Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.
Humans ; Male ; Female ; Adult ; Middle Aged ; Aged ; Lymphoma, T-Cell, Peripheral/pathology* ; Reed-Sternberg Cells/pathology* ; Epstein-Barr Virus Infections ; Hyperplasia/pathology* ; Retrospective Studies ; Herpesvirus 4, Human/genetics* ; Immunoblastic Lymphadenopathy/pathology* ; Hodgkin Disease/pathology* ; Germinal Center/pathology* ; Receptors, Antigen, T-Cell

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of TGF-β. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Co-transfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.
Allergens* ; B-Lymphocytes ; Germinal Center* ; Immunity, Humoral ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Lung ; Lymph Nodes ; Pathology ; Pneumonia ; T-Lymphocytes*

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 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

Pediatric diffuse large B-cell lymphoma (DLBCL) is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell (GCB) classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat-sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47:1. The median age was 12 years (range, 2 to 18 years), and 47 (61.8%) patients were at least 10 years old. Of the 76 patients, 48 (63.2%) had stage III/IV disease, 9 (11.8%) had bone marrow involvement, 1 (1.3%) had central nervous system (CNS) involvement, and 5 (6.6%) had bone involvement. The GCB classification was assessed in 45 patients: 26 (57.8%) were classified as GCB subtype, and 19 (42.2%) were classified as non-GCB subtype. The modified B-NHL-BFM-90/95 regimen was administered to 50 patients, and the 4-year event-free survival (EFS) rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification: 17 (54.8%) were classified as GCB subtype, with a 4-year EFS rate of 88.2%; 14 (45.2%) were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients, whereas the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified B-NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Asparaginase ; therapeutic use ; Child ; Child, Preschool ; Daunorubicin ; therapeutic use ; Disease-Free Survival ; Female ; Follow-Up Studies ; Germinal Center ; pathology ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; pathology ; Male ; Prednisone ; therapeutic use ; Survival Rate ; Vincristine ; therapeutic use

OBJECTIVETo analyze CD21 expression in diffuse large B cell lymphoma (DLBCL) and to explore its relationship with the clinicopathological characteristics and prognosis.

METHODSThe clinical data from 80 DLBCL patients who were treated in First Hospital of Jilin University from June 2005 to September 2011 were retrospectively analyzed. The cases were subjected to immunohistochemical staining (SP method) for Ki-67, CD20, CD79a, CD3, CD43, CD5, cyclin D1, bcl-2, CD10, bcl-6, GCET-1, FOXP-1 and MUM-1 protein expression in the tumor tissue. Immunohistochemistry was also used to detect CD21 expression in the tumor tissue. SPSS 18.0 was used to analyze the relationship between CD21 expression and various clinical factors, and the relationship between various clinical factors including CD21 and overall survival.

RESULTSIn the patients aged under 60 years, the incidence of CD21(+) lymphoma (64.0%, 16/25) was significantly higher than that of CD21(-) lymphoma (38.2%, 21/55). There were more CD21(+) lymphoma patients who were at clinical stages I-II (52.0%, 13/25) than patients with CD21(-)lymphomas (23.6%, 13/55). There were also more CD21(+) lymphoma patients (68.0%, 17/25) having less than two extranodal sites involvement than CD21(-)lymphoma patients (41.8%, 23/55). In addition, there were more CD21(+) lymphoma patients with IPI 0-2 (68.0%, 17/25) than CD21(-)lymphoma patients (41.8%, 23/55). There were more CD21(+) lymphoma patients with GCB subtype (60.0%, 15/25) than CD21(-)lymphoma patients (23.6%, 13/55). Death related to DLBCL was less in CD21(+) lymphoma patients (32.0%, 8/25) than CD21(-) lymphoma patients (56.4%, 31/55). Univariate analysis showed that these clinical pathological characteristics affected the overall survival of DLBCL patients, including age, ECOG score, LDH, extranodal involvement, IPI index, CD21 expression, treatment option and efficacy (P < 0.05) . Cox multivariate analysis showed that ECOG score, LDH, extranodal involvement, CD21 expression were closely related to prognosis, and the difference was statistically significant (P < 0.05). Among the 80 patients, the overall survival (OS) of CD21(+) lymphoma patients was significantly higher than that of CD21(-) lymphoma patients.

CONCLUSIONSThe expression of CD21 is associated with young age at onset, early clinical stage, small number of involvement and low IPI index. The OS and median overall survival of CD21(+) lymphoma patients are significantly higher than those of CD21(-) patients. CD21 expression, ECOG score, LDH, extranodal involvement are independent prognostic factors in DLBCL, and in particular, the expression of CD21 is more significant in the prognosis of DLBCL patients.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Child ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Gastrointestinal Neoplasms ; pathology ; Germinal Center ; pathology ; Humans ; Immunohistochemistry ; L-Lactate Dehydrogenase ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prednisone ; therapeutic use ; Prognosis ; Receptors, Complement 3d ; metabolism ; Retrospective Studies ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult

OBJECTIVETo 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).

METHODSTwo-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.

RESULTSThe 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).

CONCLUSIONSNon-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.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Germinal Center ; pathology ; Humans ; Immunophenotyping ; Lymphatic Metastasis ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Retrospective Studies ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; therapeutic use ; Female ; Germinal Center ; pathology ; Humans ; Immunohistochemistry ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; Vincristine ; therapeutic use

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; analogs & derivatives ; therapeutic use ; Female ; Follow-Up Studies ; Germinal Center ; pathology ; Humans ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Recurrence ; Retrospective Studies ; Rituximab ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult