1.HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems.
Ping LI ; Ying WU ; Yan XIE ; Feng CHEN ; Shao qiang CHEN ; Yun Hao LI ; Qing Qing LU ; Jing LI ; Yong Wei LI ; Dong Xu PEI ; Ya Jun CHEN ; Hui CHEN ; Yan LI ; Wei WANG ; Hai WANG ; He Tao YU ; Zhu BA ; De CHENG ; Le Ping NING ; Chang Liang LUO ; Xiao Song QIN ; Jin ZHANG ; Ning WU ; Hui Jun XIE ; Jina Hua PAN ; Jian SHUI ; Jian WANG ; Jun Ping YANG ; Xing Hui LIU ; Feng Xia XU ; Lei YANG ; Li Yi HU ; Qun ZHANG ; Biao LI ; Qing Lin LIU ; Man ZHANG ; Shou Jun SHEN ; Min Min JIANG ; Yong WU ; Jin Wei HU ; Shuang Quan LIU ; Da Yong GU ; Xiao Bing XIE
Chinese Journal of Preventive Medicine 2023;57(7):1047-1058
Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy
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Child
;
Humans
;
Female
;
Glycated Hemoglobin
;
Cohort Studies
;
Diabetes Mellitus/diagnosis*
;
Sensitivity and Specificity
;
ROC Curve
2.The value of transanal multipoint full-layer puncture biopsy in determining the response degree of rectal cancer following neoadjuvant therapy: a prospective multicenter study.
Jia Gang HAN ; Li Ting SUN ; Zhi Wei ZHAI ; Ping Dian XIA ; Hang HU ; Di ZHANG ; Cong Qing JIANG ; Bao Cheng ZHAO ; Hao QU ; Qun QIAN ; Yong DAI ; Hong Wei YAO ; Zhen Jun WANG
Chinese Journal of Surgery 2023;61(9):769-776
Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ2 analysis, and a paired χ2 test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ2=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ2=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ2=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ2=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ2=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.
3.Incidence of neonatal asphyxia and contributing factors for the develpment of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study.
Su-Ying WU ; Fen PENG ; Ting DING ; Hong-Yan TAN ; Qian WU ; Xin-Qiao YU ; Zhi-Ping PAN ; Hong-Ling XIE ; Hong XIA ; Bao-Min FEI ; Kai-Dian LIU ; Zuo-Fen YUAN ; Cong-Rong TAN ; Lang JIANG ; Song-Hua ZHANG ; Qiong YI ; Wei-Hua WU ; Lin-Lin LUO ; Chang-Tao SHEN ; Jin-Fan ZHANG ; Zhen-Ju HUANG ; Shi-Wen XIA
Chinese Journal of Contemporary Pediatrics 2019;21(1):6-10
OBJECTIVE:
To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China.
METHODS:
A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia.
RESULTS:
Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05).
CONCLUSIONS
The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.
Asphyxia Neonatorum
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epidemiology
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China
;
Humans
;
Incidence
;
Infant, Newborn
;
Retrospective Studies
4. Protective effect of apoptosis signal-regulating kinase 1 inhibitor against mice liver injury
Ping HE ; Bo ZENG ; Xiao-Li ZHANG ; Dian-Liang FANG ; Xia-Qia ZHOU ; Ke-Qiang WAN ; Wen-Guang TIAN
Asian Pacific Journal of Tropical Medicine 2016;9(3):283-287
Objective: To explore the protective effect and its molecular mechanism of apoptosis signal-regulating kinase 1 (ASK1) inhibitor (GS-459679) on acetaminophen-induced liver injury in mice. Methods: The model of liver injury was established by administration of acetaminophen (APAP) (300 mg/kg, i.p.) on C57BL/6 mice. Forty-eight male C57BL/6 mice were randomly divided into four groups, consisting of control group, GS group (GS-459679, 30 mg/kg, i.p.), APAP-induced group, and GS combined with APAP-induced group. For GS combined with APAP-induced group, mice were treated with GS 30 min prior to administration of APAP. After mice were euthanized at 6 h or 12 h, respectively, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed, and mRNA levels of TNF-α, IL-6 and IL-1β were tested. The activity of glutathione (GSH), oxidized GSH (GSSG) and malondialdehyde were quantified. In addition, ASK1, P-ASK1, JNK and P-JNK protein levels were tested in all groups. Results: The ASK1 and P-ASK1 levels were up-regulated in APAP-induced group. Compared to the control group, serum levels of ALT and AST, and mRNA levels of TNF-α, IL-6 and IL-1β were increased in APAP-induced group. Meanwhile, the levels of MAD and GSSG, and the ratio of GSSG/GSH were higher and the JNK was activatedin APAP-induced group compared with that in control group. However, compared to APAP-induced group, GS combined with APAP-induced group displayed a decrease of protein expression levels of ASK1, P-ASK1 and P-JNK, a reduction of serum levels of ALT and AST, a decrease in TNF-α, IL-6 and IL-1β mRNA levels, and a low ration of GSSG/GSH. Conclusions: GS-459679 treatment effectively down-regulates ASK1 and P-ASK1 expression. Addition of GS-459679 decreases the generation of liver metabolites and inflammatory factors, reduces oxidative stress reaction, inhibits JNK activation, and then protects the responsiveness to APAP-induced liver injury.
5.Mannan-Binding Lectin Inhibits Candida Albicans-Induced DC Maturation and Cytokine Secretion.
Ming-Yong WANG ; Fan-Ping WANG ; Jing-Jing ZHAI ; Jun-Peng LI ; Na ZHANG ; Hao-Dian LI ; Kang GUO ; Shi-Jun SONG ; Hai-Chuan YU ; Wen-Xia ZHAO ; Meng-Jie LI
Journal of Experimental Hematology 2015;23(2):517-521
OBJECTIVETo investigate the effects of mannan-binding lectin (MBL) on the maturation and cytokine secretion of human dendritic cells (DC) induced by Candida albicans (C. albicans).
METHODSThe plastic-adherent mononuclear cells were prepared from the blood of healthy adult volunteers. The human peripheral blood mononuclear cells-derived dendritic cells (MNC-DC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4, and then cultured for 2 days in presence or absence of C. albicans at varying concentration of human MBL ranging from 1 to 20 mg/L. DC's shape and characters were observed under inverted microscopy, the expression of CD83 and CD86 on DC was analyzed by FACS. The levels of TNF-α and IL-6 were detected by ELISA. FACS also was used to investigate the interaction of MBL with immature DC(imDC) and C. albicans. Western blot was used to detect C. albicans-induced IκBα phosphorylation and p65/NF-κB translocation in DC.
RESULTSMBL at higher concentrations (10-20 mg/L) down-regulated the expression of CD83 and CD86 on the monocyte-derived dentritic cells(MoDC) induced by C. albicans, and inhibited the production of TNF-α and IL-6 induced by C. albicans. FACS showed that MBL could not only bind to C. albicans but also bind to imDCs in a Ca2+-dependent manner. Western blot showed that MBL could decrease the phosphorylation of IκBα and the nuclear translocation of p65/ NF-κB.
CONCLUSIONMBL may inhibit TNF-α and IL-6 production induced by C. albicans in DC through NF-κB signaling pathways, suggesting that MBL can play some roles in the regulation of C. albicans-induced immune response.
Candida albicans ; Cell Differentiation ; Cytokines ; Dendritic Cells ; Humans ; Mannose-Binding Lectin ; NF-kappa B ; Protein Transport
6.Langerhans cell histiocytosis: a clinicopathologic and immunohistochemical analysis of 258 cases.
Xia XU ; Wei-ping LIU ; Qun-pei YANG ; Wei-ya WANG ; Dian-ying LIAO ; Sha ZHAO ; Cheng-feng BI ; Li LIN ; Min MIN
Chinese Journal of Pathology 2012;41(2):91-96
OBJECTIVESTo observe the clinicopathologic features of Langerhans cell histiocytosis (LCH), and to evaluate the values of langerin, CD1a and S-100 protein expression in diagnosis of the tumor.
METHODSTotal 258 cases of Langerhans cell histiocytosis in the past 18 years (from 1992 to 2008) were collected, morphologic review and immunohistochemical staining were performed.
RESULTSIn all 258 cases, the ages of patients older than 16 years or younger than 2 years were 126 (48.8%) and 37 (14.3%), respectively, in the remaining 95 (36.8%) of the cases, the age of the patients ranged from 2 to 16 years. For all of 258 cases, there were 364 diseased sites. Bony lesions accounted for 77.2% (281 cases), especially the skull (112 cases, 39.9%), followed by lymph node (25 cases, 6.9%) and skin (14 cases, 3.8%). Clinically, unisystem or unifocal disease was predominant (201 cases, 77.9%), followed by unisystem and multifocal disease (21 cases, 8.1%), multi-system disease (26 cases, 10.1%), isolated pulmonary LCH (2 cases, 0.8%), and unclassified (8 cases, 3.1%). Histologically, variable number of Langerhans cells was present in 265 samples of 258 cases. Multinucleated giant cells were found in 166 (62.6%) of the samples. Eosinophils were the major infiltrating non-neoplastic cells, and eosinophilic abscess was seen in 57 cases (21.5%). Coagulative necrosis and dead bone were detected in 29 (10.9%) and 124 (46.8%) of the cases, respectively. Immunohistochemically, the expression of S-100 protein, CD1a and langerin was 99.1% (209/211), 100% (206/206) and 98.5% (193/196), respectively, and the sensitivity of them had no statistical difference.
CONCLUSIONSIn this group of LCH cases, the ratio of adult patients is high, but the proportion of multi-organ lesion is low. No significant difference of the sensitivity is found among langerin, CD1a and S-100 expression in diagnosis of LCH.
Adolescent ; Adult ; Antigens, CD ; metabolism ; Antigens, CD1 ; metabolism ; Child ; Child, Preschool ; Diagnosis, Differential ; Eosinophils ; pathology ; Female ; Follow-Up Studies ; Histiocytosis, Langerhans-Cell ; metabolism ; pathology ; surgery ; Humans ; Immunohistochemistry ; Infant ; Langerhans Cells ; pathology ; Lectins, C-Type ; metabolism ; Lymph Nodes ; pathology ; Male ; Mannose-Binding Lectins ; metabolism ; Middle Aged ; S100 Proteins ; metabolism ; Skin ; pathology ; Survival Rate ; Young Adult
7.Low volume amplification in single cell separation and inspection.
Jun-Ping HAN ; Cai-Xia LI ; Hong YAN ; Dian ZHU ; Gen-Ping LI ; Lan HU
Journal of Forensic Medicine 2012;28(2):123-125
OBJECTIVE:
To establish optimal amplification conditions with the application of 0.2 mL test tube in single cell separation and inspection.
METHODS:
Oral epithelium cell suspension was prepared. Five or ten cells were collected with 0.2 mL test tube. Then DNA were amplified with Identifiler Plus kit in three different conditions in which the proteinase K addition, gold enzyme concentration in PCR reaction, and PCR reaction cycles were adjusted separately. Finally the detection rate, allelic dropout rate and artificial alleles were compared among the groups.
RESULTS:
In these 3 different conditions: addition of proteinase K, addition of 0.4 microL gold enzyme in PCR reaction, and use of 32 cycles, the detection rate was higher and allelic dropout rate was lower than the other conditions.
CONCLUSION
In single cell separation and inspection, the usage of 0.2 mL test tube could be an effective supplement to chip-low volume amplification.
Alleles
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Cell Separation/methods*
;
DNA/genetics*
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DNA Fingerprinting/methods*
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Endopeptidase K/administration & dosage*
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Enzymes/administration & dosage*
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Epithelial Cells/cytology*
;
Feasibility Studies
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Forensic Genetics
;
Genotype
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Humans
;
Mouth Mucosa/cytology*
;
Nucleic Acid Amplification Techniques
;
Polymerase Chain Reaction/methods*
;
Sensitivity and Specificity
8.Clinicopathologic analysis of multisystem Langerhans cell histiocytosis.
Xia XU ; Wei-ping LIU ; Qun-pei YANG ; Sha ZHAO ; Wei-ya WANG ; Dian-ying LIAO ; Xiao-qing WANG ; Li LIN ; Min MIN
Chinese Journal of Pathology 2011;40(8):551-552
Adolescent
;
Adult
;
Antigens, CD
;
metabolism
;
Antigens, CD1
;
metabolism
;
Antineoplastic Combined Chemotherapy Protocols
;
therapeutic use
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Child
;
Child, Preschool
;
Female
;
Follow-Up Studies
;
Histiocytosis, Langerhans-Cell
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drug therapy
;
metabolism
;
pathology
;
surgery
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Humans
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Infant
;
Lectins, C-Type
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metabolism
;
Male
;
Mannose-Binding Lectins
;
metabolism
;
Middle Aged
;
S100 Proteins
;
metabolism
;
Survival Rate
;
Young Adult
9.Effect of 17β-estradiol on injured dopaminergic neurons induced by 6-hydroxydopamine
Xiao-Zhou WANG ; Ya-Ping LIU ; Meng WANG ; Zi-Xiao SHI ; Xia-Hong XU ; Ting WANG ; Dian-Shuai GA0
Chinese Journal of Neuromedicine 2011;10(12):1219-1222
Objective To study the effect of 17β-estrogen(17β-E2)on injured dopaminergic (DA) neurons induced by 6-hydroxydopamine (6-OHDA),and explore whether 17β-E2 has neuroprotective effect.Methods The male SD rats aged 2-3 d were decapitated under sterile conditions; the brain slices were induced injury by 6-OHDA(200 μmol/L); cells in the slices were divided into control group and 17β-E2 treatment groups(intervention with 1.0xl0-8 mol/L,1.0xl0-9 mol/L and 1.0×10-10 mol/L of 17β-E2,respectively).The tyrosine hydroxylase(TH)expression in DA neurons was observed by Western blotting at 15,30 and 60 min after the intervention.Results The expression of TH in the 1.0×10-9 mol/L 17β-E2 treatment group was the highest,which was significantly different as compared with that in the control group(P<0.05); increasing or decreasing the concentration of 17β-E2 could not regulate the expression of TH; in the 1.0×10-9 mol/L 17β-E2 treatment group,TH expression at 15 min after intervention enjoyed the highest level; the TH expression could not increase by extending the time.Conclusion The 17β-E2 treatment at certain concentration(1.0×10-9 mol/L)for certain time(15 min)has a protective effect on injuried DA neurons
10.Intravascular large B-cell lymphoma: report of two autopsy cases with literature review.
Xia XU ; Zong-guo PANG ; Wei-ping LIU ; Shang-fu ZHANG ; Yuan TANG ; Dian-ying LIAO ; Gan-di LI
Chinese Journal of Pathology 2008;37(6):377-383
OBJECTIVETo study the clinicopathologic features of intravascular large B-cell lymphoma (IVLBCL).
METHODSTwo autopsy cases of IVLBCL were retrieved from the archival file. The clinicopathologic features, immunohistochemistry and molecular findings were studied.
RESULTSThe deceased were 70-year-old and 50-year-old males. Both of them had complained of a sudden onset of weakness and numbness of lower extremities. The clinical course deteriorated rapidly, with multi-organ failure. They died 85 days and 44 days after the presentation, respectively. Post-mortem examination did not reveal any mass lesion, except the presence of multiple skin and epicardium nodules, ranging from 0.5 cm to 2.5 cm in diameter, in the first patient. Pericardial effusion, ascites and pleural effusion were also observed. Histologically, neoplastic lymphoid cells filled up the small vessel lumina in many organs, including brain, hypophysis, spinal cord, spinal nerve roots, heart, lungs, kidneys, liver, spleen, digestive tract, pancreas, adrenal, thyroid, testes and lymph nodes. The tumor cells were relatively monotonous and of medium to large in size with round vesicular nuclei and 1 to 3 small basophilic nucleoli. Immunohistochemical study showed that the lymphoma cells expressed B-cell markers CD20 and CD79a, occasionally positive for CD5 and bcl-2 but negative for CD3, bcl-6, CD10, CD30, myeloperoxidase and cytokeratin. In-situ hybridization for Epstein-Barr virus-encoded RNA was negative. The proliferative index, as demonstrated by Ki-67 staining, was about 80%. Molecular study showed the presence of immunoglobulin heavy chain gene rearrangement in both cases, T-cell receptor-gamma gene rearrangement was not found.
CONCLUSIONSIVLBCL may present as neurological disturbance and carries distinctive morphologic characteristics, immunophenotype and molecular findings. The prognosis of this disease is often dismal.
Aged ; Antigens, CD20 ; analysis ; Autopsy ; B-Lymphocytes ; pathology ; virology ; CD79 Antigens ; analysis ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell ; immunology ; pathology ; virology ; Lymphoma, Large B-Cell, Diffuse ; immunology ; pathology ; virology ; Male

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