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Background: Histopathological analysis represents the gold standard in clinical practice for diagnosing skin neoplasms. While the current diagnostic workflow has specialized in producing robust and accurate results, interpreting tissue architecture and malignant cellular morphology correctly remains one of the greatest challenges for pathologists. This paper aims to explore the prospect of applying x‐ray virtual histology to human skin tumor excisions and correlating it with the histological validation. Materials and Methods: Seven skin biopsies containing intriguing melanoma types and pigmented skin lesions were scanned using x‐ray Computed micro‐Tomography (μCT) and then sectioned for conventional histology assessment. Results: The tissue microarchitecture reconstructed by μCT offers detailed insights into diagnosing the malignancy or benignity of the skin lesions. Three‐dimensional reconstruction via x‐ray virtual histology reveals infiltrative patterns in basal cell carcinoma and evaluated invasiveness in melanoma. The technology enables the identification of pagetoid distributions of neoplastic cells and the assessment of melanoma depth in three dimensions. Conclusion: Although the proposed approach is not intended to replace conventional histology, the non‐destructive nature of the sample and the clarity provided by virtual inspection demonstrate the promising impact of μCT as a valid support method prior to conventional histological sectioning. Indeed, μCT images can suggest the optimal sectioning position before using a microtome, as is commonly performed in histological practice. Moreover, the three‐dimensional nature of the proposed approach paves the way for a more accurate assessment of significant prognostic factors in melanoma, such as Breslow thickness, by considering the whole micro‐volume rather than a two‐dimensional observation. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms. The impact on overall survival (OS) was assessed with the Kaplan–Meier method and log-rank test and by multivariable Cox regression. Forty-six patients with glioblastoma entered this study. Immunohistochemical expression of CD99 was present in 83%. Only the CD99wt isoform was detected by qRT-PCR and was significantly correlated with CD99 expression evaluated by IHC (rho = 0.309, p = 0.037). CD99 expression was not associated with OS, regardless of the assessment methodology used (p = 0.61 for qRT-PCR and p = 0.73 for IHC). In an exploratory analysis of The Cancer Genome Atlas, casuistry of glioblastomas CD99 expression was not associated with OS nor with progression-free survival. This study confirms a high expression of CD99 in glioblastoma but does not show any significant impact on survival. Further preclinical studies are needed to define its role as a therapeutic target in glioblastoma. [ABSTRACT FROM AUTHOR]

With the advent of immunotherapies, the field of cancer therapy has been revived with new hope, especially for cancers with dismal prognoses, such as the glioblastoma multiforme (GBM). Currently, immunotherapies should potentiate the host's own antitumor immune response against cancer cells, but it has been documented that they are effective only in small subsets of patients. Therefore, accurate predictors of response are urgently needed to identify who will benefit from immune-modulatory therapies. Brain tumors are challenging in terms of treatments. The immune response in the brain is highly regulated, and the immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes (TILs, CD3+ T cells) in certain patients and, therefore, may serve as a potential treatment target. In our study, we performed immunohistochemistry for CD3 and PD-L1 along the routine assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status and the IDH1 and 2 status in a single center cohort of 69 patients with GBM (58 primary tumors and 11 recurrences) who underwent standard multimodal therapies (surgery/radiotherapy/adjuvant temozolamide). We analyzed the association of PD-L1 tumor expression and TILs with overall survival (OS). The PD-L1 expression was observed in 25 of 58 (43%) newly diagnosed primary glioblastoma specimens. The sparse-to-moderate density of TILs, identified with CD3+ expression, was found in 48 of 58 (83%) specimens. Neither PD-L1 expression nor TILs were associated with overall survival. In conclusion, TILs and/or PD-L1 expression are detectable in the majority of glioblastoma samples, and even if they slightly relate to the outcome, they do not show a statistically significant correlation. [ABSTRACT FROM AUTHOR]

Background: High‐risk human papilloma virus (HR HPV) testing and liquid‐based cytology are used for primary cervical screening. Digital cytology, based on whole‐slide scanned samples, is a promising technique for teaching and diagnostic purposes. The aim of our study was to evaluate the interobserver and intraobserver variation in low‐grade squamous lesions, HR HPV status bias, and the use of whole‐slide scanned digital cervical cytology slides. Methods: Fifteen expert cytopathologists evaluated 71 digitalized ThinPrep slides (31 atypical squamous cells of undetermined significance [ASC‐US], 21 negative for intraepithelial lesion or malignancy, and 19 low‐grade squamous intraepithelial lesion cases). HR HPV data were accessible only in the second round. Results: In interobserver analysis, Kendall's coefficient of concordance was 0.52 in the first round and 0.58 in the second round. Fleiss' kappa values were 0.29 in the first round and 0.31 in the second round. In the ASC‐US category, Fleiss kappa increased from 0.19 to 0.22 in the second round and the increase was even higher expressed by Kendall's coefficient: from 0.42 to 0.52. In intraobserver analysis, personal scores were higher in the second round. Conclusions: The interobserver and intraobserver variability in low‐grade squamous lesions was within fair agreement values in the present study, in line with previous works. The comparison of two rounds showed that expert cytopathologists are generally unbiased by the knowledge of HR HPV data, but that being informed of the HR HPV status leads to a better agreement. Stain quality and back discomfort were highlighted as factors affecting digital cytopathology use. The interobserver and intraobserver variability in low‐grade squamous lesions was within fair agreement values and knowing high‐risk human papillomavirus status leads to better agreement. Stain quality and back discomfort were highlighted as factors affecting digital cytopathology use. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The contribution of SARS‐CoV‐2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated.Post‐mortem analysis was performed among consecutive in‐patients with COVID‐19 deceased in the Province of Trieste (2020–2022). The outcomes of the study were (i) rates of in‐hospital mortality, (ii) contribution of COVID‐19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination.A total of 1038 consecutive hospitalized patients who died with SARS‐CoV‐2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS‐CoV‐2 infection was (a) the cause of death (n = 90), (b) contributing to death (n = 304) and (c) an accompanying feature (n = 114). The incidence of SARS‐CoV‐2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS‐CoV‐2 infection (HR .15, p < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple‐vaccinated, 7% double‐vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, p < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, p < .001) compared to unvaccinated patients.COVID‐19 vaccination has substantially reduced rates of death related to SARS‐CoV‐2 infection over time and may have the ability to mitigate lung damage. [ABSTRACT FROM AUTHOR]

Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a translation factor selectively expressed by heart, skeletal muscle, nervous system and some specialized cells. Its ectopic expression relates with tumorigenesis in several types of human cancer. No data are available about the role of eEF1A2 in Triple Negative Breast Cancers (TNBC). This study investigated the relation between eEF1A2 protein levels and the prognosis of TNBC. A total of 84 TNBC diagnosed in the period 2002–2011 were included in the study. eEF1A2 protein level was measured in formalin-fixed paraffin-embedded tissues by immunohistochemistry in a semi-quantitative manner (sum of the percentage of positive cells x staining intensity) on a scale from 0 to 300. Cox regression assessed the association between eEF1A2 levels and disease-free survival (DFS) and breast cancer-specific survival (BCSS). Elevated values of eEF1A2 were associated with older age at diagnosis (p = 0.003), and androgen receptors positivity (p = 0.002). At univariate Cox analysis, eEF1A2 levels were not significantly associated with DFS and BCSS (p = 0.11 and p = 0.08, respectively) whereas adjusting for stage of disease, elevated levels of eEF1A2 protein resulted associated with poor prognosis (HR = 1.05, 95% CI: 1.01–1.11, p = 0.04 and HR = 1.07, 95% CI: 1.01–1.14, p = 0.03 for DFS and BCSS, respectively). This trend was confirmed analyzing negative versus positive samples by using categorized scores. Our data showed a negative prognostic role of eEF1A2 protein in TNBC, sustaining further investigations to confirm this result by wider and independent cohorts of patients. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: This study employs clinical/radiological evaluation in establishing the optimum imaging conditions for breast cancer imaging using the X-ray propagation-based phase-contrast tomography.Materials and Methods: Two series of experiments were conducted and in total 161 synchrotron-based computed tomography (CT) reconstructions of one breast mastectomy specimen were produced at different imaging conditions. Imaging factors include sample-to-detector distance, X-ray energy, CT reconstruction method, phase retrieval algorithm applied to the CT projection images and maximum intensity projection. Observers including breast radiologists and medical imaging experts compared the quality of the reconstructed images with reference images approximating the conventional (absorption) CT. Various radiological image quality attributes in a visual grading analysis design were used for the radiological assessments.Results: The results show that the application of the longest achievable sample-to-detector distance (9.31 m), the lowest employed X-ray energy (32 keV), the full phase retrieval, and the maximum intensity projection can significantly improve the radiological quality of the image. Several combinations of imaging variables resulted in images with very high-quality scores.Conclusion: The results of the present study will support future experimental and clinical attempts to further optimize this innovative approach to breast cancer imaging. [ABSTRACT FROM AUTHOR]

Brown bowel syndrome (BBS) is an extremely unusual condition characterized by an orange-brown discoloration of the bowel and intestinal motility disorders secondary to fat-soluble vitamin deficiency and malabsorption from many different causes. We present the case of a middle-aged woman suffering for years of chronic constipation with recurrent intestinal subocclusion, who was diagnosed BBS on surgical biopsy material. Nutritional supplementary treatment was tried, but her symptoms did not improve, and a decision was finally made in favor of a surgical approach. After subtotal colectomy and continual vitamin nutritional supplementation, she has now regular transit without the use of laxatives. BBS is a rare complication of long-term malabsorption manifesting as intestinal motility disorders, which can lead to severe complications. This condition is only partially responsive to vitamin supplementation, and most cases require surgery. [ABSTRACT FROM AUTHOR]

Undifferentiated embryonal sarcoma of the liver is a malignancy with poor prognosis observed more frequently in children between 6 and 10 years old and very rarely found in adults. We present a case of embryonal sarcoma of the liver in a 60-year-old woman without significant medical history who presented to our attention with constitutional symptoms. Preoperative assessments did not show alterations in blood chemistry or tumor markers. Imaging studies showed a huge mass lying in the right abdominal quadrants, strictly adherent to the liver. The tumor was partially cystic with a thickened wall, sporadic contrast enhancement, and solid component. The patient underwent excision of the mass with associated liver bisegmentectomy S5-S6. Postoperative course was uneventful. The definitive histological diagnosis revealed the presence of embryonal sarcoma of the liver. We describe the clinical, histopathological, and therapeutic options adopted in the multimodal treatment of this disease. [ABSTRACT FROM AUTHOR]

Background. Radiofrequency ablation (RFA) has been recently advocated as an effective technique for the treatment of symptomatic benign thyroid nodules. It is not known to what extent it may affect any subsequent thyroid surgery and/or histological diagnosis. Materials and Methods. RFA was performed on 64 symptomatic Thy2 nodules (benign nodules) and 6 symptomatic Thy3 nodules (follicular lesions/follicular neoplasms). Two Thy3 nodules regrew after the procedure, and these patients accepted to undergo a total thyroidectomy. Here we present how RFA has affected the operation and the final pathological features of the surgically removed nodules. Results and Conclusions. RFA is effective for the treatment of Thy2 nodules, but it should not be recommended as first-line therapy for the treatment of Thy3 nodules (irrespective of their mutational status), as it delays surgery in case of malignancy. Moreover, it is unknown whether RFA might promote residual tumor progression or neoplastic progression of Thy3 lesions. Nevertheless, here we show for the first time that one session of RFA does not affect subsequent thyroid surgery and/or histological diagnosis. [ABSTRACT FROM AUTHOR]

CD40 triggering may result in antitumor effects of potentially high clinical relevance. To gain insights important for patient selection and to identify adequate targeting techniques, we investigated CD40 expression in human cancer tissues and generated a replication-incompetent recombinant vaccinia virus expressing CD40 ligand (rVV40L). Its effects were explored in vitro and in vivo upon direct CD40 targeting on malignant cells or macrophage activation. CD40 expression was analyzed by immunohistochemistry in tumor and stromal cells in a multi-tumor array including 836 specimens from 27 different tumor types. Established tumor cell lines were used to explore the capacity of rVV40L to induce malignant cell apoptosis and modulate functional profiles of polarized macrophages. CD40 expression was detectable in significantly higher numbers of stromal as compared to malignant cells in lung and breast cancers. CD40 ligation following rVV40L infection induced apoptosis in CD40(+) cancer cells, but only in the presence of intact specific signal transduction chain. Importantly, rVV40L infection promoted the induction of TNF-α-dependent antitumor activity of M1-like macrophages directed against CD40(-) targets. CD40-activated M1-like macrophages also displayed enhanced ability to CXCL10-dependently recruit CD8+ T cells and to efficiently present cancer cell intracellular antigens through cross-priming. Moreover, rVV-driven CD40L expression partially "re-educated" M2-like macrophages, as suggested by detectable CXCL10 and IL-12 production. Most importantly, we observed that intra-tumoral injection of rVV40L-infected human macrophages inhibits progression of human CD40(-) tumors in vivo. First evidences of anticancer activity of rVV40L strongly encourage further evaluations. [ABSTRACT FROM AUTHOR]

• A multidisciplinary approach is helpful in evaluating sudden deaths (SD) • Genetic testing can help to determine the cause of death in cases of SD. • arrhythmogenic left ventricular cardiomyopathy (ALVC) is a rare cause of SD. • the few reported autopsy cases of ALVC tend to involve desmoplakin mutations. • we present a rare and fatal case of Filamin-C mutation detected post-mortem in ALVC. Forensic pathologists are frequently asked to investigate cases of sudden death (SD), and identifying the cause of death can be of particular importance, especially where it may be necessary to perform family screening among the relatives of the victim. A multidisciplinary approach inclusive of genetic analysis is therefore strongly recommended. According to forensic practice, arrhythmogenic cardiomyopathy (ACM) is a well-known cause of SD. However, cases of SD caused by a left ventricular pattern of ACM diagnosed at autopsy are rarely reported in the literature. We present the case of an apparently healthy, 37-year-old male found dead at his home. At autopsy, multiple foci of epicardial and mid-wall fibrous and fibro-adipose tissue were observed within the left ventricle and, to a lesser extent, within the interventricular septum. Toxicology was negative, whereas a filamin C truncating mutation was detected through genetic analysis. To our knowledge, this is the first instance of arrhythmogenic left ventricular cardiomyopathy being diagnosed at autopsy. [ABSTRACT FROM AUTHOR]

Background: Cell blocks (CB) are an established technique in non-gynecological cytology, but experience in gynecological cytology is still relatively limited. In this study, we compared the diagnostic agreement between liquid-based cytology (LBC) and CB using whole slide digital imaging (WSI)., Methods: WSI of 82 specimens (41 LBC and 41 CB) were evaluated independently by three observers., Results: The overall agreement was 0.463 for all 82 cases including both LBC and CB, 0.439 for LBC alone, and 0.484 for CB alone. Agreement was highest for HSIL, NILM, cancers and lower for borderline (ASC-US, ASC-H). There was no significant difference in agreement between LBC and CB., Conclusions: WSI of CB can be used for the diagnosis of cervical lesions and may be particularly useful in cases with high atypical cellularity or large hyperchromatic cell groups., (© 2024 Wiley Periodicals LLC.)

Purpose: The aim of this observational study was to highlight high resolution CT scan characteristics of COVID-19-associated pulmonary aspergillosis (CAPA) with a focus on the detection of de-novo appeared or evolved bronchiectasis., Methods: From March 2020 to May 2021, we enrolled 350 consecutive mechanically ventilated ICU patients with COVID-19. Patients with CAPA and at least one chest CT scan performed within 15 days from the diagnosis were included. Two radiologists were asked to identify typical and atypical signs of COVID-19 pneumonia. Bronchiectasis locations were described and a modified Reiff score was calculated, as severity score. A total of 19 CAPA patients (median age 71.0, Interquartile range (IQR) 62.5-75.0; male 16, 84.2%) were included., Results: According to the 2020 ECMM/ISHAM criteria, 18 patients had probable CAPA and one had proven CAPA. The median time between hospital admission and CT scan was 21 days (IQR 14.5-25.0). The incidence of bronchiectasis in the study population was 57.9% (n = 11). Tubular bronchiectasis was detected in 10 patients and were scored as follows: three patients had a score of 1, three patients had a score of score 2, one patient had a score of 5 and four patients had a score of 6. Eight patients had a previous CT scan (performed at hospital admission), among them: 5 patients developed de-novo bronchiectasis, while 2 patients demonstrated a volumetric increase of bronchiectasis. At the 6-months follow-up, the mortality rate for patients with CAPA was >60%., Conclusion: the radiologic detection of de-novo appearance or volumetric increase of bronchiectasis in COVID-19 should lead clinicians to search for fungal superinfections., (© 2021 The Author(s). Published by BRI.)

The aim of this study was to analyze the diagnostic role of BAP1 in effusion cytology. Effusions (n = 258), consisting of 53 malignant mesotheliomas and 205 other cancers, the majority carcinomas (62 breast, 60 ovarian, 31 lung, 51 carcinomas of other origin, 1 melanoma), were analyzed for BAP1 expression using immunohistochemistry. BAP1 was lost in 46 (87%) mesotheliomas compared with 4 (2%) of 205 other cancers (P < .001), resulting in sensitivity and specificity of 87% and 98%, respectively. There was no significant difference between peritoneal (n = 14) and pleural (n = 39) mesotheliomas. The 4 carcinomas with loss of BAP1 included 1 ovarian, 1 breast, 1 uterine cervical, and 1 gastric carcinoma. The present study supports the role of BAP1 as a highly sensitive and specific marker for malignant mesothelioma in serous effusions and argues for inclusion of this test in all specimens in which this diagnosis is considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Germline mutations of the oncosuppressor gene breast cancer 1-associated protein 1 (BAP1) were recently related to an autosomal-dominant tumor predisposition syndrome (BAP1-TPDS), characterized by uveal melanoma, malignant mesothelioma (MM), cutaneous melanoma, and other malignancies. The demonstration that BAP1 mutations are strongly associated with MM has provided a real breakthrough in the study of genetic predisposition in MM, that may explain why only a fraction of asbestos-exposed individuals go on to develop MM., Materials and Methods: To evaluate the possible role of BAP1 mutations in the epidemiology of sporadic MM, and their relationship with asbestos exposure, we determined the prevalence of germline BAP1 mutations by the Sanger method in a group of 29 asbestos-exposed patients, 21 of which were diagnosed with MM. They were residents of Trieste, a ship-building town in Northeast Italy with a very high incidence of mesothelioma., Results: We identified non-obviously pathogenetic germline sequence variants of BAP1 in 3/29 patients and in 2/21 MM cases (10%)., Conclusion: Non obviously pathogenic germline sequence variants of BAP1 were found. Nevertheless, limitations of predictive web tools allowed us to comment on some interesting peculiarities of our findings., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)