Histopathological Gap in Aortic Diseases: A Prospective Analysis.

Aortic dissection (AD) is a critical cardiovascular condition with the potential for devastating consequences. This study evaluated the histological changes in the aorta wall in patients with AD and aortic aneurysm (AA) who received surgical aortic replacement. Histopathological data showed that modifications of the media layer (p = 0.0197), myxomatous aspect (p = 0.0001), and subendothelial layer degeneration (p = 0.0107) were more frequently seen in AA versus AD samples. Patients with AA were approximately twice as likely to develop histological changes than those with AD (p = 0.0037). Patients with moderate or severe medial degeneration had a higher chance of developing AD (p = 0.0001). Because the histopathological score proved to be a predictor of both in-hospital and overall mortality, its evaluation should become the standard of care in any patients who undergo aortic replacement. Individualized postoperative management might be influenced by the histopathological aspect of the aortic layer.

The Importance of Aortic Valve Bicuspid Phenotype in Valvular Evolution in Pediatric Patients: A Case Report and Literature Mini-Review.

Bicuspid aortic valve (BAV) is the most commonly encountered congenital malformation in the pediatric population, associated with aortic leaflet degeneration and aortopathy. However, studies on BAV and its complications in children are limited. We present the case of a 16-year-old with type 1B BAV with a raphe with fusion between the right and non-coronary cusps who exhibited severe aortic stenosis, regurgitation, and progressive dilatation of the ascending aorta. Surgical intervention, including aortic valve and aortic root replacement, was performed due to the patient's deteriorating condition. Histopathological examination revealed degenerative changes and calcifications in the aortic valve and mucoid fibrosis in the ascending aorta. The results are consistent with BAV patients being predisposed to aortic stenosis and regurgitation due to increased mechanical stress and hemodynamic abnormalities. Although more common in adults and a rare complication in pediatric patients, calcification was previously observed concurrently with rapid valve degeneration in our daily practice. Further studies are needed to improve our understanding of the mechanisms underlying BAV-related complications and refine treatment strategies for pediatric patients.

Matrix Metalloproteinases and Heart Transplantation-A Pathophysiological and Clinical View.

Heart transplantation is undergoing a continuous development, with rates of success increasing substantially due to advances in immunosuppressive therapy and surgical techniques. The most worrying complication occurring after cardiac transplantation is graft rejection, a phenomenon that is much affected by matrix metalloproteinases (MMPs), with the role of these proteases in the cardiac remodeling process being well established in the literature. A detailed investigation of the association between MMPs and cardiac rejection is necessary for the future development of more targeted therapies in transplanted patients, and to discover prognostic serum and immunohistochemical markers that will lead to more organized therapeutic management in these patients. The aim of this review is therefore to highlight the main MMPs relevant to cardiovascular pathology, with particular emphasis on those involved in complications related to heart transplantation, including cardiac graft rejection.

Signet-Ring Cell Squamous Cell Carcinoma: A Biphenotypic Neoplasm of the Gastro-Esophageal Junction with Uncertain Biological Potential: Case Report and Literature Review.

The signet-ring cell variant of squamous cell carcinoma (SCC) is an extremely rare histological subtype, with only 24 cases (including the present case) reported in the Medline database: 15 affecting the external surface of the body, 3 in the lung, 2 affecting the uterine cervix, 1 involving the gingiva, another one affecting the esophagus and the present case that is the first reported at the gastro-esophageal junction (GEJ). In one case, the location of the lesion was not mentioned. A 59-year-old male patient underwent segmental eso-gastrectomy for carcinoma of the GEJ. The microscopic examination showed a pT3N1-staged SCC composed of solid nests admixed in over 30% of the tumor, with cells having eccentrically located nuclei and clear vacuolated cytoplasm. The signet-ring cells did not show mucinous secretion and were positive for keratin 5/6 and vimentin, with nuclear expression of ß-catenin and Sox2 and focal membrane positivity for E-cadherin. Based on these features, the case was considered a signet-ring SCC with epithelial-mesenchymal transition. Thirty-one months after surgery, the patient was disease-free, with no local recurrence and no known distant metastases. In SCC, a signet-ring cell component might be an indicator of the dedifferentiation of tumor cells towards a mesenchymal molecular subtype.

Mucin-Phenotype and Expression of the Protein V-Set and Immunoglobulin Domain Containing 1 (VSIG1): New Insights into Gastric Carcinogenesis.

In gastric cancer (GC), intestinal metaplasia (IM) is a common precursor lesion, but its relationship to the MUC2/MUC5AC/CDX2 axis is not completely understood. Although V-set and immunoglobulin domain containing 1 (VSIG1) is supposed to be a specific marker for gastric mucosa and GC, respectively, no data about its relationship with IM or mucin phenotype have been published. The aim of our study was to explore the possible linkage between IM and these four molecules. The clinicopathological features of 60 randomly selected GCs were examined in association with VSIG1, MUC2, MUC5AC and CDX2. Two online database platforms were also used to establish the transcription factors (TFs) network involved in MUC2/MUC5AC/CDX2 cascade. IM was more frequently encountered in females (11/16 cases) and in patients below 60 years old (10/16 cases). Poorly differentiated (G3) carcinomas tended to show a loss of CDX2 (27/33 cases) but not of MUC2 and MUC5AC. MUC5AC and CDX2 were lost in parallel with the depth of invasion of the pT4 stage (28/35 and 29/35 cases), while an advanced Dukes-MAC-like stage was only correlated with CDX2 and VSIG1 loss (20/37 and 30/37 cases). VSIG1 was directly correlated with MUC5AC (p = 0.04) as an indicator of gastric phenotype. MUC2-negative cases showed a propensity towards lymphatic invasion (37/40 cases) and distant metastases, while CDX2-negative cases tended to associate with hematogenous dissemination (30/40 cases). Regarding the molecular network, only 3 of the 19 TFs involved in this carcinogenic cascade (SP1, RELA, NFKB1) interacted with all targeted genes. In GC, VSIG1 can be considered an indicator of gastric phenotype carcinomas, where carcinogenesis is mainly driven by MUC5AC. Although infrequently encountered in GC, CDX2 positivity might indicate a locally advanced stage and risk for vascular invasion, especially in tumors developed against the background of IM. The loss of VSIG1 indicates a risk for lymph node metastases.

V-set and immunoglobulin domain containing 1 (VSIG1) as an emerging target for epithelial-mesenchymal transition of gastric cancer.

V-set and Immunoglobulin domain containing 1 (VSIG1) is a cell-cell adhesion molecule which role in the genesis and evolution of gastric cancer (GC) is not understood. Only three Medline-indexed papers have focused on the role of VSIG1 in GC. The clinicopathological features of 94 GCs were examined in association with immunohistochemical (IHC) patterns of VSIG1, E-cadherin, and ß-catenin which were assessed in the tumor core (central) vs. invasive edge. Cases were classified depending on the VSIG1 expression: membrane/membrane in both core and invasive front; null/negative staining in both core and invasive front; and cases with translocational patterns: membrane core/cytoplasmic buds and cytoplasmic core/null buds. Most of the tumors showed null pattern (n = 54). Cases with translocational patterns (n = 20) were GCs with a high lymph node ratio value (≥ 0.26) and advanced Dukes-MAC-like stage. Of the 20 total cases, 9 showed membrane-to-nuclear translocation of ß-catenin and loss of E-cadherin, as indicators of epithelial-mesenchymal transition. All cases with membrane/membrane pattern (n = 20) involved the distal stomach. The poorest overall survival was registered in patients with subcellular translocation of VSIG1, compared to those with either membrane/membrane or null patterns (p = 0.002). In GC, VSIG1 acts as an adhesion membrane protein but its membrane-cytoplasmic translocation can be an indicator of epithelial-mesenchymal transition due to cytoplasmic VSIG1-mediated activation of canonical Wnt/ß-catenin signaling pathway.

In-House Validated Map of Lymph Node Stations in a Prospective Cohort of Colorectal Cancer: A Tool for a Better Preoperative Staging.

Preoperative staging of colorectal cancer (CRC) based on imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) is crucial for identification and then removal of the positive lymph nodes (LNs). The aim of this study was to evaluate the correlation between preoperatively seen morphologic criteria (number, size, shape, structure, borders, or enhancement patterns) and histopathological features of LNs using an in-house validated map of nodal stations. A total of 112 patients with CRC that underwent surgery were preoperatively evaluated by CT scans. The locoregional, intermediate, and central LNs were CT-mapped and then removed during open laparotomy and examined under microscope. The analysis of correlations was interpreted using the suspicious-to-positive ratio (SPR) parameter. The greatest correlation was found in tumors located in the sigmoid colon, descending colon and middle rectum; SPR value was 1.12, 1.18, and 1.26, respectively. SPR proved to be 0.59 for cases of the transverse colon. Regarding the enhancement type, the dotted pattern was mostly correlated with metastatic LNs (OR: 7.84; p < 0.0001), while the homogenous pattern proved a reliable indicator of nonmetastatic LNs (OR: 1.99; p < 0.05). A total of 1809 LNs were harvested, with a median value of 15 ± 1.34 LNs/case. Transdisciplinary approach of CRC focused on pre-, intra-, and postoperatively mapping of LNs might increase the accuracy of detecting metastasized nodes for tumors of the distal colon and middle rectum but not for those of the transverse colon. In addition to morphologic criteria, the enhancement pattern of LNs can be used as a predictor of nodal involvement improving the CT-based preoperative staging.

Chylous Ascites, Unusual Association with Ductal Pancreatic Adenocarcinoma with Plasmacytoid Morphology: A Case Report and Literature Review.

Chylous ascites represents a relatively uncommon condition. In this paper, we present a case of chyloperitoneum associated with pancreatic ductal adenocarcinoma (PDAC) and a review of literature regarding chylous ascites. A 76-year-old male patient was admitted in emergency department with acute abdomen. A pancreatic cancer was suspected. Subtotal spleno-pancreatectomy, for a nodular mass infiltrating the mild and distal portion of the pancreas, was necessary. During surgical intervention in the peritoneal cavity, a moderate quantity of whitish and thick consistency fluid with milk-like appearance was observed to be accumulated. After examination of the fluid, chyloperitoneum was diagnosed. The histologic examination showed a PDAC, with multiple emboli in lymph vessels, with tumor cells with plasmacytoid morphology, diagnosed as lymphangiosis carcinomatosa. The patient died at 3 weeks after surgical intervention. In patients with pancreatic cancer and chylous ascites, suspicion of tumor-related blockage of the lymphatic flow should be suspected. Prognosis of PDAC should be evaluated not only based on the number of lymph node metastases, but also considering the number of lymph vessels with tumor emboli and the architecture of tumor cells. This is the first reported case of a PDAC with plasmacytoid morphology of lymphangiosis carcinomatosa.

Benefits of the 8th American Joint Committee on Cancer System for Hepatocellular Carcinoma Staging.

PURPOSE: We aimed to emphasize the prognostic impact of differences included in the 8th versus the previous 7th edition of AJCC (American Joint Committee on Cancer) Cancer Staging manual for hepatocellular carcinoma (HCC). METHODS: A number of 87 consecutive HCCs were retrospectively evaluated and staged, using the 7th and 8th edition of AJCC staging systems. The clinicopathological parameters were correlated with the overall survival rate. No preoperative chemotherapy was received by any of the patients. RESULTS: According to the 7th edition of AJCC manual, 52 of the 87 cases were staged as pT2 and 35 as pT1. After restaging, according to the 8th edition, 23 of the 52 pT2 cases were understaged as pT1b, and the rest of the 29 remained as pT2. Regarding the 35 HCCs classified as pT1, using 7th edition, all of them were restaged as pT1a. Compared to the 7th staging system, using the 8th edition of AJCC manual, the percentage of pT2 tumors significantly decreased, from 59.77 to 33.33%. The patient's gender, age, tumor focality, and grade of differentiation did not prove to have any prognostic value. Regarding pT stage, it does not influence the overall survival rate, independently from the used staging system. CONCLUSION: The staging criteria, in the most recent edition of AJCC, are simplified and allowed tumor understaging. These changes do not have independent prognostic value. The prognostic impact of pT understaging should be evaluated in larger cohorts.

COVID-19 Like Findings in a Fatal Case of Idiopathic Desquamative Interstitial Pneumonia Associated With IgA Glomerulonephritis in a 13-Month-Old Child.

In the COVID-19 era, patients with severe acute respiratory syndrome (SARS) are suspected to be associated with SARS-CoV-2 infection. The aim of this paper is to present a case with COVID-like pneumonia, with fatal evolution. The clinical aspects were correlated with the autopsy findings and discussed on the background of the most recent data from the medical literature. A 13-month-old girl was admitted to the emergency room with acute severe shortness of breath and pulmonary bilateral ground-glass opacities and an almost complete opacified left lung. The patient suddenly deteriorated, and death was confirmed 3 h after admission. At autopsy, severe desquamative interstitial pneumonia was diagnosed and was associated with an unusual IgA glomerulonephritis. No SARS-CoV-2 infection was detected in the lung parenchyma by RT- PCR. This is a very unusual case of rapid deterioration of an infant with idiopathic desquamative interstitial pneumonia (IDP) and multiorgan involvement. Based on immunohistochemical stains, we hypothesize that, in IDP, the hyaline membranes arise from necrotizing desquamated pneumocytes. In the COVID-19 era, such cases are extremely difficult to diagnose; they can mimic SARS-CoV-2-induced lung injuries. This pattern of hyaline membrane formation might explain the poor response to oxygen therapy. The present case highlights the importance of autopsy in such challenging cases.

HER2 Heterogeneity in Gastric Cancer: A Comparative Study, Using Two Commercial Antibodies.

BACKGROUND: Although amplification of the gene encoding human epidermal growth factor receptor 2 (HER2) is used as an indicator for response to trastuzumab, the reported response rate is low, and few patients with gastric cancer (GC) benefit from this individualized therapy. The aim of this study was to examine the expression of c-erbB-2 oncoprotein (HER2), in GC samples, using two commercial immunohistochemical (IHC) antibodies, and to validate the results by checking HER2 gene amplification by fluorescence in situ hybridization (FISH). METHODS: We assessed the IHC expression of HER2 using the polyclonal antibody from Dako and CB11 clone from Leica, in 93 consecutive cases of GC samples. In all of the cases, FISH analysis was also performed using the BOND-MAX platform. RESULTS: No significant difference was observed between the two HER2 antibodies. Of the 93 cases, 22.58% demonstrated at least focal and 1+ HER2 positivity. Seven cases (7.53%) exhibited 3+ expression, and another 7 carcinomas (7.53%) were equivocal (2+). HER2 amplification was seen in 11 cases (11.83%), 10 of which were differentiated adenocarcinomas. In 5 of the cases, 2-5 sections were examined, which proved the extremely high intratumorally/intraglandular heterogeneity. FISH heterogeneity was higher in cases with only 2+ positivity on IHC assessment, compared with those showing at least one small focus of 3+ overexpression. HER2 amplification proved to be an independent negative prognostic factor. CONCLUSIONS: Due to the highly heterogeneous aspect of GC, at least 3-4 slides should be assessed by IHC, before considering a tumor to be HER2-negative. In cases with small 3+ foci representing less than 5% of tumor and in equivocal (2+) cases, FISH analysis remains the gold standard method.

Primary rhabdomyosarcoma: An extremely rare and aggressive variant of male breast cancer.

BACKGROUND: Rhabdomyosarcoma (RMS) of the breast, a mesenchymal neoplasm with skeletal muscle differentiation, is an extremely rare tumour in males, with less than 30 cases published in English-language literature. We report on the first case of a male breast RMS, with an unusual ectomesenchymal/neuroectodermal component. CASE SUMMARY: A 55-year-old, previously healthy male, underwent a radical left mastectomy for an ulcerated tumour mass, occupying the breast and left anterior thoracic wall. The biopsy specimen indicated the presence of a tumour with neural origins, namely a peripheral neuroectodermal tumour (PNET). The surgical specimens identified two components. The rhabdomyosarcomatous component (over 70%) was represented by large pleomorphic cells with positivity for desmin, sarcomeric actin and myogenin. The PNET-like ectomesenchymal component, which was admixed with the RMS cells, and was also revealed during the preoperative biopsy, consisted of small cells which expressed neurofilament, neuron specific enolase and CD99. The microscopic examination, along with the immunohistochemical profile, allowed the diagnosis of an RMS, with unusual ectomesenchymal differentiation. The patient refused the postoperative oncologic therapy and died three months after surgery. CONCLUSION: In patients with RMS of the breast, the PNET-like ectomesenchymal component increases the diagnosis difficulty, especially in biopsy specimens. This differentiation can be immunohistochemically proven and might highlight the possible development of high-grade sarcoma of the breast from remnants of the embryological ectodermal layer.

Mesangioproliferative glomerulonephritis with extracapillary crescents - unexpected fatal complication in a 17-year-old patient with implanted left ventricular assist device.

The continuous flow left ventricular assist device (cf-LVAD) is the life-saving solution for patients with end-stage global heart failure. We present the case of a young patient with biventricular dilated cardiomyopathy, who had a cf-LVAD implantation and died as result of progressive renal failure. In the first year after implantation, he suffered repeated strokes and episodes of pneumonia with Klebsiella pneumoniae and Escherichia coli. The patient had hypertension, which was kept under control with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. After multiple bleeding episodes, the patient died at 21 months after the LVAD implant. At autopsy, parenchymatous brain hemorrhage was found to be associated with pulmonary hemorrhages. The unexpected features related to mesangioproliferative and extracapillary glomerulonephritis, with focal glomerulosclerosis. The proliferated parietal cells of Bowman's capsule proved to express cluster of differentiation 44 (CD44), whereas remnant podocytes and mesangial cells showed Wilms tumor 1 (WT1) positivity. Since CD44 might be involved in fibrogenesis, but ACE inhibitors can exert a protective role against glomerular deterioration, we performed a synthesis of literature data which enabled us to propose a hypothesis with a potential clinical impact. We conclude that, in patients with LVAD implants, high blood pressure and high serum level of angiotensin II, the association between ACE inhibitors and anti-CD44 agents might exert glomerular protection and increase the survival time. Experimental studies are necessary to support our hypothesis and to explain the mechanism of possible glomerulopathy installed after LVAD implant.