Correlation Studies between S100 Protein Level and Soluble MIA or Tissue MelanA and gp100 (HMB45) Expression in Cutaneous Melanoma.

(1) Background: Cutaneous melanoma (CM) originates from melanocytes and causes 90% of skin cancer deaths; therefore, the comparison of different soluble and tissue markers could be valuable in the detection of melanoma progression and therapy monitoring. The present study is focused on the potential correlations between soluble S100B and MIA protein levels in different melanoma stages or with tissue expression of S100, gp100 (HMB45), and MelanA biomarkers. (2) Methods: Soluble S100B and MIA levels were evaluated by means of immunoassay methods in blood samples from 176 patients with CM, while tissue expressions of S100, MelanA, and gp100 (HMB45) were detected by means of immunohistochemistry in 76 melanomas. (3) Results: Soluble S100B correlated with MIA in stages III (r = 0.677, p < 0.001) and IV (r = 0.662, p < 0.001) but not in stages I and II; however, 22.22% and 31.98% of stage I and II patients, respectively, had high values for at least one of the two soluble markers. S100 tissue expression correlated with both MelanA (r = 0.610, p < 0.001) and HMB45 (r = 0.476, p < 0.01), while HMB45 and MelanA also significantly positively correlated (r = 0.623, p < 0.001). (4) Conclusions: Blood levels of S100B and MIA corroborated with melanoma tissue markers expression could help to improve the stratification process for patients with a high risk of tumor progression.

Intra-Abdominal Malignant Melanoma: Challenging Aspects of Epidemiology, Clinical and Paraclinical Diagnosis and Optimal Treatment-A Literature Review.

According to European consensus-based interdisciplinary guidelines for melanoma, cutaneous melanoma (CM) is the most deadly form of dermatological malignancy, accounting for 90% of the deaths of skin cancer patients. In addition to cutaneous melanoma, mucosal melanoma occurs in four major anatomical sites, including the upper respiratory tract, the conjunctiva, the anorectal region, and the urogenital area. As this cancer type metastasizes, a classification used in the current medical literature is the distinction between secondary lesions and primary malignant melanoma of the abdominal cavity. Given that malignant melanoma is the most common cancer that spreads to the gastrointestinal tract, different imaging modalities compete to diagnose the phenomenon correctly and to measure its extension. Treatment is primarily surgery-based, supported by immunotherapy, and prolongs survival, even when performed at stage IV illness. In the end, special forms of malignant melanoma are discussed, such as melanoma of the genito-urinary tract and amelanotic/achromic melanoma. The importance of this present literature review relies on yielding and grouping consistent and relevant, updated information on the many aspects and challenges that a clinician might encounter during the diagnosis and treatment of a patient with intra-abdominal melanoma.

Influence of the microenvironment dynamics on extracellular matrix evolution under hypoxic ischemic conditions in the myocardium.

The extracellular matrix (ECM) consists of fibrillary and non-fibrillary components in the extracellular zone, and fulfills structural and signaling roles. Cardiac insult can lead to cardiomyocyte death, which subsequently determines dynamic changes of ECM composition and regulates cellular responses, ultimately contributing to cardiac repair. The present retrospective study on a small batch selected from the database of the Pathology Department of 'Sf. Pantelimon' Hospital aimed to determine which molecules may have a role in the dynamics of ECM using histopathology and immunohistochemistry methods. The study batch was composed of cases with cardiac ischemic conditions who died at various ages of myocardial infarcts. Tissue samples were taken from the myocardium of the left ventricle (anterior and lateral walls), and multiple series of histological sections were produced and analyzed using immunohistochemistry for collagen type I (Col-1), tenascin C (Tn-C), matrix metalloproteinase 9, CD34, and CD68. Col-1 and Tn-C showed variable patterns of fibrillar plexiform network, associated with a high micro-vascular density of newly formed capillaries revealed by CD34, and an interstitial infiltrate with histiocytes demonstrated by CD68 presence. The ECM represents therefore a polymorphic microenvironment with its own dynamics that is in continuous change, involving a large spectrum of heterogenous molecules, which play different roles in myocardium remodeling under hypoxic ischemic conditions.

Cytomorphological study of thyroid carcinoma.

The most common neoplasm of the endocrine system is found in the thyroid gland with a significant increase in recent decades largely due to modern diagnostic methods. Thyroid tumors generally have a favorable evolution, but there are also aggressive variants with a poor prognosis. In these aggressive tumors, the most reliable method of detecting and making a differential diagnosis is represented by ultrasound-guided fine-needle cytopuncture, confirmed by histopathological examination. Although fine-needle aspiration puncture and cytological examination are considered to have a high sensitivity and specificity, diagnostic certainty is established later only by histopathological examination. Fine-needle aspiration cytopuncture of the thyroid gland correlated with histopathological examination has played a crucial role in recognizing and identifying variants of papillary carcinoma known to have aggressive biological behavior, especially in cases of poorly differentiated carcinoma. Recognition of aggressive variants of papillary carcinoma is of major importance in the prognosis and clinical management of patients. The aim of this study was to present the correlations found in a series of thyroid tumors from patients treated in surgery and oncology departments, as well as tumors accidentally detected during autopsies in the department of forensics. All the cases selected in the study benefited from a complex histopathological diagnosis adapted to each case in order to ensure maximum efficiency.

A multidisciplinary approach in the diagnostic challenge of GIST.

Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal lesions of the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by overexpression of the tyrosine kinase receptor, protein product of c-KIT gene (KIT). In this retrospective study, conducted over a period of 10 years, we retrieved from our database, a total number of 57 patients, admitted and operated in the surgical department of 'Sf. Pantelimon' Emergency Clinical Hospital, Bucharest, for digestive tumors, histopathologically confirmed as GISTs. More than half of the cases presented as surgical emergencies and the tumors found during the surgical procedures, which proved to be GISTs, were sometimes difficult to differentiate from other mesenchymal tumors, both for the clinician and the pathologist. The diagnosis of GIST relies mostly on pathology and immunohistochemistry, but also on clinical and imagistic data. The most common emergencies were digestive hemorrhage (associated with gastric location), followed by intestinal obstruction (especially for the ileal localization). The largest dimensions corresponded to gastric location. For selected indications (upper digestive sites), upper digestive endoscopy approaches 100% sensitivity. This study focuses on diagnosis of GISTs sustained by both clinical and imagistic methods, along with histopathology and immunohistochemistry techniques, according to the World Health Organization 2019 criteria. Even though the differential diagnosis of these tumors is challenging, an interdisciplinary cooperation with a multiple approach increases the odds of a correct positive diagnosis.

Incidence of thyroid carcinomas in an extended retrospective study of 526 autopsies.

Thyroid cancer accounts for 1% of all malignancies, and is becoming increasingly common worldwide. The literature reports a prevalence of ~50% of thyroid nodules detected during autopsies in subjects with unknown thyroid pathology. An extended retrospective study of 526 autopsy cases was performed to identify the prevalence of thyroid carcinoma, among various types of thyroid nodules identified incidentally. Tissue samples were taken from thyroid nodules, for investigation of the presence of thyroid carcinoma, along with their macroscopic and microscopic features by means of histopathology and immunohistochemistry (IHC) methods. Histopathological diagnosis of malignancy was found in 51 cases of analyzed thyroid samples. Systematic detailed studies demonstrated that a thyroid gland, apparently normal on macroscopic examination, may be the site of pathological manifestations, sometimes presenting carcinomatous findings. Among thyroid carcinomas, the highest frequency was that of papillary microcarcinomas, which have a long evolution, and are incidentally detected during autopsies. Papillary microcarcinoma is an extremely common incidental finding and the vast majority of these tumors pursue a benign course. Furthermore, it is therefore necessary to create national screening programs for the early detection of thyroid carcinoma.

Fibroblast involvement in cardiac remodeling and repair under ischemic conditions.

Cardiac fibroblasts play a main role in the physiological turnover of the extracellular matrix, as well as its pathological remodeling. A study was performed on a batch of 23 cases who died of various cardiac complications secondary to scarring myocardial infarctions. The aim of the study was to assess the fibroblast involvement in cardiac repair under ischemic conditions after myocardial infarction. Tissue myocardial samples from the left ventricle were taken from these cases for microscopy examination, in order to investigate the type and degree of fibrosis as well as the presence of cardiac interstitial fibroblasts. Multiple series of histological sections were also performed and examined, along with immunohistochemical analysis. The fibroblasts were diffusely distributed in the interstitium among the residual cardiomyocytes, showing variable expression of vimentin and smooth muscle actin. During cardiac remodeling, there was a successive interstitial deposition, first of reticulin fibers and then of collagen fibers, leading to interstitial fibrosis and myocardial replacement. There was a correlation between vimentin and smooth muscle actin expression and collagen deposition. Fibrosis with cardiac remodeling is based on maintaining proliferation capacity of the fibroblast and its capacity of protein synthesis in the extracellular matrix. Under hypoxic ischemic conditions, followed by myocardial infarction, the fibroblast switches phenotype and transdifferentiate into myofibroblast, contributing to the healing by secreting extracellular matrix proteins and collagen deposition, with subsequent cardiac remodeling and regulation of the micro-environment metabolism.

Heterogeneity of antigenic constellation in human hepatocellular carcinoma.

Hepatocellular carcinoma is one of the primary liver malignancies responsible for over a million deaths per year worldwide (approximately 10% of all deaths in the adult age range). The diagnosis of HCC can be difficult and often requires the use of more than one microscopic technique. A retrospective study was performed on a study batch of 42 cases that died of HCC due to metastasis or other secondary complications. Tissue samples were taken in order to investigate the tumour antigenic constellation by means of IHC method using a large variety of antibodies. In situ hybridization was also performed for albumin mRNA to assess the albumin expression in some selected cases. Telomerase activity was investigated using IHC method for the hTERT catalytic subunit. A cocktail of hepatic cytokeratins (CK8, 18) combined with Hep Par-1 and associated to albumin proved to be more powerful than albumin alone in differentiating HCC and increased the value of tumour diagnosis. hTERT expression was proportionally reverse to the tumour degree of differentiation, but was independent from the expression of tumour-proliferating indexes. The heterogeneity of the antigenic constellation in hepatocellular carcinoma suggests an antigenic mosaicism, which can be expressed a synchronous or metachronous manner, depending on the tumour degree of differentiation.

Dormant cardiac stem cells: A promising tool in cardiac regeneration.

Stem cells represent an old niche with various new potential therapeutics. Besides drug treatment, reperfusion procedures and surgical revascularization, stem cell therapy could be a good option in ischemic cardiac diseases. A study was performed on a small group of cases who died of cardiac arrhythmia secondary to scarring myocardial infarctions. Tissue cardiac samples were taken from these cases (from the anterior and lateral wall of the left ventricle), for microscopy examination, in order to investigate the presence of cardiac stem cells (CSC). Multiple series of histological sections were also performed and examined, along with immunohistochemical analysis (IHC). The cells were identified in close contact with the residual ischemic cardiomyocytes, in the proximity of the myocardial collagenous scar, in old myocardial infarctions. They were activated by hypoxic ischemia and were influenced by the capillary microvascular density and the interstitial micro-environment conditions. In chronic intermittent ischemia they seem to turn themselves from dormant quiescent cells into activated progenitor committed cells.

Retrohepatic Gallbladder Masquerading as Hydatid Cyst in a Patient with Right Liver Agenesis.

Agenesis of the right liver is a rare congenital anomaly which can be associated with an ectopic gallbladder. Hereby, it is presented the case of a 39-year-old man investigated for right upper quadrant abdominal pain and diagnosed at computed tomography with a cystic liver mass initially considered as hydatid cyst. At laparotomy, it was discovered agenesis of the right liver and the presumed hydatid cyst was a retrohepatic gallbladder with lithiasis. Cholecystectomy was performed with an uneventful outcome. Reassessment of the computed tomography images by an experienced radiologist confirmed the intraoperative diagnosis. Although agenesis of the right liver with retrohepatic gallbladder is an exceptional appearance, surgeons should be aware of this anomaly because it can raise challenging issues of diagnosis and surgical planning during cholecystectomy.

Sudden death due to isolated segmentary coronary vasculitis.

Coronary vasculitis is a group of conditions occurring either independently or associated with another diseases characterized by an inflammation of the blood vessel's wall and subsequent fibrinoid necrosis, occlusion, stenosis, or aneurismal dilatations. Coronary vasculitis leading to sudden cardiac death has rarely been described in the scientific literature.We present the case of an 18-year-old football player who collapsed when playing football. The patient remained in a deep coma (glasgow coma scale = 3) in the hospital for another 4 hours before dying. During hospitalization, he was diagnosed with acute anterolateral myocardial infarction with ST elevation. An autopsy was performed the next day, and on the coronary vessels were identified a dilatation with luminal extension, which, based on clinical and pathological criteria, was considered to be an isolated, coronary polyarteritis nodosa.

Gestational lung adenocarcinoma: case report.

Gestational cancer is a dramatic situation, with a deep impact on the patient and family, with an overall incidence of 1 per 100 pregnancies. Lung cancers are extremely rare during pregnancy but have become more frequent in past years, as the mean age of pregnancy has increased. The purpose of this case report is to present a gestational lung adenocarcinoma, with metastasis in the liver and ovaries, diagnosed in the third trimester, with a fatal outcome in days after birth through cesarean section.

Sudden death due to dissection of the thoracic aorta associated with dissection and rupture of the pulmonary artery: report of two cases.

We present two cases of dissection of the thoracic aorta associated with dissection and rupture of the pulmonary artery. In both cases the initial dissection was hypothesized to occur in the thoracic aorta, with secondary dissection and rupture of the pulmonary artery.

Particularities regarding the etiology of sepsis in forensic services.

If in clinical practice definitive diagnostic criteria had been established, after death sepsis is often difficult to diagnose, especially if a site of origin is not found or if no clinical data are available. This article will analyze the etiology of sepsis in a medical-legal service with emphasis on the differences in diagnosing it in clinical and forensic environments. A total of 78 cases of sepsis cases diagnosed or confirmed at the autopsy were selected. The etiological agent was determined either during the hospitalization or by postmortem bacteriology. A high prevalence of Gram-negative sepsis was found, especially multidrug-resistant micro-organisms. Most frequent etiological agents were Acinetobacter baumannii, Escherichia coli, Enterobacter, Enterococcus, Pseudomonas, and Klebsiella. Polymicrobial sepsis is much more frequent than in nonforensic cases. In legal medicine, the prevalence of Gram-negative sepsis is much higher than in nonforensic autopsies, and the point of origin is shifted toward the skin and the gastrointestinal system.

Sildenafil Reduces Inflammation and Prevents Pulmonary Arterial Remodeling of the Monocrotaline - induced Disease in the Wistar Rats.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a rare and severe disease with incompletely under stood pathogenesis. PAH is associated with pulmonary arterial remodeling and inflammation. We evaluated the effects of Sildenafil on the Monocrotaline (MCT) -induced disease in Wistar rats, for potential benefit in the early phases of inflammation and vascular remodeling. MATERIAL AND METHODS: MCT-injected rats, MCT-injected sildenafil-treated rats (starting day 1 with 2 x 0.2 mg/day; total of 2 mg/kgc/day) and saline-injected control rats were evaluated at day 14 and day 28 following MCT for pulmonary morphological changes - lesions, inflammation (inflammator y index), arterial morphometry (hypertrophy index), immunohistochemistry for smooth muscle cell marker. OUTCOMES: The administration of sildenafil following MCT significantly reduced the severity of inflammation in the acute stage of the disease (reduction of the inflammatory index by 6.038% (p <0.05)) and prevented pulmonary arterial remodeling (reduction of the hypertrophy index by 7.306% (p<0.001)). It also improved survival in the early phase with a mortality rate during the first 14 days of 4 in the MCT- exposed rats vs 1 in the MCT-exposed sildenafil-treated rate. CONCLUSIONS: Early administration of sildenafil in the MCT experimental PAH improves inflammation and survival, and prevents pulmonary vascular remodeling. Our study suggests that one of the mechanisms involved, besides vasodilatation and anti-proliferative effect, could be a direct anti-inflammatory effect of sildenafil.

Sudden death due to coronary tree hypoplasia.

A 20-year-old woman complained for several weeks before her death of unspecific epigastric pains. Such episodes were labeled as "dyspeptic episode." A month later, once again she started to complain about stomach pains, then she collapsed unconscious. She was rushed to a hospital, where she was admitted in cardiorespiratory arrest. An electrocardiogram revealed a ventricular fibrillation. All resuscitation efforts were unsuccessful. The autopsy revealed nonspecific general changes (subpleural petechiae and blood pooling). Dissection of the coronary arteries revealed a normal topography of coronary arteries but a marked hypoplasia of all the subepicardial coronary arteries (maximum diameter of left anterior descending coronary artery = 1.9 mm, maximum diameter of right coronary artery = 1.43 mm). Furthermore, the left anterior descending coronary artery was slightly compressed by a fibrous bridge at about 1.5 cm of its origin; a fibrinoleukocytic thrombus has formed immediately above this bottleneck, obstructing the entire lumen of the artery. Microscopic examination revealed an area of recent myocardial necrosis; diffuse subendocardial fibrosis, with extension into the subjacent myocardium, disorganizing the myocardial fibers; and variable thickening of the vascular walls with periarteriolar fibrosis. Weigert stain has shown marked intimal hyperplasia, either focal or diffuse, in different segments of vascular wall, accompanied by disruption of the internal elastic lamina due to subintimal cellular proliferation, in the medium branches of coronary arteries. The micrometric measurements showed that intimal thickening was at least the size of the media (∼358 vs 356.8 µm) and sometimes double.