Objective:To analyze the clinical significance of molecular classification and hereditary phenotype in endometrial carcinoma (EC) based on high throughput sequencing (NGS).Methods:97 EC samples were collected retrospectively from December 2019 to October 2022 in China-Japan Friendship Hospital. NGS technique was used to analyze the molecular classification, POLE hypermutation, microsatellite high Instability/mismatch repair dysfunction (MSI-H/MMRd), P53 protein abnormality (P53 abn), and non-specific molecular profile (NSMP). Lynch syndrome related genes and BRCA1/2 genes were detected by NGS and their genetic characteristics were analyzed. Results:Of the 97 EC cases, 77 were endometrial adenocarcinoma and 20 were other pathological subtypes. The proportions of the four molecular subtypes were 9.3% (9/97) POLE hypermutation, 16.5% (16/97) MSI-H, 17.5% (17/97) P53 abn and 56.7% (55/97) NSMP, respectively. There were significant differences in age, histological type, lymph node metastasis, pathological stage and other parameters among the four molecular types ( P＜0.05). 8.2% (8/97) were multiple molecular typing and four multiple molecular typings detected, including POLEmut-MSI-H, POLEmut-P53abn, MSI-H-P53abn, P53abn-P53abn, which accounted for 1.0% (1/97), 3.1% (3/97), 1.0% (1/97) and 3.1% (3/97), respectively. The consistent rate of MSI-H and MMR protein expression was 92.9% ( Kappa=0.818, P＜0.001). The coincidence rate between TP53 gene sequencing and P53 protein expression was 88.9% ( Kappa=0.661, P＜0.001). In MSI-H type, 25.0% (4/16) were diagnosed as Lynch syndrome, and 75.0% (12/16) were diagnosed as Lynch like syndrome. 7.2% (7/97) BRCA2 somatic variation was detected, while BRCA1/2 germline variation was not detected in 97 cases. Conclusions:EC molecular classification has feasibility and clinical value. High throughput sequencing can detect low frequency mutations of TP53 gene, suggesting that it can provide more accurate molecular information and more accurate molecular typing effect. It is suggested to further detect Lynch syndrome related genes in patients with MSI-H, so as to carry out genetic management for patients and their families and achieve better therapeutic effect.

Objective:To analyze the clinical significance of molecular classification and hereditary phenotype in endometrial carcinoma (EC) based on high throughput sequencing (NGS).Methods:97 EC samples were collected retrospectively from December 2019 to October 2022 in China-Japan Friendship Hospital. NGS technique was used to analyze the molecular classification, POLE hypermutation, microsatellite high Instability/mismatch repair dysfunction (MSI-H/MMRd), P53 protein abnormality (P53 abn), and non-specific molecular profile (NSMP). Lynch syndrome related genes and BRCA1/2 genes were detected by NGS and their genetic characteristics were analyzed. Results:Of the 97 EC cases, 77 were endometrial adenocarcinoma and 20 were other pathological subtypes. The proportions of the four molecular subtypes were 9.3% (9/97) POLE hypermutation, 16.5% (16/97) MSI-H, 17.5% (17/97) P53 abn and 56.7% (55/97) NSMP, respectively. There were significant differences in age, histological type, lymph node metastasis, pathological stage and other parameters among the four molecular types ( P＜0.05). 8.2% (8/97) were multiple molecular typing and four multiple molecular typings detected, including POLEmut-MSI-H, POLEmut-P53abn, MSI-H-P53abn, P53abn-P53abn, which accounted for 1.0% (1/97), 3.1% (3/97), 1.0% (1/97) and 3.1% (3/97), respectively. The consistent rate of MSI-H and MMR protein expression was 92.9% ( Kappa=0.818, P＜0.001). The coincidence rate between TP53 gene sequencing and P53 protein expression was 88.9% ( Kappa=0.661, P＜0.001). In MSI-H type, 25.0% (4/16) were diagnosed as Lynch syndrome, and 75.0% (12/16) were diagnosed as Lynch like syndrome. 7.2% (7/97) BRCA2 somatic variation was detected, while BRCA1/2 germline variation was not detected in 97 cases. Conclusions:EC molecular classification has feasibility and clinical value. High throughput sequencing can detect low frequency mutations of TP53 gene, suggesting that it can provide more accurate molecular information and more accurate molecular typing effect. It is suggested to further detect Lynch syndrome related genes in patients with MSI-H, so as to carry out genetic management for patients and their families and achieve better therapeutic effect.

Objective:To describe the clinicopathological features of pulmonary artery intimal sarcoma (PAIS), and to understand its molecular alterations.Methods:Sixty cases of pulmonary artery endarterectomy performed at the China-Japan Friendship Hospital, Beijing, China from January 2017 to January 2020 were reviewed. Clinical data of 5 patients with pulmonary artery intimal sarcoma were collected. Hematoxylin-eosin staining, immunohistochemistry staining and fluorescence in situ hybridization (FISH) were performed to evaluate the pathological features. RNA sequencing was conducted to assess the fusion gene changes in PAIS.Results:The detection rate of PAIS was 8.3% (5/60), with the median age of 49 years and a female predominance. Their clinical manifestations were non-specific. Histopathological examination showed that the tumors were composed of malignant spindle or epithelioid cells, with various degrees of atypia. Focal heterologous osteosarcomatous or leiomyosarcomatous differentiation was noted. The tumor cells could express PDGFRA, CDK4 and MDM2 with co-amplification of MDM2, CDK4 and EGFR genes. RNA sequencing detected multiple in-frame fusions in the tumors.Conclusions:PAIS is a rare, highly heterogeneous, and poorly-or un-differentiated sarcoma accompanied by complex changes of multiple genes.It has no known effective treatments, and thus has a poor prognosis.

Objective:To investigate the clinicopathological features and prognostic factors of primary mediastinal large B-cell lymphoma (PMBL).Methods:The clinical data of 60 patients with PMBL including 44 biopsy cases and 16 consultation cases from September 2000 to November 2019 in the Department of Pathology, China-Japan Friendship Hospital (14 cases) and Peking Union Medical College Hospital (46 cases) were enrolled. Pathologic features, immunophenotype, immunoglobulin (Ig) gene rearrangement and microRNA expression profile were retrospectively studied.Results:Of the 60 patients, 23 were males and 37 were females, age ranged from 15 to 64 years (median 28 years). Immunohistochemical staining showed that the tumor cells were positive for pan-B cell antigens, CD30 (77.4%, 24/31), CD23 (73.1%, 19/26), MUM1 (45.8%, 11/24), Ki-67 index ≥70 % (90.6%, 29/32). EBER in situ hybridization was analyzed in 21 PMBL, only one case (4.8%) was positive. Ig gene rearrangement was performed in 20 cases, and seven were positive (35.0%). MicroRNA gene expression profiles were analyzed in seven cases of PMBL and nine cases of diffuse large B-cell lymphoma, and there were 33 microRNAs with significant difference ( P<0.05). Univariate analysis indicated that the poor prognostic factors included serum lactate dehydrogenase (LDH) level,International Prognostic Index (IPI) score ≥3, stages Ⅲ-Ⅳ, chemotherapy not combined with rituximab and MUM1 positivity ( P<0.05). Multivariate analysis showed that the treatment combined with rituximab was independently related to prognosis ( P<0.05). Conclusions:PMBL is different from diffuse large B-cell lymphoma in clinicopathologic features, immunophenotypic presentation and molecular features. The prognostic factors, molecular genetics and immunological characteristics reveal that this study has enriched our understanding of the biology of PMBL, thus providing evidence and strategies for treatment.

Objective:To describe the clinicopathological features of the lung cancers in the lungs explanted from lung transplant recipients, and to understand the molecular alterations of these cancers.Methods:The patients who underwent lung transplantation in China-Japan Friendship Hospital from March 2017 to December 2018 were reviewed. Clinical data of the patients with lung cancer associated with end-stage interstitial lung diseases (ILD) were collected. Hematoxylin-eosin staining and immunohistochemistry were performed to evaluate the pathological feature. Real-time quantitative PCR was performed to analyze the hotspots and targeted regions of 9 cancer-associated genes.Results:Among the 154 identified patients, 10 met the inclusion criteria and were included. The detection rate of lung cancer in the lung transplantation patients was 6.5%(10/154). All of the included 10 patients were male, with an average age of 59 years. They all had a history of heavy smoking. Three cases had a lung cancer diagnosed before operation, while the other 7 cases were concealed in the specimen of end-stage ILD. All of lung cancers were non-small-cell carcinoma, including 8 cases of adenocarcinoma and 2 cases of squamous cell carcinoma. The proportion of mucinous adenocarcinoma components was 3/10. The mutations in KRAS gene exon 2 were detected in two patients with mucous adenocarcinoma, while no alterations in NRAS, EGFR, ALK, ROS1, BRAF, HER2, PI3KCA and RET were detected in the remaining patients.Conclusions:Lung cancers are difficult to detect in patients with end-stage ILD. They are mainly adenocarcinomas and associated with a higher frequency of mutations in KRAS gene. These cancers have limited treatment options and a poor prognosis.

Objective: To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma (FDCS). Methods: We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real-time PCR and EBER in situ hybridization was performed on 4 cases. Results: Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low-grade FDCS and 3 cases of high-grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2-40, EGFR and CXCL13, but negative for S-100, CD68, HMB45, SMA, Desmin, CD117, Dog-1, CD34, CD30, EMA and CK.Five cases were positive for PD-L1 and the its expression in high-grade FDCS were higher than that in low-grade FDCS.Two cases of low-grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in-situ hybridization showed that only the nasopharynx FDCS was positive.The follow-up information of 5 patients were available (7~43 months), 4 patients died and 1 still alive with rectum metastasis. Conclusions FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first-line antibodies including CD21, CD23, CD35 and second-line antibodies including D2-40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD-L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

Objective: To evaluate the risk factors of postoperative upgrade to pT₃a of cT₁ renal cell carcinoma, and to establish a nomogram prediction model to improve the ability of predicting locally advanced renal cell carcinoma and provide a reference for clinical surgical decision-making. Methods: Clinical data of 1 376 patients with cT₁ (diameter ≤ 7 cm) renal tumor hospitalized for surgery from January 2010 to December 2016 were retrospectively analyzed. There were 979 males and 397 females, with the mean age of (57.65±10.92) years. The mean body mass index (BMI) was (25.47±3.27) kg/m² and the average tumor size was (4.02±1.52) cm. There were 711 tumors on the left and 665 on the right. There were 363 cases with clinical symptoms, 567 patients with smoking history , 732 cases with history of chronic disease. There were 289 cases with tumor necrosis, 636 cases with tumor protrusion, 822 cases with irregular tumor , and 738 cases with renal sinus compression. Partial nephrectomy and radical nephrectomy were performed in 396 cases and 980 cases respectively. Mann-whitney U test and chi-square test were used for univariate analysis, logistic regression analysis was used for multivariate analysis to analyze the predictors of upgrading, R software was used to construct the nomogram predictive model, C-index was used to evaluate the model discrimination, and calibration curve method was used to evaluate the consistency of the model. Results: Postoperative pathology of total 1 376 cases showed that there were 1 195 cases of clear cell carcinoma of kidney, 48 cases of papillary cell carcinoma, 57 cases of chromophobe cell carcinoma, and 76 cases of other types. Among the 1 376 patients with cT₁ renal tumor, 75 patients were upgraded to pT_3a, accounting for 5.5% of all patients. Univariate analysis showed that the patients who upgraded to pT_3a were older [(63.08±10.17) years old and (57.34±10.88) years old], and the tumor length and diameter were larger [(5.24±1.35) cm and (3.95±1.51) cm]. Patients with clinical symptoms [46.7% (35/75) vs. 25.2%(328/1 301)], patients with CT indication of tumor necrosis [40.0%(30/25 975) vs. 19.9% (259/1 301)], patients with irregular tumor contour [73.3%(55/76 775) vs. 59.0%(767/1 301)], and patients with radical nephrectomy were higher [(92.1% (70/91 075) vs. 70%(910/1 301)]. All the differences were statistically significant (P<0.01). Multivariate analysis showed that the independent predictors of upgrading were age (OR=1.046, P<0.001), larger tumor (OR=1.504, P<0.001), clinically symptom (OR=2.153, P=0.004), irregular tumor profile (OR=2.466, P=0.002), and tumor necrosis on CT (OR=2.588, P<0.001). The C-index was 0.808, the calibration curve of forecasting curve with the standard curve fit was good, and the prediction of renal cancer are better in predict consistency. Conclusions Based on the five preoperative predictors, including age, tumor size, clinical presence or absence of symptoms, tumor profile, and whether or not the tumor necrosis indicated by CT, this study developed a nomogram of cT₁ renal cancer upgrade to pT_3a. This nomogram has a good statistical significance, and this model can provide prognosis consultation for patients and provide reference for doctors to make decisions before treatment.

Objective To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma ( FDCS ). Methods We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real?time PCR and EBER in situ hybridization was performed on 4 cases. Results Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low?grade FDCS and 3 cases of high?grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2?40, EGFR and CXCL13, but negative for S?100, CD68, HMB45, SMA, Desmin, CD117, Dog?1, CD34, CD30, EMA and CK.Five cases were positive for PD?L1 and the its expression in high?grade FDCS were higher than that in low?grade FDCS.Two cases of low?grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in?situ hybridization showed that only the nasopharynx FDCS was positive.The follow?up information of 5 patients were available (7～43 months), 4 patients died and 1 still alive with rectum metastasis.Conclusions FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first?line antibodies including CD21, CD23, CD35 and second?line antibodies including D2?40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD?L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

Objective To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma ( FDCS ). Methods We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real?time PCR and EBER in situ hybridization was performed on 4 cases. Results Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low?grade FDCS and 3 cases of high?grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2?40, EGFR and CXCL13, but negative for S?100, CD68, HMB45, SMA, Desmin, CD117, Dog?1, CD34, CD30, EMA and CK.Five cases were positive for PD?L1 and the its expression in high?grade FDCS were higher than that in low?grade FDCS.Two cases of low?grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren′t detected in all of 7 cases. The result of EBER in?situ hybridization showed that only the nasopharynx FDCS was positive.The follow?up information of 5 patients were available (7～43 months), 4 patients died and 1 still alive with rectum metastasis.Conclusions FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first?line antibodies including CD21, CD23, CD35 and second?line antibodies including D2?40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD?L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

Objective To investigate the clinical value of liquid-based cytology and cell paraffin blocks combined with immu-nocytochemical examination in cytopathologic diagnosis of hydrothorax and ascites.Methods One hundred and fourteen cases of hydrothorax and ascites sample were collected.The detection positive rates were compared between the liquid-based cytology and cell paraffin blocks combined with immunocyochemical examination.The suspected positive and positive cases were performed the immunocytochemical examination for further judging benign and malignancy and histological source.Results 114 cases of hydro-thorax and ascites samples,36 cases(31.58%)of positive were diagnosed by liquid-based cytologyamong and 55 cases(48.24%)of positive were diagnosed by cell paraffin blocks combined with immunocytochemical examination,the difference was statistically sig-nificant(P<0.01).There were 55 cases of malignant hydrothorax and ascites,45 cases were hydrothorax and 10 cases were ascites, in hydrothorax,there were 32 cases of lung adenocarcinoma,3 cases of small cell lung cancer,4 cases of breast cancer,1 case of en-dometrial carcinoma,1 case of lymphatic hematopoietic system tumor and 4 cases of unknown origin;in ascites,there were 2 cases of ovarian cancer,1 case of digestive system tumor,1 case of endometrial cancer,1 case of lymphatic hematopoietic system tumor and 5 cases of unknown origin.Conclusion The cell paraffin blocks combined with immunocytochemistry can significantly improve the positive detection rate of hydrothorax and ascites,and helps to judge the source of tissue.