We investigated the expression of CD99 in 35 hyperplastic perigastric lymph nodes, which were resected for gastric carcinoma or chronic peptic ulcer. Essentially, all lymphocytes in lymph nodes expressed CD99, but there were two populations with respect to the intensity of CD99 expression--CD99high and CD99low cells. We showed CD99high cells were distributed in paracortical and medullary cords by immunohistochemical study while germinal center cells were CD99low. Using three-color flow cytometric analysis with CD3, CD4, CD8, CD19, CD23, CD45RA, CD45RO, CD69, CD138, IgM, IgD, and IgG, most of CD99high cells were shown to be activated/memory T cells. CD4+CD45RO+ T cells were the subset revealing the highest intensity of CD99 expression while CD4+CD45RA+ T cells were CD99low. Among B cells, IgG+ B cells revealed a higher level of CD99 molecules than IgM+ B cells. These results suggest that CD99 is one of activation-related molecules which are upregulated in recently activated lymphocytes.
Adult ; Aged ; Antigens, CD/analysis* ; B-Lymphocytes/immunology* ; Cell Adhesion Molecules/analysis* ; Flow Cytometry ; Germinal Center/immunology ; Human ; Immunohistochemistry ; Immunologic Memory/immunology* ; Lymph Nodes/immunology* ; Middle Age ; Peptic Ulcer/immunology* ; Stomach Neoplasms/immunology* ; T-Lymphocytes/immunology*

OBJECTIVETo detect the changes of naive T cell level of thymic recent output at different stages of treatment in patients with diffuse large B-cell lymphoma (DLBCL), thereby to evaluate the relationship of thymic recent output function with prognosis and the impact of chemotherapy on the potential of immunological recovery.

METHODSThe levels of T-cell receptor rearrangement excision circles (TREC) in DNA of peripheral blood mononuclear cells (PBMNC) from 30 DLBCL patients were monitored before, during, until 3 months and 6 months after chemotherapy by real-time PCR (TaqMan), and TREC-level was detected according to the number of CD3 positive(CD3(+)) cells. Twelve normal individuals who matched in age were served as controls.

RESULTSThere was a dramatic reduction of TREC values in all DLBCL patients among which TREC values in germinal center B-cell-like-DLBCL (GCB-DLBCL) were higher than those in non-GCB-DLBCL, as compared with TREC values of normal individual in peripheral blood. The mean values of TREC were 0.91 ± 0.15/1000 PBMNCs and (1.22 ± 0.69)/1000 CD3(+) cells in GCB-DLBCL, (0.43 ± 0.29)/1000 PBMNCs and (0.64 ± 0.44)/1000 CD3(+) cells in non-GCB-DLBCL before chemotherapy. TREC values were significantly associated with lower international prognostic index (IPI) grade (r = -0.441, P = 0.015). TREC-level in DLBCL patients was further decreased after chemotherapy, and reached to the lowest level after the 6th cycle of chemotherapy, and during the corresponding period, the mean values of TREC were (0.63 ± 0.34)/1000 PBMNCs and (0.89 ± 0.65)/1000 CD3(+)cells in GCB-DLBCL, (0.19 ± 0.11)/1000 PBMNCs and (0.27 ± 0.25)/1000 CD3(+) cells in non-GCB-DLBCL. TREC-level began to rise obviously 3 months after the last cycle of chemotherapy in most of the DLBCL patients, and came close to normal level in five cases of patients 6 months after the last cycle of chemotherapy.

CONCLUSIONSThymic recent output function was impaired severely in DLBCL patients. There was an important relationship between thymic recent output function before chemotherapy and prognosis, and chemotherapy had influenced the potential of immunological recovery.

Adult ; Aged ; Case-Control Studies ; Female ; Gene Rearrangement, T-Lymphocyte ; Germinal Center ; immunology ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; immunology ; pathology ; Male ; Middle Aged ; Receptors, Antigen, T-Cell ; immunology ; Thymus Gland ; immunology ; Young Adult

OBJECTIVETo study the clinical and morphological features, immunophenotype and in situ detection of Epstein-Barr virus (EBV) infection in infectious mononucleosis (IM) to enhance the knowledge and diagnosis of the disease.

METHODUsing routine haematoxylin and eosin staining, immunohistochemistry and EBER in situ hyhridization together with clinical data analysis, 15 cases of IM were evaluated for their clinical features, morphology, immunophenotype and EBV infection status.

RESULTSIM was common in children and young adults with a median age of 18 years. It was an acute disease with lymphadenopathy and frequently fever. Most of the patients had a rapid recovery. Every case showed a markedly T zone expansion with a mottling pattern, composing of small to large lymphocytes, plasma cells and histiocytes. The cells also showed a B-cell differentiation profile ranging from activated lymphoblastoid cells, immunoblasts, plasmablasts, plasma-like cells and plasma cells. Many small lymphocytes in the expanded T zone expressed CD3. Some of the activated lymphoblastoid cells and immonoblasts were CD20 and CD30 positive with variable intensity signals. EBER positive (nuclear staining) cells were seen in every case. The number of EBER positive cells ranged from 10 to more than 100 per high power field. These cells included small to large lymphocytes locating mostly in the expanded T zone and a few were in the follicular germinal centers.

CONCLUSIONSIM is an EBV related acute sell-recovering lymphoproliferative disease, having distinct clinical, morphological and immunophenotypic characteristics as well as EBV infection. Taking these features into consideration will facilitate the correct diagnosis of IM.

Adolescent ; Adult ; B-Lymphocytes ; virology ; Child ; Epstein-Barr Virus Infections ; pathology ; Female ; Germinal Center ; Herpesvirus 4, Human ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; Infectious Mononucleosis ; immunology ; pathology ; Lymphocytes ; Lymphoproliferative Disorders ; immunology ; pathology ; Male ; Virus Diseases ; immunology ; Young Adult

OBJECTIVETo study the expression of miR-146b-5p in diffuse large B cell lymphoma (DLBCL), and its relationship with risk assessment.

METHODS62 cases of nodal DLBCL with follow-up data were collected from Shanxi Cancer Hospital, and were studied by using immunohistochemical EnVision method for CD3, CD10, CD20, Bcl-6 and MUM1. The DLBCLs were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to Hans'algorithm. Agilent Human miRNA Microarray 16.0 was used to select the miRNAs on paraffin-embedded tissues of 24 DLBCL cases. A TaqMan real-time polymerase chain reaction (RT-PCR) method was performed on 62 nodal DLBCL cases to validate the expression levels of miR-146b-5p.11 cases with reactive lymph node were elected as control.

RESULTSIn 62 cases of DLBCL, 35.5% of cases were GCB and 64.5% non-GCB subtypes, the expression of miR-146b-5p in GCB was 3.2 times as much as non-GCB subtypes (P = 0.006). The expression of miR-146b-5p was up-regulated in DLBCL, and expression level of miR-146b-5p was 5.4 times as much as reactivated lymph node. In 62 cases of DLBCL, 43.5% cases were recurrence-free and 56.5% recurrence. The expression of miR-146b-5p was remarkably up-regulated in recurrence-free group compared with recurrence group (P = 0.004). Moreover, high expression levels of miR-146b-5p in DLBCL were found to be associated with longer relapse-free survival (P = 0.005), but not for overall survival. Multivariate COX proportional hazard regression analysis revealed that low expression of miR-146b-5p (P = 0.004) and IPI ≥ 3(P = 0.011) were independent poor prognostic factors in 62 cases of DLBCL.

CONCLUSIONSThe expression of miR-146b-5p was up-regulated in recurrence-free group, and its higher expression levels in DLBCL were associated with improved relapse-free survival. Our results suggested that miR-146b-5p might be one of markers for risk assessment.

Adult ; Aged ; Aged, 80 and over ; Female ; Germinal Center ; pathology ; Humans ; Lymphoma, Large B-Cell, Diffuse ; genetics ; immunology ; pathology ; Male ; MicroRNAs ; genetics ; Middle Aged ; Prognosis ; Real-Time Polymerase Chain Reaction ; Risk Assessment ; Young Adult

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.
Adult ; Autoantibodies/blood ; C-Reactive Protein/analysis ; Demography ; Female ; Germinal Center/*pathology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Receptors, Complement 3d/metabolism ; Retrospective Studies ; Salivary Glands, Minor/*pathology ; Sjogren's Syndrome/immunology/metabolism/*pathology

OBJECTIVETo categorize diffuse large B-cell lymphoma (DLBCL) into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subgroups by immunohistochemistry; and to investigate the underlying prognostic significance.

METHODSImmunohistochemical study for CD10, bcl-6 and MUM1 was performed on 133 cases of DLBCL. The cases were then categorized into GCB and non-GCB subgroups. The 5-year overall survival and 5-year progression-free survival rates were compared between the GCB and non-GCB groups, and among the cases with different immunohistochemical expression or with different IPI.

RESULTSAmongst the 133 case studied, CD10 was expressed in 33.1%, while bcl-6 was positive in 34.6% and MUM1 in 45.1%. CD10 expression had a favorable impact on 5-year overall survival (P=0.041) and 5-year progression-free survival (P=0.031). On the other hand, bcl-6 expression had a favor able impact on 5-year progression-free survival (P=0.044). Expression of MUM1 carried an adverse effect on 5-year overall survival (P=0.031) and 5-year progression-free survival (P=0.028). GCB immunophenotype was demonstrated in 40.6% of the cases, while 59.4% showed a non-GCB profile. GCB DLBCL had a significantly longer 5-year overall survival (P=0.004) and 5-year progression-free survival (P=0.003), as compared with the non-GCB group. When dividing the cases into two groups according to their IPI score (IPI=0 to 1 and IPI=2 to 5), it turned out that the 5-year overall and progression-free survival rates of the GCB group were significantly higher than those of the non-GCB group (P=0.019 and 0.014 respectively in cases with IPI of 0 to 1 and P=0.006 and 0.009 respectively in cases with IPI of 2 to 5). The non-GCB cases with a IPI of 2 to 5 had the poorest prognosis.

CONCLUSIONDLBCL subgrouping by immunohistochemistry and analysis of the subgrouping with IPI is feasible and useful in predicting clinical outcome.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; B-Lymphocytes ; pathology ; Child ; Child, Preschool ; DNA-Binding Proteins ; metabolism ; Disease-Free Survival ; Female ; Follow-Up Studies ; Germinal Center ; pathology ; Humans ; Immunohistochemistry ; Interferon Regulatory Factors ; metabolism ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse ; classification ; immunology ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; Survival Rate ; Young Adult