Perivascular epitheloid cell tumour (PEComa) of the retroperitoneum – a rare tumor with uncertain malignant behaviour: a case report

<p>Abstract</p> <p>Introduction</p> <p>Perivascular epitheloid cell tumours are rare mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epitheloid phenotype and expression of myomelanocytic markers.</p> <p>Case presentation</p> <p>Here we present the case of a cystic perivascular epitheloid cell tumour of the retroperitoneum associated with multifocal lung lesions. A 27-year-old woman underwent laparotomy to remove a 10 × 6 × 4 cm sized retroperitoneal mass. The resected specimen was subjected to frozen and permanent histological sections with conventional and immunohistochemical stains, including antibodies against HMB45. The tumour displayed the typical morphological and immunohistochemical features of a perivascular epitheloid cell tumour. Focal necrosis and a proliferative index of 10% suggested a malignant potential. Moreover, postoperative computed tomography scans demonstrated multiple lung lesions, which were radiologically interpreted as being most likely compatible with lymphangioleiomyomatosis.</p> <p>Conclusion</p> <p>Since lymphangioleiomyomatosis, an otherwise benign condition, belongs to the family of perivascular epitheloid cell tumours, it cannot be excluded that the lung lesions in this case in fact represent metastases from the retroperitoneal perivascular epitheloid cell tumour rather than independent neoplasms. More experience with this new and unusual tumour entity is clearly needed in order to define reliable criteria for benign or malignant behaviour.</p

Qualitative and Quantitative Requirements for Assessing Prognostic Markers in Prostate Cancer

Molecular prognostic markers are urgently needed in order to improve therapy decisions in prostate cancer. To better understand the requirements for biomarker studies, we re-analyzed prostate cancer tissue microarray immunohistochemistry (IHC) data from 39 prognosis markers in subsets of 50 – &gt;10,000 tumors. We found a strong association between the “prognostic power” of individual markers and the number of tissues that should be minimally included in such studies. The prognostic relevance of more than 90% of the 39 IHC markers could be detected if ≥6400 tissue samples were analyzed. Studying markers of tissue quality, including immunohistochemistry of ets-related gene (ERG) and vimentin, and fluorescence in-situ hybridization analysis of human epidermal growth factor receptor 2 (HER2), we found that 18% of tissues in our tissue microarray (TMA) showed signs of reduced tissue preservation and limited immunoreactivity. Comparing the results of Kaplan-Meier survival analyses or associations to ERG immunohistochemistry in subsets of tumors with and without exclusion of these defective tissues did not reveal statistically relevant differences. In summary, our study demonstrates that TMA-based marker validation studies using biochemical recurrence as an endpoint require at least 6400 individual tissue samples for establishing statistically relevant associations between the expression of molecular markers and patient outcome if weak to moderate prognosticators should also be reliably identified

Characteristics and Risk Factors for Intensive Care Unit Cardiac Arrest in Critically Ill Patients with COVID-19—A Retrospective Study

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) led to an ongoing pandemic with a surge of critically ill patients. Very little is known about the occurrence and characteristic of cardiac arrest in critically ill patients with COVID-19 treated at the intensive care unit (ICU). The aim was to investigate the incidence and outcome of intensive care unit cardiac arrest (ICU-CA) in critically ill patients with COVID-19. This was a retrospective analysis of prospectively recorded data of all consecutive adult patients with COVID-19 admitted (27 February 2020–14 January 2021) at the University Medical Centre Hamburg-Eppendorf (Germany). Of 183 critically ill patients with COVID-19, 18% (n = 33) had ICU-CA. The median age of the study population was 63 (55–73) years and 66% (n = 120) were male. Demographic characteristics and comorbidities did not differ significantly between patients with and without ICU-CA. Simplified Acute Physiological Score II (SAPS II) (ICU-CA: median 44 points vs. no ICU-CA: 39 points) and Sequential Organ Failure Assessment (SOFA) score (median 12 points vs. 7 points) on admission were significantly higher in patients with ICU-CA. Acute respiratory distress syndrome (ARDS) was present in 91% (n = 30) with and in 63% (n = 94) without ICU-CA (p = 0.002). Mechanical ventilation was more common in patients with ICU-CA (97% vs. 67%). The median stay in ICU before CA was 6 (1–17) days. A total of 33% (n = 11) of ICU-CAs occurred during the first 24 h of ICU stay. The initial rhythm was non-shockable (pulseless electrical activity (PEA)/asystole) in 91% (n = 30); 94% (n = 31) had sustained return of spontaneous circulation (ROSC). The median time to ROSC was 3 (1–5) minutes. Patients with ICU-CA had significantly higher ICU mortality (61% vs. 37%). Multivariable logistic regression showed that the presence of ARDS (odds ratio (OR) 4.268, 95% confidence interval (CI) 1.211–15.036; p = 0.024) and high SAPS II (OR 1.031, 95% CI 0.997–1.065; p = 0.077) were independently associated with the occurrence of ICU-CA. A total of 18% of critically ill patients with COVID-19 suffered from a cardiac arrest within the intensive care unit. The occurrence of ICU-CA was associated with presence of ARDS and severity of illness

Severe liver dysfunction complicating course of COVID-19 in the critically ill: multifactorial cause or direct viral effect?

Background!#!SARS-CoV-2 caused a pandemic and global threat for human health. Presence of liver injury was commonly reported in patients with coronavirus disease 2019 (COVID-19). However, reports on severe liver dysfunction (SLD) in critically ill with COVID-19 are lacking. We evaluated the occurrence, clinical characteristics and outcome of SLD in critically ill patients with COVID-19.!##!Methods!#!Clinical course and laboratory was analyzed from all patients with confirmed COVID-19 admitted to ICU of the university hospital. SLD was defined as: bilirubin ≥ 2 mg/dl or elevation of aminotransferase levels (&amp;gt; 20-fold ULN).!##!Results!#!72 critically ill patients were identified, 22 (31%) patients developed SLD. Presenting characteristics including age, gender, comorbidities as well as clinical presentation regarding COVID-19 overlapped substantially in both groups. Patients with SLD had more severe respiratory failure (paO!##!Conclusion!#!One-third of critically ill patients with COVID-19 suffer from SLD, which is associated with high mortality. Occurrence of viremia and severity of illness seem to contribute to occurrence of SLD and underline the multifactorial cause

Tumour diameter is not reliable for management of non-secreting pancreatic neuroendocrine tumours

Small non-functioning pancreatic NETs (pNETs) ≤2 cm can pose a management dilemma in terms of surveillance or resection. There is evidence to suggest that a surveillance approach can be considered since there are no significant radiological changes observed in lesions during long-term follow-up. However, other studies have suggested loco-regional spread can be present in ≤2 cm pNETs. The aim of this study was to characterise the prevalence of malignant features and identify any useful predictive variables in a surgically resected cohort of pNETs. 418 patients with pNETs were identified from 5 NET centres. Of these 227 were included for main analysis of tumour characteristics. Mean age of patients was 57 years, 47% were female. The median follow-up was 48.2 months. Malignant features were identified in 38% of ≤2 cm pNETs. ROC analysis showed that the current cut-off of 20 mm had a sensitivity of 84% for malignancy. The rate of malignant features is in keeping with other surgical series and challenges the belief that small pNETs have a low malignant potential. This study does not support a 20 mm size cut-off as being a solitary safe parameter to exclude malignancy in pNETs

Functional role of Sbp in Aap-mediated <i>S</i>. <i>epidermidis</i> biofilm formation.

<p><b>(A)</b> Biofilm phenotypes of 1457-M10, 1457-M10Δ<i>aap</i>, 1457-M10Δ<i>sbp</i>, 1457-M10Δ<i>aap</i>Δ<i>sbp</i>, 1457-M10Δ<i>aap</i>(pRBDomain-B) and 1457-M10Δ<i>aap</i>Δ<i>sbp</i>(pRBDomain-B) were tested in static biofilm assays in the absence (black columns) or presence of varying rSbp concentrations (grey columns). All columns represent mean of 12 values obtained in 3 independent experiments. Error bars represent standard deviations. Significant differences (p< 0.05; one-way ANOVA with Dunnett’s correction for multiple testing) are indicated (*, p<0.05; ***, p<0.001). n.s., not significant. <b>(B)</b> Recruitment of rSbp to the surface of 1457-M10Δ<i>aap</i>Δ<i>sbp</i> in the presence of absence of <i>in trans</i> expressed Aap domain-B. Western blot of cell surface protein extracts from identical numbers of bacteria suspended in PBS containing 50, 10, or 5 μg/ml rSbp. PBS without rSbp served as a negative control. rSbp was detected by bioluminescence using a polyclonal rabbit anti-rSbp antiserum and anti-rabbit IgG coupled to peroxidase. <b>(C)</b> Distribution of Aap domain-B and rSbp in living biofilms. 1457-M10Δ<i>aap</i>Δ<i>sbp</i>(pRBDomain-B) was grown in the presence of 1.5 μg/ml rSbp-DyLight550. Bacteria were stained with SYTO 9, Aap domain-B was detected using a polyclonal anti-rDomain-B antiserum and a Cy5-labelled anti-rabbit IgG antibody. Panels I–III represent images of each fluorescence channel, image IV is a merge depicting Aap domain-B and rSbp (IV). A zoom-in shows a representative area with Aap domain-B–rSbp co-localizations (purple; double arrow head). Arrow, Aap domain-B expressing cells without Sbp-recruitment (blue); arrow head; Sbp deposition independent from Aap domain-B (red).</p