Journal of Pathology and Translational Medicine最新文献

Background: Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression.

Methods: We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually.

Results: The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression.

Conclusions: This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.

Background: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic for more than 2 years. Autopsy examination is an invaluable tool to understand the pathogenesis of emerging infections and their consequent mortalities. The aim of the current study was to present the lung and heart pathological findings of COVID-19-positive autopsies performed in Jordan.

Methods: The study involved medicolegal cases, where the cause of death was unclear and autopsy examination was mandated by law. We included the clinical and pathologic findings of routine gross and microscopic examination of cases that were positive for COVID-19 at time of death. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed through molecular detection by real-time polymerase chain reaction, serologic testing for IgM and electron microscope examination of lung samples.

Results: Seventeen autopsies were included, with male predominance (76.5%), Jordanians (70.6%), and 50 years as the mean age at time of death. Nine out of 16 cases (56.3%) had co-morbidities, with one case lacking such data. Histologic examination of lung tissue revealed diffuse alveolar damage in 13/17 cases (76.5%), and pulmonary microthrombi in 8/17 cases (47.1%). Microscopic cardiac findings were scarcely detected. Two patients died as a direct result of acute cardiac disease with limited pulmonary findings.

Conclusions: The detection of SARS-CoV-2 in postmortem examination can be an incidental or contributory finding which highlights the value of autopsy examination to determine the exact cause of death in controversial cases.

IgA plasma cell myeloma (PCM) has been linked to molecular abnormalities that confer a higher risk for adverse patient outcomes. However, since IgA PCM only accounts for approximately 20% of all PCM, there are very few reports on high-risk IgA PCM. Moreover, no such reports are found on the more infrequent biclonal IgA PCM. Hence, we present a 65-year-old Puerto Rican female with acute abdominal pain, concomitant hypercalcemia, and acute renal failure. Protein electrophoresis with immunofixation found high IgA levels and detected a biclonal IgA gammopathy with kappa specificity. Histomorphologically, bone marrow showed numerous abnormal plasma cells (32%) replacing over 50% of the marrow stroma. Immunophenotyping analysis detected CD45-negative plasma cells aberrantly expressing CD33, CD43, OCT-2, and c-MYC. Chromosomal analysis revealed multiple abnormalities including the gain of chromosome 1q. Thus, we report on an unusual biclonal IgA PCM and the importance of timely diagnosing aggressive plasma cell neoplasms.

The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn's disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

Single-cell RNA sequencing has become a powerful and essential tool for delineating cellular diversity in normal tissues and alterations in disease states. For certain cell types and conditions, there are difficulties in isolating intact cells for transcriptome profiling due to their fragility, large size, tight interconnections, and other factors. Single-nucleus RNA sequencing (snRNA-seq) is an alternative or complementary approach for cells that are difficult to isolate. In this review, we will provide an overview of the experimental and analysis steps of snRNA-seq to understand the methods and characteristics of general and tissue-specific snRNA-seq data. Knowing the advantages and limitations of snRNA-seq will increase its use and improve the biological interpretation of the data generated using this technique.

Background: The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear.

Methods: We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation.

Results: We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This "UC-like signature" was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG.

Conclusions: Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

Metallic implant-associated lymphomas are extremely rare. Only seven cases have been reported in association with knee joint arthroplasty, and all tumors were large B-cell lymphomas. This report is the first case of anaplastic large cell lymphoma occurring after total knee replacement arthroplasty. An 80‑year‑old female patient was admitted because of right knee pain for 2 years. She had undergone total knee replacement arthroplasty 10 years prior. Computed tomography showed an irregular osteolytic lesion in the right lateral femoral condyle, adjacent to the metallic prosthesis. Histologic findings reveal sheets of anaplastic tumor cells that were positive for CD2, CD4, CD5, CD43, and CD30 but negative for CD3, CD20, CD15, and anaplastic lymphoma kinase. Epstein-Barr encoding region in situ hybridization was negative. Analysis of T-cell receptor γ gene rearrangement studies using BIOMED-2-based multiplex polymerase chain reaction confirmed monoclonal T cell proliferation. The woman was finally diagnosed with ALK-negative anaplastic large cell lymphoma.

About one-fourth of the global population is either overweight or obese, both of which increase the risk of insulin resistance, cardiovascular diseases, and infections. In obesity, both immune cells and adipocytes produce an excess of pro-inflammatory cytokines that may play a significant role in disease progression. In the recent coronavirus disease 2019 (COVID-19) pandemic, important pathological characteristics such as involvement of the renin-angiotensin-aldosterone system, endothelial injury, and pro-inflammatory cytokine release have been shown to be connected with obesity and associated sequelae such as insulin resistance/type 2 diabetes and hypertension. This pathological connection may explain the severity of COVID-19 in patients with metabolic disorders. Many studies have also reported an association between type 2 diabetes and persistent viral infections. Similarly, diabetes favors the growth of various microorganisms including protozoal pathogens as well as opportunistic bacteria and fungi. Furthermore, diabetes is a risk factor for a number of prion-like diseases. There is also an interesting relationship between helminths and type 2 diabetes; helminthiasis may reduce the pro-inflammatory state, but is also associated with type 2 diabetes or even neoplastic processes. Several studies have also documented altered circulating levels of neutrophils, lymphocytes, and monocytes in obesity, which likely modifies vaccine effectiveness. Timely monitoring of inflammatory markers (e.g., C-reactive protein) and energy homeostasis markers (e.g., leptin) could be helpful in preventing many obesity-related diseases.

This compilation of new changes in the diagnosis and treatment of muscle and nerve disease is extracted from the latest publications from the European Neuromuscular Centre International workshops, FDA.gov and clinicaltrials.gov.