Postmortem Pathological Findings Research Articles

Postmortem pathologic findings in dogs that underwent total body irradiation and hematopoietic cell transplant: A case series of five dogs with B-cell multicentric lymphoma.

Alternative therapies that can help achieve complete remission in dogs with lymphoma include total body irradiation and hematopoietic cell transplant, though there are few reports describing successes and pathologic sequelae of these procedures. During a 10-year period, 94 dogs with multicentric lymphoma received a hematopoietic cell transplant following total body irradiation at North Carolina State University College of Veterinary Medicine. Seven of these 94 dogs (7%) died prior to discharge, five (5%) of which presented for postmortem examination. Of these dogs, four received an autologous hematopoietic cell transplant, while one received a haploidentical allogeneic hematopoietic cell transplant. All five dogs had bone marrow depletion with all hematopoietic lines affected. Three had systemic candidiasis, while two had bacterial infections. To the authors' knowledge, this is the first report to document pathologic findings and development of systemic mycoses in dogs post total-body irradiation therapy and hematopoietic cell transplant.

Comparative Study of Postmortem MRI and Pathological Findings in Malignant Brain Tumors.

This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.

Correlation Between the Level od Atherosclerosis and Pathological Features of Coronary Artery Disease: A Study of 100 Autopsy Cases

Objective: Atherosclerosis is a generalized, chronic disease of large and medium-sized muscular elastic arteries. Relation between intensity of atherosclerosis and coronary artery disease, and risk factors of atherosclerosis could not been revealed completely by autopsy studies. We aimed to renew this shortage of knowledge with our autopsy study prospectively. 
 Methods: One hundred cases were autopsied within 48 h after death. Atherosclerotic risk factor data were collected including age, gender, height, weight, smoking and any chronic coronary artery disease. Atherosclerosis severity was evaluated macroscopically by examining the inner surfaces of the vascular lumens and revealed with postmortem pathological findings of coronary artery disease.
 Results: The mean age was 42 ± 22 years. Seventy-four percent of cases were male, while 26% were female. Smoking duration ranged from 1 to 50 years with a mean duration of 17 ± 12 years. Existence of atherosclerosis in main vessels were also in correlation with age, duration of smoking and BMI (Body Mass Index) (p

A Systematic Review of Lung Autopsy Findings in Elderly Patients after SARS-CoV-2 Infection

Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient's age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children's and adults' autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care.

Pathological Aspects and Immunohistochemical Evaluation of Troponin C in the Cardiovascular System of Dogs With Pheochromocytoma

Functional pheochromocytomas secrete catecholamines and have been associated with cardiovascular lesions in dogs. This study aimed to describe the postmortem pathological findings in the cardiovascular system of dogs with pheochromocytoma and to evaluate the expression of cardiac troponin C in these dogs using immunohistochemical analysis. Twelve cases were identified, with a mean age of 10.6 years. The heart of all dogs was enlarged and with concentric hypertrophy of the left ventricular myocardium. Histological analysis showed cardiomyocyte necrosis and degeneration in the myocardium, with frequent bands of contraction, fibrosis, inflammation, and thickening of the medium-caliber arteries in the myocardium. There was a marked decrease or absence of immunolabeling in necrotic cardiomyocytes. We conclude that IHC for troponin C can be a useful tool for detecting myocardial necrosis in dogs with pheochromocytomas, including early cases of necrosis with only incipient cardiac changes where overt histologic abnormalities are not immediately apparent in the cardiomyocytes.

Salmonella Pullorum in a Free-range Chicken Farm in Western Bahia, Brazil

Background:Industrial poultry farming has developed progressively in Brazil, conferring the country a prominent position on the national and international scene. Likewise, alternative poultry farming is an important economic activity for small-scale family farmers. However, shortcomings related to sanitary management lead to increased occurrence of avian diseases, such as those caused by Salmonella spp. Despite salmonellosis has been described in industrial establishments, reports in alternative farms are less common, therefore the objective of this study was to describe the occurrence of salmonellosis in free-range chickens in the municipality of Barra, Western Bahia, Brazil. Cases: The poultry farmer reported the occurrence of diarrhoea in his chicken flock since the acquisition of the batch of chicks. Initially, carrying out the medicinal treatment of the birds, there was clinical improvement, however, successive recurrences of clinical signs occurred, such as diarrhoea, apathy, anorexia, and death of some birds. Upon learning about the case, an epidemiological investigation of the flock was carried out, and it was noted that some of the birds were retracted, apathetic, anorexic, and a lot of diarrheic faeces of a yellowish-white appearance were also observed. The entire flock had a history of vaccination against diseases: newcastle disease, infectious bronchitis, gumboro disease, and fowlpox. For better evaluation, five birds were necropsied, enabling the observation that the animals had a good body score. However, the necropsy revealed lesions such as splenomegaly, hepatomegaly, and enteritis in the three birds initially analysed (Animals 1, 2, and 3). The other birds (Animals 4 and 5) were submitted to evaluation for Eimeria sp. oocysts by means of scrapings from the intestinal mucosa, and there were no structures compatible with oocysts. Faecal samples were collected from another six birds in the flock for coproparasitological examination, and the presence of oocysts was not detected. Finally, sera from 20 birds in the flock were collected for the Rapid Serum Agglutination Test (SAR) for the detection anti-Salmonella Pullorum antibodies. Discussion: The diagnosis was based on clinical evaluation, post-mortem pathological findings of the necropsied birds, epidemiological data and confirmed with SAR testing, whereby 11 birds were seropositive for Salmonella enterica subspecies enterica serovar Pullorum. The prevalence of S. Pullorum is poorly described in alternative farming. Based on the farmer's report, it is believed that the chicks were purchased already infected, because birds from the same batch, also purchased by neighbouring producers, showed the same clinical signs. The unsatisfactory sanitation in the flock was another factor that may have favoured the persistence of the bacteria, since, the lack of removal of organic matter is a source of nutrients for microorganisms, and this may have favoured the multiplication and maintenance of the bacteria in the down feathers, feed, and water. The elimination of S. Pullorum through the faeces, in addition to the density of the birds, may have led to transmission to the other healthy birds. However, the knowledge and adoption of prophylactic measures in free-range chicken farms is a crucial factor in minimizing the occurrence of outbreaks and thus avoiding a future public Health Problem. Keywords: poultry pathology, alternative poultry farming, salmonellosis. Título: Samonella Pullorum em criação de galinhas caipiras no Oeste da Bahia, Brasil Descritores: patologia aviária, avicultura alternativa, salmoneloses.

Histopathological Findings in COVID-19 Cases: A Systematic Review.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has turned into one of the most serious public health crises of the last few decades. Although the disease can result in diverse and multiorgan pathologies, very few studies have addressed the postmortem pathological findings of COVID-19 cases. Active autopsy findings amid this pandemic could be an essential tool for diagnosis, surveillance, and research. We aimed to provide a comprehensive picture of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) histopathological features of different body organs through a systematic review of the published literature. A systematic search of electronic databases (PubMed, ScienceDirect, Google Scholar, medRxiv, and bioRxiv) for journal articles of different study designs reporting postmortem pathological findings in COVID-19 cases was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for conducting the review. A total of 50 articles reporting 430 cases were included in our analysis. Postmortem pathological findings were reported for different body organs: pulmonary system (42 articles), cardiovascular system (23 articles), hepatobiliary system (22 articles), kidney (16 articles), spleen and lymph nodes (12 articles), and central nervous system (seven articles). In lung samples, diffuse alveolar damage (DAD) was the most commonly reported finding in 239 cases (84.4%). Myocardial hypertrophy (87 cases, 51.2%), arteriosclerosis (121 cases, 62%), and steatosis (118 cases, 59.3%) were the most commonly reported pathological findings in the heart, kidney, and the hepatobiliary system respectively. Autopsy examination as an investigation tool could lead to a better understanding of SARS-CoV-2 pathophysiology, diagnosis, and management, subsequently improving patient care.

Nintedanib vs pirfenidone in the management of COVID-19 lung fibrosis: A single-centre study.

COVID-19 pneumonia is complicated with residual lung fibrosis, as evidenced by imaging and postmortem pathological findings. In addition to steroids, we compared the efficacy of nintedanib and pirfenidone in the management of COVID-19 lung fibrosis measured by CT severity score (CTSS). All cases of COVID-19 pneumonia diagnosed as COVID-19 positive by RT-PCR having SpO2 ⩽ 96% and CTSS ⩾ 10 even after 15 days were included in the study. The patients were divided into three groups. All three groups received steroids at a dose of 1 mg/kg body weight of prednisolone or equivalent. The first group received steroids alone, the second group received pirfenidone with steroids and the third group received nintedanib with steroids. All patients were followed up at 6 and 12 weeks. The primary endpoint of our study was to find out any improvement in CTSS. Out of 90 patients, 56 patients completed the study. Among three groups, 19 (33.9%) patients received steroids (control) only, 16 (28.6%) patients received steroids with pirfenidone and 21 (37.5%) patients received steroids with nintedanib. The study population had a mean (±SD) age of 52.5 ± 10.1 years, mean (±SD) C-reactive protein of 97.1 ± 102.2 mg/L (normal <6 mg/L), mean (±SD) serum ferritin 459.4 ± 305.5 ng/mL (normal <250 ng/mL), mean (±SD) serum d-dimer level 2.1 ± 2.6 μg/mL (normal <0.5 μg/mL) and mean (±SD) CTSS of 16.9 ± 4.3. There was significant improvement in CTSS in group receiving nintedanib compared to pirfenidone at 12 weeks (3.67 ± 1.21 vs 9.07 ± 1.12) with a p-value <0.01. Along with steroids in the treatment of COVID-19 lung fibrosis, there was a significant improvement in lung CTSS with nintedanib compared to pirfenidone.

Is Microthrombosis the Main Pathology in Coronavirus Disease 2019 Severity?-A Systematic Review of the Postmortem Pathologic Findings.

Objectives:This systematic review attempts to retrieve and report the findings of postmortem studies including the histopathologic data of deceased coronavirus disease 2019 patients and to review the manifestations of coronavirus disease 2019–associated thrombotic pathologies reported in the recent literature.Data Sources:PubMed, Excerpta Medica Database, and Cochrane library between December 1, 2019, and August 26, 2020.Study Selection:Investigators screened 360 unique references, retrieved published autopsy series, and report on the postmortem histopathologic information on patients who had died of coronavirus disease 2019.Data Extraction:Investigators independently abstracted all available data including study design, participant demographics, key histopathologic findings, disease severity markers, duration of hospital stay, and cause of death.Data Synthesis:From the 65 eligible studies, 691 total completed autopsies were included in evidence synthesis. Histopathologic evaluation of the lungs revealed presence of diffuse alveolar damage in 323 of 443 patients and pulmonary microthrombi in 242 of 326 patients. Deep venous thrombosis and pulmonary embolism were found in 41% and ~15%, respectively, of the cadavers examined for thromboembolic events. d-dimer levels were generally higher in patients with severe clinical course of coronavirus disease 2019. Plasma levels of ferritin, lactate dehydrogenase, interleukin-6, and C-reactive protein were higher in nonsurvivors when compared with survivors. Overall, microthrombi and extensive angiogenesis of lung vasculature were the most common pathologic findings in the lungs and microthrombi in most of the assessed organ-tissue.Conclusions:Diffuse alveolar damage was the most predominant feature in the lungs of coronavirus disease 2019 patients who underwent postmortem assessment. Widespread pulmonary microthrombosis and extensive pulmonary angiogenesis, in addition to frequent pulmonary and extrapulmonary microthrombotic and thromboembolic findings in patients with coronavirus disease 2019, appear to be consistent with the disease-specific hypercoagulability. Further discovery efforts in assessing the link between coronavirus disease 2019, hypercoagulable state, and immunothrombosis are warranted. In the interim, increased attention to anticoagulant treatment approaches in coronavirus disease 2019 patients is needed.

Postmortem radiologic and pathologic findings in COVID-19: The Toronto experience with pre-hospitalization deaths in the community

Over a year after the initial emergence of the disease, the COVID-19 pandemic continues to strain healthcare systems worldwide. The value of feedback and connection between clinical care, public health, and death investigation systems has never been more clear. To this end, knowledge of the radiologic and histopathologic features of fatal COVID-19 is critical for those working with the living and the dead. Most of the medical descriptions of COVID-19 are either focused on clinical in vivo medical imaging or autopsies performed following an intensive course of treatment over days to weeks prior to death, rather than deaths in the community prior to hospitalization. Here we report the postmortem computed tomography (PMCT) and lung histopathology in five fatal cases of COVID-19 that were subject to medicolegal death investigation. All individuals died in the community without medical treatment, or after a brief terminal admission to hospital. In these cases, the main PMCT findings included: diffuse lung changes including ground glass-type opacifications, a “crazy paving” appearance, variable areas of more dense consolidation, and relatively few areas of spared/less involved lung parenchyma. The unifying histopathology was diffuse alveolar damage in various stages of cellular evolution. In all cases, the pattern of PMCT and the lung histopathology corroborated the diagnosis of COVID-19. We propose the routine use of PMCT as a potential screening tool for the identification of COVID-19 related fatalities in the medicolegal setting where a paucity of historical information may not otherwise permit the identification of this disease prior to autopsy.

Abstract 16066: Genomic Autopsy of 103 Sudden Deaths in the Young Reveals the Importance of Cardiomyopathy Genes and Non-Mendelian Risk

Introduction: Genetic testing after sudden death in the young can identify pathogenic cardiac gene variants. Hypothesis: Genomic methods, coupled with phenotype evaluation, reveal non-Mendalian risks. Methods: We conducted clinical analysis and whole genome sequencing on 103 decedents aged 1-40 (mean age at death 23.7 years) accrued prospectively from 2015 to 2019 across 22 states. Postmortem pathological findings were classified as: known cardiac disorders, findings of uncertain significance (FUS), or sudden unexplained death (SUD, indicating no postmortem pathological diagnosis). Parental DNA and clinical data were obtained where possible. Variants were classified by an independent clinical genetic laboratory. Results: Among the 103 decedents, 34 had a postmortem clinical diagnosis, 23 had FUS, and 46 were classified as SUD. Pathogenic/likely pathogenic (P/LP) variants in arrhythmia or cardiomyopathy genes were identified in 17 (16.5%) decedents. The distribution of P/LP variants was not associated with age at death (OR 1.01 [0.97, 1.05], p=0.54); however, a multivariable analysis including decedent phenotype, ancestry and sex demonstrated that younger decedents had a higher burden of curated P/LP/VUS variants (effect size -1.5, p=0.0019). DNA from 31 parent-decedent trios and 14 parent-decedent dyads revealed 9 transmitted P/LP variants and 1 de novo P/LP variant. More than half of parents transmitting a P/LP variant (5/9) did not have clinical findings associated with the genotype. Conclusions: Whole genome sequencing effectively revealed P/LP variants in cases of sudden death in the young, implicating both arrhythmia and cardiomyopathy genes. In addition, both genotype and phenotype analyses suggest additional non-Mendelian risk mechanisms.

Importance and guidelines of postmortem examination on COVID-19 cases: An overview

Since the outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) occurred in December 2019, in Wuhan, China, the COVID-19 has spread to 216 countries, areas, and territories and killed more than 400,000 people worldwide. On March 11, the World Health Organization (WHO) declared COVID-19 a pandemic. The pathological findings of COVID-19 by postmortem biopsy were first reported in April 2020. Since then, there have been many publications regarding the postmortem pathological findings of different organs of COVID-19 patients. Well-performed systemic autopsy examination on patients with related diseases, acute respiratory distress syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus has provided critical information for better understanding the pathogenesis of the emerging infectious diseases in the past. An overview on the importance and guidelines of postmortem examination on suspected or confirmed COVID-19 patients is presented.

Chronic gastric impaction and dilatation in horses: Clinical signs, diagnosis, treatment options and pathologic findings – A case series

The aim of this study was to summarize and evaluate clinical appearance, laboratory parameters, special ancillary diagnostic tests, treatments and post-mortem pathological findings of chronic gastric impaction and dilatation in horses. Chronic gastric impaction and dilatation is a rare, progressive disease, which is usually detected in its advanced stage. Its aetiology has not yet been fully clarified. Acute primary gastric impaction (from excess volume intake) and secondary gastric impaction (from reflux from the small intestine) must be differentiated from chronic gastric impaction and dilatation. Suspected causes of chronic gastric impaction and dilatation include pyloric stenosis, gastric ulcers, gastric tumours, indigestible feed, feed with high fibre content and dental problems. Motility disorders with resulting gastric impaction and dilatation have also been described in the context of liver diseases. Additional theories suggest damage to the vagus nerve or the intramural nervous system of the stomach and aplasia of the autonomous ganglia of the myenteric and submucosal plexus. It is a retrospective case study of four cases of chronic gastric impaction and dilatation between 2010 and 2013 concerning clinical appearance, laboratory parameters, ancillary diagnostic tests, treatment options and post-mortem pathological findings. For comparison, an additional case of delayed gastric emptying with successful conservative treatment is presented. In one case, nerve degeneration was confirmed and could possibly explain the chronic gastric impaction. A recurrent finding was the adaptive enlargement of the stomach with significant thinning of the muscularis, which was evident in all cases. This is likely to be the result of chronic dilation with a gradually prolonged filling of the stomach leading to 'stretching' of the stomach wall and therefore also a loss of motility, which could be equated to dilated cardiomyopathy, where cardiac output volume decreases with dilation. Gross pathology revealed greatly enlarged stomachs with dry impacted feed material of 43 kg, 46 kg and 108 kg. The treatment options for the disease, whether conservative or surgical depend on the severity and cause of the gastric impaction, and are said to have a very poor or unfavourable prognosis. Chronic gastric impaction can lead to a rupture of the stomach and therefore the prognosis is generally suspected to be grave. Perhaps early identification of delayed gastric emptying and chronic gastric impaction via repetitive gastroscopy could allow for a more successful treatment.

Cardiomyopathies as a Cause of Sudden Cardiac Death (SCD) in Egypt: Recognition and Preventive Strategies Needed

This study aimed at evaluating the epidemiological characteristics and pathological features of different types of cardiomyopathies in Egypt, highlighting the role of the forensic pathologist in identifying cases of cardiomyopathies and initiating for their families a possible genetic study aiming at prevention of sudden death. All cases with sudden cardiac death (SCD) due to cardiomyopathies during the period from the beginning of January 2010 until the end of December 2014 (5 years) were included in this study. All hearts underwent detailed gross and histological examination. Circumstances of death, medical history, and post-mortem pathological findings were thoroughly&nbsp; investigated. Out of 535 cases of sudden cardiac death, there were 22 cases (4.1%) diagnosed as having cardiomyopathies; sudden death was their first presentation. Eighteen cases (81.8%) were male, with the 4th decade (11 cases, 50%) being the most affected age; severe physical activity and exertion were evident in death circumstances of 14 cases (63.6%); pathological evaluation revealed that hypertrophic cardiomyopathy was the most frequent type, being diagnosed in 10 cases (45%). Cardiomyopathies are an infrequent cause of sudden cardiac death. Most deaths are in children and adults, so cases are of high social impact that demands multidisciplinary research and resources. In all cases of SCD, forensic autopsy should be done. Forensic study is the key to identifying an affected family and the starting point regarding assessing them.

Genotypic and phenotypic spectrum of CADASIL in Japan: the experience at a referral center in Kumamoto University from 1997 to 2014.

This study elucidates the genotypic and phenotypic spectrum and histopathological findings related to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Japan. For this single-center retrospective observational study, we enrolled 215 patients who were clinically suspected of having CADASIL and were examined at Kumamoto University from 1997 to 2014, and we diagnosed CADASIL in 70 patients. We found 19 different NOTCH3 mutations in the patients, with the NOTCH3 Arg133Cys mutation being found most frequently. We also found the Arg75Pro mutation, a cysteine-sparing NOTCH3 mutation. CADASIL patients with this Arg75Pro mutation were frequently found throughout Japan, and fewer patients with the Arg75Pro mutation showed MRI hyperintensity in the anterior temporal pole compared with patients with other NOTCH3 mutations. Significantly more CADASIL patients with the NOTCH3 Arg133Cys mutation had hyperintensity in the external capsule compared with CADASIL patients with the other mutations not including the NOTCH3 Arg75Pro mutation. We also showed postmortem pathological findings of the first Japanese CADASIL case with the NOTCH3 Arg133Cys mutation, and histopathological findings of fresh frozen skin biopsy specimens of CADASIL patients. In conclusions, the spectrum of NOTCH3 mutations in Japanese CADASIL patients may be partially explained by founder effects. Genotype-phenotype correlations may exist in CADASIL, which should be considered so as to make an accurate diagnosis of CADASIL in each population. Fresh frozen skin biopsy specimens may aid detection of Notch3 deposits on vascular walls for an improved diagnosis of CADASIL.

Monochorionic twins discordant for mosaic trisomy 14

Monochorionic-diamniotic twins are usually monozygotic twins and known to be associated with adverse obstetric and perinatal outcomes. Cases of discordant karyotype of monozygotic twins are rare and most involves sex chromosomes. We present the first case of monochorionic twins with discordant karyotype manifested as mosaic trisomy 14 in one twin (B) and a normal karyotype in the other (A). We describe the postmortem pathological and imaging findings of the trisomic twin and for the first time neuropathological findings of this entity. Metaphase chromosome analysis of twin B using fetal tissue showed a 47,XX, +14 karyotype. Chromosomal microarray analysis (CMA) using fetal tissue revealed 38% mosaicism. CMA with placental tissue from both sides demonstrated normal karyotype and confirmed monozygosity, highlighting the value of array based testing on diagnosing mosaicism and zygosity.

Lesiones ateroscleróticas tempranas y nivel de colesterol post mortem en un grupo de niños colombianos

Atherosclerosis is an asymptomatic chronic disease, which begins at early age and is difficult to detect during this stage. Prospective studies suggest a causal relationship between total serum cholesterol levels during childhood and early adolescence and the development of cardiovascular diseases in adulthood. The aim of this study was to evaluate the prevalence of early atherosclerotic lesions in the aorta artery of children and its relationship with post-mortem serum cholesterol levels. Post-mortem samples of blood and aorta were taken from 43 subjects aged less than 17 years old. Histopathological analysis (intimal thickening and inflammatory infiltrates) of the thoracic aorta and measurement of total serum cholesterol were performed. The analysis showed thickening of the intima and lymphocyte infiltrates in 93% of children, and macrophage infiltrates in 79.1% of cases. A relationship between the highest terciles of total serum cholesterol levels and the presence of multiple lesions in the aorta wall was found ( P <0.05). This group of children had a high prevalence of early inflammatory atherosclerotic lesions positively related with serum cholesterol levels. To our knowledge this study represents the first report of a relationship between post-mortem total serum cholesterol levels and pathological findings of macrophages and lymphocytes infiltrates in the aorta wall.

Whole‐exome sequencing of a unique brain malformation with periventricular heterotopia, cingulate polymicrogyria and midbrain tectal hyperplasia

We report a case of an infant with unique and unreported combinations of brain anomalies. The patient showed distinctive facial findings, severe delay in psychomotor development, cranial nerve palsy and seizures. Brain magnetic resonance imaging performed at 5 days of age revealed complex brain malformations, including heterotopia around the mesial wall of lateral ventricles, dysmorphic cingulate gyrus, and enlarged midbrain tectum. The patient unexpectedly died at 13 months of age. Postmortem pathological findings included a polymicrogyric cingulate cortex, periventricular nodular heterotopia, basal ganglia and thalamic anomalies, and dysmorphic midbrain tectum. Potential candidate genes showed no abnormalities by traditional PCR-based sequencing. Whole-exome sequencing confirmed the presence of novel gene variants for filamin B (FLNB), guanylate binding protein family member 6, and chromosome X open reading frame 59, which adapt to the autosomal recessive mode or X-linked recessive mode. Although immunohistochemical analysis confirmed the expression of FLNB protein in the vessel walls and white matter in autopsied specimens, there may be functional relevance of the compound heterozygous FLNB variants during brain development.

Novel frameshift mutation (Pro171fsX21) in neonatal type 2 Gaucher's disease

Gaucher's disease is caused by a deficiency of glucocerebrosidase (GBA) and results in the accumulation of glucocerebroside within macrophages. We report on a 33+2 gestational week premature infant whose family history was significant for a previously undiagnosed premature sibling with similar clinical features, including severe hydrops fetalis, hepatosplenomegaly, skin lesions at birth followed by death. The diagnosis of Gaucher's disease type 2 in the present case was based on postmortem pathological findings and a subsequent gene analysis that indicated a heterozygous condition for the novel deletion mutation at GBA cDNA nucleotide position 630 resulting in the frameshift (Pro171fsX21) in exon 6 and a G→A transition mutation at GBA cDNA nucleotide position 887 (Arg257Gln) in exon 7.

Evolving models of tumor origin and progression

History of cancer disease models clearly illustrates the evolving nature of these concepts. Since such models undergo continual revisions and additions as a result of underlying medical research, they also tend to reorganize knowledge and allow perceiving previously unseen relationships. Growth of medical thought has been influenced for many centuries by an ancient Hippocratic concept of disease seen as a disturbance in bodily “humors.” True mechanisms of cell and tissue injury started to be elucidated only with the advent of postmortem pathological findings. Concerning cancer, when first disease-producing bacteria were identified in the nineteenth century, also neoplasms were treated as infectious diseases. Foreign organisms were thought to be present inside tumors. However, this hypothesis could not be confirmed by microscopic or histochemical studies. The latter suggested, instead, that tumors were rather formed by abnormal cells. Cancer was then started to be regarded as a disease of cells. This interpretation was radically altered by later developments in genetics which suggested that neoplasms can be treated as genetic diseases as pathologic cellular lesions are caused by mutations in specific genes. More recent models have compared carcinogenesis to evolutionary processes. Due to genetic instability, successive mutations, appearing in cells, lead to selection of cancer cells which feature specific phenotypic traits. The newest data indicate that there may be also a link between cancer and mutated stem cells. The review discusses main concepts of tumor origin forwarded since the beginnings of the nineteenth century.