Objective·To investigate the clinical,pathological,and molecular genetic features and prognosis of epithelioid hemangioendothelioma(EHE)patients.Methods·Clinical and follow-up data of 12 EHE patients diagnosed at Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to December 2023 were collected.Tissue samples were analyzed using hematoxylin-eosin(H-E)staining,immunohistochemistry(IHC),and fluorescence in situ hybridization(FISH).Results·Among the 12 patients,there were 3 males and 9 females,with a mean age of(47.17±11.15)years.Tumors were located in the liver(6 cases),lung(4 cases),mediastinum(1 case),and supraclavicular region(1 case).Nine patients were asymptomatic,while 3 presented with mild symptoms such as chest tightness and fatigue.CT imaging revealed that EHE patients with involvement of livers and lungs exhibited multiple nodules,and 2 cases had tumors in both organs.Patients with tumors in the supraclavicular region and mediastinum presented with solitary nodules.H-E staining demonstrated that tumor tissues were composed of epithelioid,dendritic,and intermediate cells,arranged in acinar,cord-like,or clustered patterns.Epithelioid cells had round vesicular nuclei and eosinophilic cytoplasm,with some showing a signet-ring appearance and cytoplasmic vacuoles.The stroma contained a mucoid matrix.IHC staining revealed that mesenchymal endothelial markers,including vimentin,CD31,ETS transcription factor ERG,and factor Ⅷ-related antigen,were positive in the tumor tissues,while epithelial markers showed low positivity with weak staining.The Ki-67 indexes were also low.FISH analysis showed that 10 patients had a calmodulin-binding transcription activator 1(CAMTA1)gene break,while 2 patients had a transcription factor E3(TFE3)gene break.Of the 12 patients,11 were followed up for 2 to 38 months,with a mean follow-up time of 21.7 months.Three patients achieved tumor-free survival,6 were alive with tumors,1 died 4 months after surgery,and 1 died of heart disease 24 months after surgery.Conclusion·EHE has atypical clinical features,a tendency to recur,a and variable prognosis.Accurate diagnosis requires a combination of histopathology,IHC,and a molecular testing.

Objective·To investigate the clinical,pathological,and molecular genetic features and prognosis of epithelioid hemangioendothelioma(EHE)patients.Methods·Clinical and follow-up data of 12 EHE patients diagnosed at Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to December 2023 were collected.Tissue samples were analyzed using hematoxylin-eosin(H-E)staining,immunohistochemistry(IHC),and fluorescence in situ hybridization(FISH).Results·Among the 12 patients,there were 3 males and 9 females,with a mean age of(47.17±11.15)years.Tumors were located in the liver(6 cases),lung(4 cases),mediastinum(1 case),and supraclavicular region(1 case).Nine patients were asymptomatic,while 3 presented with mild symptoms such as chest tightness and fatigue.CT imaging revealed that EHE patients with involvement of livers and lungs exhibited multiple nodules,and 2 cases had tumors in both organs.Patients with tumors in the supraclavicular region and mediastinum presented with solitary nodules.H-E staining demonstrated that tumor tissues were composed of epithelioid,dendritic,and intermediate cells,arranged in acinar,cord-like,or clustered patterns.Epithelioid cells had round vesicular nuclei and eosinophilic cytoplasm,with some showing a signet-ring appearance and cytoplasmic vacuoles.The stroma contained a mucoid matrix.IHC staining revealed that mesenchymal endothelial markers,including vimentin,CD31,ETS transcription factor ERG,and factor Ⅷ-related antigen,were positive in the tumor tissues,while epithelial markers showed low positivity with weak staining.The Ki-67 indexes were also low.FISH analysis showed that 10 patients had a calmodulin-binding transcription activator 1(CAMTA1)gene break,while 2 patients had a transcription factor E3(TFE3)gene break.Of the 12 patients,11 were followed up for 2 to 38 months,with a mean follow-up time of 21.7 months.Three patients achieved tumor-free survival,6 were alive with tumors,1 died 4 months after surgery,and 1 died of heart disease 24 months after surgery.Conclusion·EHE has atypical clinical features,a tendency to recur,a and variable prognosis.Accurate diagnosis requires a combination of histopathology,IHC,and a molecular testing.

Objective To investigate the expression characteristics of BRAF,RAS and TERT genes in ultrasound-guided fine needle aspiration specimens and their application value in the preoperative diagnosis of thyroid nodules.Methods A retrospective analysis was performed on 537 cases of fine needle aspiration speci-mens of thyroid nodules in the Aviation General Hospital.The cell smear and liquid-based cell section prepara-tion from each specimen conducted the Papanicolaou's stain and the results were interpreted according to the Bethesda grading system.The gene mutation situation in punctured tissues was analyzed by real-time quantita-tive PCR.Results There were 65 cases (12.10％) of Bethesda class Ⅰ nodules,153 cases (28.49％) of class Ⅱ,84 cases (15.64％) of class Ⅲ,9 cases (1.68％) of class Ⅳ,73 cases (13.59％) of class Ⅴ and 153 cases (28.49％) of class Ⅵ.There were 220 cases (40.97％) of BRAF V600E mutation,21 cases (3.91％) of NRAS mutation,6 cases (1.12％) of KRAS mutation and 2 cases (0.37％) of HRAS mutation.Among them,there was BRAF V600E and KRAS co-mutation in 1 case.BRAF V600E gene mutation had the correlation with cytological diagnostic results (P<0.05),BRAF V600E mutation was more likely to occur in younger ones (P<0.05),and BRAF V600E mutation was more common in males than in females (P<0.05).KRAS mutation was more likely to occur in nodules in the left lobe of the thyroid gland (P<0.05).Conclusion BRAF V600E gene mutation is the most common among thyroid fine needle puncture specimens,and the NRAS mu-tation is in the majority for RAS gene mutations.

Objective To analyze the effects of different age groups of children and different routes of administration on the sedation effect of chloral hydrate.Methods A retrospective analysis was performed on 10 671 children who underwent MRI examination.Children sedated with chloral hydrate were selected and divided into four groups according to their age:group A(0-1 month),group B(>1 month-1 year old),group C(>1-2 years old),group D(>2-6 years old),and each group was further divided into oral administration and enema administration.The success rate of sedation in each group was recorded.Data were analyzed using SPSS 22.0 software.Results(1)The sedation success rate of chloral hydrate in group A was 82.5%,including 87.5%by oral administration and 85.1%by enema administration;(2)The sedation success rate of chloral hydrate in group B was 71.8%,including 78.5%by oral administration and 71.2%by enema administration;(3)The sedation success rate of chloral hydrate in group C was 87.7%,including 89.6%by oral administration and 82.2%by enema administration;(4)The sedation success rate of chloral hydrate in group D was 89.6%,including 89.5%by oral administration and 90.8%by enema administration.There was a difference in the sedation success rate between group B and groups A,C and D,and there was a difference in the sedation success rate between group D and groups A,B,and C.There was a difference in the sedation success rate of oral administration versus enema administration between groups B and D.The differences were statistically significant(P<0.05).Conclusion The sedation success rate of chloral hydrate is different in different age groups,the sedation success rate in the same age group is also different due to different administration methods.Therefore,it is necessary to choose the appropriate sedation strategy according to the age of children.

Objective:To describe the special molecular and histopathological transformation of recurrent tumor in a patient with primary hepatocellular carcinoma(HCC)after liver transplantation.Methods:A case of HCC had recurrent tumor presenting special molecular and histopathological characteristics after liver transplantation.The diagnosis and treatment process of this case is reported.Results:A case of highly differentiated HCC received immune checkpoint inhibitors combined with antiangiogenic therapy after liver malignant tumor resection.Nearly one year later,due to severe liver cirrhosis,the case accepted allogeneic orthotopic transplantation of liver.More than two years later,elevated level of serum alpha fetoprotein was detected,then the PET-CT examination showed multiple suspected lesions with increased 18F-FDG metabolism in the right lobe of the liver.Liver biopsy and high-throughput sequencing were performed,and the results revealed poorly differentiated HCC with YAP1-MAML2 fusion gene.Chemotherapy with XELOX regimen and radiotherapy were administered,and no tumor progression was observed during follow-up.Conclusion:Recurrent tumors after liver transplantation in HCC patient developing into a special molecular and histopathological transformation is rarely reported.The underlying mechanism could be the dramatical alterations of immune microenvironment after liver transplantation,which consequently triggered genomic changes leading to generate novel YAP1-MAML2 fusion gene.The poor differentiation transformation after liver transplantation maybe driven by YAP1-MAML2 fusion gene.

Objective:To describe the special molecular and histopathological transformation of recurrent tumor in a patient with primary hepatocellular carcinoma(HCC)after liver transplantation.Methods:A case of HCC had recurrent tumor presenting special molecular and histopathological characteristics after liver transplantation.The diagnosis and treatment process of this case is reported.Results:A case of highly differentiated HCC received immune checkpoint inhibitors combined with antiangiogenic therapy after liver malignant tumor resection.Nearly one year later,due to severe liver cirrhosis,the case accepted allogeneic orthotopic transplantation of liver.More than two years later,elevated level of serum alpha fetoprotein was detected,then the PET-CT examination showed multiple suspected lesions with increased 18F-FDG metabolism in the right lobe of the liver.Liver biopsy and high-throughput sequencing were performed,and the results revealed poorly differentiated HCC with YAP1-MAML2 fusion gene.Chemotherapy with XELOX regimen and radiotherapy were administered,and no tumor progression was observed during follow-up.Conclusion:Recurrent tumors after liver transplantation in HCC patient developing into a special molecular and histopathological transformation is rarely reported.The underlying mechanism could be the dramatical alterations of immune microenvironment after liver transplantation,which consequently triggered genomic changes leading to generate novel YAP1-MAML2 fusion gene.The poor differentiation transformation after liver transplantation maybe driven by YAP1-MAML2 fusion gene.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

Objective To explore cost effective means for early detection of malignant tumors in individuals undergoing health check-up.Methods This was a retrospective study involving 280,477 participants who had undergone health check-up including essential items from 2012 to 2016 at the Health Assessment and Intervention Research Center of Jiangsu Province.The protocol was composed of four steps.First,essential items were decided and conducted for all health examination participants.Second,cases with a high risk of malignant tumors were collected and additional tests were specified.Third,suspected malignant tumor cases were identified and recommendations for referrals and follow-up were made.Finally,physicians in charge of follow up would urge suspected cases to visit an oncologist,update case files,give regular instructions,and track recall results.Results There were 517 microscopically confirmed cases of malignant tumors,representing a detection rate of 184/100,000(1.84‰)in individuals seeking regular health check-up and of 2,023/100,000 (20.23‰)in those receiving follow ups.The five most prevalent malignant tumors were thyroid cancer (140 cases or 0.499‰),lung cancer(120 cases or 0.428‰),breast cancer(35 cases or 0.374‰),kidney cancer(55 cases or 0.196‰)and prostate cancer (33 cases or 0.177‰).Conclusions Essential examination items in combination with subsequent special tests,specialist referrals and follow ups are a cost effective way for early detection of malignant tumors in people seeking regular health examinations.

The pediatric reference intervals in clinical laboratory play an important role in diagnosis of illness,therapeutic monitoring,prediction of prognosis and health evaluation.Compared with establishing reference interval for adults,there are more challenges to establish pediatric reference intervals.Therefore,the procedure and key technologies of direct method and indirect method are stated based on the characteristics of children population and pediatric,by which to define,transfer and validate pediatric reference intervals.This study will provide systematically methodological ideas for clinical laboratories to establish pediatric reference intervals.