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Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 750-760页

作者： Ying-Jie Zhang Meng-Xia Yuan Wu Wen Fan Li Yi Jian Chuan-Ming Zhang Ye Yang Feng-Lin Chen Department of Digestive Diseases Chengdu Second People’s HospitalChengdu 610000Sichuan ProvinceChina Graduate School Chengdu Medical CollegeChengdu 610000Sichuan ProvinceChina

BACKGROUND Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions,including colorectal adenoma.Screening colonoscopy frequently reveals chicken skin mucosa(CSM;white or yellow-white speckled mucosa)surrounding colo-rectal polyps,caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors.CSM-positive colorectal polyps are associated with various diseases;however,their prognosis varies greatly.Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps.Improved imaging is required to diagnose and treat CSM-positive colorectal polyps.METHODS This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy.All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system.Based on the pathological results,patients were classified as non-neoplastic polyps(five juvenile polyps),neoplastic polyps,non-invasive high-grade neoplasia(NHGN),or submucosal invasive carcinoma(SM stage cancer).We analyzed and compared the clinical features,suspected risk factors for malignant transformation of neoplastic polyps,and early infiltration of sub-mucosal carcinoma.RESULTS The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps.Most NHGN polyps had a deeper red mucosal color.On logistic regression analyses,diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps.Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM;type 2 CSM was more common in neoplastic polyps.Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer.Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal ca

关键词： Chicken skin mucosa Colorectal cancer Colorectal polyps Endoscopic resection malignant transformation White light endoscopy

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malignant transformation of primary mature teratoma of colon:A case report

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World Journal of Clinical Cases 2022年第20期10卷 7076-7081页

作者： Jie Liu Department of Pathology The First Affiliated Hospital of Anhui Medical UniversityHefei 230000Anhui ProvinceChina

BACKGROUND Mature teratoma is a common benign ovarian germ cell tumor,accounting for about 20%of ovarian tumors.The malignant transformation of this tumor is less than 2%.The most common type is squamous cell carcinoma,followed by adenocarcinoma.malignant transformation of colonic mature teratoma is extremely rare.We here report a case of malignant transformation of primary mature teratoma of the colon.The type of malignant transformation was adenocarcinoma.CASE SUMMARY A 63-year-old woman was admitted to our hospital due to persistent pain in her right lower abdomen for 1 mo,and she had no nausea,vomiting,blood in the stools,or other symptoms.Preoperative colonoscopy showed uplift of the sigmoid colon mucosa and submucosa.The biopsy showed squamous epithelium.However,contrast-enhanced computed tomography of abdomen and pelvis showed a localized thickening of the sigmoid wall,suggesting colon cancer.Endoscopic ultrasonography(EUS)revealed that the structure of the intestinal wall at the base of the lesion was destroyed,and the boundary between the lesion and the surroundings was unclear.According to the findings of the EUS,the patient did not undergo endoscopic submucosal dissection,but underwent radical resection of the tumor.Histologically,squamous epithelium was seen on the mucosal surface of the colon wall,cartilage and glands were seen under the epithelium,and adenocarcinoma was seen on the muscular layer and serous surface.The final pathological diagnosis was malignant teratoma of the colon.We have followed up the patient for 2 mo since the operation,and the patient recovered well.CONCLUSION This case suggests the possibility of mature teratoma in the colon and recognition of malignant types,and it should not be considered as an exclusively ovarian tumor.

关键词： Colon Mature teratoma malignant transformation Adenocarcinoma Squamous epithelium Case report

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malignant transformation of biliary adenofibroma combined with benign lymphadenopathy mimicking advanced liver carcinoma:A case report

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World Journal of Clinical Cases 2022年第25期10卷 9104-9111页

作者： Shao-Cheng Wang Yan-Yan Chen Fei Cheng Hai-Yong Wang Fu-Sheng Wu Li-Song Teng Department of Surgical Oncology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of Pathology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Biliary adenofibromas(BAFs)are rare primary hepatic neoplasms,some of which can potentially undergo malignant transformation.Here,we describe a rare case of malignant transformation of BAF.CASE SUMMARY A 51-year-old female was referred to our hospital with epigastric pain.Computed tomography showed a solitary liver mass combined with the enlargement of multiple mediastinal and cervical lymph nodes,clinically mimicking a liver carcinoma with extensive lymph node metastasis.However,core needle biopsy suggested BAF with malignant transformation.Finally,the patient underwent curative resection of the neoplasm and was recurrence-free for 12 mo.CONCLUSION Our case serves as an example of a rare manifestation of BAF.Our report and the previously published experience,reinforce that curative resection should be considered the primary treatment for BAFs with malignant transformation,leading to a favorable prognosis.

关键词： Biliary adenofibroma malignant transformation Lymphadenopathy Surgery Case report

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malignant transformation of pulmonary bronchiolar adenoma into mucinous adenocarcinoma:A case report

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World Journal of Clinical Cases 2023年第1期11卷 233-241页

作者： Xu-Ling Liu Cheng-Feng Miao Min Li Peng Li Department of Pathology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

BACKGROUND Bronchiolar adenoma(BA)and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK5/6 in the basal cell layer.Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors,including invasive mucinous adenocarcinoma,especially based on the histopathology of intraoperative frozen sections.These tumors are now considered to be benign neoplasms,with malignant transformation reported in only a few cases.CASE SUMMARY A 57-year-old woman presented with a 17.0 mm×7.0 mm nodule in the lower lobe of the left lung.Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed.The tumor consisted of a BA area and a mucinous adenocarcinoma(MA)area.In the BA area,the tumor had a bilayered structure of luminal cells and basal cells.The basal cells were positive for CK5/6 and p40,but the MA area was negative for these biomarkers.The Ki-67 proliferation index was low(1%-2%).The patient was diagnosed with BA accompanied by MA,and had a favorable outcome.CONCLUSION The present study indicated that BA may be carcinogenic,and suggests that clinicians should be aware of its potential for malignant transformation.

关键词： Bronchiolar adenoma Ciliated muconodular papillary tumors Mucinous adenocarcinoma malignant transformation Pulmonary Case report

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Biomarkers of malignant transformation in oral leukoplakia:from bench to bedside

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第10期24卷 868-882页

作者： Xinjia CAI Jianyun ZHANG Heyu ZHANG Tiejun LI Department of Oral Pathology Peking University School and Hospital of Stomatology/National Center of Stomatology/National Clinical Research Center for Oral Diseases/National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Central Laboratory Peking University School and Hospital of StomatologyBeijing 100081China Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)Beijing 100081China

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.

关键词： Oral leukoplakia Oral squamous cell carcinoma malignant transformation Biomarker Prognosis

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Radiotherapy delays malignant transformation and prolongs survival in patients with IDH-mutant gliomas

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Cancer Biology & Medicine 2022年第10期19卷 1477-1486页

作者： Yanwei Liu Huiyuan Chen Guanzhang Li Jing Zhang Kun Yao Chenxing Wu Shouwei Li Xiaoguang Qiu Department of Radiation Oncology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China National Clinical Research Center for Neurological Diseases Beijing 100070China Department of Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neuropathology Department of Neurosurgery Sanbo Brain HospitalCapital Medical UniversityBeijing 100093China

Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;Pmalignant transformation and improved survival in patients with IDHmutant gliomas.

关键词： Lower-grade gliomas IDH mutation radiotherapy malignant transformation survival

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Primary malignant tumours and malignant transformation of cysts in the retrorectal space:MRI diagnosis and treatment outcomes

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Gastroenterology Report 2022年第1期10卷 460-467页

作者： Jing Gong Yumeng Xu Yan Zhang Lichao Qiao Haixia Xu Ping Zhu Bolin Yang Department of Colorectal Surgery Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjingJiangsuP.R.China First Clinical Medical College Nanjing University of Chinese MedicineNanjingJiangsuP.R.China

Background:There are no clear guidelines for the diagnosis and treatment of malignant retrorectal tumours.The purpose of this study was to increase preoperative diagnostic knowledge and to describe the outcomes of treatment for these patients.Methods:This retrospective study was conducted on patients who underwent complete retrorectal tumour resection between May 2006 and July 2018,and had confirmed post-operative pathology reports.Demographic and clinical data(including imaging,perioperative,pathological,and prognostic data)were collected and analysed.Results:malignant lesions were identified in 15(9[60%],female)patients.The median age of the patients was 59 years(range,34–72 years).Primary malignant tumours were identified in seven patients with solid tumours,in which gastrointestinal stromal tumours accounted for 71.4%(five of seven)and the remainder were chordoma or mucinous adenocarcinoma.malignant transformation of cysts occurred in another eight patients with heterogeneous tumours,while histopathological features were present in 75%(six of eight)of patients with mucinous adenocarcinoma,and the remainder were squamouscell carcinoma or neuroendocrine tumour(Grade 2).The malignant characteristics of the solid portions observed using magnetic resonance imaging(MRI)were as follows:the cyst wall of the tumour was irregularly thickened;the surface was convex or lobed;the solid tumour had no capsule,or the capsule was destroyed;and the surface had a gyrus-like morphology.At a median follow-up time of 52 months(range,13–100 months),the overall recurrence-free survival rate was 40.0%and the survival rate was 46.7%.Conclusion:Some MRI features can be used to distinguish malignant retrorectal tumours from benign retrorectal tumours.The survival rate of patients with malignant retrorectal tumours is poor.

关键词： retrorectal tumour malignant transformation clinical features treatment prognosis

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O6-methylguanine DNA methyltransferase is upregulated in malignant transformation of gastric epithelial cells via its gene promoter DNA hypomethylation

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 664-677页

作者： Yue-Xia Chen Lu-Lu He Xue-Ping Xiang Jing Shen Hong-Yan Qi Department of Pathology and Pathophysiology and Department of Radiation Oncology of the Second Affiliated Hospital University School of MedicineZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina Department of Pathology Third Hospital of NanchangNanchang 330000Jiangxi ProvinceChina Department of Pathology the Second Affiliated HospitalZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina Department of Pathology and Pathophysiology andDepartment of Medical Oncology of the Second Affiliated Hospital Zhejiang University School of MedicineZhejiang UniversityHangzhou 310058Zhejiang ProvinceChina

BACKGROUND O_(6)-methylguanine-DNA methyltransferase(MGMT)is a suicide enzyme that repairs the mispairing base O_(6)-methyl-guanine induced by environmental and experimental carcinogens.It can transfer the alkyl group to a cysteine residue in its active site and became inactive.The chemical carcinogen N-nitroso compounds(NOCs)can directly bind to the DNA and induce the O_(6)-methylguanine adducts,which is an important cause of gene mutation and tumorigenesis.However,the underlying regulatory mechanism of MGMT involved in NOCs-induced tumorigenesis,especially in the initiation phase,remains largely unclear.AIM To investigate the molecular regulatory mechanism of MGMT in NOCs-induced gastric cell malignant transformation and tumorigenesis.METHODS We established a gastric epithelial cell malignant transformation model induced by N-methyl-N’-nitro-N-nitrosoguanidine(MNNG)or N-methyl-N-nitroso-urea(MNU)treatment.Cell proliferation,colony formation,soft agar,cell migration,and xenograft assays were used to verify the malignant phenotype.By using quantitative real-time polymerase chain reaction(qPCR)and Western blot analysis,we detected the MGMT expression in malignant transformed cells.We also confirmed the MGMT expression in early stage gastric tumor tissues by qPCR and immunohistochemistry.MGMT gene promoter DNA methylation level was analyzed by methylation-specific PCR and bisulfite sequencing PCR.The role of MGMT in cell malignant transformation was analyzed by colony formation and soft agar assays.RESULTS We observed a constant increase in MGMT mRNA and protein expression in gastric epithelial cell malignant transformation induced by MNNG or MNU treatment.Moreover,we found a reduction of MGMT gene promoter methylation level by methylation-specific PCR and bisulfite sequencing PCR in MNNG/MNU-treated cells.Inhibition of the MGMT expression by O_(6)-benzylguanine promoted the MNNG/MNU-induced malignant phenotypes.Overexpression of MGMT partially reversed the cell malignant transformation process induced by MNNG/MNU.

关键词： O6-methylguanine-DNA methyltransferase DNA methylation malignant transformation Gastric carcinogenesis Epigenetic regulation

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Granulocyte-macrophage colony-stimulating factor and interleukin 4 induce the malignant transformation of the bone marrow- derived human adult mesenchymal stem cells

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Chinese Medical Journal 2011年第5期124卷 729-733页

作者： ZHOU Xiao-gang YANG Yi YANG Jin-song ZHOU Jian FANG Tao-lin DAI Wen-da CHEN Zheng-rong Department of Orthopaedic Surgery Zhongshan Hospital Fudan University Shanghai 200032 China Department of Orthopedics The First Affiliated Hospital of Gaungxi Medical University Nanning Guangxi 530021 China

Background The purpose of the study was to examine the effects of granulocyte-macrophage colony-stimulating factor （GM-CSF） and interleukin 4 （IL-4） on the bone-marrow-derived human adult mesenchymal stem cells （hMSCs）. Methods The hMSCs were isolated and cultured with GM-CSF and IL-4 for a period of one month. A single colony of transformed cells was then isoloated and their phenotype was characterized by morphology, surface marker expression, and in vivo tumorigenesis.Results After one month culture, the transformed mesenchymal cells exhibited the morphology and phenotype similar to those of tumor cells, and also caused multiple fast growing lung deposits when it was injected into immunodeficient mice.Conclusion Cytokines-driven malignant transformation of hMSCs may be a useful model for studying signaling pathways initiating malignant transformation of hMSC.

关键词： bone marrow-derived mesenchymal stem cells malignant transformation interleukin 4 granulocyte-macrophage colony-stimulating factor

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Inhibition of the Hedgehog Signaling Pathway Depresses the Cigarette Smoke-Induced malignant transformation of 16HBE Cells on a Microfluidic Chip

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Chinese Medical Journal 2018年第10期131卷 1191-1198页

作者： Yong-Xin Qin Zhi-Hui Yang Xiao-Hui DU Hui Zhao Yuan-Bin Liu Zhe Guo Qi Wang Department of Respiratory Medicine The Second Affiliated Hospital Dalian Medical University Dalian Liaoning 116027 China Department of Critical Care Medicine The First Affiliated Hospital Dalian Medical University Dalian Liaoning 116021 China Department of Scientific Research Center The Second Affiliated Hospital Dalian Medical University Dalian Liaoning 116027 China

Background：The hedgehog signaling system （HHS） plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases.However,little is known about the involvement of HHS in the malignant transformation of cells.This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial （16HBE） cells.Methods：In this study,two microfluidic chips were designed to investigate cigarette smoke extract （CSE）-induced malignant transformation of cells.Chip A contained a concentration gradient generator,while chip B had four cell chambers with a central channel.The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation.The 16HBE cells in chip B were cultured with 12.25% CSE （Group A）,12.25% CSE ± 5 μmol/L cyclopamine （Group B）,or normal complete medium as control for 8 months （Group C）,to establish the in vitro lung inflammatory-cancer transformation model.The transformed cells were inoculated into 20 nude mice as cells alone （Group 1） or cells with cyclopamine （Group 2） for tumorigenesis testing.Expression of HHS proteins was detected by Western blot.Data were expressed as mean ± standard deviation.The t-test was used for paired samples,and the difference among groups was analyzed using a one-way analysis of variance.Results：The optimal concentration of CSE was 12.25%.Expression of HHS proteins increased during the process of malignant transformation （Group B vs.Group A,F =7.65,P 〈 0.05）.After CSE exposure for 8 months,there were significant changes in cellular morphology,which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice.Cyclopamine could effectively depress the expression of HHS proteins （Group C vs.Group B,F =6.47,P 〈 0.05） and prevent tumor growth in nude mice （Group 2 vs.Group 1,t=31.59,P〈 0.01）.Conclusions：The activity of HHS is upregulated during the CSE-induced malignant transformation of 16HBE cells.Cyclopamine can effect

关键词： Hedgehog Signaling System Lung Cancer malignant transformation Microfluidic Chip

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