A comprehensive AI model development framework for consistent Gleason grading.

BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.

Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.

[Retracted] microRNA­146b promotes neuroblastoma cell growth through targeting NUMB.

[This retracts the article DOI: 10.3892/etm.2020.8623.].

[Intravascular Large B-cell Lymphoma Presenting with Lung Adenocarcinoma:
A Case Report and Literature Review].

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive extranodal large B-cell lymphoma, cocurrence in the same organ with other malignancies is very rare, especially in the lung. Here, we report a rare case of lung adenocarcinoma with IVLBCL. The patient was admitted to the hospital due to diarrhea associated with fever and cough. A computed tomography (CT) scan of the chest showed an irregular patchy high-density shadow in the upper lobe of the right lung with ground-glass opacity at the margin. After admission, the patient was given anti-infection treatment, but still had intermittent low fever (up to 37.5 °C). The pathological diagnosis of percutaneous lung biopsy (PLB) was lepidic-predominant adenocarcinoma with local infiltration, which was proved to be invasive nonmucinous adenocarcinoma of the lung with IVLBCL after surgery. This paper analyzed the clinicopathological characteristics and reviewed the relevant literature to improve the knowledge of clinicians and pathologists and avoid missed diagnosis or misdiagnosis.
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Predicting pleural invasion of invasive lung adenocarcinoma in the adjacent pleura by imaging histology.

The aim of the present study was to develop a non-invasive method based on histological imaging and clinical features for predicting the preoperative status of visceral pleural invasion (VPI) in patients with lung adenocarcinoma (LUAD) located near the pleura. VPI is associated with a worse prognosis of LUAD; therefore, early and accurate detection is critical for effective treatment planning. A total of 112 patients with preoperative computed tomography presentation of adjacent pleura and postoperative pathological findings confirmed as invasive LUAD were retrospectively enrolled. Clinical and histological imaging features were combined to develop a preoperative VPI prediction model and validate the model's efficacy. Finally, a nomogram for predicting LUAD was established and validated using a logistic regression algorithm. Both the clinical signature and radiomics signature (Rad signature) exhibited a perfect fit in the training cohort. The clinical signature was overfitted in the testing cohort, whereas the Rad signature showed a good fit. To combine clinical and radiomics signatures for optimal performance, a nomogram was created using the logistic regression algorithm. The results indicated that this approach had the highest predictive performance, with an area under the curve of 0.957 for the clinical signature and 0.900 for the Rad signature. In conclusion, histological imaging and clinical features can be combined in columnar maps to predict the preoperative VPI status of patients with adjacent pleural infiltrative lung carcinoma.

Iris metastasis from clear cell renal cell carcinoma: A case report.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common type of tumor that can metastasize to any organs and sites. However, it is extremely rare for ccRCC to metastasize to the iris. Here, we describe a rare case of iris metastasis from ccRCC with a history of left nephrectomy in 2010. CASE SUMMARY: A 62-year-old male was admitted to the hospital due to blurred vision and red eyes, and a mass was found on the iris in the right eye. B-scan ultrasonography revealed a well-bounded high-density lesion at the corner of the anterior chamber at the 3-4 o'clock position. Phacoemulsification with simultaneous intraocular lens implantation and iridocyclectomy was performed in the right eye. The lesion was confirmed to be metastatic ccRCC by histological and immunohistochemical analyses. The patient was still alive at 9 mo after surgical treatment. Ocular metastasis can be an initial sign with a poor prognosis. Timely detection and treatment may improve survival. Clinicians should pay attention to similar metastatic diseases to prevent misdiagnosis leading to missed treatment opportunities. CONCLUSION: This report of the characteristics and successful management of a rare case of iris metastasis from ccRCC highlights the importance of a comprehensive medical history, histopathology, immunohistochemistry, and clinical manifestation for successful disease diagnosis.

Construction and validation of a novel and superior protein risk model for prognosis prediction in esophageal cancer.

Esophageal cancer (EC) is recognized as one of the most common malignant tumors in the word. Based on the biological process of EC occurrence and development, exploring molecular biomarkers can provide a good guidance for predicting the risk, prognosis and treatment response of EC. Proteomics has been widely used as a technology that identifies, analyzes and quantitatively acquires the composition of all proteins in the target tissues. Proteomics characterization applied to construct a prognostic signature will help to explore effective biomarkers and discover new therapeutic targets for EC. This study showed that we established a 8 proteins risk model composed of ASNS, b-Catenin_pT41_S45, ARAF_pS299, SFRP1, Vinculin, MERIT40, BAK and Atg4B via multivariate Cox regression analysis of the proteome data in the Cancer Genome Atlas (TCGA) to predict the prognosis power of EC patients. The risk model had the best discrimination ability and could distinguish patients in the high- and low-risk groups by principal component analysis (PCA) analysis, and the high-risk patients had a poor survival status compared with the low-risk patients. It was confirmed as one independent and superior prognostic predictor by the receiver operating characteristic (ROC) curve and nomogram. K-M survival analysis was performed to investigate the relationship between the 8 proteins expressions and the overall survival. GSEA analysis showed KEGG and GO pathways enriched in the risk model, such as metabolic and cancer-related pathways. The high-risk group presented upregulation of dendritic cells resting, macrophages M2 and NK cells activated, downregulation of plasma cells, and multiple activated immune checkpoints. Most of the potential therapeutic drugs were more appropriate treatment for the low-risk patients. Through adequate analysis and verification, this 8 proteins risk model could act as a great prognostic evaluation for EC patients and provide new insight into the diagnosis and treatment of EC.

Correlation and significance of COX-2, Ki67, VEGF and other immune indexes with the growth of malignant pulmonary nodules.

OBJECTIVE: This study intends to explore the factors affecting the growth of pulmonary nodules in the natural process by immunohistochemical method. METHODS: 40 cases of pulmonary nodules followed up for more than 3 years were divided into growth group (n = 20) and stable group (n = 20). The expressions of cyclooxygenase-2 (COX-2), Ki67, vascular endothelial growth factor (VEGF), CD44V6, epidermal growth factor receptor (EGFR), double microsome 2 (MDM2) and transforming growth factor (TGF)-ß1 in pulmonary nodules were detected by immunohistochemical method so as to explore the relationship between it and the growth of pulmonary nodules. RESULTS: Compared with stable pulmonary nodules, the positive rates of COX-2, Ki67 and VEGF in the growth group were 85%, 80% and 55%, respectively. There was significant difference between the stable group and the growth group (P < 0.05). The correlation between other indexes and the growth of pulmonary nodules was not statistically significant (Pcd44v6 = 0.104;PEGFR = 0.337; PMDM2 = 0.49; PTGF-ß1 = 0.141). In the subgroup of patients with non-invasive lung cancer, there was a correlation between VEGF and the growth of pulmonary nodules (P < 0.05). CONCLUSION: The high expression of COX-2, Ki67 and VEGF proteins may be significantly related to the growth of pulmonary nodules, and VEGF may be an important factor affecting the growth of malignant pulmonary nodules. This study intends to provide a research direction for further searching for the essential causes of the growth of pulmonary nodules.

Case Report: Misdiagnosis of Lung Carcinoma in Patients with Shrunken Lung Cyst After High Altitude Travel.

Background: Lung cancer associated with cystic airspace is a rare disease, and the imaging understanding of lung cancer with cystic cavity is still unclear. Little is known in the literature on whether cystic lung cancer is caused by emphysema or ruptured bullae. Case Reports: We report the case of a 50-year-old female patient after finishing a business trip in November 2021, when another chest CT demonstrated an unexpected reduction in the cyst, with a solid mural nodule on the posterior wall. The airspace of the cyst is only about 13 mm × 12 mm × 6 mm in size. The size of the mural nodule in the posterior wall is about 10 mm × 6 mm × 5 mm. The patient felt anxious due to suspicion of lung cancer. 2.5 months after the last chest CT, she accepted minimally invasive thoracoscopic surgery on the posterior basal segment of the left lower lobe. The postoperative pathology showed benign lesions. Conclusion: For radiologists, it is important to recognize the process from lung cysts or bullae to LC-CAS, especially the morphological changes of the cyst airspace and the cyst wall, in order to identify the malignant features of lung cysts in time.

Construction of a novel necroptosis-related lncRNA signature for prognosis prediction in esophageal cancer.

BACKGROUND: Esophageal cancer (EC), one highly malignant gastrointestinal cancer, is the 6th leading cause of cancer-related deaths worldwide. Necroptosis and long non-coding RNA (lncRNA) play important roles in the occurrence and development of EC, but the research on the role of necroptosis-related lncRNA in EC is not conclusive. This study aims to use bioinformatics to investigate the prognostic value of necroptosis-related lncRNA in EC. METHODS: Transcriptome data containing EC and normal samples, and clinical information were obtained from the Cancer Genome Atlas database. 102 necroptosis-related genes were obtained from Kanehisa Laboratories. Necroptosis-related lncRNAs were screened out via univariate, multivariate Cox and the least absolute shrinkage and selection operator regression analyses to construct the risk predictive model. The reliability of the risk model was evaluated mainly through quantitative real-time PCR (qRT-PCR), the receiver operating characteristic (ROC) curves and the constructed nomogram. KEGG pathways were explored in the high- and low-risk groups of EC patients via gene set enrichment analyses (GSEA) software. Immune microenvironment and potential therapeutic agents in risk groups were also analyzed. RESULTS: A 6 necroptosis-related lncRNAs risk model composed of AC022211.2, Z94721.1, AC007991.2, SAMD12-AS1, AL035461.2 and AC051619.4 was established to predict the prognosis level of EC patients. qRT-PCR analysis showed upregulated Z94721.1 and AL035461.2 mRNA levels and downregulated AC051619.4 mRNA level in EC tissues compared with normal tissues. According to clinical characteristics, the patients in the high-risk group had a shorter overall survival than the low-risk group. The ROC curve and nomogram confirmed this model as one independent and predominant predictor. GSEA analysis showed metabolic and immune-related pathways enriched in the risk model. Most of the immune cells and immune checkpoints were positively correlated with the risk model, mainly active in the high-risk group. For the prediction of potential therapeutic drugs, 16 compounds in the high-risk group and 2 compounds in the low-risk group exhibited higher sensitivity. CONCLUSIONS: Our results supported the necroptosis-related lncRNA signature could independently predict prognosis of EC patients, and provided theoretical basis for improving the clinical treatment of EC.

Skimmianine as a novel therapeutic agent suppresses proliferation and migration of human esophageal squamous cell carcinoma via blocking the activation of ERK1/2.

Esophageal squamous cell carcinoma (ESCC), one of the main histopathological subtypes of esophageal cancer (EC), is characterized by high morbidity and mortality. Clinical treatment for ESCC lacks specific molecular targets and effective therapeutic drugs. Skimmianine (SK), one of the natural fluroquinolone alkaloids, is widely present in Rutaceae family plants. Here, we mainly used CCK-8 assay, clone formation, flow cytometry analysis, wound-healing assay, Transwell assay, western blot, quantitative real-time PCR (qRT-PCR), molecular docking analysis, tumor xenograft assay, and immunohistochemistry (IHC) staining to investigate the potential anti-tumor effect of SK on ESCC. We demonstrated that SK inhibited the proliferation of TE-1 and Eca109 cells via inducing the G0/G1 phase cell cycle arrest, prevented the migration and invasion of tumor cells via regulating epithelial-mesenchymal transition (EMT) in vitro. In addition, SK obviously suppressed the growth of xenografted Eca109 tumors in nude mice. The anti-tumor mechanism of SK could be blocking the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. Our basic research suggests that SK can be a potential therapeutic agent for ESCC.

Resveratrol ameliorates diabetic kidney injury by reducing lipotoxicity and modulates expression of components of the junctional adhesion molecule-like/sirtuin 1 lipid metabolism pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes, and previous studies have shown that lipid deposits in the kidneys can lead to diabetic kidney damage. Resveratrol reduces circulating glucose and lipid concentrations, but it is unknown whether it can reduce renal lipid deposition and lipotoxic damage by regulating local lipid metabolism. We first showed that abnormal lipid metabolism is closely related to DKD in patients. There were excessive lipid deposits in the kidneys of patients with various stages of DKD, alongside abnormal expression of the junctional adhesion molecule-like (JAML)/sirtuin 1 (Sirt1) lipid synthesis pathway (P < 0.05). Next, we fed C57BL/6J mice a high-fat diet for 12 weeks, which caused an increase in body mass, blood glucose concentration, and blood lipid concentrations; and abnormalities in renal function (P < 0.05). Resveratrol administration ameliorated the defects in circulating lipid and glucose concentrations, renal dysfunction, the renal expression of components of the JAML/Sirt1 lipid synthesis pathway, and the expression of the adipose differentiation-related protein in the mice (P < 0.05). Histological staining also showed less lipid deposition and kidney damage. Thus, resveratrol regulates the JAML/Sirt1 lipid synthesis pathway, reduces lipid deposition in the kidney, and ameliorates diabetic kidney damage.

Double primary germ cell tumor in a 45 year old woman: one case report and literature review.

We report a rare case of double primary germ cell tumor: right ovarian yolk sac tumor and left ovarian dysgerminoma. A 45 year-old woman was admitted to our hospital due to irregular bleeding for 2 days and extended menstrual period. Right ovarian mass was discovered on transvaginal ultrasound. The pathology results revealed that right ovarian yolk sac tumor and left ovarian dysgerminoma. Total abdominal hysterectomy with bilateral salpingo-oophorectomy with debulking with pelvic lymphadenectomy was performed. The patient underwent adjuvant chemotherapy with BEP six courses in four months and AFP dropped from 8490 ng/ml to nearly 10 ng/ml. Conclusion: Total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by combination chemotherapy must be the treatment of first choice of germ cell tumor.

Primary synchronous colloid adenocarcinoma and squamous cell carcinoma in the same lung: A rare case report.

RATIONALE: Double primary lung cancer (DPLC) is a relatively rare type of lung cancers. According to whether the diagnosis interval between lesions is more than 6 months, it can be divided into synchronous DPLC (sDPLC) and metachronous DPLC (mDPLC). Here, we describe a case of sDPLC in which one of the components is a rare colloid adenocarcinoma (CA). PATIENT CONCERNS: A 69-year-old male was admitted to the hospital due to chest distress and shortness of breath for 1 year, getting worse in the last 15 days. DIAGNOSIS: Both HE staining and IHC supported the diagnosis of CA in the right lower lobe and moderately differentiated squamous cell carcinoma in the right upper lobe. INTERVENTIONS: The patient was treated with 3 cycles of adjuvant chemotherapy with pemetrexed and lobaplatin after the right upper lobectomy, wedge resection of the right lower lobe and lymph node dissection under video-assisted thoracoscope. OUTCOMES: Our plan was to follow him up with general physical examination, chest-abdomen CT and serum tumor markers every 6 months for 2 years. The patient was still alive until the last follow-up in November 2020. LESSONS: CA of the lung is a rare primary lung adenocarcinoma. The diagnosis should be based on the patient's clinical characteristics, imaging examination and pathological characteristics, and also need to be differentiated from other mucinous adenocarcinomas. Interestingly, our patient developed not only a CA in the right lower lobe, but also a moderately differentiated squamous cell carcinoma in the right upper lobe.

microRNA-146b promotes neuroblastoma cell growth through targeting NUMB.

Accumulating evidence has demonstrated that the abnormal expression of microRNA (miRNA/miR) serves a crucial role in the development of numerous types of human cancer, including neuroblastoma (NB). The present study aimed to investigate the expression levels and biological roles of miR-146b in NB. miR-146b expression levels in NB cell lines and human umbilical vein endothelial cells (HUVECs) were analyzed using reverse transcription-quantitative PCR, and the regulatory effects of miR-146b on NB cell proliferation, invasion and apoptosis in vitro were investigated using CCK-8 assay, transwell invasion assay and flow cytometry. In addition, bioinformatics analysis, western blotting and dual-luciferase reporter assays were used to determine whether NUMB was a target gene of miR-146b. miR-146b expression levels were increased in NB cell lines compared with HUVECs. The knockdown of miR-146b using a miR-146b inhibitor significantly inhibited NB cell proliferation and invasion, but promoted cell apoptosis in vitro. Furthermore, it was revealed that miR-146b promoted NB cell proliferation through targeting NUMB. In conclusion, miR-146b was suggested to serve as an oncogene, at least in part, through directly targeting NUMB, which indicated that miR-146b may be a potential therapeutic target for NB treatment.

Histiocytoid breast carcinoma, neither lobular nor ductal? A case report and literature review.

Histiocytoid breast carcinoma (HBC) is a rare type of breast cancer with controversial histogenesis, which is characterized by abundant foamy cytoplasm, fuzzy cell boundary, linear or annular infiltration, eccentric large irregular nuclei or prominent nucleoli and low mitotic activity. HBC has been considered to be a variant of lobular carcinoma, a variant of apocrine ductal carcinoma, and an apocrine variant of lobular carcinoma and to resemble lipid-rich carcinoma. We presented a case of 75-year-old woman with a 5-cm mass in the left breast. The mass was yellow-beige on cut section. HBC was diagnosed including invasive carcinoma (IC) of apocrine differentiation (diameter about 5 mm) which was surrounded by extensive carcinoma in situ (CIS, diameter about 25 mm) of apocrine type, and a 4-mm invasive ductal carcinoma (IDC) in grade II. The distance between HBC and IDC was 4 mm. There was extensive (42 of 43 lymph nodes) metastasis and intravascular tumor emboli. The tumor extended into peripheral nerve. The pathology showed histiocytoid breast carcinoma with a smaller conventional invasive ductal carcinoma in adjacent area. She received a left modified radical mastectomy. However, on the follow-up imaging techniques, the mass showed no response. We discussed the pathology and immunohistochemical finding, and reviewed the literatures. We found that this case was a unique type of HBC.

Rare pancreatic carcinosarcoma in a patient with medical history of esophageal cancer: A case report and literature review.

RATIONALE: Pancreatic carcinosarcoma (PCS) is a very rare pancreatic cancer with an extremely poor prognosis. Interestingly, PCS can coexist with other metachronous malignant cancers. Here we report a case of PCS combined with esophageal cancer (EC). PATIENT CONCERNS: The patient was a 66-year-old man who presented with abdominal pain and progressive nausea. He had undergone esophagectomy for EC 5 years previously. DIAGNOSIS: Both EC and PCS were confirmed via postoperative pathological diagnosis. INTERVENTIONS: Owing to the patient's previous esophagectomy for EC, pancreaticoduodenectomy for the PCS could not be performed. Instead, he underwent cholecystectomy with bile duct-jejunum Roux-en-Y anastomosis and radioactive seed implantation. OUTCOMES: The patient is still alive for >1 year. LESSONS: To our knowledge, this is the first report of PCS combined with EC and thus of metachronous multiple primary carcinoma. A detailed literature review of the clinical and histologic features of PCS reveals important information about the epidemiology and biology of this rare disease.