The Prognostic Value of Proliferative Activity in Cutaneous Melanoma: A Pilot Study Evaluating the Mitotic Rate and Ki67 Index to Predict Patient Outcomes.

Proliferative activity in cutaneous melanomas can be appreciated both histopathologically by counting mitotic figures and immunohistochemically through the Ki67 index, but the prognostic value of each method is still a matter of debate. In this context, we performed a retrospective study on 33 patients diagnosed with cutaneous melanomas between 2013 and 2018 in order to evaluate progression-free survival and overall survival. Multivariate Cox proportional hazards regression was performed by considering both clinical histopathological and immunohistochemical features. The mitotic rate was significantly independently associated with both outcomes, while the Ki67 index was not an independent prognostic factor. However, the Ki67 predictive accuracy could be improved by establishing both a cut-off value and a standardized protocol for evaluating its expression. Until these desiderata are met, the mitotic rate remains superior to the Ki67 index for predicting prognosis in cutaneous melanomas, as also has the advantage of being easily interpreted in a standard histopathological examination regardless of the pathologist's experience and with no further financial expenses. Importantly, this is one of very few articles that has shown perineural invasion to be an independent prognostic factor for both progression-free survival and overall survival in cutaneous melanomas. As a consequence, this parameter should become a mandatory feature in the histopathological evaluation of cutaneous melanomas as it can improve the identification of patients who are at high risk for disease progression.

The Role of Mannose-Binding Lectin and Inflammatory Markers in Establishing the Course and Prognosis of Community-Acquired Pneumonia in Children.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the most significant childhood diseases worldwide and a leading infectious cause of death in children. This study aimed to evaluate the prognostic value of the inflammatory markers-C-reactive protein (CRP) and procalcitonin (PCT)-and the polymorphic glycoprotein mannose-binding lectin (MBL), deficiency of which is associated with severe infections, in the determination of the optimal type and timing of therapeutic intervention for CAP in childhood. METHODS: Retrospective evaluation was conducted on a cohort of 204 children aged 4 months-17 years hospitalized with CAP. Their levels of CRP, PCT, and MBL were assessed for their association with a variety of outcomes, including the incidence of local and systemic complications, admission to the ICU, duration of antibiotic treatment and hospital stay, and death. RESULTS: CRP and PCT proved to be better predictors of complications of CAP than MBL. The area under the curve (AUC) value was highest for PCT as a predictor of systemic complications (AUC = 0.931, 95%CI 0.895-0.967), while CRP (AUC = 0.674, 95%CI 0.586-0.761) performed best as a predictor of local complications (AUC = 0.674, 95%CI 0.586-0.761). Regarding admission to the ICU, CRP was the weakest predictor (AUC = 0.741), while PCT performed the best (AUC = 0.833), followed by MBL (AUC = 0.797). Sensitivity and specificity were calculated for the optimal threshold generated by receiver operating characteristic (ROC) curves, rendering sensitivity of 90% and specificity of 87% for PCT in assessing the risk of systemic complications, compared to sensitivity of 83% and specificity of 90% for CRP. MBL showed relatively high sensitivity (96%) but low specificity (25%) for predicting the need for ICU admission. CONCLUSIONS: Early measurement of CRP, PCT, and MBL provides clinicians with important information regarding the course and prognosis of children diagnosed with CAP, thus ensuring prompt, optimal therapeutic management.

Role of Tumor Microenvironment in Pituitary Neuroendocrine Tumors: New Approaches in Classification, Diagnosis and Therapy.

Adenohypophysal pituitary tumors account for 10-15% of all intracranial tumors, and 25-55% display signs of invasiveness. Nevertheless, oncology still relies on histopathological examination to establish the diagnosis. Considering that the classification of pituitary tumors has changed significantly in recent years, we discuss the definition of aggressive and invasive tumors and the latest molecular criteria used for classifying these entities. The pituitary tumor microenvironment (TME) is essential for neoplastic development and progression. This review aims to reveal the impact of TME characteristics on stratifying these tumors in view of finding appropriate therapeutic approaches. The role of the pituitary tumor microenvironment and its main components, non-tumoral cells and soluble factors, has been addressed. The variable display of different immune cell types, tumor-associated fibroblasts, and folliculostellate cells is discussed in relation to tumor development and aggressiveness. The molecules secreted by both tumoral and non-tumoral cells, such as VEGF, FGF, EGF, IL6, TNFα, and immune checkpoint molecules, contribute to the crosstalk between the tumor and its microenvironment. They could be considered potential biomarkers for diagnosis and the invasiveness of these tumors, together with emerging non-coding RNA molecules. Therefore, assessing this complex network associated with pituitary neuroendocrine tumors could bring a new era in diagnosing and treating this pathology.

The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas.

Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.

The role of glomerular morphometric features in pediatric podocytopathies - a single center study.

Podocytopathies represent a well-studied subgroup of glomerulopathies, being characterized by proteinuria due to damage or dysfunction of podocytes. Glomerular size in podocytopathies has been studied in different population, but only a few studies take in consideration the pediatric population. There are different methods to assess the glomerular size, but most of the studies report the maximal profile area as being the most accurate one. The aim of this study is to determine the range values of glomeruli in pediatric population with glomerulopathies and to establish a correlation between the measured size and several laboratory features. The patients that undergo renal biopsy in the Department of Nephrology, "Maria Sklodowska Curie" Clinical Emergency Hospital for Children, Bucharest, Romania, were divided into two groups: control vs. affected∕patient group. The control group included children that require renal biopsy for renal impairments other than high-range proteinuria (most of them recurrent microscopic asymptomatic hematuria), while the affected group had nephrotic-range proteinuria. Thirty patients were selected to be part of the control group and 30 patients in the affected group. In control group, the mean value diameter was 166.23±13.04 µm, and the area of the glomerulus had a mean value of 19 126.86±3070.83 µm². In the affected group, we obtained the following results: the mean value diameter was 192.42±28.15 µm, while the glomerular cross-sectional area had a mean value of 23 535.55±6456.57 µm². Using the linear regression, we concluded that all the cases with increased-size glomeruli had more urinary protein loss compared with the ones that had small-size glomeruli and low-range proteinuria.