Not only a small liver - The pathologist's perspective in the pediatric liver transplant setting

open8Pediatric liver transplantation represents a safe and long-lasting treatment option for various disease types, requiring the pathologist's input. Indeed, an accurate and timely diagnosis is crucial in reporting and grading native liver diseases, evaluating donor liver eligibility and identifying signs of organ injury in the post-transplant follow-up. However, as the procedure is more frequently and widely performed, deceptive and unexplored histopathologic features have emerged with relevant consequences on patient management, particularly when dealing with long-term treatment and weaning of immunosuppression. : In this complex and challenging scenario, this review aims to depict the most relevant histopathologic conditions which could be encountered in pediatric liver transplantation. We will tackle the conditions representing the main indications for transplantation in childhood as well as the complications burdening the post-transplant phases, either immunologically (i.e., rejection) or non-immunologically mediated. Lastly, we hope to provide concise, yet significant, suggestions related to innovative pathology techniques in pediatric liver transplantation.openGambella, Alessandro; Mastracci, Luca; Caporalini, Chiara; Francalanci, Paola; Mescoli, Claudia; Ferro, Jacopo; Alaggio, Rita; Grillo, FedericaGambella, Alessandro; Mastracci, Luca; Caporalini, Chiara; Francalanci, Paola; Mescoli, Claudia; Ferro, Jacopo; Alaggio, Rita; Grillo, Federic

Pathologist's approach to paediatric and neonatal eosinophilic gastrointestinal disorders

Children are not simply miniature adults. The evaluation of their gastrointestinal disorders is therefore different from that in full-grown adults and requires a particular clinical/pathologic approach. : Different studies have tried to assess the normal eosinophil distribution in the gastrointestinal tract in adults while very few studies have investigated the paediatric population, consequently complicating the pathologist's ability in identifying an abnormal number of eosinophils in this setting of patients. : When evaluating gastrointestinal tract biopsies with eosinophilia, eosinophilic count must be considered along with other histological features like eosinophil distribution in the gastrointestinal wall, their degranulation, cryptitis and crypt abscesses, other accompanying inflammatory cells, apoptotic bodies, foreign material or microorganisms; these findings, although rarely specific, may be a useful aid for diagnosis. : Reports should not include a diagnosis of primary eosinophilic gastrointestinal disorders (EoGID) if clinical data and test results do not rule out other forms of gastrointestinal eosinophilia. A more descriptive definition like "with eosinophilic pattern" should be favoured over a specific diagnosis of "eosinophilic disorder" in order to avoid potential confusion between different entities

Genesi di una forma tra idea, geometria e materia. Francesco Berarducci. Analisi della Chiesa di San Valentino a Villaggio Olimpico

Il complesso parrocchiale di S. Valentino si trova all’ interno del Villaggio Olimpico a Roma. Gli edifici nati per ospitare gli atleti partecipanti ai Giochi Olimpici di Roma del 1960 si trasformeranno succes- sivamente in un vero e proprio quartiere. Nel 1979 l’architetto Francesco Berarducci fu incaricato della realizzazione del progetto dell’attuale chiesa. Tramite i suoi disegni ideali e utopici possiamo cercare di comprendere al meglio la sua visione del mondo e della sua architettura. Tramite questi piccoli pezzi di carta, a volte stropicciati e rovinati ritroviamo la filosofia di intervento e i valori fondanti della propria ricerca. Possiamo dire senza enfasi che questi schizzi rappresentano la vera essenza del pensiero di Berarducci nei confronti del tema del- la chiesa.Al centro della propria riflessione Berarducci auspicava e affermava la necessità del ritorno ad un linguaggio formale più lineare e pacato che mettesse in risalto la serenità spirituale dell’edificio ecclesiastico. Il modello di riferimento è l’architettura romana.The parish complex of S.Valentino is located inside the OlympicVillage in Rome.The buildings created to house the athletes participating in the 1960 Olympic Games in Rome will later be transformed into a real neighborhood. In 1979 the architect Francesco Berarducci was commissioned to carry out the project for the current church.Through his ideal and utopian designs we can try to better understand his vision of the world and its architecture.Through these small pieces of paper, sometimes wrinkled and damaged, we find the philosophy of intervention and the founding values of our research.We can say without emphasis that these sketches represent the very essence of Berarducci’s thinking towards the theme of the church.At the center of his reflection Berarducci hoped and affirmed the need for a return to a more linear and calm formal language that would highlight the spiritual serenity of the ecclesiastical building. The reference model is Roman architectur

Morphology and Molecular Features of Rare Colorectal Carcinoma Histotypes

Several histopathological variants of colorectal carcinoma can be distinguished, some associated with specific molecular profiles. However, in routine practice, ninety/ninety-five percent of all large bowel tumors are diagnosed as conventional adenocarcinoma, even though they are a heterogeneous group including rare histotypes, which are often under-recognized. Indeed, colorectal cancer exhibits differences in incidence, location of tumor, pathogenesis, molecular pathways and outcome depending on histotype. The aim is therefore to review the morphological and molecular features of these rare variants of intestinal carcinomas which may hold the key to differences in prognosis and treatment

Genesi di una forma tra idea, geometria e materia, Francesco Berarducci. Analisi della Chiesa di San Valentino al Villaggio Olimpico

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A New Fully Automated Processing and Embedding Technique for Cytological Cell Blocks

Minimally invasive approaches have become standard operating procedure in the collection of tissue and cells for diagnosis, prognosis and therapeutic prediction

Ultrastructural examination of lung “cryobiopsies” from a series of fatal COVID-19 cases hardly revealed infected cells

Ultrastructural analysis of autopsy samples from COVID-19 patients usually suffers from significant structural impairment possibly caused by the rather long latency between death of the patient and an appropriate sample fixation. To improve structural preservation of the tissue, we obtained samples from ventilated patients using a trans-bronchial “cryobiopsy” within 30 min after their death and fixed them immediately for electron microscopy. Samples of six COVID-19 patients with a documented histopathology were systematically investigated by thin section electron microscopy. The different samples and areas inspected revealed the ultrastructural correlates of the different phases of diffuse alveolar damage, including detachment of the alveolar epithelium, hyperplasia of type 2 cells, exudates, and accumulation of extracellular material, such as the hyaline membranes and fibrin. Macrophages and neutrophilic granulocytes were regularly detected. Structural integrity of endothelium was intact in regions where the alveolar epithelium was already detached. Aggregates of erythrocytes, leukocytes with fibrin, and thrombocytes were not observed. Coronavirus particles were only found in and around very few cells in one of the six patient samples. The type and origin of these cells could not be assessed although the overall structural preservation of the samples allowed the identification of pulmonary cell types. Hence, the observed alveolar damage is not associated with virus presence or structural impairment due to ongoing replication at later stages of the disease in fatal cases, which implies that the lung damage in these patients is at least propagated by alternative mechanisms, perhaps, an inappropriate immune or stress response.Peer Reviewe

Ultrastructural examination of lung "cryobiopsies" from a series of fatal COVID-19 cases hardly revealed infected cells

Ultrastructural analysis of autopsy samples from COVID-19 patients usually suffers from significant structural impairment possibly caused by the rather long latency between death of the patient and an appropriate sample fixation. To improve structural preservation of the tissue, we obtained samples from ventilated patients using a trans-bronchial "cryobiopsy" within 30 min after their death and fixed them immediately for electron microscopy. Samples of six COVID-19 patients with a documented histopathology were systematically investigated by thin section electron microscopy. The different samples and areas inspected revealed the ultrastructural correlates of the different phases of diffuse alveolar damage, including detachment of the alveolar epithelium, hyperplasia of type 2 cells, exudates, and accumulation of extracellular material, such as the hyaline membranes and fibrin. Macrophages and neutrophilic granulocytes were regularly detected. Structural integrity of endothelium was intact in regions where the alveolar epithelium was already detached. Aggregates of erythrocytes, leukocytes with fibrin, and thrombocytes were not observed. Coronavirus particles were only found in and around very few cells in one of the six patient samples. The type and origin of these cells could not be assessed although the overall structural preservation of the samples allowed the identification of pulmonary cell types. Hence, the observed alveolar damage is not associated with virus presence or structural impairment due to ongoing replication at later stages of the disease in fatal cases, which implies that the lung damage in these patients is at least propagated by alternative mechanisms, perhaps, an inappropriate immune or stress response

Very Early Onset-IBD: evidence for the need of a multidisciplinary approach

Very early onset inflammatory bowel disease (VEO-IBD) represents approximately 25% of cases of IBD-like colitis occurring during childhood and, by definition, it is characterized by an onset prior to 6 years of age. This subgroup of patients presents significant differences from IBD occurring in older children and in adults, including a more severe clinical course, a reduced responsiveness to conventional IBD therapy, and a greater proportion of cases featuring an underlying monogenic disorder. Histological findings from gastro-intestinal (GI) biopsies are characterized by an IBD-like, apoptotic or enterocolitis-like pattern, complicating the differential diagnosis with other pediatric diseases involving GI tract. Moreover, individuals with monogenic disorders may develop significant comorbidities, such as primary immunodeficiency (PID), impacting treatment options. Without an appropriate diagnosis, the clinical course of VEO-IBD has greater potential for escalated treatment regimens involving extensive surgery, more intensive medical therapies and, even more important, inadequate recognition of underlying monogenic defect that may lead to inappropriate (sometimes fatal) therapy. For these reasons, an adequate context leading to an appropriate diagnosis is imperative, calling for a close collaboration between pediatricians, pathologists, geneticists, and immunologists

Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: Interplay between germline and somatic variations

Due to the high mutational somatic burden of Cutaneous Malignant Melanoma (CMM) a thorough profiling of the driver mutations and their interplay is necessary to explain the timing of tumorigenesis or for the identification of actionable genetic events. The aim of this study was to establish the mutation rate of some of the key drivers in melanoma tumorigenesis combining molecular analyses and/or immunohistochemistry in 93 primary CMMs from an Italian cohort also characterized for germline status, and to investigate an interplay between germline and somatic variants. BRAF mutations were present in 68% of cases, while CDKN2A germline mutations were found in 16 % and p16 loss in tissue was found in 63%. TERT promoter somatic mutations were detected in 38% of cases while the TERT -245T > C polymorphism was found in 51% of cases. NRAS mutations were found in 39% of BRAF negative or undetermined cases. NF1 was expressed in all cases analysed. MC1R variations were both considered as a dichotomous variable or scored. While a positive, although not significant association between CDKN2A germline mutations, but not MC1R variants, and BRAF somatic mutation was found, we did not observe other associations between germline and somatic events. A yet undescribed inverse correlation between TERT -245T > C polymorphism and the presence of BRAF mutation was found. It is possible to hypothesize that -245T > C polymorphism could be included in those genotypes which may influence the occurrence of BRAF mutations. Further studies are needed to investigate the role of -245T > C polymorphism as a germline predictor of BRAF somatic mutation status