified with diverticulosis of the vermiform appendix. Two of these patients had diverticulitis of the vermiform appendix without appendicitis, three had diverticulitis with consecutive localized appendicitis, and four had proper acute appendicitis with a noninflamed diverticulum of the vermiform appendix. One patient had perforated appendicitis. Two patients had an obstructing neuroendocrine carcinoid which may have caused diverticular formation. CONCLUSIONS: Diverticula of the vermiform appendix are rare. If inflamed, they mimic acute appendicitis and are treated by appendectomy. If not inflamed, and diagnosed intraoperatively, incidental appendectomy is recommended.