International journal of clinical and experimental pathology最新文献

Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC) is a rare entity described in the latest WHO Classification of Urinary and Male Genital Tumours (2022 edition). It is a neoplasm that occurs most often in a sporadic setting, with no association with tuberous sclerosis complex (TSC). It typically presents as a well demarcated, non-encapsulated lesion, with solid and cystic architecture, composed of cells with voluminous eosinophilic cytoplasm and cytoplasmic stippling. Tumor cells are at least focally immunohistochemically (IHC) reactive for CK20. CD10 and Cathepsin K are positive in most cases. Consistent somatic mutually exclusive mutations in the TSC1 and TSC2 genes are detected in ESC RCC. We describe two ESC RCC cases diagnosed at our institution. Both cases occurred in female patients, ages of 33 and 64, respectively. Both patients had no evidence of TSC and both lesions were found incidentally, by imaging studies, at an early stage. Macroscopic and microscopic findings in both neoplasms were classic. One case was analyzed by molecular testing and TSC2 gene mutation was detected. Both cases had focal positivity of CD10 and Cathepsin K by IHC. Both tumors were stage pT1a at diagnosis and the patients remained free of disease after resection. It has been proposed that TSC1/2 can be a molecular marker for ESC RCC and be used to expand the morphologic spectrum of ESC RCC. As a novel rare subtype of renal cell carcinoma, with very limited data on molecular evaluation, it is useful to document these newly diagnosed ESC RCC cases.

Objectives: Human Amniotic Mesenchymal Stem Cells (hAMSCs) have strong multidirectional differentiation ability. Studies have found that transfection of target genes into target cells by lentivirus can enhance the differentiation potential of the cells. Angiotensin-Converting Enzyme 2 (ACE2) was found to improve vascular remodeling. Research is lacking on ACE2-hAMSCs. Therefore, this study aimed to investigate the ability to improve pulmonary arterial hypertension using ACE2-hAMSCs.

Methods: Lentiviruses overexpressing ACE2 were mixed with hAMSCs. Then, ACE2-hAMSCs and hAMSCs with good growth in logarithmic growth phase were collected. We detected their migration and angiogenesis. RT-qPCR technology was used to detect the expression levels of genes related to angiogenesis, and inflammation in the two cell lines, and western-blotting was used to detect the expression levels of ACE2. As an animal study, 21 rats were randomly divided into four different groups. Right heart hypertrophy, pulmonary angiogenesis, and serum inflammatory factors were measured before dissection. H&E staining was used to observe the inflammatory infiltration of lung tissues.

Results: The migration and angiogenesis of ACE2-hAMSCs were strongerthan that of hAMSCs alone. The expressions of genes in ACE2-hAMSCs were higher, and the expression of ACE2 protein in ACE2-hAMSCs was less. H&E staining showed that the inflammatory infilration of lung tissue in ACE2-hAMSCs groups was significantly improved. In addition, the ACE2-hAMSCs group had stronger pro-angiogenesis and anti-inflammatory effects.

Conclusion: These results suggest that ACE2-hAMSCs can repair pulmonary vascular endothelial cell injury caused by pulmonary hypertension by promoting angiogenesis and anti-inflammatory ability. This shows that ACE2-hAMSCs have stronger ability to improve pulmonary vascular remodeling than hAMSCs alone.

An unusual, small cell-predominant, high-grade glioneuronal tumor in the occipital lobe of a 49-year-old man that co-existed with a low-grade tumor is reported. The tumor consisted of two distinct components: the major component was a dense proliferation of primitive small cells showing bidirectional neuronal and glial differentiation; and the minor component consisted of a proliferation of well-differentiated astrocytes intermingled with mature neuronal cells. In the former component, perivascular pseudorosette-like or pseudopapillary growth reminiscent of ependymoma or papillary glioneuronal tumor (PGNT), respectively, was prominent, and hypertrophic astrocytic cells were located just outside the central blood vessels. Small cells were immunoreactive for Olig2, synaptophysin, and, less frequently, for glial fibrillary acidic protein. The low-grade component included Rosenthal fibers, hemosiderin deposition, and perivascular lymphocytic infiltration, thus closely resembling ganglioglioma. Cytogenetic studies did not demonstrate any mutations or rearrangements of the genes IDH1, IDH2, H3F3A, BRAF, FGFR1, or TERT promoter. The tumor recurred and spread along the ventricular surface three years after total removal. The small cell-predominant, high-grade component was considered to have evolved from the ganglioglioma-like, low-grade component. The histopathologic resemblance of the high-grade component to PGNT was a special feature.

Extrarenal Wilms tumor (ERWT) is rare, and its occurrence in the adult recto-vaginal septum is even more uncommon. Importantly, instances of a BRCA2 gene mutation associated with ERWT have not been documented. In this report, we present an unusual case of ERWT situated in the recto-vaginal septum of a 49-year-old woman, accompanied by a concurrent BRCA2 gene mutation. After the tumor's second recurrence, the patient experienced symptomatic relief after administering poly (ADP-ribose) polymerase (PARP) inhibitor therapy. Given the limited exposure and understanding of optimal treatment strategies for this distinct tumor, there is a definite need to accumulate further clinical experiences and insight. Consequently, we propose that genetic testing be considered in cases involving tumor recurrence or metastasis, since this may offer valuable information for identifying targets for therapeutic intervention.

Objective: We searched for a predictive biomarker that also predicts whether patients would benefit from immune checkpoint blockade (ICB) treatment from a few angles, because existing biomarkers no longer wholly replicate the interconnections of distinctive elements in the tumor microenvironment (TME).

Methods: We identified 55 pivotal IRGs by performing a WGCNA and univariate Cox regression analysis on a lung adenocarcinoma dataset from the TCGA database. The IRGPI model was then constructed using multivariate Cox regression analysis, which identified 16 genes and verified the use of the GSE68465 database. The AUC of the IRGPI was compared to those of the current biomarkers to determine its predictive potential. Then we examined the molecular and immunological properties of ICB and assessed its effectiveness using CTLA4 expression and TIDE.

Results: Patients with a high IRGPI had a later clinical stage, more severe symptoms, and a worse prognosis. Patients with a low IRGPI had a higher immune escape potential and were less responsive to immunotherapy.

Conclusion: The IRGPI may be a biomarker for determining the prognosis of patients and whether they respond favorably to ICB therapy.

[This retracts the article on p. 831 in vol. 6, PMID: 23638214.].

Objectives: Neuroendocrine tumors (NETs) are a heterogeneous group of tumors that arise at various sites throughout the body. The gastroenteropancreatic (GEP) tract is the most common site of NETs. We investigated the clinicopathologic features of patients with GEP-NETs and the utility of digital image analysis, which was compared to eyeball estimation, a conventional method used to determine the Ki-67 labeling index.

Methods: The clinicopathologic data of GEP-NET patients at Gangnam Severance Hospital from January 2008 to October 2019 were retrospectively analyzed. Each case was reclassified according to the 2019 World Health Organization classification system, to which the classification of grade 3 was added. Comparisons between eyeball estimation and the digital image analysis method for Ki-67 index assessment were performed by calculating Cohen's kappa (k) coefficient.

Results: In total, 345 patients with GEP-NETs were enrolled. The mean age was 49.3 (range 13-79) years, with more male (61.1%) than female patients. The primary tumor sites were the rectum (70.1%), pancreas (12.5%), stomach (6.7%), and duodenum (5.8%). Overall, 298 (86.4%), 35 (10.1%), 2 (0.6%), and 10 (2.9%) patients exhibited grade 1, 2, and 3 and neuroendocrine carcinoma, respectively. Statistical analysis revealed that age > 50 years, tumor size > 2 cm, and presence of lymphovascular invasion, nodal metastasis, and distant metastasis were significantly associated with short overall survival. Additionally, 283 patients underwent digital image analysis of the Ki-67 index, and substantial agreement was found between the two methods (κ value: 0.765).

Conclusions: Eyeball estimation revealed non-inferior results compared with digital image analysis. Further research is needed to evaluate the possibility of using digital image analysis as an alternative analysis method.

Background: Semaphorin4F (Sema4F) is a member of the semaphorin family and exhibits important regulatory functions in cancer biology. We aimed to explore the prognostic value and biologic function of Sema4F in gastric cancer (GC) through clinical data, laboratory studies, and bioinformatic methods.

Methods: We investigated Sema4F-related data and the prognostic values of patients with GC based on several databases, including Tumor Immune Estimation Resource (TIMER), the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), The University Of Alabama At Birmingham Cancer Data Analysis Portal (UALCAN) and Kaplan-Meier Plotter. We detected the expression of Sema4F in cell lines and tumor tissues by reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The prognostic value of Sema4F expression on patient overall survival was analyzed retrospectively using Kaplan-Meier survival and Cox regression analyses. Moreover, we used Kyoto encyclopedia of genes and genomes (KEGG), Gene Ontology (GO) and Gene-set enrichment analysis (GSEA) analyses to explore the relevant pathways of Sema4F in GC.

Results: The expression of Sema4F was markedly increased in cancer tissues and cancer cell lines. Furthermore, high Sema4F expression was positively associated with various clinicopathologic data and independently predicted poor prognosis for overall survival in GC. Our functional enrichment analysis revealed that Sema4F was mainly involved in oxidative phosphorylation and tumor-related signaling pathways.

Conclusions: Sema4F may be a valuable prognostic biomarker and a novel target for gastric cancer.

Solitary fibrous tumor (SFT) of the urinary bladder has been rarely reported and malignant bladder SFT is even rarer. Here we present a case of an African-American male with SFT of the urinary bladder (intermediate risk) initially treated by cystoprostatectomy at the age of 59 years. Eight years later, he developed recurrence with widespread metastases to the liver, lungs, and abdominal cavity. He then received temozolomide and bevacizumab with good disease control. However, treatment was paused due to declining performance status. Follow-up at 1 year demonstrated growth of the metastatic lesions. Despite restarting therapy, the patient expired, 11 years after the original diagnosis. Autopsy was performed and revealed widespread metastases within the abdominal cavity (abdominal sarcomatosis) as well as liver, bilateral lung, and diaphragmatic involvement. The cause of death was determined to be metastatic SFT. A comprehensive literature review was performed. Although SFTs are commonly considered benign, a subset of SFTs of the urinary bladder behave aggressively. Risk assessment and proper follow-up for recurrence and metastasis is necessary. The patient was also found at autopsy to have two gastrointestinal stromal tumors (GISTs) in the stomach and near the gastroesophageal junction. To the best of our knowledge, this is the first reported case of a primary urinary bladder SFT resulting in death or having concurrent, multifocal GISTs, and only the second case of a bladder SFT that developed metastases after the initial diagnosis.

Uterine sarcomas are a group of rare malignant tumors of mesenchymal tissue of the uterus, and their diagnosis is often difficult because they have variable morphologies and no typical immunophenotype. This report describes a 48-year-old woman who underwent laparoscopic myomectomy and relapsed within 5 years with a large mass in the pelvic cavity. Morphologically, the tumor was composed of oval cells and small arteries, and the cells showed moderate to severe atypia. Immunohistochemical results showed that the tumor cells expressed desmin, smooth muscle actin, and h-caldesmon, which supported myogenic differentiation. They were strongly positive for Cyclin D1, estrogen receptors (ER), and estrogen receptors (PR), supporting their origin from uterine mesenchymal cells. Next-generation sequencing (NGS) revealed a GATAD2B::MMRN1 rearrangement. The patient was diagnosed with uterine sarcoma resembling high-grade endometrial mesenchymal sarcoma with a GATAD2B-MMRN1 fusion. We review the relevant literature and discuss the diagnostic and differential diagnostic points for this disease.