Benign Research Articles

Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer.

Increased extracellular matrix (ECM) and matrix stiffness promote solid tumor progression. However, mechanotransduction in cancers arising in mechanically active tissues remains underexplored. Here, we report upregulation of multiple ECM components accompanied by tissue stiffening in vocal fold cancer (VFC). We compare non-cancerous (NC) and patient-derived VFC cells - from early (mobile, T1) to advanced-stage (immobile, T3) cancers - revealing an association between VFC progression and cell-surface receptor heterogeneity, reduced laminin-binding integrin cell-cell junction localization and a flocking mode of collective cell motility. Mimicking physiological movement of healthy vocal fold tissue (stretching/vibration), decreases oncogenic nuclear β-catenin and YAP levels in VFC. Multiplex immunohistochemistry of VFC tumors uncovered a correlation between ECM content, nuclear YAP and patient survival, concordant with VFC sensitivity to YAP-TEAD inhibitors in vitro. Our findings present evidence that VFC is a mechanically sensitive malignancy and restoration of tumor mechanophenotype or YAP/TAZ targeting, represents a tractable anti-oncogenic therapeutic avenue for VFC.

Exosomal ROR1 in peritoneal fluid identifies peritoneal disseminated PDAC and is associated with poor survival.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters. Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed. PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482). With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.

Abstract 5484: Spatial transcriptomic profiling reveals characteristic gene expression patterns of cancer-associated fibroblasts in lung adenocarcinoma with interstitial pneumonia

Abstract Background: Interstitial pneumonia (IP) is a risk factor for lung cancer (LC). LC, a significant contributor to mortality, shows improved prognosis with molecular targeted drugs. However, LC combined with IP (LC with IP) has a poor prognosis because of acute exacerbations. Therefore, developing effective drugs for LC with IP is necessary. Cancer-associated fibroblasts (CAFs), influencing cancer progression through interactions with the microenvironment are anticipated as a new therapeutic target. Therefore, we hypothesized that CAFs in LC with IP, having undergone repeated destruction and regeneration, exhibit distinct characteristics from those in LC without IP and exert varied influences on carcinogenesis and cancer progression. Methods: Six cases of lung adenocarcinoma, the predominant type of LC, were enrolled in this study. Spatial profiling was performed on FFPE specimens from three LC with IP and three LC without IP cases, using GeoMx whole-transcriptome atlas assay. Immunostaining for α-SMA, a major CAFs-marker, and pan-cytokeratin (CK), an epithelial marker, were employed to identify regions of interest (ROIs). In LC with IP, two ROIs were designated for cancerous and non-cancerous areas, respectively, whereas in LC without IP, two ROIs were selected for cancerous areas. Each ROI was segmented for epithelium and cancer (CK+/α-SMA -) and α-SMA-positive stroma (CK-/α-SMA +) areas of illumination. NGS data were analyzed using the edgeR to compare mRNA expressions in cancerous (LC-IP) and non-cancerous (NC) areas of LC with IP. Additionally, comparisons were made between LC-IP and cancerous areas of LC without IP (LC-nonIP) for mRNA expression. Results: Analysis of α-SMA-positive stroma revealed 86 differentially expressed genes (DEGs) in LC-IP vs. NC. Notably, COTL1 and NFKB2 increased, whereas TNC and MMP7 were decreased in LC-IP α-SMA-positive stroma. Pathway Enrichment analysis indicated activation of the response to cytokines. Between LC-IP and LC-nonIP, 151 DEGs were detected. CXCL8 and NFKB2 were elevated, whereas ACAN and ELN decreased in LC-IP α-SMA-positive stroma. KEGG pathway analysis demonstrated inactivated ECM-receptor interactions. Analysis of CK-positive regions showed 710 DEGs in LC-IP vs. NC, and KEGG pathway analysis indicated inactivated ECM-receptor interaction. In LC-IP vs. LC-nonIP, 321 DEGs were detected, with KEGG pathway analysis suggesting inactivation of ECM-receptor interaction and activation of a chemokine signaling pathway and cytokine-cytokine receptor interaction. Conclusion: These findings suggest that inflammatory factors may play a more critical role than extracellular matrix in the interaction between α-SMA-positive stroma and CK-positive cancer cells in LC with IP. Future plans include conducting in vitro experiments, as well as immunohistological studies. Citation Format: Chihiro Inoue, Yasuhiro Miki, Yayoi Aoyama, Saori Shibata, Yoshinori Okada, Takashi Suzuki. Spatial transcriptomic profiling reveals characteristic gene expression patterns of cancer-associated fibroblasts in lung adenocarcinoma with interstitial pneumonia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5484.

A combinatorial model of plasma proteins and LDCT imaging and the diagnosis of pulmonary nodules.

8568 Background: Low dosage computer tomography (LDCT) has been widely adopted as a sensitive method to detect early-stage lung cancer; however, debate regarding its accuracy and overdiagnosis is still ongoing. An accurate non-invasive test is needed to identify malignant nodules and reduce unnecessary invasive procedures. Studies show that plasma proteins and LDCT imaging features may be used to discriminate malignant pulmonary nodules from benign ones. We aimed to develop a combinatorial approach integrating serum protein markers and imaging features to improve the classification of pulmonary nodules. Methods: This study established a prospective research cohort, which enrolled 608 patients of pulmonary nodules. Plasma samples were collected to measure protein levels using Proximity Extension Assay (PEA) technology. The imaging features of the pulmonary nodules were extracted using the python 'radiomics' package. Following feature extraction, a deep learning networks model was built using training cases. The model was then tested in the testing set to evaluate its accuracy and robustness. Results: From the study cohort, 184 benign (BN) and 184 malignant (MT) samples matched for sex and age were chosen to have a representative training set. The rest 240 samples (81 BN and 159 MT) were used as a testing set. Image features were extracted from 448 patients (119 BN and 153 MT in training; 57 BN and 119 MT in testing) with raw LDCT image available. In the testing set, the model trained using only protein levels had an AUC of 0.83 [0.782-0.877] (sensitivity = 71.1% [95% CI 63.6-77.6]; specificity = 82.7% [73.1-89.4]) when classifying plasma samples of lung cancers from those of benign nodules. In comparison, the imaging features-only model had an AUC of 0.874 [0.821-0.916] (sensitivity = 81.5 [73.6-87.5]; specificity = 73.7 [61.0-83.4]). The combinatorial model integrating both protein and imaging features had an AUC of 0.878 [0.830-0.921] (sensitivity = 83.2% [75.5-88.8]; specificity = 77.2% [64.8-86.2]). Notably, the combinatorial model was highly sensitive for early-stage lung cancer, achieving a sensitivity of 93.1% [78.0-98.1] when classifying stage-0 lung cancer cases(n = 29) and 94.8% [85.9-98.2] for stage-I cases (N = 58). Its sensitivity for stage II-IV (n = 7) and clinically diagnosed lung cancers cases (n = 25) were 100% [64.6-100] and 40.0% [23.4-59.3], respectively. Conclusions: This study aimed to construct a model to distinguish malignant pulmonary nodules from benign lung diseases using protein levels and LDCT imaging features. The resulted combinatorial model showed by utilizing both types of features, it was able to accurately differentiate benign and malignant pulmonary nodules, suggesting it may provide guidance for the clinical management of these nodules.

Insulin-like growth factor 1 serum levels in different stages of gastric cancer and their association with Helicobacter pylori status

High serum insulin-like growth factor 1 (IGF-1) and positive Helicobacter pylori (H. pylori) may increase the risk of gastric cancer (GC). We aimed to investigate IGF-1 serum levels in different stages of GC patients and their association with H. pylori status. A total of 90 participants, including 60 GC patients and 30 noncancerous (NC) individuals, were included in the present study. IGF-1 serum levels and candidate proteins were assessed using enzyme-linked immunosorbent and immunohistochemistry techniques. Likewise, Giemsa staining was applied to detect H. pylori infection. The candidate genes' expression, including IGF-1R, PI3KCA, AKT1, mTOR1, KRAS, BRAF, and ERK1, was also evaluated by a real-time PCR assay. The results of advanced GC stages indicated a significantly high IHC score for IGF-1R and phosphorylated AKT, mTOR, and ERK proteins compared to the early stages. Moreover, IGF-1 serum levels and the expression of candidate genes were considerably increased in the advanced GC patients compared to the early stages and the positive H. pylori status compared to the negative H. pylori status (P < 0.05). As a result, high IGF-1 serum levels and positive H. pylori status may be correlated with gastric tumor progression, and the inhibition of IGF-1 and the eradication of H. pylori infection might be new therapeutic targets in GC patients.

Food Intake of Patients with Thyroid Nodules: a Brazilian Food Guides-Based Analysis

Introduction: The thyroid gland has the function of secreting hormones that play an important role in metabolism. Alterations in this function may bring complications to individuals, among them thyroid nodules. The prevalence of thyroid nodules is higher in white people, older adults, women, smokers, with accumulated body fat and larger waist circumference. Objective: The aim of this study was to compare dietary intake of patients with benign (BN) and malignant (MN) thyroid nodules. Method: A cross-sectional study was conducted with 62 patients. Dietary intake was assessed using 24-hour dietary recall, according to the 2006 and 2014 Dietary Guidelines for the Brazilian Population. Mean consumption of each food group was compared between patients with BN and MN by Student’s t-test. Results: The sample consisted mostly of females with mean age of 43 years old. Based in the 2006 Guide, patients with BN and MN presented low consumption of fruits, vegetables, milk and dairy products, and high consumption of meat. Total caloric intake (p=0.03) and of the group of sugars and sweets (p=0.03) were higher among individuals with MN compared with BN. Considering the 2014 Guide, the highest caloric contribution for the diet was from minimally processed foods from minimally processed foods group. Conclusion: Patients with MN had higher energy intake of sugars and sweets. For all other food groups investigated, no significant difference between individuals with MN and BN was encountered.

Classification of Breast Ultrasound Images: An Analysis Using Machine Intelligent Based Approach

Purpose: Breast Cancer (BC) is considered as one of the most dangerous diseases, especially in women. The survivability of the patient is a challenging task if the breast cancer is in severe stage. It is very much essential for the early classification of breast ultrasound images (BUIs) into several categories such as benign (BN), malignant (MG) and normal (NL), etc. so that preventive measures can be taken accordingly at the earliest. Approach: In this work, a machine intelligent (MI) based approach is proposed for the classification of BUIs into the BN, MG and NL types. The proposed approach is focused on the stacking (hybridization) of Logistic Regression (LRG), Support Vector Machine (SVMN), Random Forest (RFS) and Neural Network (NNT) methods to carry out such classification. The proposed method is compared with other machine learning (ML) based methods such as LRG, SVMN, RFS, NNT, Decision Tree (DTR), AdaBoost (ADB), Naïve Bayes (NBY), K-Nearest Neighbor (KNNH) and Stochastic Gradient Descent (SGDC) for performance analysis. Result: The proposed method and other ML based methods have been implemented using Python based Orange 3.26.0. In this work, 750 TLDIs having 250 numbers of each type such as BN, MG and NL are taken from the Kaggle source. The performance of all the methods is assessed using the performance parameters such as classification accuracy (CA), F1, Precision (PR) and Recall (RC). From the results, it is found that the proposed method is capable of providing better classification results in terms of CA, F1, PR and RC as compared to other ML based methods such as LRG, SVMN, RFS, NNT, DTR, ADB, NBY, KNNH and SGD. Originality: In this work, a MI based approach is proposed by focusing on the stacking of LRG, SVMN, RFS and NNT methods to carry out the classification of BUIs into several types such as BN, MG and NL. The proposed approach performs better in terms of CA, F1, PR and RC as compared to LRG, SVMN, RFS, NNT, DTR, ADB, NBY, KNNH and SGDC methods. Paper Type: Conceptual Research.

Abstract 1375: The intra-tumoral spatial heterogeneity of T-cell antigens in glioblastoma: An integrated multi-omics approach

Abstract Glioblastoma is the most common primary malignant neoplasm of the central nervous system in adults. Current treatment options comprise maximal surgical resection followed by radiation and/or chemotherapy with temozolomide. However, these procedures are unable to eliminate all tumor cells, which in turn lead to disease recurrence accounting for the poor prognosis. Glioblastoma is a highly infiltrative tumor in which recurrence originates from the unresectable peritumoral infiltration zone. Thus, novel treatment options specifically targeting the tumor cells in the infiltration zone are needed to prevent relapse and enable long-lasting remission. In this work, we performed multi-omics spatial analysis of the necrotic center (NEC), the gadolinium contrast-enhanced region (T1), and the infiltration zone (INF) to assess immunological relevant aspects of tumor heterogeneity. By integrating mass spectrometry-based immunopeptidome analysis with next generation sequencing methods (whole exome and RNA sequencing, DNA methylation), we aimed to identify the intra-tumoral regional heterogeneity of T cell antigens with a special focus on the peritumoral infiltration zone. For multi-omics analysis, HLA peptides and genetic material from 15 glioblastoma patients were extracted and analyzed from the three zones NEC, T1, INF and for four patients additionally from adjacent benign (BEN) brain tissue. A total of 24,699 unique HLA class I and 17,394 HLA class II peptides were identified. Comparative profiling of peptides from our study and a benign tissue database (in-house (n=429) combined with HLA ligand atlas (https://hla-ligand-atlas.org)) revealed that 6% (970/15,579), 5% (829/16,442) and 5% (725/13,891) of HLA class I peptides were exclusively presented in the INF, T1 and NEC zone, respectively. 6% (394/7,150), 7% (589/8,736) and 13% (1,725/12,908) of HLA class II peptides showed exclusive representation in the INF, T1 and NEC zone, respectively. Importantly, due to the spatial analysis of the immunopeptidome, we revealed 970 HLA class I and 394 HLA class II peptides exclusively presented in the INF zone. Interestingly, one INF-associated HLA class I peptide, which showed frequent presentation in 36% of glioblastoma immunopeptidomes, is derived from the brain and acute leukemia cytoplasmic protein (BAALC), a highly expressed cell cycle inducer (via MEK kinase-1) in several cancers, including glioblastoma. Integrated RNA/DNA sequencing enabled a greater understanding of spatial tumor antigen presentation and lead to the identification of INF-specific neoepitopes derived from tumor-specific mutations. In summary, we identified the intra-tumoral regional heterogeneity of tumor antigens, which could be used in the future for specific immunotherapy approaches targeting the infiltration zone of glioblastoma. Citation Format: Marcel Wacker, Gioele Medici, Marissa Dubbelaar, Jens Bauer, Annika Nelde, Luca Regli, Michael Weller, Helmut R. Salih, Hans-Georg Rammensee, Marian C. Neidert, Juliane S. Walz. The intra-tumoral spatial heterogeneity of T-cell antigens in glioblastoma: An integrated multi-omics approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1375.

Синдром доброкачественных фасцикуляций (клинические наблюдения, обзор литературы)

В статье приводится описание трех клинических случаев синдрома доброкачественных фасцикуляций. Обсуждаются основные причины возникновения, механизмы развития, особенности клинической и электромиографической картины, вопросы дифференциальной диагностики и принципы лечения синдрома доброкачественных фасцикуляций. Описывается пошаговый алгоритм менеджмента пациентов с фасцикуляциями.

Lung cancer classification using fuzzy c-means and fuzzy kernel c-means based on CT scan image

Cancer is one of the diseases with the highest mortality rate in the world. Cancer is a disease when abnormal cells grow out of control that can attack the body's organs side by side or spread to other organs. Lung cancer is a condition when malignant cells form in the lungs. To diagnose lung cancer can be done by taking x-ray images, CT scans, and lung tissue biopsy. In this modern era, technology is expected to help research in the field of health. Therefore, in this study feature extraction from CT images was used as data to classify lung cancer. We used CT scan image data from SPIE-AAPM Lung CT Challenge 2015. Fuzzy C-Means and Fuzzy Kernel C-Means were used to classify the lung nodule from the patient into benign or malignant. Fuzzy C-Means is a soft clustering method that uses Euclidean distance to calculate the cluster center and membership matrix. Whereas Fuzzy Kernel C-Means uses kernel distance to calculate it. In addition, the Support Vector Machine was used in another study to obtain 72% average AUC. Simulations were performed using different k-folds. The score showed Fuzzy Kernel C-Means had the highest accuracy of 74%, while Fuzzy C-Means obtained 73% accuracy.

Ovarian Low-grade Basaloid Carcinoma Arising in Brenner Tumor: A New Variant of Malignant Brenner Tumor

Brenner tumors are uncommon ovarian neoplasms, most of which are benign, although borderline and malignant variants occur. We report 2 unusual ovarian neoplasms composed of an admixture of typical benign Brenner tumor and a low-grade epithelial neoplasm which we designate as low-grade basaloid carcinoma. The latter component morphologically and immunohistochemically resembled "salivary gland-type/myoepithelial" neoplasms with variable positive staining with cytokeratins, p63, S100, and CD117. One tumor exhibited aggressive behavior with local recurrence and distant metastasis. This neoplasm exhibited focal "high-grade" transformation with diffuse mutation-type p53 staining, in contrast to the wild-type immunoreactivity in the low-grade component. As far as we are aware, such neoplasms have not previously been reported in the literature and this represents a newly described morphologic variant of malignant Brenner tumor.

Vaginal Myomectomy and Total Vaginal Hysterectomy on Large Prolapsed Cervical Myoma: A Case Report

Cervical myomas are benign tumors originating from cervical muscle tissue with a very rare incidence of only about 8% of all myomas. The surgical approach depends on the position of cervical myoma. This case report discusses a 44-year-old woman who complained of a lump discharge from her birth canal 6 months ago, and currently discharging from her vagina. We performed vaginal myomectomy, and the cervical myoma measuring 8 × 8 × 6 cm with solid consistency was removed. We continued with total vaginal hysterectomy. Post-operative recovery was progressing well. The histopathology report was consistent with leiomyoma. Large prolapsed cervical myoma can be disturbing and discomforting for many patients. It is relatively rare and can be successfully removed vaginally with minimal morbidity. J Med Cases. 2021;12(7):288-290 doi: https://doi.org/10.14740/jmc3698

Detection of circulating tumor cells with chromosomes 7 and 8 polysomy in non-small cell lung cancer and its correlation with epidermal growth factor receptor mutations in cancer tissue

Objective: To investigate the value of chromosomes 7 and 8 polysomy in circulating tumor cells (CTCs) for the diagnosis of non-small cell lung cancer, and the correlation of CTCs with clinical pathological characteristics and epidermal growth factor receptor (EGFR) mutations in cancer tissue. Methods: Fifty-seven patients with non-small cell lung cancer and 21 patients with benign lung diseases were enrolled at Beijing Chaoyang Hospital, Capital Medical University, Beijing, China from November 2017 to October 2020. Negative enrichment combined with immunofluorescence in situ hybridization (imFISH) was used to identify CTCs polysomy on chromosomes 7 and 8. EGFR mutations in 56 lung cancer patients was detected using ARMS-PCR. Results: CTCs were detected in 93.0% (53/57) of non-small cell lung cancers and 28.6% (6/21) benign lung lesions. The difference between lung cancer patients and the control cohort was statistically significant (P<0.01). Receive operator curve (ROC) analyses showed that, when the cut-off value was 1 cell/3.2 mL, Youden index had the highest sensitivity of 93.0% and specificity of 71.4% (AUC=0.906, 95%CI:0.833-0.980, P<0.01). The positive rate of CTCs in stage Ⅲ-Ⅳ cancers was significantly higher than that in stage Ⅰ-Ⅱ (P=0.023). No significant correlation was observed between positive rate of CTCs or chromosome polysomy and age, gender, smoking status, pathologic types and EGFR mutation status. The number of CTCs in EGFR mutated group was higher than that in the non-mutated group (6.5±1.1 vs. 3.7±0.7, P=0.045). The detection rate for CTCs ≥5 in the EGFR mutated group was also higher than the EGFR non-mutated group (52.0% vs. 19.4%,P=0.010). Conclusion: Detection of CTCs with chromosomes 7 and 8 polysomy has potential value in auxiliary diagnosis of non-small cell lung cancer, and the number of CTCs is correlated to TNM stage and EGFR gene mutation status.

Salivary gland tumours in the intraoral region: A retrospective study of cases treated in a teaching hospital in North-West Nigeria

Tumours of the minor salivary glands occurring in the oral cavity are uncommon. The oral cavity has many tiny salivary glands which occur in the lip, palate, floor of the mouth, cheeks, tongue and pharynx. Tumour could develop from any of these minor salivary glands. We conducted a retrospective study of twenty-four cases of these tumours treated in our Centre over a period of eleven years. The objective of this study is to investigate the nature, clinical features, pathology, and treatment of these tumours in North-West, Nigeria. This was a retrospective study of all patients with minor salivary gland tumours that were treated at Barau Dikko Teaching Hospital, Kaduna, Nigeria. The study covered a period of eleven years from January, 2009 to December, 2019. Information was extracted from case files of patients. Data collected includes: age of patient at presentation, sex, location of tumour, clinical features, treatment giving, complications and histological diagnosis. The age of the patients ranged from 16 to 70 years, with the mean SD = 43.0 ± 6.6 years and male-to-female ratio was 1: 2. Benign tumours were the most common compared to malignancies. Palate was the commonest site of occurrence; followed by upper lip. The treatment was surgical excision. Palatal fistula was the commonest complication of the surgery. Tumour of minor salivary glands need urgent attention as it greatly interferes with oral functions and could destroy maxillary bone resulting in untoward debilitating effect. Key words: Salivary glands, tumour, intraoral, palate, benign, malignant.

Gastroenterological clinical case

Gastrointestinal polyps are frequent in children and represent the most common cause of colorectal bleeding in this age group. Among those, juvenile polyps are the most frequently found. Intermittent mild hematochezia is the main symptom of colon polyps. Most polyps are pedunculated and, when located in the rectum, may prolapse. In most cases, juvenile polyps are solitary and located in rectosigmoid. Although malignancy risk of a solitary juvenile polyp is very small, excision is recommended to confirm benign nature. Total colonoscopy should be considered to exclude multiple or proximal polyps.

Cerebral Infiltrative Lesion and Chronic Clinical Course of the Rosai-Dorfman Disease: Case Report

Rosai-Dorfman disease (RDD) is a rare disorder of an unknown etiology, characterized by a benign histiocytic proliferation in the lymph nodes, as well as the extranodal sites. Painless bilateral lymphadenopathy is the classic presentation of RDD in the majorityof patients. The exteranodal disease involves the skin, soft tissues, bones, the genitourinary system, the lower respiratory tract, and the central nervous system. A seven-year-old boy was referred to our hospital with left parietal swelling, headache, fever, imbalance, weight loss, and speech and walking impairments. In early examinations, he showed a hyposignal infiltrative lesion in the lateral ventricle and the choroid plexus, expanding to the subcortical white matter of the bilateral temporooccipital areas. After surgery and sampling, he was diagnosed with cerebral RDD. According to his history, he had bilateral cervical lymphadenopathy at the age of two years, femoral soft tissueinvolvement at the age of three, and a skin disorder that improved with local treatments at the age of five. However, at the time of referral to the hospital, there were no other symptoms in other areas, except for brain symptoms. In the differential diagnosis of brain lesions with specific borders in high-contrast radiological views, the probability of RDD should be considered, similar to meningioma. The presence of painless and extensive bilateral cervical lymphadenopathy can improve the diagnosis of this disease. Isolated brain involvement in RDD is very rare, and it can be seen in less than 5% of cases. Nevertheless, by early diagnosis and intervention, the risk of complications is reduced, and the prognosis is improved.

Promotion of the High-Quality Development of Data Element Markets by Competition Law

At present, Chinese data element market construction has entered a period of rapid development, which has become an important part of promoting the development of socialist market economy and deepening the reform of factor marketization. Competition mechanism is one of the basic mechanisms of market economy. The realization of the core connotation of high-quality development of data element markets needs the promotion of competition mechanism. However, there are problems in the operation of China’s data element markets at present in enterprise （operator） behavior, market structure and state （government） intervention: Firstly, the new unfair competition and monopoly behavior of enterprises in data element markets have an impact on the market competition order; secondly, the construction of regional data trading platform has the possibility of cutting off the regional market; thirdly, the government’s improper intervention in data element markets is likely to breed administrative monopoly. Therefore, how to maintain the competition order of data element markets according to its own characteristics, and then realize the scientific and efficient data circulation, has become an urgent problem to be solved. Therefore, we should solve the problems in three aspects, and promote the establishment of benign competition ecosystem of data element markets: Firstly, for the new types of unfair competition and monopoly behavior in data element markets, we should promote the identification standard of unfair competition behavior, the relevant market definition of monopoly behavior and the improvement of anti-competitive effect evaluation system, so as to build a dynamic, flexible and efficient system of competition law; secondly, we should speed up the construction of domestic unified data element markets, break the regional market barriers, and promote the construction of national data element markets, so as to realize the cross regional flow of data; thirdly, for the problem of administrative monopoly in the process of data element market construction, we should strengthen the standardization of government administrative behavior, implement the fair competition review system, improve or abolish the policies that have a negative impact on competition, accelerate the promotion of government data opening, and improve the quantity and quality of government data opening, so as to avoid the improper interference of administrative power from damaging the competition mechanism. Through the solution of the three problems, we should coordinate the interests of various parties and balance the needs of multiple values, create a scientific and reasonable competition order in data element markets, promote the effective competition , and create a data element markets.

Is it time to include p40 as a standard myoepithelial marker of breast? A comparative study of expression of p63 and p40 in benign breast diseases and invasive ductal carcinomas of the breast

Context: The expression of p40 in breast tissue as a myoepithelial marker is not extensively studied. This study was designed to find the expression of two markers p63 and p40 in benign breast diseases and Invasive ductal carcinomas (IDCs) of the breast. Aim: A series of cases of fibroadenoma and IDC of breast were studied for expression of p40 and compared to the p63 staining profile. Settings and Design: A total of 118 cases of breast disease were selected for this study from the archives of a tertiary care hospital, which included 41 cases of benign and 77 cases of malignant etiology. After the exclusion, 30 cases of fibroadenoma and 68 cases of IDC, were selected for the study. Subjects and Methods: Samples (n = 98) included fibroadenoma (n = 30) and IDC (n = 68). IDC was studied as a whole group and was also divided as triple negative breast cancer (TNBCs, n = 12) and Non-Triple TNBCs (NTNBC, n = 56). The expression of p63 and p40 was assessed in myoepithelial cells (MECs) in fibroadenoma and tumor cells in IDC. Results: Both the antibodies performed similarly to highlight MECs in fibroadenoma in all 30 cases. In IDC, TNBC and NTNBC subgroups p63 stained the tumor cells more than p40. None of the tumor cells in the NTNBC group exhibited positivity for p40. Conclusions: As a MEC marker, both p63 and p40 perform similarly but in IDC (TNBC and NTNBC), the tumor cells of IDC stain significantly more for p63 than p40. It appears that p40 does not come positive in the tumor cells of NTNBC.

Melanocytic Tumors

Primary melanocytic neoplasms of the central nervous system(CNS)presumably arise from leptomeningeal melanocytes that are derived from the neural crest. Melanocytic neoplasms associated with neurocutaneous melanosis likely derive from melanocyte precursor cells that reach the CNS after somatic mutations, mostly, of the NRAS. They should be distinguished from other melanotic tumors involving the CNS, including metastatic melanoma and other primary tumors that undergo melanization, such as melanocytic schwannomas, medulloblastomas, paragangliomas, and various gliomas, because these lesions require different patient workups and therapy. Primary melanocytic neoplasms of the CNS that are diffuse and do not form macroscopic masses are called melanocytoses, whereas malignant diffuse or multifocal lesions are collectively called melanomatoses. Benign and intermediate-grade tumoral lesions are called melanocytomas. Discrete malignant tumors are called melanomas. CT and MRI of melanocytosis and melanomatosis show diffuse thickening and enhancement of the leptomeninges, often with focal or multifocal nodularity. Depending on the melanin content, diffuse and circumscribed melanocytic tumors of the CNS may show some characteristics on CT and MRI: iso- to hyperattenuation on CT and paramagnetic properties of melanin on MRI resulting in an isointense signal on T1WIs and iso- to hypointensity on T2WIs.

A Long-Standing Giant Mandibular Ameloblastoma and its Management with Microvascular Free Fibular Graft: a Case Report.

Ameloblastoma is one of the most common benign epithelial odontogenic tumors of jaws. We report a case of long-standing slow-growing giant ameloblastoma involving almost all of mandibular bone. The solid multicystic lesion was excised, and the histopathological examination showed the follicular type of ameloblastoma. Furthermore, the defect was reconstructed with microvascular osteocutaneous free fibular graft.