Conventional Ultrasound Combined With Contrast-Enhanced Ultrasound in Differential Diagnosis of Gallbladder Cholesterol and Adenomatous Polyps (1-2 cm).

OBJECTIVES: This study aimed to determine ultrasonic image characteristics that enable differentiation between cholesterol and adenomatous polyps and to assess the diagnostic efficacy of combining conventional ultrasound (CUS) with contrast-enhanced ultrasound (CEUS). METHODS: Eighty-nine patients with gallbladder polyps of 1-2 cm in diameter were enrolled and examined by CUS and CEUS before cholecystectomy. The appearances on CUS and CEUS were recorded and analyzed. The receiver operating characteristic (ROC) curve was used to calculate the optimal size threshold for distinguishing cholesterol from adenomatous polyps. A logistic regression analysis was performed to identify diagnostic variables. ROC analysis was performed to evaluate the diagnostic efficacy of the size, the independent variables, and the combined factors. RESULTS: There were differences in size, number, vascularity on CUS and intralesional vascular shape, wash-out, and area under the curve on CEUS between the two groups (P < .05). ROC analysis indicated that a maximum diameter of 1.45 cm was the optimal threshold for the prediction of adenomatous polyps. The logistic regression analysis proved that the single polyp, presence of vascularity, and intralesional linear vessels were associated with adenomatous polyps (P < .05). ROC analysis showed that the area under the ROC curve, sensitivity, and specificity for the combination of the three independent variables were 0.858, 87.3%, and 67.6%. The number combined with intralesional vascular shape had the highest diagnostic sensitivity of 91.2%. CONCLUSIONS: The combination of CUS and CEUS demonstrated great significance in the differential diagnosis of cholesterol and adenomatous polyps.

Risk factors evaluation of post-transplant lymphoproliferative disorders after allogeneic haematopoietic stem cell transplantation with comparison between paediatric and adult.

To describe the clincopathological features and evaluate risk factors of post-transplant lymphoproliferative disorder (PTLD) after allogeneic haematopoietic stem cell transplants (allo-HSCT), with comparison between paediatric and adult .Clinicopathological features of 81 cases of PTLD after allo-HSCT were analysed by histopatholgy, immunohistochemistry and in situ hybridisatioin.The cases included 58 males and 23 females with a median age of 26.7 years (range 6-55 years) and the PTLDs developed 1-60 months post-transplant (mean 5.9 months). The histological types indicated 10 cases of non-destructive PTLD, including 4 of plasmacytic hyperplasia, 5 of infectious mononucleosis and 1 of florid follicular hyperplasia. Fifty-six cases were polymorphic PTLD, and 15 were monomorphic PTLD, including thirteen of diffuse large B cell lymphoma, 1 of extranodal nasal type natural killer (NK)/T cell lymphoma and 1 of plasmablastic lymphoma. Foci and sheets of necrosis were observed in 31 cases. The infected ratio of Epstein-Barr virus (EBV) was 91.4%. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion or anti-CD20 monoclonal rituximab. Thirty-three cases died. Compared with that of adult, overall survival of paediatric recipient may be better.The first half year after allo-HSCT is very important for the development of PTLD. Type of PTLD, EBV infection and graft-versus-host disease are risk factors. The prognosis of PTLD is poor, and PTLD after allo-HSCT exhibits some features different from that after solid organ transplantation and some differences existing between adult and paediatric recipients.

Overexpression of anillin is related to poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Anillin (ANLN) is required for tumor growth. It has been proven that knockdown of ANLN effectively reduces the occurrence of hepatocellular carcinoma (HCC) in transgenic mice. However, the functional role of ANLN in HCC patients remains to be elucidated. METHODS: Both microarray and TCGA project were used for the analyses of ANLN expression and regulation in HCC. The effect of ANLN on proliferation and cell cycle was detected by CCK-8, colony formation assay and flow cytometry. ANLN expression was measured by immunohistochemistry. Correlation between ANLN expression and clinicopathological features was assessed by Pearson Chi-square test and 5-year overall survival after liver resection was evaluated by Kaplan-Meier method. RESULTS: Increased copy number, decreased methylation levels in the CpG island and upregulated histone hypermethylation of ANLN were found in HCC. Knockdown of ANLN inhibited proliferation and induced G2/M phase arrest in SMMC-7721 cells. ANLN was mainly expressed in the nucleus and showed significantly higher expression levels in cancerous tissues than those in paired adjacent tissues. Moreover, nuclear ANLN expression levels in HCC metastases were significantly higher than those in primary HCC. The results of Cox proportional hazards regression model suggested that ANLN nuclear expression in HCC was an independent risk factor for poor 5-year overall survival of patients after liver resection. CONCLUSIONS: ANLN is a potential therapeutic target for HCC. Patients with nuclear ANLN overexpression in HCC tissue may need adjuvant therapy after liver resection.

Comparison of different cytomegalovirus diseases following haploidentical hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.

Paradoxical effects of cellular senescence-inhibited gene involved in hepatocellular carcinoma migration and proliferation by ERK pathway and mesenchymal-like markers.

BACKGROUND: Cellular senescence-inhibited gene (CSIG) strongly prolongs the progression of replicative senescence. However, roles and mechanisms of CSIG in tumor progression have not been studied widely. METHODS: Roles of CSIG in migration and proliferation of SMMC7721 and Huh7 cells were analyzed by transwell or cell viability assays, respectively. Tumorigenicity assays were used to study whether CSIG knockdown could affect SMMC7721 proliferation in vivo. Next, Western blotting and RT-PCR were preformed to evaluate the effects of CSIG on P-ERK cascade and epithelial mesenchymal transformation markers. Then, the location and expression of CSIG protein was detected by immunofluorescence and Western blotting, respectively. Finally, the Cancer Genome Atlas dataset was used to analyze CSIG mRNA levels in hepatocellular carcinoma (HCC) and adjacent non-tumor tissues. RESULTS: In this study, we found that CSIG overexpression promoted SMMC7721 cell migration, and CSIG knockdown suppressed tumorigenicity of SMMC7721 cells. In contrast to expectation, CSIG up-regulation could significantly inhibit Huh7 cell growth and migration. CSIG could promote P-ERK activation and levels of mesenchymal-like markers in SMMC7721 cells, whereas CSIG suppressed P-ERK activation and levels of mesenchymal-like markers in Huh7 cells. CSIG protein was located in nucleoli as well as nucleoplasm of SMMC7721 cells, whereas CSIG protein was mainly expressed in the nucleoli rather than nucleoplasm of Huh7 cells. Finally, due to individual differences, raised or down-regulated trends of CSIG in HCC as compared with adjacent non-tumor tissues are different among various patient populations. CONCLUSION: In summary, these results indicate that CSIG might play different roles in SMMC7721 and Huh7 cells through regulating P-ERK pathway and mesenchymal-like markers. The differential distribution of CSIG might be an important factor that causes its different functions in SMMC7721 and Huh7 cells. CSIG might play different roles in various patient populations.

Clinicopathological features of splenic tumours of lymphoid tissue.

BACKGROUND: To study the effects of splenectomy on treatment and diagnosis of tumours of lymphoid tissue of the spleen. METHODS: Fifty-three cases were reviewed from Peking University People's Hospital from 2002 to 2017. According to WHO classification of tumours of haematopoietic and lymphoid tissues (2008) and classification updated (2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization, combined with the bone marrow biopsy and clinical examination. RESULTS: In 53 cases, the male to female ratio was 3.4:1, the mean age was 55.4 years old, the median survival time was 17.0 months, and all patients present with variable degree of splenomegaly. The elevated percentage of lymphocyte in peripheral blood can be seen in 22 cases, and elevated LDH level in 24 cases. Abnormal blood counts can be seen in 26 cases before operation, and 22 cases remission to normal level partly or completely after operation. The clinical symptoms included abdominal pain or distension, fatigue, fever, and weight loss, etc. Seventeen cases present with lymphoadenopathy of abdomen or other sites. Fourteen cases were stage I or II, whereas 6 were stage III, 28 were stage IV. Forty-three cases were splenic B-cell marginal zone lymphoma (SMZL)(48.8%,21/43), DLBCL(23.3%,10/43), splenic diffuse red pulp small B-cell lymphoma (SDRPSBL)(11.6%,5/43), mantle cell lymphoma (MCL)(9.3%,4/43), follicular lymphoma (FL)(4.7%,2/43), composite lymphoma (CL, DLBCL and classical Hodgkin lymphoma)(2.3%,1/43) in turn, and the remaining 10 cases were chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) (n = 4), hairy cell leukaemia (HCL) (n = 1), hepatosplenic T-cell lymphoma (HSTL) (n = 5). The survival period of SMZL and DLBCL was 25.7, 18.6 months, respectively. Thirteen cases were dead (27.1%, 13/48). The chemotherapy protocol included Hyper-CVAD A/B with/without R (Rituximab), COP, CHOP with/without R etc. The prognosis of those with elevated LDH level, high clinical staging, B symptom, and older than 60 year old was obviously worse, and the prognosis of DLBCL was worse than that of SMZL. CONCLUSIONS: Most splenic lymphoid tumors present with splenomegaly and abnormal blood counts, and complete or part remission of blood counts can be seen after splenectomy, and splenectomy is also helpful for pathological diagnosis. The most common pathological types are SMZL and DLBCL. The definite diagnosis can be made by combining with clinical features, histopathology, immunophenotype, genetics, bone marrow biopsy and laboratory examination.

[Expression profiling of microRNA and their target genes in peripheral T cell lymphoma, not otherwise specified].

OBJECTIVE: To study the expression profile of microRNAs (miRNAs) in peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) and to explore the underlying molecular characteristics. METHODS: Twenty-one cases of PTCL-NOS were enrolled into the study. The tumor presented either as nodal (15/21) or extranodal (6/21) disease. TaqMan low density array was used to assess the expression level of 754 miRNAs in six cases of PTCL-NOS and three control cases of reactive lymphoid hyperplasia. Prediction of target genes for significant and differential expression of miRNAs was carried out using Targetscan and miRanda software. Bioinformatics tools were employed for GO-Analysis and Pathway-Analysis of target genes. The expression patterns of the three miRNAs were further analyzed in the remaining 15 cases of PTCL-NOS and 10 cases of reactive lymphoid hyperplasia, using single tube Taqman miRNA assays. RESULTS: Eight miRNAs showed statistically significant difference in expression between PTCL-NOS and reactive lymphoid hyperplasia. miR-886-3p, miR-511, miR-1291, miR-572, miR-27a-3p, miR-25-3p and miR-886-5p were significantly overexpressed in PTCL-NOS while miR-182-5p was significantly underexpressed (P < 0.05). Target gene prediction showed that 1646 candidate genes involved in the pathogenesis and progression of PTCL-NOS. Further GO and Pathway-Analyses found that these genes significantly focused on 63 GO terms and 61 pathways. The results of three miRNA qRT-PCR confirmed that miR-572 and miR-1291 expression in PTCL-NOS had statistical significance. CONCLUSIONS: Eight miRNAs are aberrantly expressed in PTCL-NOS, which may be involved in molecular regulation during the development of PTCL-NOS. The underlying mechanism is also related to a number of target genes and signaling pathways.

[Clinical characteristics of splenic marginal zone lymphoma with abnormal complete blood count].

The aim of this study was to investigate the clinical and laboratorial characteristics of splenic marginal zone lymphoma (SMZL) with an abnormal complete blood count (CBC). Data of 19 newly diagnosed SMZL patients with abnormal CBC were analyzed retrospectively. Seven patients were diagnosed by using splenic histology, 12 patients who did not undergo splenectomy were diagnosed on the basis of typical clinical presentation and cytologic, immunophenotypic and histologic characteristics of peripheral blood and bone marrow, according to SBLG guidelines. The results showed that leukocytosis (≥ 10.0×10(9)/L) was seen in 5 cases (26.3%); leukocytopenia (< 4.0×10(9)/L) was found in 6 cases (31.6%), hemoglobin concentration less than 120 g/L was found in 14 cases (73.7%) and thrombocytopenia was found in 11 (57.9%) patients. Fourteen (73.7%) patients had cytopenia in one or more lineage. As a specific morphologic character, villous lymphocytes were found in 10 (52.6%) patients. Similar immunophenotype was determined by histology in both bone marrow and spleen. Various histological infiltration patterns including intrasinusoidal pattern were found in bone marrow. Nine out of 16 (56.3%) patients displayed an increase of serum monoclonal immunoglobin. Autoimmune phenomena was found in 12 out of 15 (80.0%) patients. Splenectomy, as the only treatment could not achieve a ≥ 50% improvement of CBC in 4 patients, and then was judged as no response. Splenectomy followed by chemotherapy achieved partial response (PR) in 1 patient. Overall response rate of the therapeutic strategies with Rituximab was 100.0% (11/11). Furthermore, complete response was achieved in 9 out of 11 (81.8%) patients. It is concluded that SMZL with abnormal CBC has a higher incidence of cytopenia, bone marrow involvement and autoimmune phenomena. Therapeutic strategies consisting of Rituximab show a better efficacy.

Clinicopathologic spectrum and EBV status of post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation.

Post-transplant lymphoproliferative disorders (PTLDs) are serious, life-threatening complications of solid-organ transplantation (SOT) and bone marrow transplantation, and are associated with high mortality. PTLDs represent a heterogeneous group of lymphoproliferative diseases, which show a spectrum of clinical, morphologic, and molecular genetic features ranging from reactive polyclonal lesions to frank lymphomas. We describe clinicopathologic features of 17 cases of PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which were analyzed by in situ hybridization for EBV and a panel of antibodies directed against numerous antigens, including CD20, PAX5, CD3, bcl-6, CD10, MUM-1/IRF4, CD138, Kappa, Lambda, CD30, CD15, and Ki67. The cases included 13 males and 4 females with a median age of 31 years (range 9-49 years) and the PTLDs developed 1.5-19 months post-transplant (mean 4.7 months). The histological types indicated five cases of early lesions, two of plasmacytic hyperplasia and three of infectious mononucleosis-like PTLD. Eight cases were polymorphic PTLD, and four were monomorphic PTLD, including three of diffuse large B cell lymphoma, and one of plasmablastic lymphoma. Foci and sheets of necrosis were observed in five cases. The infected ratio of EBV was 88.2 %. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion, or anti-CD20 monoclonal rituximab. Eight cases died. The first half year after allo-HSCT is very important for the development of PTLD. The diagnosis of PTLD relies on morphology and immunohistochemistry, and EBV plays an important role in the pathogenesis of PTLD. The prognosis of PTLD is poor, and, notably, PTLD after allo-HSCT exhibits some features different from those of PTLD after SOT.

[Post-transplant lymphoproliferative disorder: a clinicopathologic study of 15 cases].

OBJECTIVE: To study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD). METHODS: The clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues. RESULTS: Amongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease. CONCLUSIONS: The diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.

[Clinicopathologic study of 40 cases of mediastinal tumours of haematopoietic and lymphoid tissues].

OBJECTIVE: To study clinical and histopathological features, and diagnosis of mediastinal tumours of haematopoietic and lymphoid tissues (MTHL). METHODS: Forty cases of MTHL were analyzed for clinicopathology by microscopy and immunohistochemical staining and in situ hybridization, according to the updated 2008 WHO classification of tumours of haematopoietic and lymphoid tissues. RESULTS: In 40 cases of MTHL, there were 20 males and 20 females. The ratio of male/female was 1:1. The mean age was 31.8 years and median age was 29 years (range, 12 - 70 years).Superior vena cava syndrome was observed in 28 cases. The specimens of 4 cases were obtained by lumpectomy, whereas 36 cases by biopsy (25 cases by thoracoscopy, 1 by core needle aspiration). Twenty cases lay in anterior mediastinum, and 2 in posterior, 1 in superior, 8 in anterior and superior, 2 in posterior and superior, 2 in anterior and middle, 1 in middle and anterior mediastinum.Frozen section were performed in 28 cases, and 17 cases were diagnosed as tumours of haematopoietic and lymphoid tissues (consistency ratio was 60.7%). Twelve cases were classical Hodgkin lymphomas (cHL) (8 were nodular sclerosis subtype, and 3 were mixed cellarity, 1 was lymphocyte-rich subtype), and 10 were primary mediastinal (thymic) large B cell lymphoma (PMBCL), 10 were precursor lymphocyte neoplasm [8 were T lymphoblastic leukemia/lymphomas (T-LBL), 2 were B-LBL], 1 was MALT lymphoma, 1 was composite lymphoma (PMBCL and cHL), 2 were myeloid sarcomas, 4 were gray zone lymphomas (GZL) (3 had morphology reminiscent of cHL, and 1 of DLBCL, all cases were positive for CD20, PAX5, CD30 and CD15).EBER were detected in 11 cases by in situ hybridization, 2 of which were positive (18.2%), and the 2 positive cases were cHL. CONCLUSIONS: MTHLs occur predominantly in adolescents and young adults, mainly present as superior vena cava syndrome and anterior mediasinal masses. cHL, PMBCL, T-LBL were the most common MTHLs.GZLs mainly occur in young adults, those whose morphology reminiscent of cHL, immunohistochemistry reminiscent of PMBCL, and vice versa. Thoracoscopy, frozen section and a suitable panel of antibodies were practical approaches to MTHL.