Zi-fen Gao

Peking University Health Science Center, Peping, Beijing, China

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Publications (26)14.45 Total impact

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    ABSTRACT: Objective: To evaluate the expression of interleukin-6 (IL-6) and its clinicopathological significance in Castleman's disease (CD). Methods: Clinical data and paraffin blocks of 92 CD patients and 20 cases of lymph node reactive hyperplasia (LRH) as a control group were collected from department of pathology of Peking University Health Science Center. The expression of IL-6 was detected by using immunohistochemical method. Results: The 92 patients were composed of 42 multicentric variant (MCDs) and 50 unicentric variant (UCDs) clinically, and 30 hyaline-vascular variant (HV-CDs) and 62 plasma cell variant (PC-CDs) morphologically. None of them was positive for HIV tests. There were 56 males and 36 females, and their ages ranged from 4 years to 90 years with the median 41 years. IL-6 was expressed in 77 (83.7%) of 92 CD cases and 1 (5.0%) of 20 LRH cases. The expression rate of IL-6 was 90.5% in MCDs, 78.0% in UCDs, 93.6% in PC-CDs and 63.4% in HV-CDs, respectively. PC-CD cases showed a significantly higher expression rate of IL-6 than HV-CD cases (P = 0.001). All cases with positive IL-6 expression in plasmacytes were PC-CDs, showing obviously higher expression in MCDs than that in UCDs (P = 0.003). Compared with HV-CD cases, much more PC-CD cases showed IL-6 positivity in endothelial cells (P = 0.008). However, IL-6 was rarely expressed by both FDCs and macrophages, with only 3.3% and 10.9% positive cases, respectively. There are 53.2% (41/77) of the IL-6 positive cases and 20.0% (3/15) of IL-6 negative cases suffered from systemic symptoms, showing a significant difference between the two groups (P = 0.018). Cases with IL-6 expression in plasmacytes and macrophages were more likely to suffer from systemic symptoms, especially B type symptoms (P < 0.05). Conclusion: There is a high expression rate of IL-6 in CD, which is different from LRH. The expression of IL-6 has close relationship with CD subtypes and the presence of systemic symptoms. In all, the evaluation of interleukin-6 is of great value to guide the diagnosis and therapy of CD.
    No preview · Article · May 2013 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
  • Min Li · Cui-Ling Liu · Xiao-Yan Wang · Xue-Min Xue · Zi-Fen Gao
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    ABSTRACT: To investigate the clinical significance of bcl-2 protein expression and three classification algorithms including Hans model, Chan model and Muris model in patients with diffuse large B-cell lymphoma (DLBCL). Two-hundred and thirty-seven cases were collected. Standard two-step EnVision method of immunohistochemical staining was used to assess the expression of Ki-67, CD3, CD45RO, CD20, CD79a, bcl-2, bcl-6, CD10, MUM-1, GCET-1, and FOXP-1. The phenotypic classifications were assessed according to the standard of the three models. The male (131 cases) to female (106 cases) ratio was about 1.24:1, the average age was 52.6 years. Seventy-five cases (31.6%, 75/237) showed primarily lymph node involvement. Gastrointestinal tract (71 cases) was the most commonly involved extra-nodal organ. All cases expressed one or more pan B cell markers such as CD20 (99.1%, 231/233). All patients with complete clinical follow-up data survived from 1 - 120 months. The expression of bcl-2 protein indicated an adverse prognosis (P = 0.019). Two-hundred and thirty cases were classified according to Hans model, with ninety five GCB cases and one-hundred and thirty five non-GCB cases. Survival analysis showed no difference between GCB and non-GCB subtypes (P = 0.102). According to the Chan's algorithm, sixty eight case of one-hundred and eighty one were belong to GCB group, with one-hundred and thirteen non-GCB cases. GCB subtype showed much better prognosis than non-GCB subtype according to survival analysis (P = 0.031). Additionally, bcl-2 protein expression in non-GCB subtype showed the worst survival. In Muris' model, 154 of 218 cases were classified as Group 1, while 64 cases were classified as Group 2. Group 1 showed better prognosis than Group 2 (P < 0.05). Non-GCB group is the more common type of DLBCL in China. High expression of bcl-2 protein is detected in the non-GCB group. Not all subgroups classified with different classification models indicate different prognosis. Bcl-2 expression combined with Chan's algorithm may be the best tool to predict outcome.
    No preview · Article · Dec 2012 · Zhonghua bing li xue za zhi Chinese journal of pathology
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    ABSTRACT: To investigate the clinicopathologic features, pathogenesis, diagnostic criteria and the relationship between different classification models and prognosis in Chinese patients with DLBCL, and try to look for the most appropriate classification model to predict clinical prognosis and therapeutic responses for Chinese patients with DLBCL. 181 cases of Chinese DLBCLs diagnosed according to the WHO 2008 classification were collected. Standard two-step Envision method of immunohistochemical staining was used to assess the expressions of CD20, CD3ε, CD79a, CD10, Mum-1, Bcl-6, GCET-1, FOXP1 and Ki-67. The phenotypic classifications were assessed according to the standard of Hans model and Chan model. Data were analyzed by χ(2) test and Life Table survival analysis with the SPSS14.0 statistical package. The ratio of male to female in this cohort was 1.26:1. The median age of all patients was 57 yrs with the average age of 53.5 yrs. Of 61 cases (33.7%) primarily showed lymph node involvement. Gastrointestinal tract as the most involved extra-nodal organ was observed in 43 cases (35.8%). All patients with complete clinical follow-up materials survived from 1 - 120 months. The patients showed a high risk for death in the initial one and half years. Three year survival rate was 49.7% (90/181). Three year survival of 44 cases received R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, bolus) was 76.9% (20/26), whereas 61.9% (60/97) in 119 cases received CHOP alone, R-CHOP group showed better prognosis (P = 0.017). All cases expressed one or more pan B cell markers, such as CD20 (176/179, 98.3%) and CD79a (62/77, 80.5%). For Hans model, 78 cases were classified as GCB group, while 103 cases as Non-GCB group. The ratio of Non-GCB to GCB was 1.32 without difference on the survival (P > 0.05). For the Chan's algorithm, 68 cases belonged to GCB subgroup, while 113 cases non-GCB subgroup. The ratio of non-GCB to GCB was 1.66. GCB subtype showed much better prognosis than non-GCB subtype according to Life Table survival analysis (P < 0.05). The epidemiology and clinicopathologic features of Chinese DLBCLs were similarly with the western cases. Chan's algorithm was a significant tool to predict the cell origin and clinical biology of Chinese DLBCLs.
    No preview · Article · Oct 2012 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
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    ABSTRACT: To study the clinicopathologic features, immunotype and cytogenetics of Chinese mantle cell lymphoma (MCL). 114 MCL cases were collected from hematopathology lab of department of pathology, Peking University, HSC. Routine HE stain and immune stain were used to investigate the clinicopathologic features and immune type. Breaks of CCND1 and IgH/CCND1 fusion genes were detected by FISH. The ratio of male to female was 3.56:1 (89:25) with the median age of 60 years old (20 - 83 years old). 78 cases (68.42%, 78/114) primarily showed lymph node involvement, including 49 cases (49/78, 62.82%) jugular node involvement; 36 cases (31.58%, 36/114) showed extra-nodal involvement. 23 cases (23/114, 20.18%)showed bone marrow involvement. The expressions of CD3ε, CD20, CD79a, PAX5, CD5, cyclinD1 and Bcl-2 were 0% (0/114), 99.12% (113/114), 96.43% (27/28), 97.56% (40/41), 67.89% (74/109), 100% (114/114) and 94.12% (48/51), respectively. Break of CCND1 gene was found in 20 cases (80%, 20/25), the fusion gene of IgH-CCND1 in 16 cases (80%, 16/20), the break of IgH gene in 9 cases (100%, 9/9)and its fusion gene in 8 cases (88.89%, 8/9). We followed up 75 cases with a period of 2-57 months. The median survival was 40.78 months. The survivals at 1 year, 2 year and 3 year were 84.13% (53/63), 68.09% (32/47) and 37.5% (12/32), respectively. The median survival of group with more than 40% expression of Ki-67 was 36 months, the group with less than 40% expression of Ki67 57 months (P = 0.003). 7 of 13 patients accepted Rituximab plus traditional chemotherapy attained CR, 3 cases PR. 11 of 44 cases accepted traditional chemotherapy attained CR, 9 cases PR (P = 0.052). Most of Chinese MCL occured in older male, multi-lymphadehypertrophy and bone marrow involvement were common in MCL as a aggressive tumor. High expression of Ki-67 was an adverse prognostic indicator. Rituximab could improve the survival. Change of CCND1 gene was the most common cytogenetic abnormality.
    No preview · Article · Sep 2012 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
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    ABSTRACT: Systemic anaplastic large cell lymphoma (S-ALCL) is a rare disease with a highly variable prognosis and no standard chemotherapy regimen. Anaplastic lymphoma kinase (ALK) has been reported as an important prognostic factor correlated with S-ALCL in many but not all studies. In our study, we retrospectively analyzed 92 patients with S-ALCL from the Peking University Lymphoma Center for clinical and molecular prognostic factors to make clear the role of ALK and other prognostic factors in Han Chinese S-ALCL. The majority of Chinese S-ALCL patients were young male patients (median age 26, male/female ratio 1.7) and the median age was younger than previous reports regardless of ALK expression status. The only statistically significant different clinical characteristic in S-ALCL between ALK positive (ALK+) and ALK negative (ALK-) was age, with a younger median age of 22 for ALK+ compared with 30 for ALK-. However, when pediatric patients (≤ 18) were excluded, there was no age difference between ALK+ and ALK-. The groups did not differ in the proportion of males, those with clinical stage III/IV (49 vs 51%) or those with extranodal disease (53 vs 59%). Of 73 evaluable patients, the 3-year and 5-year survival rates were 60% and 47%, respectively. Univariate analysis showed that three factors: advanced stage III/IV, lack of expression of ALK, and high Ki-67 expression, were associated with treatment failure in patients with S-ALCL. However, ALK expression correlated with improved survival only in patients younger than 14 years, while not in adult patients. In multivariate analysis, only clinical stage was an independent prognostic factor for survival. Expressions of Wilms tumor 1 (WT1) and B-cell lymphoma 2 protein (BCL-2) correlated with the expression of ALK, but they did not have prognostic significance. High Ki-67 expression was also a poor prognostic factor. Our results show that ALK expression alone is not sufficient to determine the outcome of ALCL and other prognostic factors must be considered. Clinical stage is an independent prognostic factor. Ki-67 expression is a promising prognostic factor.
    Full-text · Article · Jul 2012 · Journal of Hematology & Oncology
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    ABSTRACT: To investigate the clinicopathologic features of primary nodal marginal zone B-cell lymphoma (NMZL). Hematoxylin-Eosin staining and immunohistochemistry were used to evaluate the histological and immunophenotypic characteristics of lymph node (LN) tissue in 22 NMZL cases. Additionally, interphase fluorescence in-situ hybridization (FISH) was carried out to detect the presence of t(11;18) (q21;q21)/API2-MALT1 and/or t(14;18)(q32;q21)/IGH-MALT1 in 9 cases. The median age of the 22 patients was 62 (16 - 77) ys. The male-to-female ratio was 1.2:1. All patients exhibited asymptomatic lymphadenopathy with the cervical region as the most often site to be involved (\%n\% = 11), followed by axillary (\%n\% = 9), inguinal (\%n\% = 7), submandibular (\%n\% = 6), mediastinal (\%n\% = 4), supraclavicular (\%n\% = 2) and retroperitoneal lymph nodes (\%n\% = 1). The Ann Arbor stages were I/II in 13 (59%) cases and III/IV in 9 (41%). Immunohistochemical study showed a consistently strong expression of CD20 and an absence in the expression of CD3ε, CD10, CD21, CD23, CyclinD1 and BCL6 by the tumor cells in all the cases. Frequency of expression of CD5 and BCL2 were 39% (7/18) and 30% (3/14) respectively. Among the 9 cases performed with FISH, 2 cases harbored t(14;18)and another 1 case positive for t(11;18) and t(14;18). Complete follow-up data were available for 13 cases. The follow-up time was 6 to 44 months. 3 of them died. 3-year cumulative survival rate was 67%. NMZL patients are often elderly, which mainly present with multiple lymphadenopathy, rare involvement of extranodal organ and early stage. The diagnosis must be based on a combination of clinicopathologic features, especially those patients detected t(11;18) and/or t(14;18).
    No preview · Article · May 2012 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
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    ABSTRACT: Data on symptoms and radiographic changes in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) pneumonia during convalescence have not been reported. During October 26, 2009, and January 23, 2010, adult patients with pneumonia with laboratory-confirmed or clinically suspected A(H1N1) infections were observed for clinical characteristics, high-resolution chest CT scan, and lung function test changes during acute and 3-month convalescent phases. Of the 65 case subjects, the median age was 41 (interquartile range [IQR], 28-57) years, 60.0% were men, and 55.4% had at least one underlying medical condition. Sixty-two patients started oseltamivir therapy within a median of 5 (IQR, 4-6) days from the onset of illness, and 31 received IV corticosteroids. ARDS developed in 33 patients, and 24 were treated initially with noninvasive positive pressure ventilation (NPPV). In this group, NPPV was successful in 13 patients (54.2%). Nine patients died at a median of 16 (IQR, 10-24) days after onset of illness. Multivariate Cox regression identified two independent risk factors for death: progressive dyspnea after resolution of fever (relative risk, 5.852; 95% CI, 1.395-24.541; P = .016) and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score on presentation (relative risk for each point, 1.312; 95% CI, 1.140-1.511; P < .001). At 3-month follow-up of survivors with A(H1N1), ground-glass opacities were still present, although diminished, in 85.7%, and diffusing capacity for carbon monoxide was mildly reduced in 61.5%. Ground-glass opacities and decreased diffusing capacity were the main abnormalities observed at 3-month follow-up of survivors of A(H1N1).
    No preview · Article · May 2011 · Chest
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    ABSTRACT: To find histopathological changes on major organs of Influenza A H1N1-infected patients and its relationship to clinical symptoms. The autopsies were performed following conventional protocols and strict safety procedures. Tissue samples from all major organs of three cases were collected and fixed in 4% formalin. The histopathological changes on these samples were observed under a light microscope. The lungs of some damaged areas of three cases showed diffuse alveolar damage (DAD) with hyaline membranes formation and intra-alveolar edema and/or fibrin. Most areas of the lungs in the three cases showed necrotizing bronchiolitis, hemorrhage, secondary infection, thrombosis and focal alveolar necrosis. The lungs exhibited proliferation of pneumocytes and fibrosis of the interstitium in one case. In one case, the brain showed focal hemorrhage and focal liquefactive necrosis. In one case, the heart showed edema. The respiratory tract is the major target of influenza A H1N1 virus. The changes of DAD with secondary infection in the lung resulted in hypoxia, leading to multiple organ failure and death.
    No preview · Article · Apr 2010 · Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
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    ABSTRACT: To study the role of pathogenic microorganisms commonly associated with chronic eye disease, including Chlamydia psittaci, Chlamydia trachomatis, Chlamydia pneumoniae, herpes simplex virus (HSV) type 1 and type 2, and adenovirus type 8 and type 19, in the development of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma in Chinese patients. Sixty-eight archival cases of primary ocular adnexal lymphoproliferative lesions, including 38 cases of MALT lymphoma, 3 cases of non-MALT lymphoma and 27 cases of chronic inflammation, were enrolled into the study. DNA was extracted from the paraffin-embedded tissue samples. The presence of DNA of C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 were analyzed by multiplex touchdown enzyme time-release polymerase chain reaction (TETR-PCR). All of the specimens yielded PCR products of over 100 base pairs and were thus suitable for TETR-PCR screening of infectious agents. The prevalence of DNA of C. psittaci, C. trachomatis and adenovirus type 19 were 0 in MALT lymphoma, non-MALT lymphoma and chronic inflammation. There were 2 cases positive for C. pneumoniae DNA, amongst the 38 cases of MALT lymphoma studied (5.3%, 2/38). HSV type 1, HSV type 2 and adenovirus type 8 DNA was found in each of the 3 patients with chronic inflammation. The study indicates that C. psittaci, C. trachomatis, C. pneumoniae, HSV type 1, HSV type 2, adenovirus type 8 and adenovirus type 19 probably play little role in the pathogenesis of ocular adnexal MALT lymphoma in Chinese patients.
    No preview · Article · Aug 2009 · Zhonghua bing li xue za zhi Chinese journal of pathology
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    ABSTRACT: To investigate the diagnostic application of molecular detection of enterovirus type 71 (EV71) infection using post-mortem paraffin-embedded tissue. Two autopsy cases of EV71 infection were studied by histopathological and immunohistochemical methods. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the viral RNA in paraffin-embedded tissue samples. Characteristic features of acute encephalitis were seen in the brain, with most prominent lesions found in the brain stem in both cases. Inflammatory cells were largely CD68-positive microglia with a few CD15-positive neutrophils in the areas of neuronal necrosis. The 5'-untranslated region of EV71 was detected in the medulla by RT-PCR using paraffin-embedded tissues of both cases. Sequencing analysis of the RT-PCR products showed 100% homology to the EV71 strain, recently submitted to the GenBank database from Fuyang, Anhui province. Molecular detection of EV71 can be performed on formalin-fixed, paraffin-embedded tissue samples from fatally infected patients. Timely and accurate diagnosis of the infection by such molecular approach is crucial for the proper clinical and public health intervention.
    No preview · Article · May 2009 · Zhonghua bing li xue za zhi Chinese journal of pathology
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    ABSTRACT: To investigate the genetic aberrations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t (11; 18) (q21; q21)/API2-MALT1, t (1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t (11; 18) (q21; q21) API2-MALT1 13% (29/217), t (1; 14) (p22; q32) IGH-BCL10 in 1% (3/217), t (14; 18) (q32; q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t (11; 18) (q21; q21) API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47%, 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6%, 4/68). t (1; 14) (p22; q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t (14; 18) (q32; q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17%, 1/6) and stomach (4%, 3/84). It is demonstrated that the four translocations occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.
    No preview · Article · Apr 2009 · Zhonghua nei ke za zhi [Chinese journal of internal medicine]
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    ABSTRACT: To study the clinicopathologic features of fatal enterovirus 71 (EV71) infection. Autopsy was performed in 5 neonates died of EV71 infection. Tissue samples from major organs were collected, formalin-fixed and examined under light microscopy. Immunohistochemical study was carried out in selected examples. Four of the 5 cases showed predominant changes in central nervous system, with encephalitis and encephalomyelitis identified mainly in brainstem and upper cervical spinal cord. Histologic findings included neuronal degeneration and necrosis, neuronophagia, perivascular cuffing and diffuse or nodular hyperplasia of macrophages/microglia. Cerebral edema, brain herniation and aseptic meningitis were also noted. The lungs showed mainly pulmonary congestion, neurogenic pulmonary edema and focal hemorrhage. There were minimal changes in the intestinal epithelium. The intestinal lymphoid tissue however was hyperplastic and associated with apoptosis of follicular center cells. The remaining case had cerebral edema and mild meningitis. The lung alveolar septa were thickened with lymphocytic infiltrates. Some alveolar cells were hyperplastic and associated with diffuse hyaline membrane formation. No specific abnormalities were identified in gastrointestinal tract. In all the 5 cases studied, there was enlargement of lung hilar and mesenteric lymph nodes, coupled with apoptosis of follicular center cells. In general, no significant pathologic changes were demonstrated in heart, liver and kidneys. In fatal EV71 infection, the major pathologic changes lie in the central nervous system. The pulmonary lesions are mainly secondary in nature. The usual cause of death is cerebral edema complicated by brain herniation and pulmonary edema. It is also noteworthy that some cases show only lung damages, without classic neurologic changes.
    No preview · Article · Mar 2009 · Zhonghua bing li xue za zhi Chinese journal of pathology
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    ABSTRACT: To investigate clinicopathological and genetic characteristics of primary ocular adnexal lymphoproliferative lesions. Clinical, morphological and immunohistochemical features of 37 archival cases of primary ocular adnexal lymphoproliferative lesions were studied including 5 cases of reactive lymphoid hyperplasia and 32 lymphomas retrospectively. Classification of the lymphomas were made according to the WHO classification of tumors of haematopoietic and lymphoid tissues. All cases were studied by interphase fluorescence in situ hybridization (FISH) using dual color break apart probes of IgH, MALT1, bcl-6, c-Myc, bcl-2, CCND1, bcl-10, and FOXP1 for detection of chromosomal aberrations involving IgH, MALT1, bcl-6, c-Myc, bcl-2, cyclinD1, bcl-10 and FOXP1 genes, respectively. FISH with IgH / bcl-2 dual color dual fusion probe was used for detection of t(14;18)(q32;q21)/IgH-bcl-2. CEP18 spectrum orange probe was used for detection of aneuploidy of the chromosome 18. Among 32 cases of lymphomas, 28 cases (87.5%) were extranodal marginal zone B-cell lymphomas of mucosa associated lymphoid tissue (MALT lymphoma), 2 cases were follicular lymphoma (FL) and 2 cases diffuse large B cell lymphoma (DLBCL). Among the 28 cases of MALT lymphoma, chromosomal aberrations were found in 60.7% (17/28) by interphase FISH analysis. One case showed positive IgH break-apart signal with unknown partner. 16 cases showed three copies of different genes, of which, three copies of MALT1, bcl-6, and c-Myc were identified in 7 cases (25%), 12 cases (43%), and 2 cases (8%) of MALT lymphomas, respectively. In addition, 5 cases showed two genes including three copies of bcl-6 and MALT1 in 4 cases, and three copies of bcl-6 together with c-Myc in one case. Furthermore, all cases with three copies of MALT1 had trisomy 18. t(14;18)(q32;q21) was detected in both follicular lymphomas. Of the 2 DLBCL cases, one showed three copies of bcl-6 together with trisomy 18 and the other one showed three copies of bcl-6 together with IgH and c-Myc rearrangements. Chromosomal aberration was not found in all 5 cases of reactive lymphoid hyperplasia. The most common entity of primary ocular adnexal lymphomas is MALT lymphoma and FISH is helpful for their differential diagnosis and classification. Trisomy 18 and three copies of bcl-6 are common chromosomal aberrations in primary ocular adnexal MALT lymphomas.
    No preview · Article · Jan 2009 · Zhonghua bing li xue za zhi Chinese journal of pathology
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    ABSTRACT: To study the expression of anaplastic lymphoma kinase (ALK) and chromosome breakage of the anaplastic lymphoma kinase (ALK) gene retrospectively and to investigate their possible value as indicators of prognosis in primary systemic anaplastic large cell lymphomas (S-ALCL). Twenty-eight cases of S-ALCL were collected from the Lymphoma Lab, the Department of Pathology, Peking University Health Science Center and Beijing Children's Hospital. The morphologic characteristics were studied under light microscope, and essential immunohistochemical staininings (IHC) were performed and reviewed to confirm the diagnosis of S-ALCL. ALK-1 monoclonal antibody was used to assess ALK fusion protein expression, and EnVision method was used in IHC. Locus specific interphase fluorescence in situ hybridization (LSI-FISH) was also performed on the neoplastic cells using paraffin-embedded tissues to detect ALK gene abnormality. ALK-1 protein was expressed in 19 of the 28 cases. In 14 ALCL cases, ALK gene breakage was detected by LSI-FISH, using a dual-color break-apart ALK gene DNA (LSI-ALK) probe. Of the other 14 cases which did not show ALK gene breakage, 5 showed 2 copies of ALK gene as normal, and 9 showed multi-copies of ALK gene. Of all the 28 cases, 22 had complete follow-up materials. Sixteen survived and 6 died, their survival time ranged from 0.5 to 36.0 months, and the survival time on average was 12.8 months, cumulative proportion survival rate was 73.9% in the 1st year. Those cases showing multi-copies of ALK gene might have the worst outcome, with only 47.6% of cumulative proportion survival rate in the 1st year. IHC detection for ALK fusion protein is important to the diagnosis of S-ALCL. ALK gene breakage detected by interphase LSI-FISH might not be always consistent with abnormal expression of ALK fusion protein. Complex abnormalities of ALK gene exist in S-ALCL cases, and different types of ALK gene might lead to different clinical outcome. Those cases with multi-copies of ALK gene probably have the poorest prognosis.
    No preview · Article · Sep 2008 · Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
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    ABSTRACT: Primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL) is difficult to be distinguished from other gastrointestinal tumors because of its onset sites and clinical features, which results in frequent misdiagnoses. The standard chemotherapy regimen for PGI-DLBCL is uncertain. This study was to analyze the clinical characteristics, cell origin, and prognosis of PGI-DLBCL, and explore effective combined chemotherapy for PGI-DLBCL. Clinical data of 40 PGI-DLBCL patients, diagnosed and treated in Peking University Third Hospital from 1998 to 2007, were analyzed by Kaplan-Meier method, log-rank test, and Cox regression model. The cell origins of PGI-DLBCL in 34 patients were analyzed by immunohistochemistry. The patients were treated with combined chemotherapy, surgery plus combined chemotherapy and/or radiotherapy, or surgery alone. The combined chemotherapy included CHOP and CHOP-like regimens. The median age of the 40 patients was 56.5 years. The ratio of sex (male:female) was 1.86:1. The ratio of onset sites (gastric versus intestinal) was 1.05:1. Among the 38 patients who had been followed up, 12 (31.6%) died, both the 3-and 5-year overall survival rates were 64.7%. Of the 9 patients with multiple sites involvement, 8 (88.9%) died within 3 years after diagnosis. Of the 34 patients received immunohistochemical examination, 9 (26.5%) had lymphomas of germinal center origin, and 25 (73.5%) had non-germinal center origin. Log-rank test revealed that International Prognostic Index (IPI) score and B symptom were important prognostic factors of PGI-DLBCL. Cox multivariable analysis showed that the death risk of the patients with high level of LDH was 2.87 times higher than that of the patients with normal level of LDH. PGI-DLBCL is often seen in male patients at middle ages. Multiple sites involvement is an important death cause of these patients. Tumor cell origin, IPI score and B symptom are important prognostic factors of PGI-DLBCL. The serum level of LDH at diagnosis is an independent prognostic factor.
    No preview · Article · Jul 2008 · Ai zheng = Aizheng = Chinese journal of cancer
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    ABSTRACT: To summarize the histological and clinical characteristics of 40 cases with Burkitt's and Burkitt-like lymphoma in children, to evaluate the effects of treatment with international regimen, and to explore the treatment-related complications and prognostic factors. Forty patients with Burkitt's and Burkitt-like lymphoma were registered in Beijing Children Hospital from Feb 2003 to Apr 2006. The diagnosis was confirmed by histology and immunohistochemistry of biopsy, and clinical staging by the examination of imaging, cerebrospinal fluid and bone marrow based on St. Jude system. Intensive, short-term chemotherapy witch was modified from LMB89 protocol was given to the patients. Of the 40 patients, 30 were diagnosed as Burkitt's lymphoma (BL) and 10 as Burkitt-like lymphoma (BLL). Antibody against Epstein-Barr virus (EBV-Ab) was positive in 19 cases at diagnosis, only 7 of the patients were positive for EBER. Thirty-three of the cases were male and 7 female (M:F = 4.7:1); the median age was 6 years 9 months. The most frequently seen clinical characteristics were abdominal masses and surgical abdomen. Nine cases were at stage I - II and 31 cases at stage III - IV at diagnosis; CNS was involved in 4 cases and bone marrow in 2 cases. The courses of treatment were approximately 2 - 8 months. All the patients were followed up, the median follow-up period was 22.6 months. After chemotherapy, 35 patients (88.7%) were still alive during the one-year follow-up. The 3-year event-free survival (EFS) rate was 81.8%. Major toxicity was myelosuppression and mucositis. Stage III to IV of myelosuppression occurred in the most patients with unresected tumor and CNS-involvement. Of 5 patients who died, 2 died of infection, 2 died of lymphoma progression during chemotherapy, and 1 died of relapse. Burkitt's and Burkitt-like lymphoma are the most common NHL in children with rapid clinical process. Outcome was greatly improved by current intensive, short-term chemotherapy regimen, the 3-year EFS was 81.8% including the patients who were in advanced stage. Childhood lymphoma with short clinical history, stage IV and residual disease after 3 months of therapy are associated with poor prognosis.
    No preview · Article · Apr 2008 · Zhonghua er ke za zhi. Chinese journal of pediatrics
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    ABSTRACT: To identify histopathologic changes of major organs and to correlate clinical symptoms in patients infected by avian influenza H5N1. Autopsy study was performed in two patients died of avian influenza HSN1 infection, following conventional protocols and strict safety procedures. Tissue samples from all major organs of two cases and lung samples of one case were collected and fixed in 4% formaldehyde. Histopathologic changes were evaluated by light microscope. Diffuse alveolar damage (DAD) of the lung was seen in both cases. Lesions at various stages of development were seen involving different areas of the lung. At the early stages, the lungs exhibited exudative changes, including capillary congestion, necrosis of alveolar epithelial cells, and intra-alveolar edema. Hyaline membranes were prominent and diffusely distributed along alveoli. In the middle-late stages of the disease, the lungs exhibited proliferative and fibrotic changes, including proliferation of pneumocytes and bronchial epithelium, fibrosis of the interstitium and alveolar spaces. Lung biopsy tissue of one case showed DAD and interstitial fibrosis in a background of bronchiectasis. Lymph nodes and spleens showed quantity reduction of lymphocytes and active hemophagocytosis. Other changes in major organs included interstitial carditis in one case and acute renal tubular necrosis in one case. In one case, the brain showed edema with cytoplasmic eosinophilia, loss of structure, axon welling and focal necrosis around ventricle. Multiple foci of trophoblastic necrosis with dystrophic calcification were observed in placenta of one pregnant patient. Acute necrotizing deciduitis was found focally. Sections of fetal lung showed edema and scattered interstitial neutrophils were consistent with acute interstitial pneumonitis. The respiratory tract is the major target of avian influenza A H5N1 virus infection. The changes of DAD in the lungs resulted in hypoxia, leading to multiple organ failure and death.
    No preview · Article · Apr 2008 · Zhonghua bing li xue za zhi Chinese journal of pathology
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    ABSTRACT: To explore the relationship of clinic features, lab findings, the origin of tumor cell as well as prognosis in Chinese patients with diffuse large B-cell lymphoma( DLBCL). Seventy four cases of primarily diagnosed DLBCL were analyzed. Immunohistochemistry stain was used to check the expressions of Bcl-6,CD10 and MUM1. Among the 74 patients, the average age was 58.5 years, the ratio of male to female was 1.64:1. 23.2% (16/69) cases developed in lymph node, 15.9% (11/ 69) in the extra node area. Among 55 follow-up cases, 13 (23.6%) died, and 12 (92.3%) died in the first year after diagnosis. The prognosis analysis showed that diagnosed at age > 65 years (P = 0.036), and the international prognostic index (IPI) (P = 0.009) were independent prognostic factors; origin of tumor cell had a trend to be a prognostic factor, but no statistic difference (P = 0.086). beta2-MG and Bcl-6 expression had no relation with the prognosis. The middle and old-aged male patients are the most common in DLBCL and the first-year mortality rate is higher. The age at diagnosis and IPI can predict the clinical outcome. The origin of tumor cell might suggest the prognosis.
    No preview · Article · Oct 2007 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

  • No preview · Article · Aug 2007 · Zhonghua bing li xue za zhi Chinese journal of pathology
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    ABSTRACT: To describe the clinical, laboratory and radiological presentation of a human case infected by influenza A (H5N1), and to understand its management and prognosis. The clinical and autopsy data of the first human case infected by influenza A (H5N1) in Jiangxi Province were collected and analyzed. The first case infected by influenza A (H5N1) in Jiangxi Province was confirmed by laboratory findings with reverse transcription-polymerase chain reaction (RT-PCR) and influenza A (H5N1) isolation. The patient had been healthy in the past and exposed to the environment of bird flu before illness. The initial symptoms included high fever with influenza-like symptoms, and then cough and purulent sputum mixed with blood appeared. The clinical situation deteriorated progressively with occurrence of diarrhea and dyspnea. Laboratory abnormalities included decrease of peripheral white blood cells and lymphocytes, urine protein, dramatic increase of enzymes associated with hepatic injury and myocarditis and decrease of serum albumin. Six days later, penicillin-resistant streptococcus pneumoniae was isolated from multiple sputum cultures. With the deterioration of clinical situation, several other bacteria and fungi were found in sputum culture. Pulmonary infiltrates were evident in right middle and lower lobe at day 5 after illness, and rapidly progressed to involve bilateral lungs as acute respiratory distress syndrome (ARDS)-like changes. The patient was treated with antiviral, antibacterial, and antifungal reagents, and corticosteroids and invasive mechanical ventilation were also administered, but without any improvement. The patient died 27 days after the onset of symptoms and an autopsy was performed. Pathologically, the lungs exhibited diffuse alveolar damage. The lymphocytes in the spleen, the lymph nodes and the tonsils were depleted prominently with histiocytic hyperplasia and hemophagocytic phenomena. Edema and degeneration of myocytes in the heart and extensive acute tubular necrosis in the kidney were observed. The prognosis was very poor if influenza A (H5N1) infected human cases was developed as ARDS with multiple organ damage or failure.
    No preview · Article · Jun 2006 · Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases